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10.1101/2022.04.21.22273594 | DBS for substance use disorders? An exploratory qualitative study of perspectives of people currently in treatment | Background and AimsDeep brain stimulation (DBS) has shown promise as a treatment option for substance use disorders (SUDs), but may have unique ethical risks due to stigma and other factors. Previous studies have elicited researcher and clinician opinions on those risks, but none have studied perspectives of people living with SUDs.
MethodsParticipants were recruited through a national inpatient treatment network employing purposive sampling for representation of minoritized groups and diversity of substances. Participants viewed a short video introducing DBS, followed by a 1.5 hour semi-structured interview on their experiences with SUDs and their perspectives on DBS as a future treatment option. Interviews were analyzed by multiple coders who iteratively identified salient themes.
ResultsWe interviewed 20 people in 12-step based, inpatient treatment programs (10 [50%] white/Caucasian, 7 Black/African American [35%], 2 Asian [10%], 1 Hispanic/Latino [5%], and 1 [5%] Alaska Native/American Indian; 11 [45%] women). Interviewees described a variety of barriers they currently faced through the course of their disease that mirrored barriers often associated with DBS (stigma, invasiveness, maintenance burdens, privacy risks). The majority of respondents expressed interest in DBS as a future treatment option, emphasizing the importance of exploring novel treatment options and keeping individual treatment goals as key guiding considerations.
ConclusionsThe perspectives of people with lived experience of SUDs contrasted with previous surveys of provider attitudes on DBS for SUDs. Individuals with SUDs gave relatively less weight to surgical risks and clinical burdens associated with DBS. These differences derived largely from their experiences living with an often-fatal disease, encountering limitations of current treatment options, and their familiarity with 12-step treatment paradigms that prioritize having multiple therapeutic "tools." These findings support the study of DBS as a treatment option for SUDs, with extensive input from people with SUDs and advocates. | addiction medicine |
10.1101/2022.04.24.22274149 | Ribavirin antiviral combination therapy in COVID 19, a single-center experience | BackgroundCOVID 19 infection has a similar clinical spectrum of disease presentation such as SARS and MERS in the past. These led to the assumption of the possibility to treat COVID 19 infection with antivirals which had been used to treat SARS and MERS.
MethodsA retrospective analysis was done on the data of SEV COVID Trial in symptomatic adult patients of COVID 19 infection with objectives to explore whether ribavirin antiviral combinations reduces the need of both noninvasive and invasive ventilators in treatment of COVID 19 infections.
ResultsThe patients were categorized as "Cohort A" consisting of 40 patients and "Cohort B" of 61 patients as Cohort A being the group of patients who received the standard therapy and Cohort B the group of patients who received the ribavirin combination therapy.
ConclusionThe study concluded that there was no statistically significant difference in regard to the need of noninvasive ventilation and invasive ventilation and also the development of multi-organ dysfunction in between the two Cohorts. Also, with progress of time, the proportion of patients with single organ dysfunctions in the two cohorts showed gradual recovery without any statistically significant differences. | infectious diseases |
10.1101/2022.04.20.22273990 | Revisiting IgG antibody reactivity to Epstein-Barr virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and its potential application to disease diagnosis | Infections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls. In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis. With this purpose, we re-analysed a previously published microarray data on the IgG antibody responses against 3,054 EBV-related antigens in 92 patients with ME/CFS and 50 HCs. This re-analysis consisted of constructing different regression models for binary outcomes with the ability to classify patients and HCs. In these models, we tested for a possible interaction of different antibodies with age and gender. When analyzing the whole data set, there were no antibody responses that could be used to distinguish patients from healthy controls. A similar finding was obtained when comparing patients with noninfectious or unknown disease trigger to healthy controls. However, when data analysis was restricted to the comparison between HCs and patients with a putative infection at disease onset, we could identify stronger antibody responses against two candidate antigens (EBNA4_0529 and EBNA6_0070). Using antibody responses to these two antigens together with age and gender, the final classification model had an estimated sensitivity and specificity of 0.833 and 0.720, respectively. This reliable case-control discrimination suggested the use of the antibody levels related to these candidate viral epitopes as biomarkers for disease diagnosis in this subgroup of patients. When a bioinformatic analysis was performed on these epitopes, it revealed a potential molecular mimicry with several human proteins. To confirm these promising findings, a follow-up study will be conducted in a separate cohort of patients. | infectious diseases |
10.1101/2022.04.22.22274113 | Heme Oxygenase-1 Promoter (GT)n Alleles and Neurocognitive Functioning in Thai Youth with Perinatally-Acquired HIV: A Pilot Study | BackgroundHeme oxygenase-1 (HO-1) gene promoter (GT)n dinucleotide repeat length variations may modify HIV-associated neurocognitive impairment (HIV-NCI) risk. Among adults, short HO-1 (GT)n alleles associate with greater HO-1 antioxidant enzyme inducibility and lower rates of HIV-NCI. This pilot study examined associations between HO-1 (GT)n alleles and neurocognitive outcomes in a sample of Thai youth (13-23 years) with perinatally-acquired HIV (PHIV) and demographically-matched HIV-negative controls.
MethodsParticipants completed neurocognitive testing and provided blood samples for DNA extraction and sequencing of HO-1 promoter (GT)n dinucleotide repeat lengths. Allele lengths were assigned based on number of (GT)n repeats: <27 Short (S); 27-34 Medium (M); >34 Long (L). Relationships between HO-1 (GT)n repeat lengths and neurocognitive measures were examined, and differences by HO-1 (GT)n allele genotypes were explored.
ResultsNearly half (48%) of all HO-1 (GT)n promoter alleles were short. Longer repeat length of participants longest HO-1 (GT)n alleles significantly associated with poorer processing speed (Total sample: r=-.36, p=.01; PHIV only: r=-.69, p<.001). Compared to peers and controlling for covariates, SS/SM genotypes performed better in processing speed, and SS genotypes performed worse in working memory.
ConclusionsA high frequency of short HO-1 (GT)n alleles was found among these Thai youth, as previously observed in other cohorts of people of Asian ancestry. In contrast to previous adult studies, the presence of a short allele alone did not associate with better neurocognitive performance, suggesting additional modifying effects among the different alleles. Research is needed to determine whether HO-1 (GT)n promoter genotypes differentially influence neurocognitive functioning across the lifespan and different ethnic backgrounds. | hiv aids |
10.1101/2022.04.23.22274199 | Anti SARS-CoV2 seroprevalence in Zanzibar in 2021 before the Omicron wave | ObjectivesFor Tanzania including Zanzibar, The development of the COVID-19 pandemic has remained unclear, since reporting cases was suspended during2020/21. The present study provides first data on the COVID-19 seroprevalence among Zanzibari before the omicron variant wave starting in late 2021.
DesignDuring August through October 2021 representative cross-sectional data were collected from randomly selected households in 120 wards of the two main islands, Unguja and Pemba. Participants voluntarily provided blood samples to test their sera for antibodies against SARS-CoV2 in a semiquantitative enzyme-linked immunosorbant assay (ELISA).
Results57% of the 2080 sera analysed were positive without significant differences between Unguja and Pemba or between rural and urban areas, similar to observations from other sub-Saharan Africa countries.
ConclusionsThe antibody levels observed are most likely to previous infections with SARS-CoV2, since vaccination was basically not available before the survey. Therefore, this study provides first insight, how many Zanzibari have had COVID-19 before the Omicron variant. Further, it provides the appropriate basis for a follow-up survey addressing how this seroprevalence influenced the susceptibility to the Omicron variants, given harmonised methodologies are used. | infectious diseases |
10.1101/2022.04.24.22274200 | Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell depleting agents | BackgroundAdministration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell depleting agents that hinder the endogenous humoral response. However, little is known on the impact of anti-CD20 pre-exposition and the use of different sources of plasma (convalescent versus vaccinated) on the kinetics of SARS-CoV-2-specific antibodies and viral evolution after plasma therapy.
MethodsEligible COVID-19 patients (n = 36), half of them after anti-CD20 targeted therapy, were treated with therapeutic plasma from convalescent (n = 17) or mRNA-vaccinated (n = 19) donors. Each plasma-transfused patient was thoroughly monitored over time by anti-S IgG quantification and whole-genome SARS-CoV-2 sequencing.
ResultsThe majority of anti-CD20 pre-exposed patients (15/18) showed progressive declines of anti-S protein IgG titers following plasma therapy, indicating that they mostly relied on the passive transfer of anti-SARS-CoV-2 antibodies. Such antibody kinetics correlated with prolonged infection before virus clearance, contrasting with the endogenous humoral response predominantly present in patients who had not received B-cell depleting agents (15/18). No relevant differences were observed between patients treated with plasma from convalescent and/or vaccinated donors. Finally, 4/30 genotyped patients showed increased intra-host viral evolution and 3/30 included 1 to 4 spike mutations, potentially associated to immune escape.
ConclusionsConvalescent and/or vaccinated plasma therapy may provide anti-SARS-CoV-2 antibodies and clinical benefit to B-cell depleted COVID-19 patients. Only a limited number of patients acquired viral mutations prior to clinical recovery, yet our study further emphasizes the need for long-term surveillance for intra-host variant evolution, to guide best therapeutic strategies. | infectious diseases |
10.1101/2022.04.24.22273395 | Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta and Delta-plus variants | As SARS-CoV-2 continues to evolve, several variants of concern (VOCs) have arisen which are defined by multiple mutations in their spike proteins. These VOCs have shown variable escape from antibody responses, and have been shown to trigger qualitatively different antibody responses during infection. By studying plasma from individuals infected with either the original D614G, Beta or Delta variants, we show that the Beta and Delta variants elicit antibody responses that are overall more cross-reactive than those triggered by D614G. Patterns of cross-reactivity varied, and the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta plus (Delta+) which differs from Delta by a single K417N mutation in the receptor binding domain, suggesting the plasma response targets the N417 residue. To probe this further, we isolated monoclonal antibodies from a Beta-infected individual with plasma responses against Beta, Delta+ and Omicron, which all possess the N417 residue. We isolated a N417-dependent antibody, 084-7D, which showed similar neutralization breadth to the plasma. The 084-7D mAb utilized the IGHV3-23*01 germline gene and had similar somatic hypermutations compared to previously described public antibodies which target the 417 residue. Thus, we have identified a novel antibody which targets a shared epitope found on three distinct VOCs, enabling their cross-neutralization. Understanding antibodies targetting escape mutations such as K417N, which repeatedly emerge through convergent evolution in SARS-CoV-2 variants, may aid in the development of next-generation antibody therapeutics and vaccines.
ImportanceThe evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring varying immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants, and to define shared epitopes. We show that Beta and Delta infection resulted in antibody responses that were more cross-reactive compared to the original D614G variant, but each with differing patterns of cross-reactivity. We further isolated an antibody from Beta infection, which targeted the N417 site, enabling cross-neutralization of Beta, Delta+ and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics. | infectious diseases |
10.1101/2022.04.20.22274076 | Safety, tolerability and immunogenicity of Biological Es CORBEVAX vaccine in children and adolescents: A Prospective, Randomised, Double-blind, Placebo controlled, Phase-2/3 Study. | BackgroundAfter establishing safety and immunogenicity of Biological Es CORBEVAX vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study.
MethodsThis is a phase-2/3 prospective, randomised, double-blind, placebo controlled, study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX vaccine in children and adolescents of either gender between <18 to [≥]12 years of age in Phase-II and <18 to [≥]5 years of age in Phase-III with placebo as a control. This study has two age sub groups; age subgroup-1 with subjects <18 to [≥]12 years of age and age subgroup-2 with subjects <12 to [≥]5 years of age. In both age sub groups eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAX vaccine or Placebo in 3: 1 ratio.
FindingsThe safety profile of CORBEVAX vaccine in both pediatric cohorts was comparable to the placebo control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all the reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAX vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing antibody (nAb)-titers against Ancestral Wuhan and Delta strains. Significantly high interferon gamma immune response (cellular) was elicited by CORBEVAX vaccinated subjects with minimal effect on IL-4 cytokine secretion.
InterpretationsThe safety profile of CORBEVAX vaccine in <18 to [≥]5 years children and adolescents was found to be safe and tolerable. The adverse event profile was also found to be acceptable. Significant increase in anti-RBD IgG and nAb titers and IFN-gamma immune responses were observed post vaccination in both pediatric age sub groups. Both humoral and cellular immune responses were found to be non-inferior to the immune responses induced by CORBEVAX vaccine in adult population. This study shows that CORBEVAX vaccine is highly immunogenic and can be safely administered to pediatric population as young as 5 years old.
The study was prospectively registered with clinical trial registry of India-CTRI/2021/10/037066 | infectious diseases |
10.1101/2022.04.25.22274259 | Oral Cancer Prevalence, Mortality, and Costs in Medicaid and Commercial Insurance Claims Data | ObjectivesThis study compared prevalence, incidence, mortality rates, treatment costs, and risk factors for oral and oropharyngeal cancer (OC/OPC) between two large cohorts of adults in 2012-2019.
MethodsMedicaid and commercial claims data were from the IBM Watson Health MarketScan Database. Logistic regression analyses estimated incidence and risk factors for OC/OPC. Mortality was calculated by merging deceased individuals Medicaid files with those of the existing cancer cohort. Costs were calculated by summing costs of outpatient and inpatient services.
ResultsThe prevalence of OC/OPC in the Medicaid cohort decreased each year (129.8 cases per 100,000 enrollees in 2012 to 88.5 in 2019); commercial enrollees showed a lower and more stable prevalence (64.7 per 100,000 in 2012 and 2019). Incidence trended downward in both cohorts, with higher incidence in the Medicaid (51.4-37.6 cases per 100,000) than in the commercial cohort (31.9-31.0 per 100,000). OC/OPC mortality rates decreased in the Medicaid cohort during 2012-2014 but increased in the commercial cohort. Total OC/OPC treatment costs were higher for commercial enrollees by an average of $8.6 million during 2016-2019. In both cohorts, incidence of OC/OPC was higher among adults who were older, male, white, used tobacco or alcohol, or had prior HIV/AIDS diagnosis, and lower among those who had seen a dentist within the prior year.
ConclusionsMedicaid enrollees experienced higher OC/OPC incidence, prevalence, and mortality compared with commercially insured adults. Having seen a dentist within the prior year was associated with a lower risk of OC/OPC diagnosis. | dentistry and oral medicine |
10.1101/2022.04.23.22274192 | Excess all-cause mortality across counties in the United States, March 2020 to December 2021 | Official Covid-19 death tallies have underestimated the mortality impact of the Covid-19 pandemic in the United States. Excess mortality, which compares observed deaths to deaths expected in the absence of the pandemic, is a useful measure for assessing the total effect of the pandemic on mortality levels. In the present study, we produce county-level estimates of excess mortality for 3,127 counties between March 2020 and December 2021. We fit two hierarchical linear models to county-level death rates from January 2015 to December 2019 and predict expected deaths for each month during the pandemic. We compare these estimates with the observed numbers of deaths to obtain excess deaths for each county-month. An estimated 936,911 excess deaths occurred during 2020 and 2021, of which 171,168 were not assigned to Covid-19 on death certificates. Urban counties in the Far West, Great Lakes, Mideast, and New England experienced a substantial urban mortality disadvantage in 2020, whereas rural counties in these regions had higher mortality in 2021. In the Southeast, Southwest, Rocky Mountain, and Plains regions, there was a rural mortality disadvantage in 2020, which was exacerbated in 2021. The proportion of excess deaths assigned to Covid-19 was lower in 2020 (76.3%) than in 2021 (87.0%), suggesting fewer Covid-19 deaths went unassigned later in the pandemic. However, in rural areas and in the Southeast and Southwest a large share of excess deaths were still not assigned to Covid-19 during 2021.
SIGNIFICANCEDeaths during the Covid-19 pandemic have been primarily monitored through death certificates containing reference to Covid-19. This approach has missed more than 170,000 deaths related to the pandemic between 2020 and 2021. While the ascertainment of Covid-19 deaths improved during 2021, the full effects of the pandemic still remained obscured in some regions. County-level estimates of excess mortality are useful for studying geographic inequities in the mortality burden associated with the pandemic and identifying specific regions where the full mortality burden was significantly underreported (i.e. Southeast). They can also be used to inform resource allocation decisions at the federal and state levels and encourage uptake of preventive measures in communities with low vaccine uptake. | epidemiology |
10.1101/2022.04.23.22274192 | Excess all-cause mortality across counties in the United States, March 2020 to December 2021 | Official Covid-19 death tallies have underestimated the mortality impact of the Covid-19 pandemic in the United States. Excess mortality, which compares observed deaths to deaths expected in the absence of the pandemic, is a useful measure for assessing the total effect of the pandemic on mortality levels. In the present study, we produce county-level estimates of excess mortality for 3,127 counties between March 2020 and December 2021. We fit two hierarchical linear models to county-level death rates from January 2015 to December 2019 and predict expected deaths for each month during the pandemic. We compare these estimates with the observed numbers of deaths to obtain excess deaths for each county-month. An estimated 936,911 excess deaths occurred during 2020 and 2021, of which 171,168 were not assigned to Covid-19 on death certificates. Urban counties in the Far West, Great Lakes, Mideast, and New England experienced a substantial urban mortality disadvantage in 2020, whereas rural counties in these regions had higher mortality in 2021. In the Southeast, Southwest, Rocky Mountain, and Plains regions, there was a rural mortality disadvantage in 2020, which was exacerbated in 2021. The proportion of excess deaths assigned to Covid-19 was lower in 2020 (76.3%) than in 2021 (87.0%), suggesting fewer Covid-19 deaths went unassigned later in the pandemic. However, in rural areas and in the Southeast and Southwest a large share of excess deaths were still not assigned to Covid-19 during 2021.
