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[ { "role": "user", "content": "Abstract: Background\nHospitalised newborn neonates frequently undergo painful invasive procedures that involve penetration of the skin and other tissues by a needle. One intervention that can be used prior to a needle insertion procedure is application of a topical local anaesthetic.\nObjectives\nTo evaluate the efficacy and safety of topical anaesthetics such as amethocaine and EMLA in newborn term or preterm infants requiring an invasive procedure involving puncture of skin and other tissues with a needle.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase and CINAHL up to 15 May 2016; previous reviews including cross-references, abstracts, and conference proceedings. We contacted expert informants. We contacted authors directly to obtain additional data. We imposed no language restrictions.\nSelection criteria\nRandomised, quasi-randomised controlled trials, and cluster and cross-over randomised trials that compared the topical anaesthetics amethocaine and eutectic mixture of local anaesthetics (EMLA) in terms of anaesthetic efficacy and safety in newborn term or preterm infants requiring an invasive procedure involving puncture of skin and other tissues with a needle\nData collection and analysis\nFrom the reports of the clinical trials we extracted data regarding clinical outcomes including pain, number of infants with methaemoglobin level 5% and above, number of needle prick attempts prior to successful needle-related procedure, crying, time taken to complete the procedure, episodes of apnoea, episodes of bradycardia, episodes of oxygen desaturation, neurodevelopmental disability and other adverse events.\nMain results\nEight small randomised controlled trials met the inclusion criteria (n = 506). These studies compared either EMLA and placebo or amethocaine and placebo. No studies compared EMLA and amethocaine. We were unable to meta-analyse the outcome of pain due to differing outcome measures and methods of reporting. For EMLA, two individual studies reported a statistically significant reduction in pain compared to placebo during lumbar puncture and venepuncture. Three studies found no statistical difference between the groups during heel lancing. For amethocaine, three studies reported a statistically significant reduction in pain compared to placebo during venepuncture and one study reported a statistically significant reduction in pain compared to placebo during cannulation. One study reported no statistical difference between the two groups during intramuscular injection.\nOne study reported no statistical difference between EMLA and the placebo group for successful venepuncture at first attempt. One study similarly reported no statistically significant difference between Amethocaine and the placebo group for successful cannulation at first attempt.\nRisk for local redness, swelling or blanching was significantly higher with EMLA (typical risk ratio (RR) 1.65, 95% confidence interval (CI) 1.24 to 2.19; typical risk difference (RD) 0.17, 95% CI 0.09 to 0.26; n = 272; number needed to treat for an additional harmful outcome (NNTH) 6, 95% CI 4 to 11; I2 = 92% indicating considerable heterogeneity) although not for amethocaine (typical RR 2.11, 95% CI 0.72 to 6.16; typical RD 0.05, 95% CI -0.02 to 0.11, n = 221). These local skin reactions for EMLA and amethocaine were reported as short-lasting. Two studies reported no methaemoglobinaemia with single application of EMLA. The quality of the evidence on outcomes assessed according to GRADE was low to moderate.\nAuthors' conclusions\nOverall, all the trials were small, and the effects of uncertain clinical significance. The evidence regarding the effectiveness or safety of the interventions studied is inadequate to support clinical recommendations. There has been no evaluation regarding any long-term effects of topical anaesthetics in newborn infants.\nHigh quality studies evaluating the efficacy and safety of topical anaesthetics such as amethocaine and EMLA for needle-related pain in newborn term or preterm infants are required. These studies should aim to determine efficacy of these topical anaesthetics and on homogenous groups of infants for gestational age. While there was no methaemoglobinaemia in the studies that reported methaemoglobin, the efficacy and safety of EMLA, especially in very preterm infants, and for repeated application, need to be further evaluated in future studies.\n\nGiven the provided abstract, please respond to the following query: \"Results and quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review of trials found that overall there is not enough good quality evidence to say if topical local anaesthetics applied to the skin help relieve pain during needle-related pain in newborn infants. Large well-design clinical trials are needed." } ]

[ { "role": "user", "content": "Abstract: Background\nInfertility is a prevalent problem that has significant consequences for individuals, families, and the community. Modifiable lifestyle factors may affect the chance of people with infertility having a baby. However, no guideline is available about what preconception advice should be offered. It is important to determine what preconception advice should be given to people with infertility and to evaluate whether this advice helps them make positive behavioural changes to improve their lifestyle and their chances of conceiving.\nObjectives\nTo assess the safety and effectiveness of preconception lifestyle advice on fertility outcomes and lifestyle behavioural changes for people with infertility.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, trial registers, Google Scholar, and Epistemonikos in January 2021; we checked references and contacted field experts to identify additional studies.\nSelection criteria\nWe included randomised controlled trials (RCTs), randomised cross-over studies, and cluster-randomised studies that compared at least one form of preconception lifestyle advice with routine care or attention control for people with infertility.\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane. Primary effectiveness outcomes were live birth and ongoing pregnancy. Primary safety outcomes were adverse events and miscarriage. Secondary outcomes included reported behavioural changes in lifestyle, birth weight, gestational