SIGNIFICANCEDeaths during the Covid-19 pandemic have been primarily monitored through death certificates containing reference to Covid-19. This approach has missed more than 170,000 deaths related to the pandemic between 2020 and 2021. While the ascertainment of Covid-19 deaths improved during 2021, the full effects of the pandemic still remained obscured in some regions. County-level estimates of excess mortality are useful for studying geographic inequities in the mortality burden associated with the pandemic and identifying specific regions where the full mortality burden was significantly underreported (i.e. Southeast). They can also be used to inform resource allocation decisions at the federal and state levels and encourage uptake of preventive measures in communities with low vaccine uptake. | epidemiology |
10.1101/2022.04.22.22274058 | Coronavirus and incomes: the COVID-19 pandemic dynamics in Africa in February 2022 | The relative accumulated and daily characteristics of the COVID-19 pandemic dynamics in Africa were used to find links with the gross domestic product per capita (GDP), percentages of fully vaccinated people and daily numbers of tests per case. A simple statistical analysis of datasets corresponding to February 1, 2022 showed that accumulated and daily numbers of cases per capita, daily numbers of deaths per capita and vaccination levels increase with the increase of GDP. As in the case of Europe, the smoothed daily numbers of new cases per capita in Africa increase with the increasing of the vaccination level. But the increase of the accumulated numbers of cases and daily number of deaths with increasing the vaccination level was revealed in Africa. In comparison with Europe, no significant correlation was revealed between the vaccination level and the number of deaths per case. As in the case of Europe, African countries demonstrate no statistically significant links between the pandemic dynamics characteristics and the daily number of tests per case. It looks that countries with very small GDP are less affected by the COVID-19 pandemic. The cause of this phenomenon requires further research, but it is possible that low incomes limit the mobility of the population and reduce the number of contacts with infected people. In order to overcome the pandemic, quarantine measures and social distance should not be neglected (this also applies to countries with a high level of income and vaccination). | epidemiology |
10.1101/2022.04.25.22274252 | A systematic review of the reporting and methodological quality of studies that use Mendelian randomisation in UK Biobank | BackgroundMendelian randomisation (MR) is a method of causal inference that uses genetic variation as an instrumental variable (IV) to account for confounding. While the number of MR articles published each year is rapidly rising (partly due to large cohort studies such as the UK Biobank making it easier to conduct MR), it is not currently known whether these studies are appropriately conducted and reported in enough detail for other researchers to accurately replicate and interpret them.
MethodsWe conducted a systematic review of reporting and analysis quality of MR studies using only individual level data from the UK biobank to calculate a causal estimate. We reviewed 64 eligible articles on a 25-item checklist (based on the STROBE-MR reporting guidelines and the Guidelines for performing Mendelian Randomisation investigations). Information on article type and journal information was also extracted.
ResultsOverall, the proportion of articles which reported complete information ranged from 2% to 100% across the different items. Palindromic variants, variant replication, missing data, associations between the IV and variables of exposure/outcome and bias introduced by two-sample methods used on a single sample were often not completely addressed (<11%).
There was no clear evidence that Journal Impact Factor, word limit/recommendation or year of publication predicted percentage of article completeness (for the eligible analyses) across items, but there was evidence that whether the MR analyses were primary, joint-primary or secondary analyses did predict completeness.
ConclusionsThe results identify areas in which the reporting and conducting of MR studies needs to be improved and highlights that this is independent of Journal Impact Factor, year of publication or word limits/recommendations. | epidemiology |
10.1101/2022.04.25.22274258 | Prevalence and characteristics of hazardous and harmful drinkers receiving general practitioners' brief advice on and support with alcohol consumption in Germany: results of a population survey | ObjectiveThe German treatment guideline on alcohol-related disorders recommends that general practitioners (GPs) offer brief advice on, and support with, reducing alcohol consumption to hazardous (at risk for health events) and harmful (exhibit health events) drinking patients. We aimed to estimate the implementation of this recommendation using data from the general population in Germany.
DesignCross-sectional analysis of data (2021/2022) of a nationally representative household survey.
SettingPopulation of Germany.
ParticipantsRepresentative sample of 2,247 adult respondents (>18 years) who reported hazardous or harmful drinking according to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; score females: 4-12, males: 5-12).
Main outcome measureEver receipt of "brief GP advice on, or support with, reducing alcohol consumption". Differences in the likelihood of ever receiving advice and/or support (yes/no) relative to respondents sociodemographic, smoking, and alcohol consumption characteristics were estimated using logistic regressions.
ResultsEver receipt of GP advice on/support with reducing alcohol was reported among 6.3% (95%CI=5.3%-7.4%), and the offer of support among 1.5% (95%CI=1.1%-2.1%) of the hazardous and harmful drinking respondents. The likelihood of having ever received advice/support was positively associated with being older (odds ratio (OR)=1.03 per year, 95%CI=1.01-1.04), a current or former (versus never) smoker (OR=2.36, 95%CI=1.46-3.80; OR=2.17, 95%CI=1.23-3.81), and with increasing alcohol consumption (OR=1.76 per score, 95%CI=1.59-1.95). One in two harmful drinking respondents (AUDIT-C score 10-12) reported appropriate advice/support. The likelihood was negatively associated with being female (e.g., OR=0.32, 95%CI=0.21-0.48), having a medium and high (versus low) education, and with increasing household income.
ConclusionsA small proportion of people drinking at hazardous and harmful levels in Germany report having ever received brief GP advice on, or support with, reducing alcohol consumption. The implementation of appropriate advice or support seems to be strongly linked to specific sociodemographic characteristics, tobacco smoking, and the alcohol consumption level.
Strengths and limitations of this studyO_LIThe principal strength of this study is the large, nationally representative population sample.
C_LIO_LIThe cross-sectional study design and temporality issues with our measures (alcohol consumption was measured with reference to the present and the outcome as "ever receipt of GP advice or support") limited our ability to explore causal relationships.
C_LIO_LIThe outcome measure had a complex, not entirely hierarchical structure, which may have led to respondents being unsure of which response option to select.
C_LIO_LIData were collected during the COVID-19 pandemic, during which alcohol consumption in Germany seemed to have changed. It is unclear how this might have influenced GPs behaviour.
C_LIO_LIDue to the socially loaded topic, respondents may not have answered truthfully or repressed a previous conversation with their GP on their alcohol consumption. We did not assess the GPs view on the topic.
C_LI | primary care research |
10.1101/2022.04.22.22274169 | Global burden of mental health problems among children and adolescents during COVID-19 pandemic: A systematic umbrella review | Mental health problems among children and adolescents are increasingly reported amidst the coronavirus disease (COVID-19) pandemic. In this umbrella review, we aimed to synthesize global evidence on the epidemiologic burden and correlates of child and adolescent mental health (CAMH) problems during this pandemic from existing systematic reviews and meta-analyses. We evaluated 422 citations and identified 17 eligible reviews on the epidemiology of CAMH in the context of COVID-19. Most of the reviews reported a high prevalence of anxiety, depression, sleep disorders, suicidal behavior, stress-related disorders, attention-deficit/hyperactivity disorder, and other mental health problems. Also, factors associated with CAMH such as age, gender, place of residence, educational attainment, household income, sedentary lifestyle, social media and internet use, comorbidities, family relationships, parents psychosocial conditions, COVID-19 related experiences, closure of schools, online learning, and social support were reported across reviews. As most studies were cross-sectional and used nonrepresentative samples, future research on representative samples adopting longitudinal and intervention designs is needed. Lastly, multipronged psychosocial care services, policies, and programs are needed to alleviate the burden of CAMH problems during and after this pandemic. | psychiatry and clinical psychology |
10.1101/2022.04.22.22274154 | Allogeneic Hematopoietic Cell Transplants as Dynamical Systems: Effect of Early-Term Immune Suppression Intensity on Long-Term T Cell Recovery | Reduced intensity conditioning (RIC) is fraught with risk for disease relapse. This may be overcome by donor T cell alloreactivity. Reducing the duration of intense immune suppression in the early term following transplantation may create an immunologic environment favoring rapid T cell reconstitution to influence longer term transplant outcomes. Twenty-six patients were adaptively randomized based on donor-derived T cell recovery, between 2 different dosing schedules of mycophenolate mofetil (MMF): MMF for 30 days post-transplant, with filgrastim for cytokine support (MMF30 arm, 11 patients), or MMF for 15 days post-transplant, with sargramostim (MMF15 arm, 15 patients). All patients were treated with anti-thymocyte globulin at a dose of 1.7 mg/kg/day from day - 9 through day -7 and total body irradiation, 450 cGy given in 3 fractions. Patients were well matched between the study arms and underwent HLA matched related and unrelated donor hematopoietic cell transplantation (HCT). The MMF15 arm demonstrated superior T cell recovery in the first month. This difference persisted through the first year for total T cells, T cell subsets and NK cells. T cell repertoire tended to be more diverse in the MMF15 arm. The long term superior immune recovery in the MMF15 arm is consistent with a disproportionate impact of early interventions in HCT. Clinically, shorter course MMF post-transplant was not associated with increased risk of acute or chronic graft vs. host disease (GVHD), and relapse and there was a trend toward improved overall survival in the MMF15 arm. Reducing the duration of intense immunosuppression in the early term and the use of sargramostim following allogeneic HCT is feasible and leads to superior long-term T cell recovery. This regimen should be studied to improve immune recovery in large cohorts of patients undergoing HCT with RIC. | oncology |
10.1101/2022.04.26.22274015 | Effectiveness of oral aciclovir in preventing maternal chickenpox: A comparison with VZIG | ObjectivesAlthough often presenting as a self-limiting childhood disease, chickenpox can have serious consequences if acquired in pregnancy. The UK recommendations are that varicella immunoglobulin (VZIG) is administered intramuscularly to susceptible pregnant women exposed to chickenpox prior to 20 weeks gestation. Oral aciclovir or VZIG is recommended if exposure occurs at 20+ weeks gestation. Our objective was to compare the effectiveness of oral aciclovir to VZIG in preventing maternal and neonatal chickenpox.
MethodsWe identified and followed up 186 pregnant women who were exposed to chickenpox and compared their outcomes.
Results171/186 (91.9%) of these women received either VZIG or oral aciclovir. 53 of the 145 (36.6%) women who received VZIG went on to develop chickenpox compared to 8 of the 26 (30.8%) women who received oral aciclovir (p=0.32). No statistical difference was found between the oral aciclovir and VZIG groups even after controlling for maternal age, gestational stage, type of exposure and IgG titre (adjusted OR:0.83; 95%CI:0.26-2.65; p=0.751).
ConclusionsThese findings support the use of oral aciclovir as first-line prophylaxis in pregnant women exposed at 20+ weeks, (and possibly second-line <20 weeks) as they suggest its effectiveness at preventing maternal chickenpox is either better or equal to VZIG. | infectious diseases |
10.1101/2022.04.25.22274178 | Medical Students Perception of Anatomage: A 3D Interactive (Virtual) Anatomy Dissection Table | IntroductionThe rising number of Medical Schools and the increasing demand for cadavers, amid its scarcity, has prompted the search for alternatives in Anatomy Education. This study assessed students thought of the use of Anatomage as an Anatomy teaching and learning tool in medical school.
MethodsA five-point scale questionnaire with a free hand comment section was completed by 50 medical students exposed to the use of Anatomage alongside the traditional cadaveric dissection for 2 academic sessions.
ResultsOur results findings showed that there were preference pattern variations in the use of the Anatomage for various fields of anatomy such as Gross Anatomy (48%), Histology (46%), and Neuroanatomy (2%) respectively. Furthermore, 66% opined that Anatomage and Cadaveric dissection should be complementary in teaching and learning anatomy. However, been satisfied with Anatomage was 76% (52% completely and 24% generally agreed respectively), while Anatomage increasing their interest in Anatomy was 66% (40% completely agreed and 26% generally agreed) and 74% (40% completely agreed and 34% generally agreed) of learning outcomes been achieved using Anatomage. Also, 68% stated that the micrographs were well displayed for histology teaching. Overall, 60% of the students agreed that Anatomage should be encouraged in teaching and learning Anatomy, along with other teaching aids.
DiscussionAnatomage increased students interest in Anatomy as its 3D-image display enabled better visualization of relevant anatomical structures. Anatomage has the potential to be a beneficial supplement to standard learning methods in the acquisition of 3D anatomy information. | medical education |
10.1101/2022.04.24.22273652 | Octreotide may improve pharyngocutaneous fistula healing through downregulation of cystatins: a pilot study | ObjectivePharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide.
Materials and MethodsFour healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration.
ResultsThere were 3,076 human, 332 S. mitis, 102 G. haemolyans and 42 G. adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and [~]300 proteins that had a p<0.05 between the pre-and post-octreotide groups [~]50 proteins with an FDR-corrected p<0.05 between pre-and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment.
ConclusionThis pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotides effects on saliva and reports of improved PCF healing. | otolaryngology |
10.1101/2022.04.25.22274123 | Impact of HIV and recreational drugs on cognitive functions in young men having sex with men. | ObjectivesThis study characterizes the structural and metabolic cerebral correlates of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) in a preclinical setting that considers the lifestyle of young European men exposed to HIV, including recreational drugs.
DesignProspective inclusion of participants.
MethodsSimultaneous structural brain magnetic resonance imaging (MRI) and positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) were acquired on a hybrid PET-MRI system in 23 asymptomatic young men with HIV+ (mean age: 33.6 years, age range: 23-60 years; normal CD4+ cell count, undetectable viral load). Neuroimaging data were compared with that of a group of 26 young HIV-men, highly well matched for what concerns age, lifestyle, named pre-exposure prophylaxis users (HIV-PrEP), and to a group of 23 undifferentiated matched young men (i.e., healthy controls). A comprehensive neuropsychological assessment was also administered to the HIV+ and HIV-PrEP subjects.
ResultsHIV+ subjects had lower performances in executive, attentional and working memory functions compared to HIV-PrEP subjects. No structural or metabolic differences were found between those two groups. Compared to healthy controls, HIV+ and HIV-PrEP exhibited a common frontal hypometabolism in the right prefrontal cortex that correlated with the level of recreational drug use. No structural brain abnormality was found.
ConclusionA dynamic prevention of recreational drugs use in HIV+ and HIV-PrEP subjects is mandatory to cope with their negative impact on brain function and their neurocognitive consequences. A complex interplay between recreational drugs and HIV might be involved in the development of neurocognitive disorders in young men with HIV. | hiv aids |
10.1101/2022.04.24.22274022 | Barriers to access to HIV care services in host countries: views and experiences of Indonesian male ex-migrant workers living with HIV | This study aimed to understand barriers to accessing HIV care services in host countries among Indonesian, male, former (returned) migrant workers living with HIV. The study utilised a qualitative design employing in-depth interviews to collect data from twenty-two returned migrant workers from Eastern Indonesia, recruited using the snowball sampling technique. A qualitative data analysis framework was used to guide a step-by-step analysis of the findings. Findings demonstrated that limited host-country language proficiency, lack of knowledge regarding healthcare systems in host countries and having undocumented worker status were barriers to accessing HIV care services. Data also revealed unavailability of HIV care services nearby migrants work locations, long distance travel to healthcare facilities, and challenges in accessing public transportation as barriers that impeded their access to the services. Other factors limiting the participants access to HIV services were identified as the transient and mobile nature of migrant work requiring frequent relocation and disrupting work life stability. Additionally, in lieu of formal HIV services, many participants self-medicated by using over-the-counter herbal or traditional medicines, often because of peer or social group influence regarding selection of informal treatment options. Recommendations arising from this study demonstrate the need to improve pre-departure information for migrant workers regarding healthcare system and access procedure in potential host countries. Data from this study also indicate that social services should be available to assist potential migrants to access legal channels for migrant work overseas, to ensure that Indonesian migrants can safely access healthcare services in the countries for which they are providing migrant labour. Future studies to understand barriers to accessing HIV care services among various migrant groups living with HIV are warranted to build evidence for potential social policy change. | hiv aids |
10.1101/2022.04.21.22273567 | Impact of the additional/booster dose of COVID-19 vaccine against severe disease during the epidemic phase characterized by the predominance of the Omicron variant in Italy, November 2021 - March 2022 | Despite the stunning speed with which highly effective and safe vaccines have been developed, increasingly transmissible variants are emerging. Using surveillance data from Italy (November 2021-March 2022), during the epidemic phase characterized by the predominance of the Omicron variant, vaccination with additional/booster dose significantly reduces the risk at all ages for hospitalization (relative risk (RR): 0.16; 95% confidence interval (CI): 0.13-0.19), admission to ICU (RR: 0.08; 95% CI: 0.06-0.09) and death (RR: 0.13; 95% CI: 0.10-0.16). Results support the importance of receiving a third dose of mRNA COVID-19 vaccine. | epidemiology |
10.1101/2022.04.21.22273567 | Impact of the additional/booster dose of COVID-19 vaccine against severe disease during the epidemic phase characterized by the predominance of the Omicron variant in Italy, November 2021 - March 2022 | Despite the stunning speed with which highly effective and safe vaccines have been developed, increasingly transmissible variants are emerging. Using surveillance data from Italy (November 2021-March 2022), during the epidemic phase characterized by the predominance of the Omicron variant, vaccination with additional/booster dose significantly reduces the risk at all ages for hospitalization (relative risk (RR): 0.16; 95% confidence interval (CI): 0.13-0.19), admission to ICU (RR: 0.08; 95% CI: 0.06-0.09) and death (RR: 0.13; 95% CI: 0.10-0.16). Results support the importance of receiving a third dose of mRNA COVID-19 vaccine. | epidemiology |
10.1101/2022.04.26.22274332 | Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden | Background Analyses of COVID-19 suggest specific risk factors make communities more or less vulnerable to pandemic related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics. Methods We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality. Results We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100,000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden. Conclusion These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics. | epidemiology |
10.1101/2022.04.26.22274332 | Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden | Background Analyses of COVID-19 suggest specific risk factors make communities more or less vulnerable to pandemic related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics. Methods We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality. Results We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100,000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden. Conclusion These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics. | epidemiology |
10.1101/2022.04.23.22273730 | SARS-CoV-2 detection in wastewater as an early warning: the case of metropolitan area of the city of Buenos Aires (AMBA). | Agua y Saneamientos Argentinos S.A. (AySA) delivers essential services as drinking water production and wastewater treatment for more than 14.5 million inhabitants of Buenos Aires Metropolitan Area (AMBA), Argentina, and collects residual liquids of 8.5 million through 16,178 km network. Since the very moment the World Health Organization (WHO) declared the COVID-19 pandemic, AySA developed a methodology to determine SARS-CoV-2 viral genetic load in untreated wastewater as an epidemiological surveillance tool, based on international experiences. In order to monitor viral load in the representative areas of the sewage collection system, more than 1500 samples where concentrated, by using an adapted ultracentrifugation method followed by RNA extraction and quantitative reverse transcription polymerase chain reaction (RT-qPCR), to measure the target Orf1ab gene of SARS-CoV-2 in our molecular microbiology laboratory.
This research was developed for a period that lasted from January 01 to June 02, 2021, in order to anticipate to the current second wave. The results achieved have demonstrated that changes in SARS-CoV-2 RNA are satisfactorily related to local epidemiological data for COVID-19. The association of variables is statistically significant when analyzing data from four large wastewater treatment plants, (R2 > 0.5 and p-value < 0.05), obtaining significant correlations between log10 viral genomic load and log10 positive cases reported one and two weeks later after samples were analyzed.
From the results obtained, it is concluded that the virus sewage system levels were a good predictor of clinical cases to be diagnosed in the immediate future and it is feasible to use this methodology, at local level, as an additional tool for decision-making in public health strategy.
Highlights Development of an integrated molecular sampling, analysis and detection system that can alert about the circulation of SARS-CoV-2.
Early warning of infected population.
First laboratory in a public water company to develop a monitoring method in Argentina.
Use of poly aluminum chloride (PAC) as a coagulant in the viral concentration stage. | epidemiology |
10.1101/2022.04.23.22274112 | Real-world study of the effectiveness of BBIBP-CorV (Sinopharm) COVID-19 vaccine in the Kingdom of Morocco | The Kingdom of Morocco approved BBIBP-CorV (Sinopharm) COVID-19 vaccine for emergency use on 22 January 2021 in a two-dose, three-to-four-week interval schedule. We conducted a case-control study to determine real-world BBIBP-CorV vaccine effectiveness (VE) against serious or critical hospitalization of individuals RT-PCR-positive for SARS-CoV-2 during the first five months of BBIBP-CorV use in Morocco.
The study was conducted among adults 18-99 years old who were tested by RT-PCR for SARS-CoV-2 infection between 1 February and 30 June 2021. RT-PCR results were individually linked with outcomes from the COVID-19 severe or critical hospitalization dataset and with vaccination histories from the national vaccination registration system. Individuals with partial vaccination (<2 weeks after dose two) or in receipt of any other COVID-19 vaccine were excluded. Unadjusted and adjusted VE estimates against hospitalization for serious or critical illness were made by comparing two-dose vaccinated and unvaccinated individuals in logistic regression models, calculated as (1-odds ratio) * 100%.
There were 348,190 individuals able to be matched across the three databases. Among these, 140,892 were fully vaccinated, 206,149 were unvaccinated, and 1,149 received homologous BBIBP-CorV booster doses. Unadjusted, full-series, unboosted BBIBP-CorV VE against hospitalization for serious or critical illness was 90.2% (95%CI: 87.8% - 92.0%). Full-series, unboosted VE, adjusted for age, sex, and calendar day of RT-PCR test, was 88.5% (95%CI: 85.8% - 90.7%). Calendar day- and sex-adjusted VE ranged from 93.9% to 100% for individuals <60 years, and was 53.3% for individuals 60 years and older. There were no serious or critical illnesses among BBIBP-CorV-boosted individuals.
Effectiveness of Sinopharms BBIBP-CorV was consistent with phase III clinical trial results. Two doses of BBIBP-CorV was highly protective against COVID-19-associated serious or critical hospitalization in working-age adults under real-world conditions and moderately effective in older adults. Booster dose VE should be evaluated, as booster doses of BBIBP-CorV are recommended and are being used. | public and global health |
10.1101/2022.04.26.22273923 | Implementation of a pediatric telemedicine and medication delivery service in a resource-limited setting: A pilot study of clinical safety and feasibility | ObjectiveDetermine the clinical safety and feasibility of implementing a telemedicine and medication delivery service (TMDS) to address gaps in nighttime healthcare access for children in low-resource settings.
MethodsWe implemented a TMDS in Haiti called MotoMeds: (i) A parent/guardian of a child [≤]10 years contacted the call center (6pm-5am). (ii) A provider used paper clinical decision support tools to triage the case as mild, moderate, or severe. Severe cases were referred to emergency care. For non-severe cases, call center providers gathered clinical findings to generate an assessment and plan. (iii) For households within the delivery zone, a provider and driver were dispatched with medications/fluids; the provider performed a paired in-person exam. For households outside the delivery zone, the family received phone consult alone. All families received a follow-up call at 10-days. Data were analyzed for clinical safety and feasibility.
ResultsA total of 391 cases were enrolled from September 9th, 2019 to January 19th, 2021; 89% (347) received a household visit. Most cases were triaged as mild or moderate (92%; 361). Among the severe cases, 83% (20) sought subsequent referred care. The most common complaint was a respiratory problem (63%; 246). At 10-days, 95% (329) of parents reported their childs condition as "improved" or "recovered". Ninety-nine percent (344) rated the TMDS as "good" or "great". The median phone consultation was 20 minutes, time to arrival at the household was 73 minutes and total workflow per case was 114 minutes.
ConclusionThe TMDS was a feasible healthcare delivery model with high rates of improved clinical status at 10-days.
Study registration (clinicaltrials.gov)NCT03943654 | public and global health |
10.1101/2022.04.23.22273766 | Analytical performance of 17 commercially available point-of-care tests for CRP to support patient management at lower levels of the health system | Accurate and precise point-of-care (POC) testing for C-reactive protein (CRP) can help support healthcare providers in the clinical management of patients. Here, we compared the analytical performance of 17 commercially available POC CRP tests to enable more decentralized use of the tool. The following CRP tests were evaluated. Eight quantitative tests: QuikRead go (Aidian), INCLIX (Sugentech), Spinit (Biosurfit), LS4000 (Lansionbio), GS 1200 (Gensure Biotech), Standard F200 (SD Biosensor), Epithod 616 (DxGen), IFP-3000 (Xincheng Biological); and nine semi-quantitative tests: Actim CRP (ACTIM), NADAL Dipstick (nal von minden), NADAL cassette (nal von minden), ALLTEST Dipstick (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10-40-80 (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10-30 (Hangzhou Alltest Biotech), Biotest (Hangzhou Biotest Biotech), BTNX Quad Line (BTNX), BTNX Tri Line (BTNX). Stored samples (n=660) had previously been tested for CRP using Cobas 8000 Modular analyzer (Roche Diagnostics International AG, Rotkreuz, Switzerland (reference standards). CRP values represented the clinically relevant range (10-100 mg/L) and were grouped into four categories (<10 mg/L, 10-40 mg/L or 10-30 mg/L, 40-80 mg/L or 30-80 mg/L, and > 80mg/L) for majority of the semi-quantitative tests. Among the eight quantitative POC tests evaluated, QuikRead go and Spinit exhibited better agreement with the reference method, showing slopes of 0.963 and 0.921, respectively. Semi-quantitative tests with the four categories showed a poor percentage agreement for the intermediate categories and higher percentage agreement for the lower and upper limit categories. Analytical performance varied considerably for the semi-quantitative tests, especially among the different categories of CRP values. Our findings suggest that quantitative tests might represent the best choice for a variety of use cases, as they can be used across a broad range of CRP categories. | public and global health |
10.1101/2022.04.25.22274291 | Epidemiological behavior of the contamination curve by COVID-19 in Brazil: a time series study | The Brazil is experiencing the greatest episode of sanitary collapse ever known in the countrys history. Therefore, the relevance of this study is highlighted for the scientific advance on the epidemiological behavior of the virus in Brazil, enabling the development of analyses and discussions on the factors that influenced the high rates of contamination by SARS-CoV-2 in the country. Given the above, the study in question aims to analyze the epidemiological behavior of the contamination curve by COVID-19 by epidemiological week (EW), in the years 2020-2021, in Brazil. This is an ecological study of time series, prepared using information collected through secondary means. The country of origin of the study is Brazil, and its main theme is the number of those infected during the pandemic of COVID-19, this being the dependent variable of the study. The data been analyzed from February 23, 2020, when the first case was confirmed in Brazil, to January 1, 2022. In 2021, the countrys graph shows an exorbitant growth, reaching a peak of approximately 250 new cases per 100,000 inhabitants in the 12th EW. This data became the highest rate of the pandemic in Brazil, and did not vary significantly for the next twelve weeks. Thus, it was identified that Brazil was severely impacted by the new coronavirus, considering the high rates of confirmed cases of the virus in the country, the low adhesion of the population to preventive measures, the late start of mass vaccination in the Brazilian population, and the lack of structure in the health system, which was not properly prepared for the high demand generated by COVID-19. | public and global health |
10.1101/2022.04.25.22273197 | Clinical characteristics and outcome of immunocompromised patients with COVID-19 caused by the Omicron variant: a prospective observational study | BackgroundIn the general population, illness after infection with the SARS-CoV-2 Omicron variant is less severe compared with previous variants. Data on the disease burden of Omicron in immunocompromised patients are lacking. We investigated the clinical characteristics and outcome of a cohort of immunocompromised patients with COVID-19 caused by Omicron.
MethodsSolid organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients on immunosuppressive therapy infected with the Omicron variant, were included. Patients were contacted regularly until symptom resolution. Clinical characteristics of consenting patients were collected through their electronic patient files. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed.
ResultsA total of 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received three mRNA vaccinations. While only one patient died, 23 (20%) required hospital admission for a median of 11 days. A low SARS-CoV-2 IgG antibody response (<300 BAU/mL) at diagnosis, higher age, being a lung transplant recipient, more comorbidities and a higher frailty were associated with hospital admission (all p<0.01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of them, of which one died.
ConclusionsWhile the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. Besides vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.
SummaryCOVID-19-associated morbidity and mortality in immunocompromised patients is unknown for the SARS-CoV-2 Omicron variant. This prospective registry, demonstrated low COVID-19-associated mortality in these vulnerable patients. However, morbidity remained substantial. Other interventions to abate COVID-19 severity are needed. | infectious diseases |
10.1101/2022.04.25.22273197 | Clinical characteristics and outcome of immunocompromised patients with COVID-19 caused by the Omicron variant: a prospective observational study | BackgroundIn the general population, illness after infection with the SARS-CoV-2 Omicron variant is less severe compared with previous variants. Data on the disease burden of Omicron in immunocompromised patients are lacking. We investigated the clinical characteristics and outcome of a cohort of immunocompromised patients with COVID-19 caused by Omicron.
MethodsSolid organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients on immunosuppressive therapy infected with the Omicron variant, were included. Patients were contacted regularly until symptom resolution. Clinical characteristics of consenting patients were collected through their electronic patient files. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed.
ResultsA total of 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received three mRNA vaccinations. While only one patient died, 23 (20%) required hospital admission for a median of 11 days. A low SARS-CoV-2 IgG antibody response (<300 BAU/mL) at diagnosis, higher age, being a lung transplant recipient, more comorbidities and a higher frailty were associated with hospital admission (all p<0.01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of them, of which one died.
ConclusionsWhile the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. Besides vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.
SummaryCOVID-19-associated morbidity and mortality in immunocompromised patients is unknown for the SARS-CoV-2 Omicron variant. This prospective registry, demonstrated low COVID-19-associated mortality in these vulnerable patients. However, morbidity remained substantial. Other interventions to abate COVID-19 severity are needed. | infectious diseases |
10.1101/2022.04.26.22271727 | Risk of COVID-19 breakthrough infection and hospitalization in individuals with comorbidities | BackgroundStudies have shown that those with certain high-risk comorbidities such as diabetes, chronic kidney disease (CKD), chronic lung disease, or those with immunocompromising conditions have increased risk of hospitalization from COVID-19. Here we estimate the elevated risks of breakthrough infection and hospitalization in fully vaccinated individuals with comorbidities.
MethodsUsing a population of fully-vaccinated patients in the de-identified Truveta Platform of electronic health records from January 1, 2019, to January 10, 2022, we used logistic regression to estimate risk of 1) a patient experiencing a breakthrough COVID-19 infection after being fully vaccinated, and 2) rate of hospitalization in those experiencing breakthrough infection. Potential confounding was adjusted with inverse probability weighting for each comorbidity by age, race, ethnicity, and sex. We present ORs and percentages of breakthrough infections by comorbidity status.
ResultsOf 3,424,965 fully vaccinated patients, 2.79%, 2.63%, 2.38%, 1.83% with CKD, chronic lung disease, diabetes, and those in an immunocompromised state experienced breakthrough infection, respectively, compared to 1.95% in the overall population. All cormorbidities were associated with significantly increased odds of breakthrough infections and subsequent hospitalizations. Breakthrough infection hospitalizations in populations with comorbidities ranged from 26.43% for CKD to 10.23% for chronic lung disease, with corresponding ORs of 2.22 (95% CI: 1.88 - 2.63) and 1.37 (95% CI: 1.21 - 1.55), respectively.
ConclusionsFully-vaccinated individuals with certain comorbidities experienced increased risk of breakthrough COVID-19 infection and subsequent hospitalizations compared to the general population. Individuals with comorbidities should remain vigilant against infection even if vaccinated.
HighlightsO_LICOVID-19 infection has greater severity in those with comorbidities.
C_LIO_LIHere we investigate the risk of breakthrough infections and hospitalizations in fully-vaccinated individuals with and without comorbidities.
C_LIO_LIWe find increased rates of breakthrough infections with all comorbidities, with CKD having the greatest risk.
C_LIO_LIIndividuals with chronic lung disease had the highest rate of breakthrough infection, but the lowest subsequent risk of hospitalization.
C_LIO_LIIndividuals with comorbidities should remain vigilant against infection even if vaccinated.
C_LI | infectious diseases |
10.1101/2022.04.27.22273307 | A systematic review of the experiences of minority language users in health and social care research | To obtain the most rigorous results in health and social care research (HSCR), it is important to have a representative sample. Culture can sometimes be overlooked but can be important to the individual concerned. Ethnic minorities are often not accounted for in HSCR. Migration, equality, and diversity issues are now important priorities and therefore need to be considered by researchers. Therefore, it is important to explore the literature examining the experiences of minority language users in HSCR. A systematic review (SR) of the literature was conducted to answer the research question. SPIDER framework and Cochrane principles were utilized for the SR. Five databases were searched, yielding 5311 papers initially. A SR protocol was developed and published in PROSPERO. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020225114analysis. Following the title and abstract review by two authors, 74 papers were included, and a narrative account was provided. Six themes were identified: 1. Disparities in health care; 2. Maternal health; 3. Mental health; 4. Methodology in health research; 5. Migrant and minority health care; 6. Racial and ethnic gaps in health care. It was evident that language barriers (including language proficiency) and cultural barriers still exist in terms of recruitment, possibly effecting the validity of the results. Several papers acknowledged language barriers but did not act on this information. Ethnic minorities needs are not completely addressed in HSCR. Despite research acknowledging different cultures over the past 40 years, there is a need for this to be fully acknowledged and embedded in the research process. We propose that future research should include details of ethnicity and languages spoken so that readers can understand the sample composition to be able to interpret the results in the best way, recognising the significance of culture and language.
2-4 Key messages, detailing the main points made in the paperO_LIEthnic minorities needs are not completely addressed in health and social care research. Despite research acknowledging different cultures over the past 40 years, there is a need for this to be fully acknowledged and embedded in the research process.
C_LIO_LIEthnic background and languages spoken by the research participants should be identified and addressed throughout the research process (from design of the study to dissemination of findings).
C_LIO_LILanguage and cultural preferences should be appropriately considered/included in the analysis.
C_LIO_LIFuture research should include details of ethnicity and languages spoken so that readers can understand the sample composition to be able to interpret the results in the best way, recognising the significance of culture and language.
C_LI | health systems and quality improvement |
10.1101/2022.04.26.22274261 | Spatio-temporal dynamics of malaria in Zanzibar, 2015-2020 | BackgroundDespite the continued high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years. The aims of the analyses presented here were to (i) assess the spatio-temporal dynamics of malaria in Zanzibar between 2015 and 2020, and (ii) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting, thereby allowing for more effective programmatic resource allocations.
MethodsData routinely collected by Zanzibars Malaria Case Notification (MCN) system were analyzed. The system collects detailed socio-demographic and epidemiological data from all malaria cases who are passively detected and reported at the islands 313 public and private health facilities (defined as primary index cases), as well as through case follow-up and reactive case detection (defined as secondary cases). Using these data, spatio-temporal analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons and its correlation with 2015-2020 rainfall.
ResultsFrom January 1, 2015, to April 30, 2020, 22,686 index cases were notified by health facilities and reported through the MCN system. Number of cases reported showed declining trends from 2015 to 2017, followed by an increase from 2018 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed-up index cases was approximately 70% for all years. Change point analysis identified 10 distinct periods of malaria transmission across the study period, and the seasonality of reported index cases was significantly correlated to the amount of precipitation that occurred during the previous rainy season. Out of Zanzibars 388 shehias, 79 (20.3%) were identified as malaria hotspots in any given year between 2015 and 2020; these hotspots reported 52% of all index cases during the study period. Of the 79 shehias identified as hotspots, 12 (3% of all shehias) were hotspots in more than four years, i.e., considered temporally stable, reporting 14.5% of all index cases.
ConclusionsOur findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006, with mean annual shehia incidence being 3.8 cases per 1,000 over the 2015-2020 study period. Spatio-temporal analyses identified hotspots, some of which were stable across multiple years. From a programmatic perspective, malaria efforts should progress from an approach that is based on universal coverage of interventions to an approach that is more tailored and nuanced, with resources prioritized and allocated to a select number of hotspot shehias. | epidemiology |
10.1101/2022.04.25.22274279 | Recent advances in efficacy of corticosteroids as adjunct therapy for the treatment of community-acquired pneumonia in children: a systematic review and meta-analysis. | It has been recently shown that the adjunct use of corticosteroids in the treatment of community-acquired pneumonia shorten the time taken to reach clinical stability (time to clinical stability) in patients with community-acquired pneumonia (CAP). Considering the hyperglycemic effects of corticosteroids, there are concerns about the efficacy and safety of this therapy for children with CAP. Our objective is to evaluate the influence of recent advances in adjunct corticosteroid use and/or aerosolized antibiotic administration on admission to hospital with our main outcome being duration of fever and hospital stay, and additional outcomes as the time to clinical stability therapeutic efficacy, C-reactive protein and defervescence at 24, 48, and 72 hours after starting treatment in a well-defined cohort of children with community-acquired pneumonia. Therapeutic efficacy is defined as the rate of achieving clinical recovery with no fever, improvement or disappearance of cough, and improved or normal laboratory values. Five academic literature databases will be searched using Boolean keyword searches. Articles eligible for inclusion are those that present original research with the study topic as CAP, the study was designed as a randomized controlled trial (RCT) or clinical trial (CT) or an observational study with controls. The review will result in a narrative synthesis that summarizes the effectiveness of corticosteroid use in children. | pediatrics |
10.1101/2022.04.22.22274171 | Application and reflection of blended learning in theoretical and practice courses of periodontology education | BackgroundBlended learning mode has been widely applied in medical education, especially during the current COVID-19 pandemic. This study is to evaluate the effectiveness of blended learning mode in periodontal education for further promotion.
MethodsThe blended learning mode consists of face-to-face classes and SPOCs built on the Xfaike online course platform. The preparation before the courses included the optimization of teaching calendar, establishment of online learning platform, integration of the online and offline content. The feedback was evaluated by a questionnaire involving instruction method, instruction content and learning outcomes.
ResultsAll of the participants (n=65) answered the questionnaire. According to the questionnaire, the blended learning mode has been approved by all of the students. More than 95% of students convinced that blended learning mode can improve their self-learning ability. About 84.62% of students could finish the preview and review task of online courses. All of the students believed that they can exchange their questions with teachers more pertinently in offline classes after online learning, and online learning videos can be viewed smoothly and repeatedly at any time.
ConclusionsThe blended learning mode has been highly accepted among students, as the learning platform could provide abundant learning materials, improve self-learning ability, and provide a deeper understanding of knowledge. Thus, the blended learning could be considered as a promising educational mode for medical students to meet higher educational requirements. | medical education |
10.1101/2022.04.21.22272785 | Digital therapy to improve stuttering symptoms in patients with a deficit of spectral power in the EEG beta frequency band | BackgroundStuttering is a speech disorder that affects more than 70 million people worldwide, limiting their ability to communicate and socialize. In recent decades, several studies have demonstrated a link between stuttering and a deficit of {beta} electroencephalographic (EEG) power.
Aim and MethodsThis study investigates the efficacy of a novel auditory neuro modulating technology that leverages euphonic music tracks with broad-spectrum binaural beats to induce selective EEG spectral power changes. Adults with stuttering (AWS, n=6) and participants from the control group (n=6) were exposed to euphonic binaural stimuli for 5 minutes. The EEG and electrocardiographic (ECG) bio-signals were recorded prior, during, and after exposure.
ResultsDuring standard reading tasks without stimulation, {beta}-power in the left hemisphere in the adults without stuttering and with stuttering differed. The left-right hemisphere asymmetry in {beta}-wave power was observed in the control group but not in AWS. After the stimulation, the power of {beta}-band in AWS participants in the left hemisphere increased 1.54-fold, while changes in the right hemisphere activity were not significant. Average {beta}-band power within left frontotemporal area and temporoparietal junction after stimulation in AWS participants shows an increase of {beta}-band in left frontotemporal junction by 1.65-fold and in left temporoparietal by 1.72-fold. The changes in the quality of speech were assessed based on the speech rate and the rate of speech disfluencies evaluated by speech therapists. The rate of disfluencies dropped significantly after the stimulation (median 74.70% of the baseline rate), but the effect was not significantly different from the baseline 10 min later (median 65.51% of the baseline rate). Similarly, the speech rate significantly increased immediately after the stimulation (median 133.15%) but was not significantly different 10 min later (median 126.63% of the baseline rate). In this study, we found significant correlations of {beta}-activation level in left temporoparietal projection (Spearman{rho} =-0.54,) and left frontotemporal area (Spearman{rho} =-0.58) with disfluency rate of speech.
ConclusionsWe show for the first time that auditory binaural beats stimulation can substantially improve speech fluency in AWS and its effect is related to boost of EEG {beta}-band power in speech-production centers. The changes in {beta} power are detected immediately after the exposure and persist 10 min later. Additionally, these effects are accompanied by a reduction in stress level as monitored by ECG markers. This suggests that auditory binaural beats stimulation temporarily improves speech quality in AWS by increasing {beta}-band power of EEG in speech centers of the brain. | neurology |
10.1101/2022.04.25.22274179 | Intra-myonuclear inclusions are diagnostic of oculopharyngeal muscular dystrophy | The pathologies of oculopharyngeal muscular dystrophy (OPMD) and oculopharyngodistal myopathy (OPDM) are indistinguishable. We found that p62-positive intra-nuclear inclusions (INIs) in myonuclei (myo-INIs) were significantly more frequent in OPMD (11.4 {+/-} 4.1%, range 5.0- 17.5%) than in OPDM and other rimmed vacuolar myopathies (RVMs) (1-2% on average, range 0.0-3.5%, p<0.0001). In contrast, INIs in nonmuscle cells (nonmuscle-INIs) were present in OPDM, but absent in other RVMs, including OPMD. These results indicate that OPMD can be differentiated from OPDM and other RVMs by the frequent presence of myo-INIs ([≥]5%) and the absence of nonmuscle-INIs in muscle pathology. | neurology |
10.1101/2022.04.23.22274207 | Patient Experience with Amputation or Limb Loss: Literature Review | BackgroundsAmputation which is the removal of body parts, the reality faced by patients who must be amputated raises various responses ranging from rejection to acceptance. The process of each patient is certainly different according to the experience experienced by each patient.
MethodsThis literature review uses articles published from 2018-2022 with source from databased ScienceDirect, Pubmed, Scopus, Sage Journals, EBSCO-Host, BMC Journal, Springer Link, Taylor and Francis, and ProQuest. The keywords used are patient experience, perspectives of patients, amputations, limb loss, low extremity amputation, qualitative, qualitative study. Article selection follows "PRISMA" flow.
ResultsThis systematic review have a total of 6 articles meet the criteria for analysis. Respondents involved in this qualitative research amounted to 109 respondents who had undergone the amputation process. There are several themes that are used to explore the patients experience, the themes used are divided into several aspects in the form of aspects of physical changes, aspects of psychological changes, and also aspects of social adaptation that patients must go through after undergoing the amputation process.
ConclusionThrough a qualitative study, it was found that the average patient expressed feelings of worry, fear, anxiety, feeling useless, no longer liking his body, feeling lost in self-confidence, and no longer wanting to interact socially because of the negative response from the surrounding environment towards the patients. | nursing |
10.1101/2022.04.21.22274130 | Weight-Normative Messaging Predominates on TikTok - A Qualitative Content Analysis | Tiktok is a social media platform with many adolescent and young adult users. Food, nutrition, and weight-related posts are popular on TikTok, yet there is little understanding of the content of these posts, and whether nutrition-related content is presented by experts. The objective was to identify key themes in food, nutrition, and weight-related posts on TikTok. 1000 TikTok videos from 10 popular nutrition, food, and weight-related hashtags each with over 1 billion views were downloaded and analyzed using template analysis. The one-hundred most viewed videos were downloaded from each of the ten chosen hashtags. Two coders then coded each video for key themes. Key themes included the glorification of weight loss in many posts, the positioning of food to achieve health and thinness, and the lack of expert voices providing nutrition information. The majority of posts presented a weight-normative view of health, with less than 3% coded as weight-inclusive. Most posts were created by white, female adolescents and young adults. Nutrition-related content on TikTok is largely weight normative, and may contribute to disordered eating behaviors and body dissatisfaction in the young people that are TikToks predominant users. Helping users discern credible nutrition information, and eliminate triggering content from their social media feeds may be strategies to address the weight-normative social media content that is so prevalent. | nutrition |
10.1101/2022.04.22.22274153 | Leg ulcers are associated with an increased risk of Sickle eye disease in Lagos. | Key PointPatients with sickle cell Leg ulcers are 5.9 times more likely to develop sickle retinopathy.
Leg ulcers are a common sign in Sickle Cell Disease. But to what extent are they indicative of Sickle cell eye disease in these patients? This short communication assesses to what extent leg ulcers predict the presence of sickle eye disease in Nigerian patients.
This was a clinic based, comparative non-interventional study, conducted at both the Hematology Clinic and Eye clinic in Lagos University Teaching Hospital (LUTH). One hundred consecutive cases of Sickle Cell Disease (SCD) patients (HbSS and HbSC) attending the Haematology Clinic were compared with 100 age and sex matched non-SCD HbAA controls. The presence of leg ulcers was sought in both groups, and all had assessment for ocular anterior and posterior signs of SCD. Cases and controls were comparable in age and sex. Amongst 100 Cases, 85 were HbSS and 15 HbSC. Leg ulcers were present in 18 patients. Eighty-two cases had either anterior or posterior SCD related ocular manifestations. Patients with leg ulcer were found to be at higher risk of developing Conjunctival Sickle Sign, Retinal Venous Tortuosity and Proliferative Sickle Retinopathy with an increased likelihood of 22.9, 7.1 and 5.9 times respectively. We believe this is the first study to quantify this association.
ConclusionsThis study suggests that sickle cell eye disease is more likely to develop in sickle cell disease patients with leg ulcers. Internists managing SCD patients are advised to refer patients with leg ulcers for early ocular assessment in order to prevent complications. | ophthalmology |
10.1101/2022.04.23.22274209 | A mesocorticolimbic dopamine gene network moderates the effect of early adversity on the risk for psychiatric and cardio-metabolic comorbidities | Psychiatric and cardio-metabolic conditions are commonly comorbid, being a leading cause of disability. Early adversity is a risk factor for both conditions, however, biological pathways remain unknown. The dopamine (DA) system is sensitive to early adversity and influences the development of comorbidities. We hypothesized that early life adversity would functionally link these conditions with the mesocorticolimbic dopamine system as a critical moderator pathway. We computed a co-expression based polygenic score (ePRS) reflecting variations in the function of the dopamine transporter (DAT) gene network in the prefrontal cortex and striatum, the final targets of the mesocorticolimbic pathway. We explored the interaction effects of the ePRS with a score of early life adversity on presence of psychiatric and cardio-metabolic comorbidities in adults (UK Biobank, N= 60016) and adolescents (ALSPAC, N= 910). In adults we also explored genetic and environment effects on gray matter density variations. As predicted, the mesocorticolimbic DAT1 ePRS significantly moderated the impact of early life adversity on the risk for both psychiatric (schizophrenia, neuroticism, mood and substance use disorders) and cardio-metabolic (type 2 diabetes, atherosclerosis, cardiovascular disease) comorbidities in adults and adolescents. Brain gray matter densities in the insula and prefrontal cortex were significantly associated with SNPs from the DAT1 ePRS implicating these regions as critical dopaminergic targets for psychiatric/cardio-metabolic comorbidities. These results reveal that psychiatric and cardio-metabolic comorbidities share common developmental pathways and underlying biological mechanisms. | genetic and genomic medicine |
10.1101/2022.04.24.22274229 | Using genotyping and whole-exome sequencing data to improve genetic risk prediction in deep venous thrombosis | BackgroundDeep Vein Thrombosis (DVT) is a common disease that can lead to serious complications such as pulmonary embolism and in-hospital mortality. More than 60% of DVT risk is influenced by genetic factors, such as Factor V Leiden (FVL) and prothrombin G20210A mutations (PTM). Characterising the genetic contribution and stratifying participants based on their genetic makeup can favourably impact risk prediction. Therefore, we aimed to develop and evaluate a genetic-based prediction model for DVT based on polygenic risk score (PRS) in the UK Biobank cohort.
MethodsWe performed a genome-wide association study (GWAS) and constructed a PRS in the 60% (N=284,591) of the UK Biobank cohort. The remaining 40% (N=147,164) was employed to evaluate the PRS and to perform gene-based tests on exome-sequencing data to identify effects by rare variants.
ResultsIn the GWAS, we discovered and replicated a novel variant (rs11604583) near TRIM51 gene and in the exome-sequencing data, and we identified a novel rare variant (rs187725533) located near CREB3L1, associated with 2.2-fold higher risk of DVT. In our PRS model, the top decile is associated with 3.4-fold increased risk of DVT, an effect that is 2.3-fold, when excluding FVL carriers. In the top PRS decile, cumulative risk of DVT at age of 80 years is 10% for FVL carriers, contraposed to 5% for FVL non-carriers.
ConclusionWe showed that common and rare variants influence DVT risk and that the PRS improves risk prediction on top of FVL. This suggests that individuals classified with high PRS scores could benefit from early genetic screening. | genetic and genomic medicine |
10.1101/2022.04.23.22274218 | Machine learning approaches for electronic health records phenotyping: A methodical review | ObjectiveAccurate and rapid methods for phenotyping are a prerequisite to realizing the potential of electronic health records (EHRs) data for clinical and translational research. This study reviews the literature on machine learning (ML) approaches for phenotyping with respect to the phenotypes considered, the data sources and methods used, and the contributions within the wider context of EHR-based research.
Materials and MethodsWe searched for relevant articles in PubMed and Web of Science published between January 1, 2018 and April 14, 2022. After screening, we collected data on 52 variables across 106 selected articles.
ResultsML-based methods were developed for 156 unique phenotypes, primarily using EHR data from a single institution or health system. 72 of 106 articles leveraged unstructured data in clinical notes. In terms of methodology, supervised learning is the most prevalent ML paradigm (n = 64, 60.4%), with half of the articles employing deep learning. Semi-supervised and weakly-supervised approaches were applied to reduce the burden of obtaining gold-standard labeled data (n = 21, 19.8%), while unsupervised learning was used for phenotype discovery (n = 20, 18.9%). Federated learning has been applied to develop algorithms across multiple institutions while preserving data privacy (n = 2, 1.9%).
DiscussionWhile the use of ML for phenotyping is growing, most articles applied traditional supervised ML to characterize the presence of common, chronic conditions.
ConclusionContinued research in ML-based methods is warranted, with particular attention to the development of advanced methods for complex phenotypes and standards for reporting and evaluating phenotyping algorithms. | health informatics |
10.1101/2022.04.22.22274183 | Systematic Review of Supervised Machine Learning Models in Prediction of Medical Conditions | Machine learning (ML) models for analyzing medical data are critical for both accelerating development of novel diagnostic and treatment strategies and improving the accuracy of medical care delivery. Our objective was to comprehensively review supervised ML models for diagnosis or treatment prediction. Publications indexed in PubMed were reviewed to identify articles utilizing supervised predictive ML models in medicine. Articles published between 01/01/2020-01/01/2022 were included in this review. Initially, PubMed was searched using MeSH major terms, and if more extensive search results were needed, a broader search was applied (titles/abstracts).
PubMed indexed 21,268 published articles (MeSH Major topic) describing ML methods implemented in medicine. Of those, 11,726 articles were published within the last 2 years. Most of the published ML models in medicine in the last two years were different types of deep learning models (about 75%). Fifty articles were included in this review.
Almost all categories of disease were subjects of ML predictions. Positive and negative factors in each of the scenarios need to be evaluated before the most optimal ML model is selected. Domain knowledge and collaborations between physicians and ML experts can improve the selection and prediction performance of ML models in medicine and facilitate implementation in clinical practice. Predictive ML models could provide recommendations to recruit suitable patients for clinical trials. Prediction ML models may contribute to development of more effective diagnostic and therapeutic choices, founded on evidence-based medicine. A broad range of methodological approaches have been taken toward this goal, and those approaches are presented here with their various advantages and disadvantages.
AUTHOR SUMMARYOver the last decade, there has been rapid development of Machine learning (ML) methods to analyze Big Data in medicine. ML is aimed to make the computer learn from past experiences and make predictions by recognizing patterns in medical data. We performed a comprehensive systematic literature review of recent publications (last two years), indexed in PubMed/MEDLINE that have described either traditional or deep supervised prediction ML models in medicine. We identified 21,268 articles describing ML implementation in medicine. 11,726 articles were published in the last 2 years. We presented the number of publications describing each of the most often ML methods to show current trends in development of these models. Most of the recently published ML models in medicine were deep learning models. We found that the understanding of disease is likely to lead to more accurate prediction. An important dilemma is the selection of optimal ML models for a specific task, considering amount and type of available data. Domain knowledge and collaborations between physicians and ML experts can improve the prediction performance of ML models, which could help clinicians to select the most effective diagnostic and therapeutic choices available and decrease medical errors. | health informatics |
10.1101/2022.04.24.22274125 | Towards Equitable Patient Subgroup Performance by Gene-Expression-Based Diagnostic Classifiers of Acute Infection | Host-response gene expression measurements may carry confounding associations with patient demographic characteristics that can induce bias in downstream classifiers. Assessment of deployed machine learning systems in other domains has revealed the presence of such biases and exposed the potential of these systems to cause harm. Such an assessment of a gene-expression-based classifier has not been carried out and collation of requisite patient subgroup data has not been undertaken. Here, we present data resources and an auditing framework for patient subgroup analysis of diagnostic classifiers of acute infection. Our dataset comprises demographic characteristics of nearly 6500 patients across 49 studies. We leverage these data to detect differences across patient subgroups in terms of gene-expression-based host response and performance with both our candidate pre-market diagnostic classifier and a standard-of-care biomarker of acute infection. We find evidence of variable representation with respect to patient covariates in our multi-cohort datasets as well as differences in host-response marker expression across patient subgroups. We also detect differences in performance of multiple host-response-based diagnostics for acute infection. This analysis marks an important first step in our ongoing efforts to characterize and mitigate potential bias in machine learning-based host-response diagnostics, highlighting the importance of accounting for such bias in developing diagnostic tests that generalize well across diverse patient populations. | health informatics |
10.1101/2022.04.22.22274184 | The nature and extent of enterprise virtual care physician services in Canada: an environmental scan | BackgroundEmployers in Canada are increasingly offering physician services to their employees, often through enterprise virtual care platforms. To date however, little work has been done to understand this method of organizing and delivering care.
ObjectiveTo understand the nature, extent and implications of enterprise virtual care in Canada.
MethodsWe conducted structured internet and database searches to identify enterprise virtual care platforms and their public websites. To answer our research question, we extracted data from their websites, and linked company documents, including investor reports, and information from Mergent Intellect, a web-based application with business data on Canadian companies.
FindingsWe identified nine companies offering enterprise virtual care physician services to employees in Canada on behalf of their employers. According to enterprise virtual care company claims, over four million Canadian employees and their family members have access to enterprise virtual care services. All platforms offer virtual physician services to employees and four also offer in person visits arranged through their platforms. Eight of the platforms provide primary care services and one offers only addiction medicine services. Four of the platforms offer to communicate and share information with an employees regular primary care provider. Four state they share aggregate or de-identified health data with employers.
ImplicationsEnterprise virtual care companies provide millions of Canadian employees and their families with access to physician services. These services appear to disrupt continuity of care (care by the same provider over time) and pose risks to privacy. As other Canadians do not have access to these services, enterprise virtual care is also introducing two-tiered health care broadly across Canada. | health policy |
10.1101/2022.04.24.22274236 | Estimates of Cross-Border Menthol Cigarette Sales Following the Comprehensive Tobacco Flavor Ban in Massachusetts | On June 1, 2020, Massachusetts became the first state in the US to ban all flavored tobacco product sales, including menthol cigarettes. Recent research has estimated the reduction in cigarette sales in Massachusetts following the comprehensive tobacco flavor ban, but noted that missing data on border states was a major limitation of the findings. This letter replicates the procedures of Asare et al. with 1540 state-months and then adds Asare et al.s missing states with 2420 total observations for the period January 2017 to July 2021. The replication confirms Asare et al.s adjusted estimate for the reduction in menthol cigarettes, which falls within their 95% confidence interval. However, assigning Massachusetts and its bordering states as a single treatment group leads to an increase of 191.95 (95% CI, 96.82 to 287.09) total cigarette packs sold per 1000 people in the six-state region. In the 12-month period following the comprehensive flavor ban in Massachusetts, the state sold 29.96 million fewer cigarette packs compared to the prior period. However, a total of 33.36 million additional cigarette packs were sold during the same post-ban period in the counties that bordered Massachusetts. Given decreasing rates of smoking in all five bordering states between 2019 and 2020, the increase in border-state cigarette sales following the comprehensive flavor ban should be interpreted as a lower-bound estimate for cigarettes that were ultimately consumed in Massachusetts. | health policy |
10.1101/2022.04.23.22274217 | GroceryDB: Prevalence of Processed Food in Grocery Stores | The offering of grocery stores is a strong driver of consumer decisions, shaping their diet and long-term health. While processed food has been increasingly associated with unhealthy diet, information on the degree of processing characterising an item in a store is virtually impossible to obtain, limiting the ability of individuals to make informed choices. Here we introduce GroceryDB, a database with over 50,000 food items sold by Walmart, Target, and Wholefoods, unveiling the degree of processing characterizing each food. GroceryDB indicates that 73% of the US food supply is ultra-processed, and on average ultra-processed foods are 52% cheaper than minimally-processed alternatives. We find that the nutritional choices of the consumers, translated as the degree of food processing, strongly depend on the food categories and grocery stores. We show that there is no single nutrient or ingredient "bio-marker" for ultra-processed food, allowing us to quantify the individual contribution of over 1,000 ingredients to ultra-processing. GroceryDB and the associated http://TrueFood.Tech/ website make this information available, aiming to simultaneously empower the consumers to make healthy food choices, and aid policy makers to reform the food supply. | health policy |
10.1101/2022.04.25.22274278 | Do panic values cause panic? Reporting of critical laboratory results in a tertiary hospital in Kenya | Prompt communication of critical laboratory results is important for patient safety. Various standardisation bodies have proposed procedures for handling critical results, with notification parameters outlined. However, few studies exist in low- and middle-income countries (LMIC) to document how critical results are handled. We tracked 12 types of laboratory tests over a three-week period in December 2018 and documented if and how critical test results were communicated, the time-frame for communication, and evidence of action taken on the results. During the period, 331 of 5,500 (6.1%) test results were identified as critical. Only 71 (21%) of the critical results were documented as having been communicated to the destination departments. Of the communicated results, clinicians were unaware of 21 (29.6%). Of the 12 test types, critical results were only communicated for three tests namely: potassium, haemoglobin and positive malaria tests. Communication of critical results to inpatient settings was significantly higher than to outpatient settings (p <0.05), with communication rates decreasing as the week progressed, during weekends and around holidays. The observed poor communication of critical results in an LMIC setting raise significant patient safety concerns. Laboratories in these settings need to adhere to international standards, like ISO 15189:2009, to assure safe practice. Training of staff, establishment of standard operating procedures guiding these results, and implementation of fail-proof critical result dissemination mechanisms are essential. It is important that all critical results are communicated within one hour of availability. Implementation of Order Entry and Laboratory systems should be highly considered. | health systems and quality improvement |
10.1101/2022.04.22.22273686 | Clinical evaluation of an automated, rapid mariPOC(R) antigen test in screening of symptomatics and asymptomatics for SARS-CoV-2 infections | A novel automated mariPOC(R) SARS-CoV-2 antigen test was evaluated in a Health care center laboratory among symptomatic and asymptomatic individuals seeking SARS-CoV-2 testing. According to the national testing strategy, RT-PCR was used as a reference method. A total of 962 subjects were included in this study, 4.8% (46/962) of their samples were SARS-CoV-2 RT-PCR positive, and 87% (40/46) of these were from symptomatics. Among the symptomatics, the overall sensitivity of the mariPOC(R) SARS-CoV-2 test was 82.5% (33/40), though the sensitivity increased to 97.1% (33/34) in samples with a Ct value <30. The mariPOC(R) SARS-CoV-2 test detected 2/6 PCR positive samples among the asymptomatics, four cases that remained antigen test negative had Ct values between 28 and 36. The specificity of the mariPOC(R) SARS-CoV-2 test was 100% (916/916). The evaluation showed that the mariPOC(R) SARS-CoV-2 rapid antigen test is very sensitive and specific for the detection of individuals who most probably are contagious. | infectious diseases |
10.1101/2022.04.23.22274223 | Vaping preferences of individuals who vaporise dry herb cannabis, cannabis liquids and cannabis concentrates | In 2019 an estimated 200 million people aged 15-64 used cannabis, making cannabis the most prevalent illicit substance worldwide. The last decade has seen a significant expansion in the cannabis vaporiser market, introducing cannabis vaporisation as a common administration method alongside smoking and ingestion. Despite reports of increased prevalence of cannabis vaporisation there has been little research into the use of these devices. To remedy the current dearth of data in this area this study utilised an anonymous online survey of individuals who self-reported past cannabis vaporisation. The respondents (N=557) were predominantly young (<35 years) and male. Most (91.4%) stated they had ever vaped dry herb cannabis, 59.1% reported vaporisation of cannabis oil or liquids, and 34.0% reported vaporisation of cannabis concentrates. This study identifies the types of vaporisation devices (including brands and models) employed by cannabis vapers, as well as the vaporisation temperatures and puff durations commonly used for dry herb, cannabis liquids and cannabis concentrates. To the best of our knowledge, this is the first time the usual operating temperatures of these vaporisation devices and user specific consumption patterns such as puff duration have been reported for cannabis vaping. This information will allow for more realistic experimental conditions in research settings. | addiction medicine |
10.1101/2022.04.25.22274161 | Delayed booster dosing improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine | BackgroundAntibodies are crucial for vaccine-mediated protection against many pathogens. Modifications to vaccine delivery that increase antibody magnitude, longevity, and/or quality are therefore of great interest for maximising efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6mo) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared to monthly dosing (0-1-2mo; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing was unclear.
MethodsImmunokinetics of PfRH5-specific Ig across multiple isotypes were compared between DFx and monthly regimen vaccinees. Peak responses were characterised in-depth with a systems serology platform including biophysical and functional profiling. Computational modelling was used to define the humoral feature set associated with DFx dosing. PfRH5-specific B cells were quantified by flow cytometry and sorted for single cell RNA sequencing (scRNA-seq). Differential gene expression between DFx and monthly dosing regimens was explored with Seurat, DESeq2 and gene set enrichment analysis.
ResultsDFx dosing increases the frequency of circulating PfRH5-specific B cells and longevity of PfRH5-specific IgG1, as well as other isotypes and subclasses. At the peak antibody response, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn-binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. At the same time point, scRNA-seq of PfRH5-specific B cells revealed enriched plasma cell and Ig / protein export signals in the monthly dosing group as compared to DFx vaccinees.
ConclusionsDFx dosing of the RH5.1/AS01B vaccine had a profound impact on the humoral response. Our data suggest plausible mechanisms relating to improved FcRn-binding (known to improve Ig longevity) and a potential shift from short-lived to long-lived plasma cells. Recent reports of the positive impact of delayed boosting on SARS-CoV-2 vaccine immunogenicity highlight the broad relevance of these data. | allergy and immunology |
10.1101/2022.04.23.22274206 | Pronounced Regional Variation in Esketamine and Ketamine Prescribing to US Medicaid Patients | BackgroundKetamine, and its isomer esketamine are useful for treatment resistant depression (depression not responsive to traditional antidepressants). Compared to other antidepressants, ketamine and esketamine lack a therapeutic delay and do not increase risk of suicidality in adolescents. Esketamine gained FDA approval in March of 2019.
ObjectiveThis study aimed to geographically characterize ketamine and esketamine prescriptions in the United States among Medicaid patients.
MethodsKetamine and esketamine prescription rate data per state per quarter were obtained from the Medicaid State Drug Utilization Database for 2019-2020. Total prescription rates per year for ketamine and esketamine were obtained for 2009-2020.
ResultsBetween 2009-2020, ketamine prescribing rates peaked in 2013 followed by a general decline. For ketamine and esketamine prescriptions in 2019, Montana and Indiana showed significantly higher prescription rates, respectively, relative to the national average. A total of 21 states prescribed neither ketamine or esketamine in 2019. Since its approval, esketamine prescriptions have surpassed those of ketamine. There was a 121.3% increase in esketamine prescriptions from 2019 to 2020. Ten states prescribed neither ketamine or esketamine in 2020.
ConclusionDespite the effectiveness of ketamine and esketamine for treatment resistant depression, their use among Medicaid patients was limited and variable in many areas of the US. | psychiatry and clinical psychology |
10.1101/2022.04.23.22274206 | Pronounced Regional Variation in Esketamine and Ketamine Prescribing to US Medicaid Patients | BackgroundKetamine, and its isomer esketamine are useful for treatment resistant depression (depression not responsive to traditional antidepressants). Compared to other antidepressants, ketamine and esketamine lack a therapeutic delay and do not increase risk of suicidality in adolescents. Esketamine gained FDA approval in March of 2019.
ObjectiveThis study aimed to geographically characterize ketamine and esketamine prescriptions in the United States among Medicaid patients.
MethodsKetamine and esketamine prescription rate data per state per quarter were obtained from the Medicaid State Drug Utilization Database for 2019-2020. Total prescription rates per year for ketamine and esketamine were obtained for 2009-2020.
ResultsBetween 2009-2020, ketamine prescribing rates peaked in 2013 followed by a general decline. For ketamine and esketamine prescriptions in 2019, Montana and Indiana showed significantly higher prescription rates, respectively, relative to the national average. A total of 21 states prescribed neither ketamine or esketamine in 2019. Since its approval, esketamine prescriptions have surpassed those of ketamine. There was a 121.3% increase in esketamine prescriptions from 2019 to 2020. Ten states prescribed neither ketamine or esketamine in 2020.
ConclusionDespite the effectiveness of ketamine and esketamine for treatment resistant depression, their use among Medicaid patients was limited and variable in many areas of the US. | psychiatry and clinical psychology |
10.1101/2022.04.23.22274186 | Determinants of motivated behavior are linked to fatigue and its perturbation by SARS-CoV-2 vaccination | BackgroundFatigue has an adaptive function and serves as a temporary signal to rest and save energy often in response to immune activation. It may, however, also persist in a pathological condition incurring significant burden. While subjective symptoms and scientific consensus indicate that both physical and mental determinants of motivated behavior are affected in fatigue, the underlying processes are rarely examined using objective, task-based indicators.
MethodsIn three consecutive studies, including validation (N = 48) and reliability assessments (N = 27), we use an experimental task to jointly objectify reward learning and effort execution as two determinants of behavioral motivation. In addition, we tested how fatigue and its acute perturbation in response to immune activation after SARS-CoV-2 vaccination are linked to these task-based indicators of motivation in a longitudinal cross-over design (N = 55).
ResultsThe validation study showed the utility of the experimental task for simultaneously assessing learning, effort exertion, and its regulation based on subjective confidence. The reliability assessment over a one-week period indicated that symptoms of fatigue and task behavior are highly reliable and that repetition effects have little impact on motivated behavior. Finally, in the vaccination trial, we found significant links between fatigue and task behavior. Baseline levels of fatigue predicted how effort is gauged in dependence of current confidence about reward outcomes, and state perturbations of fatigue in the context of the SARS-CoV-2 vaccination reduced confidence during learning. Importantly, task success was significantly lower in subjects who reported high fatigue at baseline and who additionally experienced stronger increase in fatigue in response to vaccination.
DiscussionOur results demonstrate that the experimental task allows to jointly assess determinants of motivated behavior, and to link its constituent processes to subjective fatigue. This suggests that our understanding of fatigue and its perturbation due to acute immune activation can benefit from objective, task-based indicators of the underlying motivational mechanisms. Future studies could build on these findings to further deepen the understanding of neurobehavioral mechanisms underlying fatigue in the context of immune activation. | psychiatry and clinical psychology |
10.1101/2022.04.24.22273790 | Specificity of cortical area and thickness as biomarkers for comorbid internalizing and externalizing mental disorders in pre-adolescence | BackgroundComorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical changes represent a simple aggregate of the effects on each disorder, and if comorbidity-related cortical surface changes relate to a distinct genetic underpinning.
MethodsWe studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (Dysthymia, Major Depressive Disorder, Disruptive Mood Dysregulation Disorder, Agoraphobia, Panic Disorder, Specific Phobia, Separation Anxiety Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder, Post-Traumatic Stress Disorder), externalizing diagnostic groups (Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct disorder) a group with comorbidity of the two and a healthy control group. Genome-wide association analysis and cell type specificity analysis were performed on 4,716 unrelated European participants from this cohort.
ResultsReduced cortical surface area but increased thickness occurs across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT changes, while those patient groups without comorbidity had significant thickness increases. Distinct biological pathways were implicated for regional SA and CT changes. Specifically, CT changes were associated with immune-related processes implicating microglia, while SA-related changes related mainly to excitatory neurons.
ConclusionsThe emergence of comorbidity across distinct clusters of psychopathology is unlikely to be a simple additive neurobiological effect. Distinct risk-adaptation processes, with unique genetic and cell-specific factors may underlie SA and CT changes. Children with highest risk but lowest resilience, both captured in their developmental morphometry, develop a comorbid illness pattern. | psychiatry and clinical psychology |
10.1101/2022.04.24.22273790 | Specificity of cortical area and thickness as biomarkers for comorbid internalizing and externalizing mental disorders in pre-adolescence | BackgroundComorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical changes represent a simple aggregate of the effects on each disorder, and if comorbidity-related cortical surface changes relate to a distinct genetic underpinning.
MethodsWe studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (Dysthymia, Major Depressive Disorder, Disruptive Mood Dysregulation Disorder, Agoraphobia, Panic Disorder, Specific Phobia, Separation Anxiety Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder, Post-Traumatic Stress Disorder), externalizing diagnostic groups (Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct disorder) a group with comorbidity of the two and a healthy control group. Genome-wide association analysis and cell type specificity analysis were performed on 4,716 unrelated European participants from this cohort.
ResultsReduced cortical surface area but increased thickness occurs across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT changes, while those patient groups without comorbidity had significant thickness increases. Distinct biological pathways were implicated for regional SA and CT changes. Specifically, CT changes were associated with immune-related processes implicating microglia, while SA-related changes related mainly to excitatory neurons.
ConclusionsThe emergence of comorbidity across distinct clusters of psychopathology is unlikely to be a simple additive neurobiological effect. Distinct risk-adaptation processes, with unique genetic and cell-specific factors may underlie SA and CT changes. Children with highest risk but lowest resilience, both captured in their developmental morphometry, develop a comorbid illness pattern. | psychiatry and clinical psychology |
10.1101/2022.04.23.22274204 | Non-pharmacological measures for the treatment of iron deficiency anemia: A systematic review and meta-analysis | ObjectiveTo conduct a systematic review and meta-analysis to evaluate the effectiveness of non-pharmacological measures for the treatment of iron-deficiency anemia (IDA).
Data sourcesMEDLINE (via PubMed), Cochrane library, SciELO/LILACS and EMBASE up to June 2021
Study selection and data extractionWe identified all randomized controlled trials (RCTs) that used non-pharmacological measures to treat IDA including iron pots/ingots, or food use were included. The outcomes of interest were hemoglobin (Hb) concentrations and prevalence of anemia.
Results479 studies were retrieved from the databases, of which 4 duplicate records were removed. After, all titles and abstracts were reviewed, 23 articles were considered potentially relevant, and were read in full and checked for eligibility. Three articles met all inclusion criteria. We also conducted a manual search for citations and a further 8 records were identified and checked for eligibility. Eleven RCTs were included in this review. Estimates showed that the use of non-pharmacological measures was associated with a statistically significant overall increase in mean Hb (MD +0.45 g/dL, 95% CI 0.05 to 0.85, p=0.03). The effect of non-pharmacological measures on the prevalence of IDA was analyzed in only 5 RCTs. Participants in the intervention groups were 2.78 times less likely to suffer from IDA than those in the control groups, OR=2.78, 95% CI 0.93, 8.29, however without significance for the overall effect (p=0.07).
ConclusionNon-pharmacological therapies have a positive effect on iron balance, and can a useful adjunct to programs to prevent and treat IDA in at-risk populations. (PROSPERO registration number CRD42021261773). | public and global health |
10.1101/2022.04.25.22274251 | Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study. | The immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety ("physio-affective") symptoms three to four months later. The present study was performed to characterize whether the effects of SpO2 and PBT on the physio-affective phenome of Long COVID are mediated by immune, oxidative and nitrosative stress (IO&NS) pathways. This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia-Fatigue (FF) scores. Around 60% of the variance in the physio-affective phenome of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Both PBT and SpO2 strongly predict OSTOX/ATIOX during Long COVID. In conclusion, the impact of acute COVID-19 on the physio-affective symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. Post-viral physio-affective symptoms have an inflammatory origin and are partly mediated by neuro-oxidative toxicity. | public and global health |
10.1101/2022.04.25.22274280 | The prevalence of SARS-CoV-2 antibodies within the community of a private tertiary university in the Philippines: a serial cross sectional study | The antibody testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to detect the presence of antibodies in a private university setting. This serial cross-sectional study determined the seroprevalence of SARS-CoV-2 antibodies using qualitative and quantitative tests. Between June 2021 to December 2021, samples from 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021. However, a decreasing trend in IgG reactivity was found in vaccinated individuals over time. IgG antibody formation was observed across all brands of vaccines. | public and global health |
10.1101/2022.04.25.22274226 | A Systematic Review of the Beighton Score Compared with Other Commonly Used Measurement Tools for Assessment and Identification of Generalised Joint Hypermobility (GJH) | This systematic review compares the validity and reliability of the Beighton Score to those of other commonly used scores for identifying generalised joint hypermobility (GJH). Inclusion criteria: English language, studies on humans, all types of study designs, publications in academic journals, publications from the year two thousand onwards, publications in print and theses. Exclusion criteria: studies not in English, studies measuring single joints only, studies published before the year 2000, cadaveric studies, papers with only abstracts available. An electronic literature search was undertaken of Pub Med/MEDLINE, Embase, Scopus, Cochrane Database, SPORT Discus, Pedro databases, followed by a manual search between August and November 2021. The final review included 73 papers. The PRISMA (2021) COSMIN (2010) guidelines and CASP (2019) criteria were used to evaluate methodological quality and bias. The Beighton Scores intra-rater and inter-rater reliability ranged between ICC 0.74-0.99 and ICC 0.72-0.98 respectively. The BS has reasonable intra-rater and inter-rater reliability, however validity cannot be accurately determined as incorporation bias was identified as a major issue in study methodology, not previously identified in the literature. Paucity of data prevented accurate assessment of other scoring systems. Urgent research is required to clarify these issues and compare the BS to other tests. No source of funding was received in in undertaking this review. The author has no conflict of interests to disclose. This review was not registered. This review has been conducted as closely as possible in accordance with the PRISMA guidelines for reporting systematic reviews. | rheumatology |
10.1101/2022.04.27.22273297 | Workplace and lifestyle heterogeneity in subjective wellbeing: Latent Class Analysis of UK Time Use Survey before and during COVID-19 | BackgroundMental health in the UK had deteriorated compared with pre-pandemic trends. The impact of COVID-19 on the subjective wellbeing of working populations with distinct lifestyles is not yet studied.
MethodsCombining time use surveys collected pre- and during COVID-19, latent class analysis was used to identify distinct lifestyles based on aggregated daily activity patterns and reported working modes. We provide qualitative pen portraits alongside pre-versus-during pandemic comparisons of intraday time use and wellbeing patterns. Lifestyle heterogeneity in wellbeing was quantified in relation to aggregated activity types.
ResultsCOVID-19 impact on wellbeing varied significantly between usual working hours (6am-6pm) and rest of the day. The decline in wellbeing outside of usual working hours was significant and consistent across lifestyles. During usual working hours, the direction of impact varied in line with working modes: wellbeing of homeworkers decreased, remained relatively stable for commuters, and increased for certain hybrid workers. Magnitude of impact correlates strongly with lifestyle: those working long and dispersed hours are more sensitive, whereas non-work dominated lifestyles are more resilient.
ConclusionThe direction and magnitude of impact from COVID-19 were not uniformly manifested across activity types, time of day, and latent lifestyles. Blurring work-life boundaries and general anxiety about the pandemic may be key determinants of the decline outside of usual working hours. During usual working hours, strong yet complex correlations between wellbeing and time-use changes suggested that policies aiming to enhance wellbeing of workers need to consider not only spatial flexibility but also provide wider support for temporal flexibility.
What is already knownIn the UK, mental health deteriorated compared with pre-pandemic trends. It is presumed that not everyone was affected equally, but there has been little evidence distinguishing population groups with distinct working modes and lifestyles.
What are the new findingsDirection of COVID-19 impact strongly correlates with working mode and extent of spatial flexibility: wellbeing decreased for homeworkers, but increased for some hybrid workers. Magnitude of COVID-19 impact strongly correlates with lifestyle and extent of temporal flexibility: those working long and dispersed hours more were sensitive, whereas non-work dominated lifestyles were more resilient.
How might this impact policyPolicymakers and employers need to consider the important function workplace has on mental health. As homeworking arrangements become permanent, the psychosocial function of traditional workplaces will become more pertinent. Flexibility around the established work-time regime will also benefit workers mental health, and give them greater control to choose and transition between lifestyles. | occupational and environmental health |
10.1101/2022.04.23.22274222 | Grandfathers and Grandsons: Social Security Expansion and Child Health in China | We examine the multigenerational impacts of a nationwide social pension program in China, the New Rural Pension Scheme (NRPS). NRPS was rolled out in full scale since 2012, and rural enrollees over age 60 are eligible to receive a minimum of 70 CNY non-contributory monthly pension. We leverage age eligibility and variations in pension receipt to identify the inter-generational effect of NRPS on health among grandchildren. We find NRPS substantially increases child weight without impacting height. Overall, child BMI z score increases by 1.09, which is largely driven by grandfathers pension receipt raising rates of overweight and obesity among grandsons. Among the potential mechanisms, our findings are more plausibly explained by a mixture of income effect, son preference, and rising inter-generational co-residence and childcare. | health economics |
10.1101/2022.04.23.22274201 | Systematic searching in Ovid Embase: understanding the MEDLINE document collection and identifying conference records | Ovid Embase is an important database in systematic searches for health and medical topics. This paper shows how the document collections on Ovid Embase can be used to limit searches and isolate the unique content from MEDLINE that is available on Embase. This is used to test a method for identifying conference records from Embase. The recommended method found 5,108,945 conference records on Embase on Ovid March 1 2022, about 14% of the database. Search strategies are provided for the scenarios that are most likely to be encountered in systematic searches. | health informatics |
10.1101/2022.04.24.22274211 | Critical Arterial Stenosis Revisited | IntroductionStenosis of an organ/tissue primary artery may produce ischemia, malfunction or only reduce blood flow reserve. Despite incomplete hemodynamic understanding of critical arterial stenosis, degree of diameter stenosis continues to be an index for patient management. This study aims to use conservation of energy to; quantitate the arterial pressure gradient produced by stenosis, determine organ/tissue perfusion pressure, blood flow and reserve as a function of degree of diameter stenosis and identify critical diameter stenosis, if it exists.
MethodsA three-component system is considered, parallel stenotic artery and collateral circulation supplying organ/tissue. Energy analysis of arterial stenosis gives the pressure gradient produced and stenosis vascular resistance. Organs/tissues intrinsically autoregulate blood flow when perfusion pressure is greater than threshold value. System energy analysis defines collateral vascular resistance and gives perfusion pressure, blood flow and reserve as a function of diameter stenosis. Renal and internal carotid artery (ICA) stenosis provide numerical examples.
ResultsThe magnitude of stenosis energy dissipation, K, is a fourth power function of stenosis diameter with a steep slope between 65% and 80%, (K = 67 to 625). Systems without collaterals, C = 0, have discrete critical stenosis values within this range. Renal critical stenosis is 74% (K = 233). Systems with poor collaterals, C < 1, have critical stenosis from 65% to 99% depending on collateral magnitude. Critical ICA stenosis begins at 70% and up to 99%, (K = 132 to {infty}). Degree of cerebral ischemia is non-linearly inversely proportional to collateral magnitude,C. Systems with good collateral circulation, C > 1, do not have critical stenosis, including the ICA (cerebral hemisphere). In these systems stenosis progression reduces blood flow reserve but does not produce ischemia.
ConclusionCritical diameter arterial stenosis may or may not exist for specific organ/tissue systems depending on the magnitude of collateral circulation. | cardiovascular medicine |
10.1101/2022.04.22.22273002 | Effect of two methods of soft tissue augmentation for socket closure on soft tissue landmarks and ridge dimensions- Results from software-based analysis of clinical data | PurposeThe aim of this study was to evaluate the effect of connective tissue grafts (CTG) and pediculated connective tissue grafts (P-CTG) for extraction socket closure on soft tissue landmarks and ridge dimensions.
Methods45 subjects were randomized into two groups, where the soft tissue closure of extraction sockets was done by pediculated connective tissue grafts (P-CTG group) and connective tissue grafts (CTG group). On photographs taken at different time-points, four markers corresponding to marginal gingiva (MG), mucogingival junction (MGJ), mesial papilla (MP) and distal papilla (DP) were placed. After image alignment and stacking, the markers were tracked through five photographs taken during the course of the therapy. The displacement, total displacement (TD), divergence and angle of maximum divergence (AMD) for each marker were recorded. Buccolingual and mesiodistal dimensions of edentulous sites were measured, and the difference from the baseline to 6-months in both the dimensions was calculated and was described as buccolingual gain (BL gain) and mesiodistal gain (ML gain) respectively.
ResultsIntergroup comparison of displacement and divergence of markers across both the groups showed varying levels of significance. P-CTG resulted in higher buccolingual dimensions at 3 months (P=0.001) and 6 months (P=0.002) when compared to the CTG group. From baseline to 6-months, the BL and MD gains were 2.82{+/-}1.29mm & 1.68{+/-}1.12mm and 1.27{+/-}0.65mm & 1.48{+/-}0.67mm in P-CTG and CTG group respectively. In the P-CTG group, TD (r=0.4; P=0.001) & AMD (r=0.5; P=0.05) of MG and TD (r=0.2; P=0.005) of MGJ resulted in BL gains. In the CTG group, TD (r=0.7; P=0.004) and AMD (r=0.3; P=0.004) of MP and AMD of MGJ was associated with a significant BL gain.
ConclusionsP-CTG and CTG had significant effects on displacement and divergence of soft tissue landmarks respectively. The relocation of these landmarks, seem to result in an improvement in the buccolingual dimensions of the post-extraction ridge. | dentistry and oral medicine |
10.1101/2022.04.23.22274214 | Estimating the period prevalence of SARS-CoV-2 infection during the Omicron (BA.1) surge in New York City (NYC), January 1-March 16, 2022 | In a population-based survey of NYC adults, we assessed positive SARS-CoV-2 tests (including via exclusive at-home testing) and possible cases among untested respondents. An estimated 27.4% (95%CI: 22.8%-32.0%) or 1.8 million adults (95%CI: 1.6-2.1 million) had SARS-CoV-2 infection. SARS-CoV-2 prevalence was high among groups that are more vulnerable to severe SARS-CoV-2 and death, including unvaccinated persons (21.7%, 95%CI 9.6%-33.8%) and those aged 65+ (17.8%, 95%CI 10.2-25.4%). Population-based representative surveys are an important adjunct surveillance tool to standard testing-based SARS-CoV-2 surveillance. | epidemiology |
10.1101/2022.04.25.22274266 | Higher contact among vaccinated can be a mechanism for negative vaccine effectiveness | Evidence from early observational studies suggested negative vaccine effectiveness for the SARS-CoV-2 Omicron variant. Using transmission modeling, we illustrated how increased contact between vaccinated individuals, vaccinated contact heterogeneity, paired with lower vaccine efficacies could produce negative measurements and how we can identify this mechanism via a key temporal signature. | epidemiology |
10.1101/2022.04.25.22274266 | Higher contact among vaccinated can be a mechanism for negative vaccine effectiveness | Evidence from early observational studies suggested negative vaccine effectiveness for the SARS-CoV-2 Omicron variant. Using transmission modeling, we illustrated how increased contact between vaccinated individuals, vaccinated contact heterogeneity, paired with lower vaccine efficacies could produce negative measurements and how we can identify this mechanism via a key temporal signature. | epidemiology |
10.1101/2022.04.23.22273899 | A comparison of different methods for handling measurements affected by medication use | In epidemiological research it is common to encounter measurements affected by medication use, such as blood pressure lowered by antihypertensive drugs. When one is interested in the relation between the variables not affected by medication, ignoring medication use can cause bias. Several methods have been proposed, but the problem is often ignored or handled with generic methods, such as excluding individuals on medication or adjusting for medication use in the analysis. This study aimed to investigate methods for handling measurements affected by medication use when one is interested in the relation between the unaffected variables and to provide guidance for how to optimally handle the problem. We focused on linear regression and distinguish between the situation where the affected measurement is an exposure, confounder or outcome. In the Netherlands Epidemiology of Obesity study and in several simulated settings, we compared generic and more advanced methods, such as substituting or adding a fixed value to the treated values, regression calibration, censored normal regression, Heckmans treatment model and multiple imputation methods. We found that often-used methods such as adjusting for medication use could result in substantial bias and that methods for handling medication use should be chosen cautiously. | epidemiology |
10.1101/2022.04.24.22274231 | Spatially regulated designs of incidence surveys can match the precision of classical survey designs whilst requiring smaller sample sizes: the case of snakebite in Sri Lanka | BackgroundSnakebite envenoming is a neglected tropical disease. Data from the worst affected countries are limited because conducting epidemiological surveys is challenging. We assessed the utility of inhibitory geostatistical design with close pairs (ICP) to estimate snakebite incidence.
MethodsThe National Snakebite Survey (NSS) in Sri Lanka adopted a multistage cluster sampling design, based on population distribution, targeting 1% of the countrys population. Using a simulation-based study, we assessed predictive efficiency of ICP against a classical survey design at different fractions of the original sample size of the NSS. We also assessed travel distance, time taken to complete the survey, and sensitivity and specificity for detecting high-risk areas for snake envenoming, when using these methods.
ResultsA classical survey design with 33% of the original NSS sample size was able to yield a similar predictive efficiency. ICP yielded the same at 25% of the NSS sample size, a 25% reduction in sample size compared to a classical survey design. ICP showed >80% sensitivity and specificity for detecting high-risk areas of envenoming when the sampling fraction was >20%. When ICP was adopted with 25% of the original NSS sample size, travel distance was reduced by >40% and time to conduct the survey was reduced by >75%.
ConclusionsThis study showed that snakebite envenoming incidence can be estimated by adopting an ICP design with similar precision at a lower sample size than a classical design. This would substantially save resources and time taken to conduct epidemiological surveys and may be suited for low resource settings.
Key messagesO_LIInhibitory geostatistical design with close pairs (ICP) for incidence surveys can match the precision of classical survey designs at lower sample sizes.
C_LIO_LIThe ICP design showed a lower predictive variance than classical design, indicating ICP designs were able to produce more reliable predictions.
C_LIO_LIThe ICP design showed a lower time to complete the survey than the classical sampling method.
C_LIO_LIAlthough primary sampling units in the ICP design maintain a minimum distance between two units, ICP did not increase travel distance compared to the classical survey design.
C_LIO_LIResource requirements and time to complete surveys can be reduced without increasing the distance to travel by adopting ICP design for epidemiological surveys.
C_LI | epidemiology |
10.1101/2022.04.22.22274162 | Is there a higher risk of exposure to Coxiella burnetii for pre-clinical veterinary students? | Coxiella burnetii is globally distributed but evidence of zoonotic transmission in the Caribbean region is scarce. The presence of the bacterium is suspected on the Caribbean island of St. Kitts. The risk of exposure of veterinary students was reported in other regions of the world but is not documented in the Caribbean region. The present study aimed to evaluate the risk of exposure to C. burnetii for pre-clinical veterinary students attending an island-based veterinary school. A cross-sectional study was conducted to compare incoming and outgoing veterinary students seroprevalence. Serology was performed using indirect immunofluorescence assay to test Coxiella burnetii Phase I and Phase II immunoglobulins M and G. Background data were gathered using a standardized questionnaire.
Of the 98 participants (48 incomings and 50 outgoings), 41 (41.8 %, 95 %CI: 31.9-52.2) were seropositive to C. burnetii. There was no significant difference between the two groups (45.8% for incoming vs. 38.0% for outgoing) (p=0.4). No risk factors were significantly more reported in the seropositive group. U.S. state of origin of the students was not associated with seropositivity either.
Pre-clinical veterinary students do not have a higher risk of exposure to C. burnetii by attending the veterinary school in St. Kitts, but they are highly exposed before arrival on the island. Most of these participants had experience with animals either through farming or previous veterinary technician employment. This indicates a high exposure in the U.S. young population aiming to become veterinarians. There is an urgent need to increase C. burnetii surveillance in animals and humans to apply relevant prevention and control measures, including recommendations for vaccination of students and professionals at risk.
Author SummaryQ fever is a zoonosis present worldwide. Risk of exposure is higher in livestock farmers and other animal-related professions, including veterinary students. The presence of the bacterium is suspected on the Caribbean island of St. Kitts. We aimed to evaluate the risk of exposure to C. burnetii for students attending an American veterinary school based in St. Kitts. By comparing seroprevalence in incoming and outgoing students, we observed no risk of exposure by attending the school. These findings are different from studies in other veterinary schools. Future studies could explain these geographical differences and inform veterinary schools worldwide on appropriate measures to protect students from exposure to C. burnetii. Moreover, we detected a high seroprevalence in the incoming population, proving an anterior exposure. This indicates a high exposure in the U.S. young population aiming to become veterinarians. There is an urgent need to increase C. burnetii surveillance in animals and humans to apply relevant prevention and control measures, including recommendations of vaccination of students and professionals at risk. | epidemiology |
10.1101/2022.04.25.22274272 | Analyses of Omicron genomes from India reveal BA.2 as a more transmissible variant | This is the first study on omicron genomes from India to focus on phylodynamics and phylogenomics trait to provide an insight into the evolution of omicron variants. We analyzed 564 genomes deposited to GISAID database from various states of India. Pangolin COVID-19 Lineage Assigner tool was used to determine lineage assignment of all retrieved genomes. A Maximum likelihood (MLE) tree construction further confirms the separation of genomes into two distinct clades, BA. 1. and BA. 2. A very high reproduction number (R0) of 2.445 was estimated for the lineage BA.2. The highest R0 value in Telangana confirms the prevalence of lineage BA.2 in the state. Construction of the Reduced Median (RM) network shows evolution of some autochthonous haplogroups and haplotypes, which further supports the rapid evolution of omicron as compared to its previous variants. Phylogenomic analyses using maximum likelihood (ML) and RM show the potential for the emergence of sub-sublineages and novel haplogroups respectively. Due to the recombinant property and high transmissibility of omicron virus, we suggest continuous and more widespread genome sequencing in all states of India to track evolution of SARS-CoV-2 in real time. | epidemiology |
10.1101/2022.04.21.22274152 | Health care use attributable to COVID-19: A propensity matched national electronic health records cohort study of 249,390 people in Wales, UK. | BackgroundTo determine the extent and nature of changes in infected patients healthcare utilization, we studied healthcare contact in the 1-4 weeks and 5-24 weeks following a COVID-19 diagnosis compared to propensity matched controls.
MethodsSurvival analysis was used for time to death and first clinical outcomes including clinical terminology concepts for post-viral illness, fatigue, embolism, respiratory conditions, mental and developmental conditions, fit note, or hospital attendance. Increased instantaneous risk for the occurrence of an outcome for positive individuals was quantified using hazard ratios (HR) from Cox Regression and absolute risk was quantified using relative risk (RR) from life table analysis.
ResultsCompared to matched individuals testing negative, surviving positive community-tested patients had a higher risk of post-viral illness (HR: 4.57, 95%CI: 1.77-11.80, p=0.002), fatigue (HR: 1.47, 95%CI: 1.24-1.75, p<0.001) and embolism (HR: 1.51, 95%CI: 1.13-2.02, p=0.005) at 5-24 weeks post-diagnosis. In the four weeks after COVID-19 higher rates of sick notes were being issued for community-tested (HR: 3.04, 95%CI: 0.88 to 10.50, p<0.079); the risk was reduced after four weeks, compared to controls. Overall healthcare attendance for anxiety, depression was less likely in those with COVID-19 in the first four weeks (HR: 0.83, 95%CI: 0.73-1.06, p=0.007). After four weeks, anxiety, depression is less likely to occur for the positive community-tested individuals (HR: 0.87, 95%CI: 0.77-1.00, p=0.048), but more likely for positive hospital-tested individuals (HR: 1.16, 95%CI: 1.00-1.45, p=0.053). Although statistical associations between positive infection and post-infection healthcare use are clear, the absolute use of healthcare is very.
ConclusionsCommunity COVID-19 disease is associated with increased risks of post-viral illness, fatigue, embolism, depression, anxiety and respiratory conditions. Despite these elevated risks, the absolute healthcare burden is low. Either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare.
Trial registrationData held in SAIL databank are anonymised and therefore, no ethical approval is required. All data in SAIL has the permission from the relevant Caldicott Guardian or Data Protection Officer and SAIL-related projects are required to obtain Information Governance Review Panel (IGRP) approval. The IGRP approval number for this study is 1259. | epidemiology |
10.1101/2022.04.24.22274227 | Uncovering the linguistic characteristics of psychotherapy: a computational approach to measure therapist language timing, responsiveness, and consistency | Although individual psychotherapy is generally effective for a range of mental health conditions, little is known about the moment-to-moment language use of effective therapists. Increased access to computational power, coupled with a rise in computer-mediated communication (telehealth), makes feasible the large-scale analyses of language use during psychotherapy. Transparent methodological approaches are lacking, however. Here we present novel methods to increase the efficiency of efforts to examine language use in psychotherapy. We evaluate three important aspects of therapist language use - timing, responsiveness, and consistency - across five clinically relevant language domains: pronouns, time orientation, emotional polarity, therapist tactics, and paralinguistic style. We find therapist language is dynamic within sessions, responds to patient language, and relates to patient symptom diagnosis but not symptom severity. Our results demonstrate that analyzing therapist language at scale is feasible and may help answer longstanding questions about specific behaviors of effective therapists. | psychiatry and clinical psychology |
10.1101/2022.04.23.22274132 | Precise Language Responses Challenge Easy Rating Scales - Comparing Clinicians and Respondents Views | BackgroundClosed-ended rating scales are the most used response format for researchers and clinicians to quantify mental states, whereas in natural contexts people communicate with natural language. The reason for using such scales is that they are typically argued to be more precise in measuring mental constructs, whereas the respondents views as to what best communicates mental states are frequently ignored.
MethodsWe assessed respondents (N = 304) degree of depression using rating scales, descriptive words, selected words, and free text responses and probed the respondents and clinicians (N = 40) for their attitudes to the response formats across twelve dimensions related to the precision of communicating their mental states and the ease of responding.
ResultsRespondents found free text to be more precise (e.g., precision d = .88, elaboration d = 2.0) than rating scales, whereas rating scales were rated as easier to respond to (e.g., easier d = - .67, faster d = -1.13). Respondents preferred the free text responses to a greater degree than rating scales compared to clinicians.
ConclusionsThese finding supports the idea that future assessment of mental health can be aided by computational method based on text data. | psychiatry and clinical psychology |
10.1101/2022.04.23.22274202 | Does living in major towns favor institutional delivery in Somalia? | BackgroundAn institutional delivery is a childbirth that takes place at a health facility in which the birth is assisted by a skilled healthcare provider. Institutional delivery could reduce approximately 33% of maternal deaths. However, the use of institutional healthcare is failing in many Sub-Saharan African countries because of many factors, including poverty, a lack of access, distance, a lack of transport and other socio-cultural factors. In Somalia, only 32% of births are delivered in a health facility with the assistance of a skilled healthcare provider. We aim to investigate the factors hindering women from giving birth at health facilities in major towns in Somalia, where most of the health facilities in the country are concentrated.
MethodsA community-based health survey was carried out from 11 major towns in Somalia between October and December 2021. A structured and pretested questionnaire was used to collect data from 430 women who gave birth last five years. A logistic regression analysis was carried out to establish the association between the covariates of interest and the outcome variable.
ResultsThe overall prevalence of institutional delivery was 57%. Approximately 38% of women who live in Mogadishu and 53% of women living in another ten towns give birth at home. Women who had a poor knowledge of the importance of health facility delivery had nearly four times higher odds of delivering at home (OR 3.645 CI: 1.488-8.928). Similarly, those who did not receive antenatal care (OR 2.551, CI: 1.017-6.399), and those who did not receive a consultation on the place of delivery (OR 2.145, CI: 1.167-3.942) were more likely to give birth at home. The reasons for home delivery included financial reasons, must use transport to reach the nearest health facility and it is easier to deliver at home.
ConclusionThe study shows that home delivery is high in major towns in Somalia. It is important for health providers to communicate with women and men about the risks related to pregnancy and educate them about the importance of a health facility delivery. Antenatal care should be considered universal for pregnant women, while central and federal governments should guarantee access to free and within-reach ANC for women and girls. In conflict settings in Somalia, this should be done by training community health workers and auxiliary nurses who provide ANC for women through home visits. | public and global health |
10.1101/2022.04.26.22274257 | Immediate, remote smoking cessation intervention in participants undergoing a targeted lung health check: QuLIT2 a randomised controlled trial. | BackgroundLung cancer screening programs provide an opportunity to support smokers to quit, but the most appropriate model for delivery remains to be determined. Immediate face to face smoking cessation support for people undergoing screening can increase quit rates, but it is not known whether remote delivery of immediate smoking cessation counselling and pharmacotherapy in this context is also effective.
Materials and MethodsIn a single-blind randomised controlled trial, smokers aged 55-75 years attending a Targeted Lung Health Check (TLHC) were allocated by day of attendance to receive either immediate telephone smoking cessation support (TSI) (starting immediately and lasting for 6 weeks) with appropriate pharmacotherapy, or usual care (very brief advice to quit and signposting to smoking cessation services) (UC). The primary outcome was self-reported 7-day point prevalence smoking abstinence at three months. Differences between groups were assessed using logistic regression.
Results315 current smokers taking part in the screening programme, mean (SD) age 63(5.4) years, 48% female, were randomised to telephone smoking cessation (n=152) or usual care (n=163). The two groups were well-matched at baseline. Self-reported quit rates were higher in the intervention arm, 21.1% vs 8.9% (odds ratio [OR]: 2.83, 95% CI 1.44-5.61, p=0.002). Controlling for participant demographics, baseline smoking characteristics or the discovery of abnormalities on low dose CT scanning did not modify the effect of the intervention.
ConclusionImmediate provision of an intensive telephone-based smoking cessation intervention, delivered within a targeted lung screening context, is associated with increased smoking abstinence at three months.
Trial registrationThis study is registered online: ISRCTN12455871.
Take home messageProviding immediate, telephone smoking cessation support with pharmacotherapy to smokers enrolled in a TLHC program increases quit rates in this population by almost a third. | respiratory medicine |
10.1101/2022.04.24.22274232 | Barriers and facilitators to the implementation of cell phone interventions to improve the use of family planning services among women in Sub-Saharan Africa: a systematic review | BackgroundMobile health (mHealth) interventions are being tested to improve contraceptive uptake in SubSaharan Africa (SSA). However, few attempts have systematically reviewed the mHealth programs aiming to improve family planning (FP) services among women in SSA. This review identifies and highlights facilitators and barriers to implementing cell phone interventions designed to target women FP services.
MethodsDatabases including PubMed, CINAHL, Epistemonikos, Embase, and Global Health were systematically searched for studies from January 01, 2010, to December 31, 2020, to identify various mHealth interventions used to improve the use of FP services among women in SSA. Two authors independently selected eligible publications based on inclusion/exclusion criteria, assessed study quality and extracted data using a pre-defined data extraction sheet. In addition, a content analysis was conducted using a validated extraction grid with a pre-established categorization of barriers and facilitators.
ResultsThe search strategy led to a total of 8,188 potentially relevant papers, of which 16 met the inclusion criteria. The majority of included studies evaluated the impact of mHealth interventions on FP services; access (n = 9) and use of FP outcomes (n = 6). The most-reported cell phone use was for women reproductive health education, contraceptive knowledge and use. Barriers and facilitators of the use of mhealth were categorized into three main outcomes: behavioral outcomes, data collection and reporting, and health outcomes. mHealth interventions addressed barriers related to provider prejudice, stigmatization, discrimination, lack of privacy, and confidentiality. The studies also identified barriers to uptake of mHealth interventions for FP services, including decreased technological literacy and lower linguistic competency.
ConclusionThe review provides detailed information about the implementation of mobile phones at different healthcare system levels to improve FP services; outcomes. Barriers to uptake mHealth interventions must be adequately addressed to increase the potential use of mobile phones to improve access to sexual reproductive health awareness and family planning services.
Systematic review registrationPROSPERO CRD42020220669 (December 14, 2020) | sexual and reproductive health |
10.1101/2022.04.24.22274237 | Hospitalized patients with severe COVID-19 during the Omicron wave in Israel - benefits of a fourth vaccine dose | ImportanceWaning immunity against COVID-19 in parallel with an increased incidence during the Omicron outbreak led the Israeli Ministry of Health to recommend a second booster dose of BNT162b2 (Pfizer) to high-risk individuals. Israel was the first country to recommend this, allowing evaluation of the added protection of a fourth vaccine dose to hospitalized patients with severe diseases.
ObjectiveTo assess the effect of a fourth dose for hospitalized patients with severe/critical breakthrough COVID-19.
DesignA cohort study of hospitalized adults from 01/15/2022-01/31/2022.
SettingsA multi-center study of 14 medical centers in Israel.
ParticipantsHospitalized adult patients with PCR-confirmed severe/critical COVID-19. Excluded were patients lacking data on vaccination status.
ExposureCases were divided according to the total number of vaccine doses received up to 7 days before diagnosis. Unvaccinated adults and single-dose recipients were grouped into an unvaccinated group.
Main OutcomeA composite of mechanical-ventilation or in-hospital death was defined as poor outcome. Outcomes were compared between 3- and 4-dose vaccinees.
ResultsIncluded were 1,049 patients with severe/critical COVID-19, median age 80 (IQR 69-87), 51% males. Among them, 360 unvaccinated, 34, 172, 386 and 88 were after 1, 2, 3 or 4 doses, respectively. Patients after 3 doses were older, had more males and immunosuppression, but with similar outcomes, 49% vs. 51% compared to unvaccinated patients (p=0.72). Patients after 4 doses were similarly older and immunosuppressed, but had improved outcomes compared to unvaccinated patients, 34% vs. 51% (p<0.01). We proceeded to examine independent predictors for poor outcome in fully-vaccinated patients with either 3 doses given a median of 161 (IQR 147-168) days earlier, or 4 doses given a median of 14 (IQR 10-18) days before diagnoses. Receipt of the fourth dose conferred significant protection: OR 0.51 (95%CI 0.30.87).
Conclusion and RelevanceWithin a population of hospitalized patients with severe/critical breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death, compared to fully vaccinated single-boosted individuals.
Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the benefit of a fourth vaccine dose (second booster) for hospitalized patients with severe COVID-19?
FindingsIn this multicenter cohort study in Israel during the Omicron wave, hospitalized severe COVID-19 patients that received a recent fourth dose had a 49% lower odds for a poor outcome (mechanical ventilation or death) compared with those who received 3 doses approximately 5 months before diagnosis, a significant difference.
MeaningA vaccine booster given at the onset of a COVID-19 wave can benefit vulnerable individuals. | infectious diseases |
10.1101/2022.04.26.22274244 | The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis | ObjectiveThis systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants.
MethodsThe study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV- associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI).
ResultsThe eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%).
ConclusionThere was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
What is already known on this topicThe epidemiology of RSV infection which accounts for most bronchiolitis and viral pneumonias in infants was changed during the COVID-19 pandemic. During the spring or summer seasons, a resurgence in RSV positivity among bronchiolitis cases was noted globally during the COVID-19 pandemic.
What this study addsIn spite of reporting lower number of bronchiolitis cases, more number of RSV associated bronchiolitis cases were detected among infants during the COVID-19 pandemic. Meanwhile, countries perceiving a very low number of RSV cases are at an increased risk of resurgence of RSV activity, mainly among older RSV-naive children.
How this study might affect research, practice or policyMonitoring the effect of COVID-19 on RSV activity in infants is essential and regular sentinel surveillance of RSV must be carried out along with influenza and SARS-CoV-2 viruses to minimise the burden of hospitalisation and mortality. Health care professionals and hospitals must be prepared to tackle the rising number of paediatric RSV cases throughout the year. This review also emphasises the importance of promoting RSV maternal vaccines and passive childhood immunisation with monoclonal antibodies (mAbs). | infectious diseases |
10.1101/2022.04.26.22274244 | The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis | ObjectiveThis systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants.
MethodsThe study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV- associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI).
ResultsThe eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%).
ConclusionThere was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
What is already known on this topicThe epidemiology of RSV infection which accounts for most bronchiolitis and viral pneumonias in infants was changed during the COVID-19 pandemic. During the spring or summer seasons, a resurgence in RSV positivity among bronchiolitis cases was noted globally during the COVID-19 pandemic.
What this study addsIn spite of reporting lower number of bronchiolitis cases, more number of RSV associated bronchiolitis cases were detected among infants during the COVID-19 pandemic. Meanwhile, countries perceiving a very low number of RSV cases are at an increased risk of resurgence of RSV activity, mainly among older RSV-naive children.
How this study might affect research, practice or policyMonitoring the effect of COVID-19 on RSV activity in infants is essential and regular sentinel surveillance of RSV must be carried out along with influenza and SARS-CoV-2 viruses to minimise the burden of hospitalisation and mortality. Health care professionals and hospitals must be prepared to tackle the rising number of paediatric RSV cases throughout the year. This review also emphasises the importance of promoting RSV maternal vaccines and passive childhood immunisation with monoclonal antibodies (mAbs). | infectious diseases |
10.1101/2022.04.26.22274244 | The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis | ObjectiveThis systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants.
MethodsThe study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV- associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI).
ResultsThe eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%).
ConclusionThere was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
What is already known on this topicThe epidemiology of RSV infection which accounts for most bronchiolitis and viral pneumonias in infants was changed during the COVID-19 pandemic. During the spring or summer seasons, a resurgence in RSV positivity among bronchiolitis cases was noted globally during the COVID-19 pandemic.
What this study addsIn spite of reporting lower number of bronchiolitis cases, more number of RSV associated bronchiolitis cases were detected among infants during the COVID-19 pandemic. Meanwhile, countries perceiving a very low number of RSV cases are at an increased risk of resurgence of RSV activity, mainly among older RSV-naive children.
How this study might affect research, practice or policyMonitoring the effect of COVID-19 on RSV activity in infants is essential and regular sentinel surveillance of RSV must be carried out along with influenza and SARS-CoV-2 viruses to minimise the burden of hospitalisation and mortality. Health care professionals and hospitals must be prepared to tackle the rising number of paediatric RSV cases throughout the year. This review also emphasises the importance of promoting RSV maternal vaccines and passive childhood immunisation with monoclonal antibodies (mAbs). | infectious diseases |
10.1101/2022.04.26.22274244 | The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis | ObjectiveThis systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants.
MethodsThe study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV- associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI).
ResultsThe eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%).
ConclusionThere was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
What is already known on this topicThe epidemiology of RSV infection which accounts for most bronchiolitis and viral pneumonias in infants was changed during the COVID-19 pandemic. During the spring or summer seasons, a resurgence in RSV positivity among bronchiolitis cases was noted globally during the COVID-19 pandemic.
What this study addsIn spite of reporting lower number of bronchiolitis cases, more number of RSV associated bronchiolitis cases were detected among infants during the COVID-19 pandemic. Meanwhile, countries perceiving a very low number of RSV cases are at an increased risk of resurgence of RSV activity, mainly among older RSV-naive children.
How this study might affect research, practice or policyMonitoring the effect of COVID-19 on RSV activity in infants is essential and regular sentinel surveillance of RSV must be carried out along with influenza and SARS-CoV-2 viruses to minimise the burden of hospitalisation and mortality. Health care professionals and hospitals must be prepared to tackle the rising number of paediatric RSV cases throughout the year. This review also emphasises the importance of promoting RSV maternal vaccines and passive childhood immunisation with monoclonal antibodies (mAbs). | infectious diseases |
10.1101/2022.04.24.22273777 | Effects of the introduction of interprofessional conferences on the intensive care unit: Comparison of the length of stay in the intensive care unit before and after the introduction of interprofessional conferences | Recently, interprofessional team medicine has been practiced to achieve medical safety and improve patient outcomes. This study evaluated the effects of interprofessional conferences on intensive care units (ICUs) by comparing outcomes before and after their introduction. This study was conducted at a single center and included 1,765 patients who were admitted to the ICU between April 2017 and March 2019. There were 898 patients in the group before the introduction of conferences (before group) and 867 patients in the group after the introduction of conferences (after group). The interprofessional conferences involved physicians, nurses, physical therapists, nutritionists, and pharmacists. Data were extracted from the medical records. The primary outcome measure was the ICU length of stay (LOS). The secondary outcome measures were hospital LOS and rehabilitation and nutrition started within 48 hours of ICU admission. These outcomes were compared before and after the introduction of interprofessional conferences. The adjusted variables were gender, age, body mass index, ICU readmission, outcome, Barthel index at admission, and disease (classified by the International Statistical Classification of Diseases and Related Health Problems 10th edition). The ICU LOS (regression coefficient: -0.08; 95% confidence interval [CI]: -0.13 to -0.04) and hospital LOS (regression coefficient: -2.96; 95% CI: -5.20 to -0.72) were significantly shorter in after group than in the before group. Moreover, the proportion of patients who commenced nutrition (odds ratio [OR]: 1.45; 95% CI: 1.14 to 1.84) and rehabilitation (OR: 0.77; 95% CI: 0.51 to 1.17) within 48 hours of ICU admission was significantly higher in the after group than in the before group. Interprofessional conferences effectively reduced the ICU LOS and hospital LOS and improved the likelihood of commencing nutrition and rehabilitation within 48 hours of ICU admission. | intensive care and critical care medicine |
10.1101/2022.04.26.22273986 | The Association of Marital/Partner Status with Patient-Reported Health Outcomes Following Acute Myocardial Infarction or Stroke: Protocol for a Systematic Review and Meta-analysis | IntroductionMarital/Partner support is associated with lower mortality and morbidity following acute myocardial infarction (AMI) and stroke. Despite an increasing focus on the effect of patient-centered factors on health outcomes, little is known about the impact of marital/partner status on patient-reported outcome measures (PROMs).
ObjectiveTo synthesize evidence of the association between marital/partner status and PROMs after AMI and stroke and to determine whether associations differ by sex.
Methods and analysisWe will search MEDLINE (via Ovid), Web of Science Core Collection (as licensed by Yale University), Scopus, EMBASE (via Ovid), and PsycINFO (via Ovid) from inception to January 10, 2022. Two authors will independently screen titles, abstracts, and then full texts as appropriate, extract data, and assess risk of bias. Conflicts will be resolved by discussion with a third reviewer. The primary outcomes will be the associations between marital/partner status and PROMs. Meta-analysis will be conducted if appropriate. Subgroup analysis by sex and meta-regression with a covariate for the proportion of male participants will be performed to explore differences by sex.
Ethics and disseminationThis research is exempt from ethics approval because the study will be conducted using published data. We will disseminate the results of the analysis in a related peer-reviewed journal.
PROSPERO registration numberCRD42022295975 | cardiovascular medicine |
10.1101/2022.04.22.22274034 | A Prospective Study to Improve Automated Blood Culture Diagnostics in Gram Negative Sepsis by Implementing a "Diagnostic Stewardship Care-Bundle" | ObjectivesWe implemented a diagnostic stewardship care-bundle (DSB): "Sepsis-48" with the aim of evaluating its impact on changes in duration of key steps in automated blood culture diagnostics (aBCD), compliance to care-bundle and turnaround time (TAT).
MethodsIn this prospective study, a care-bundle checklist for automated blood culture bottles (BCBs) received from adult intensive care units (AICUs) was implemented between July 2020-June 2021 (intervention period, P2) and compared with a retrospective, pre-intervention period (P1) between March-June 2020. Microbial identification in positive BCBs with gram-negatives (+nBCBs) was enabled by inoculating conventional biochemical tests directly (dID) and direct antimicrobial susceptibility testing (dAST) was done as per EUCAST RAST standard. Clinical reports were issued only if a RAST reportable gram-negative was identified in dID.
ResultsWe observed significant reductions in the Loading time (LT) [63.5 (104.5-24.5) vs 32 (55-14) minutes, P<0.001] & time to dID+dAST performance (TTD) [186 (288.25-202.25) vs 115 (180-68) minutes, P=0.0018] in +nBCBs received from AICUs during P2. There was a significant increase in compliance to the bundle targets [LT[≤]45: 44% vs 66%, P=.006 and TTD[≤]120: 34% vs 51.7%, P=.03] during P2 (Table 2). Using dID+dAST method, provisional results could be read [~]13 hours earlier than those generated by VITEK(R). Similar improvements were also noted for +nBCBs received from other locations.
O_TBL View this table:
org.highwire.dtl.DTLVardef@1da2dceorg.highwire.dtl.DTLVardef@f5367corg.highwire.dtl.DTLVardef@cc3fcdorg.highwire.dtl.DTLVardef@170be9aorg.highwire.dtl.DTLVardef@f1a063_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 2:C_FLOATNO O_TABLECAPTIONPerformance and interpretation of direct microbial identification (dID) method by directly inoculating conventional biochemical tests
C_TABLECAPTION C_TBL ConclusionsThe "diagnostic stewardship care-bundle" strategy to improve aBCD was successfully implemented leading to significant reductions in duration of targeted steps. Laboratories should implement "diagnostic stewardship care-bundles" as per their needs to improve microbiological diagnostics. | infectious diseases |
10.1101/2022.04.26.22274327 | Does greater longevity come with lower life disparity in India? A comparative study between Kerala and Delhi | BackgroundLife expectancy and life disparity are two important measures for determining societys health condition. Over last decades, Indian life expectancy has increased, reaching 69.4 years in 2018, with highest life expectancies being registered in Kerala and Delhi, with 75.3 years for both-sexes. Delhi has overtaken Kerala and is now top-ranking state in life expectancy. However, whether Delhi also has a lower disparity than Kerala is still unknown.
ObjectivesTo assess age-at death distributions, trends in life expectancy and life disparity for Delhi and Kerala from 2010-2018; to assess patterns of life disparity and their relation to rising longevity; to show that, despite having similar life expectancies, life disparity varies between Delhi and Kerala.
MethodsAbridged-life table from Sample Registration System from 2010-18 for Kerala and Delhi. Decomposition approach is performed to calculate age-specific contribution to changes in life expectancy and life disparity for each population.
ResultsKerala showed inverse relationship between life expectancy and life disparity but not Delhi. Despite having a better Delhis life expectancy than Kerala during the study period, Delhis life disparity is still higher than Keralas. Disparities in life expectancy and life disparity between the two groups are closely related to their differences in age-specific mortality.
ConclusionsGiven the ongoing demographic transition in India and spatial variations in it, this study is a welcome contribution to our understanding of Indias mortality decline. Our study has revealed that the life disparity in Delhi is higher than that in Kerala. This is because infant mortality in Delhi is higher than in Kerala whereas old age mortality is higher in Kerala than in Delhi.
ContributionBeneficial in allocating healthcare resources to minimize both infants and old deaths and to attain equality in longevity and health. | health policy |
10.1101/2022.04.25.22274292 | Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium | IntroductionTimely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes.
MethodsThe International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEAs 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys.
ResultsThe survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposis sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate.
ConclusionIeDEAs approach for site survey development approach has broad relevance for HIV research networks and other priority health conditions. | health systems and quality improvement |
10.1101/2022.04.25.22274292 | Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium | IntroductionTimely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes.
MethodsThe International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEAs 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys.
ResultsThe survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposis sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate.
ConclusionIeDEAs approach for site survey development approach has broad relevance for HIV research networks and other priority health conditions. | health systems and quality improvement |
10.1101/2022.04.26.22274317 | High sensitivity of a novel rapid test for the diagnosis of clinical and subclinical Plasmodium falciparum infections in a high transmission setting in Burundi | Rapid diagnostic tests (RDTs) are a key tool for the diagnosis of malaria infections among febrile and subclinical individuals. Low-density infections, and deletions of the P. falciparum hrp2/3 genes (encoding for the HRP2 and HRP3 proteins detected by many RDTs) present challenges for RDT-based diagnosis. The novel Rapigen Biocredit three-band Plasmodium falciparum HRP2/LDH RDT was evaluated among 444 febrile and 468 subclinical individuals in a high transmission setting in Burundi. Results were compared to the AccessBio CareStart HRP2 RDT, and qPCR with a sensitivity of <0.1 parasites/{micro}L blood. Sensitivity among clinical patients was 80.0% (250/313, either of HRP2/LDH positive), compared to 73.2% (229/313) for CareStart (P=0.048). Among subclinical infections, sensitivity was 72.3% (162/224) compared to 58.5% (131/224) for CareStart (P=0.003), and reached 88.3% (53/60) in children <15 years. No (0/362) hrp2 and 2/366 hrp3 deletions were observed. In conclusion, the novel RDT showed improved sensitivity for the diagnosis of P. falciparum. | infectious diseases |
10.1101/2022.04.27.22274357 | Observed strong pervasive positive selection in the N-terminal domain, receptor-binding domain and furin-cleavage sites of SARS-CoV-2 Spike protein sampled from Zimbabwean COVID-19 patients. | Mutations primarily in the Spike (S) gene resulted in the emergence of many SARS-CoV-2 variants like Alpha, Beta, Delta and Omicron variants. This has also caused a number of COVID-19 pandemic waves which have impacted human lives in different ways due to restriction measures put in place to curb the spread of the virus. In this study, evolutionary patterns found in SARS-CoV-2 sequences of samples collected from Zimbabwean COVID-19 patients were investigated. High coverage SARS-CoV-2 whole genome sequences were downloaded from the GISAID database along with the GISAID S gene reference sequence. Biopython, NumPy and Pandas Data Science packages were used to load, slice and clean whole genome sequences outputting a fasta file with approximate Spike (S) gene sequences. Alignment of sliced dataset with GISAID reference sequence was done using Jalview 2.11.1.3 to find exact sequences of SARS-CoV-2 S gene. Evidence of recombination signals was investigated using RDP 4.1 and pervasive selection in the S gene was investigated using FUBAR algorithm hosted on the Datamonkey webserver. Matplotlib and Seaborn Python packages were used for Data Visualisation. A plot of Bayes factor hypothesizing non-synonymous substitution being greater than synonymous substitution ({beta} > ) in the S protein sites showed 3 peaks with evidence of strong divergence. These 3 diverging S protein sites were found to be D142G, D614G and P681R. No evidence of recombination was detected by 9 methods of RDP which use different approaches to detect recombination signals. This study is useful in guiding drug, vaccine and diagnostic innovations toward better control of the pandemic. Additionally, this study can guide other non-biological interventions as we better understand the changes in various viral characteristics driven by the observed evolutionary patterns. | infectious diseases |
10.1101/2022.04.26.22274329 | Mobile Primary Healthcare for post-COVID Patients in Rural Areas: a Proof-of-Concept Study | IntroductionPost-COVID syndrome is increasingly recognized as a new clinical entity after SARS-CoV-2 infection. Patients living in rural areas may have to travel long with subjectively great effort to be examined using all necessary interdisciplinary tools. This problem could be addressed with mobile outpatient clinics.
MethodsIn this prospective observational study, we investigated physical fitness, fatigue, depression, cognitive dysfunction and dyspnea in patients with post-COVID syndrome in a mobile interdisciplinary post-COVID outpatient clinic. Upon referral from their primary care physician, patients were offered an appointment at a mobile post-COVID outpatient clinic close to their home.
ResultsWe studied 125 patients (female, n=79; 63.2%) in our mobile unit. All patients reported symptoms lasting for more than 12 weeks after acute infection. 88.3% and 64.1% of patients reported significant impairment in physical and mental quality of life. Patients reported a median of three symptoms. The most frequently reported symptoms were fatigue (86.4%), cognitive dysfunction (85.6%), and dyspnea (37.6%). 56.0% of patients performed at <2.5th percentile at the 1 min sit-to-stand test compared to age and sex-matched healthy controls and 25 patients (20.0%) exhibited a drop in oxygen saturation. A questionnaire given to each patient regarding the mobile unit revealed a very high level of patient satisfaction.
ConclusionThere is an increasing need for high-quality and locally available care for patients with post-COVID syndrome. A mobile post-COVID outpatient clinic is a new concept that may be particularly suitable for use in rural regions. Patients satisfaction following visits in such units is very high. | infectious diseases |
10.1101/2022.04.26.22274321 | Non-inferiority of essential medicines for caries arrest and prevention in a school-based program: Results from the CariedAway pragmatic clinical trial | BackgroundDental caries is the most common global childhood disease. To control caries, the Centers for Disease Control and Prevention recommends school-based caries prevention, and the World Health Organization lists glass ionomer cement and silver diamine fluoride as essential dental medicines. The CariedAway trial tested the comparative effectiveness of these essential medicines when used in a school-based dental care program.
MethodsThis cluster-randomized non-inferiority pragmatic trial was conducted in children from 2018 to 2022. Subjects were randomized at the school level to receive either silver diamine fluoride ("simple care") or an active comparator of glass ionomer sealants and atraumatic restorations ("complex care"). All subjects received tooth brushes, fluoride toothpaste, and fluoride varnish. We assessed caries arrest and incidence at two years using mixed-effects multilevel models and two-sample proportion tests with clustering adjustment.
Results1398 subjects received treatment and completed follow-up observations after two years. The proportion of subjects with arrested caries in simple and complex groups was 0.56 and 0.46, respectively (difference = -0.11, 95% CI = -0.22, 0.01). Prevention rates for no new caries were 0.81 and 0.82 (difference = 0.01, 95% CI = -0.04, 0.06).
ConclusionsOver a two-year, non-intervention period, simple care was non-inferior to complex care for both caries arrest and prevention. Results support the utilization of silver diamine fluoride as an arresting and preventive agent in school-based oral health programs and questions the periodicity of current caries prevention recommendations. | dentistry and oral medicine |
10.1101/2022.04.25.22274260 | Muscle pathology of antisynthetase syndrome according to antibody subtypes | Antisynthetase syndrome is recently recognized as one of the major entities of autoimmune myositis. The prototype of antisynthetase syndrome is anti-Jo-1 antibody associated syndrome while the syndromes associated with non-Jo-1 antisynthetase antibodies are clinically and pathologically less recognized. Identifying a non-Jo-1 antisynthetase syndrome patient could be challenging because the full panel serology test may not be available at the time of diagnosis in addition to technical difficulty especially for anti-OJ antibody detection. This study aimed to characterize the muscle pathology and explore the utility of myofiber HLA-DR expression for the diagnosis of antisynthetase syndrome.
We retrospectively compared 212 muscle biopsies from antisynthetase syndrome patients regarding four pathology domains and histology of interests using t test and Fishers exact test as appropriate. We further compared the myofiber HLA-DR expression pattern in antisynthetase syndrome with 602 muscle biopsies with other autoimmune myositis and 140 muscle biopsies with other myopathies potentially containing myositis-like pathology and calculated sensitivity, specificity, positive predictive value, and negative predictive value to identify the most diagnostic pattern for antisynthetase syndrome.
The most common myopathological pattern in antisynthetase syndrome was necrotizing myopathy (46.2%). Perifascular necrosis was present in 28.3% of antisynthetase syndrome. Anti-OJ and anti-EJ antisynthetase syndrome were associated with high muscle fiber scores. Anti-OJ also showed high inflammatory domain score. If muscle biopsies suspicious for dermatomyositis by sarcoplasmic myxovirus resistance protein A immunohistochemical expression and those with inclusion body myositis clinicopathology were excluded, myofiber HLA-DR expression was the most diagnostic of antisynthetase syndrome with 95.4% specificity, 61.2% sensitivity, 85.9% positive predictive value, and 84.2% negative predictive value. HLA-DR expression in perifascicular fibers was highly specific to anti-Jo-1 antisynthetase syndrome.
Anti-OJ antisynthetase syndrome has more prominent myopathology than the other antisynthetase syndrome subtypes. Presence of myofiber HLA-DR expression in a clinicopathologically approved non-dermatomyositis and non-inclusion body myositis muscle biopsy is highly indicative of antisynthetase syndrome. Presence of HLA-DR expression suggests the involvement of type II interferon in the pathogenesis in antisynthetase syndrome subpopulation although the detailed mechanism and the reason for preferential perifascicular localization are yet to be identified. | pathology |
10.1101/2022.04.26.22274241 | Optimizing multi-domain hematologic biomarkers and clinical features for the differential diagnosis of unipolar depression and bipolar depression | There is a lack of objective features for the differential diagnosis of unipolar and bipolar depression, especially those that can be easily accessible in practical settings. Some studies have shown that unipolar and bipolar depression have different associations with hematologic biomarkers and clinical features such as the age of onset. However, none of them have used these features for differential diagnosis. We investigated whether biomarkers of complete blood count, blood biochemical markers and clinical features could accurately classify unipolar and bipolar depression using machine learning methods.
1,160 eligible patients were included in this retrospective study (918 with unipolar depression and 242 with bipolar depression). 27 biomarkers of complete blood count,17 blood biochemical markers and 2 clinical features were investigated for the classification. Patient data was split into training (85%) and test set (15%). Using ten-fold cross validation for training, logistic regression (LR), support vector machine (SVM), random forest (RF) and Extreme Gradient Boosting (XGBoost) were compared with feature selection.
We calculated the AUC, sensitivity, specificity and accuracy. The optimal performance was achieved by XGBoost using a combination of selected biomarkers of complete blood count (WBC, PLR, MONO, LYMPH, NEUT Ratio, MCHC, BASO Ratio, LYMPH Ratio), blood biochemical markers (albumin, potassium, chlorine, HCT, calcium, LDL, HDL) and clinical features (disease duration, age of onset). The optimal performances achieved on the open test set were AUC 0.889, sensitivity 0.831, specificity 0.839 and accuracy 0.863. Hematologic biomarkers and onset features seem to be reliable information that could be easily accessible in clinical settings to improve diagnostic accuracy. In addition, we further analyzed the importance of specific blood biomarkers in samples of disease durations <= 3 years and > 3 years. WBC and MONO remained informative across different disease durations. Meanwhile, NEUT, BASO Ratio, HCT and LYMPH, and albumin were more indicative in the short course (<= 3 years), whereas NLR and chlorine were more indicative in the longer course (> 3 years). This may suggest that, given the overall stability of the model, longitudinal changes in biomarkers should be investigated across different disease courses and age groups. | psychiatry and clinical psychology |
10.1101/2022.04.26.22274299 | AI-VDT can Help in Detecting Primary Lung Cancer | The current study shows that measuring volume doubling time could accelerate the detection of primary lung cancer in chest CT imaging. Thirty tumors were selected from surgical cases of primary lung cancer at a university hospital in Japan, and the CT scan data and radiology reports were extracted retrospectively. The CT scan data were processed by a commercial pulmonary nodule AI and volume doubling time was calculated for each historical study time point. 43% of the 30 tumors had an VDT below 400 days in earlier study than the tumor was reported as a nodule on the radiology report. The average days of earlier detection was 299 days. Interpolation of the detailed mortality reduction data from the NELSON study predicted a 5.6% reduction in 10-year mortality from lung cancer. | radiology and imaging |
10.1101/2022.04.27.22273667 | Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: a Mendelian Randomisation study | Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomisation approaches can help control for such confounding. SCALLOP consortium data on 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness (CIMT) and left ventricular mass (LVM) were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309). We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF-23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with CIMT or LVM index. This suggests that previously reported observational associations of FGF-23 with risk of atherosclerotic and non-atherosclerotic cardiovascular diseases are unlikely to be causal. | nephrology |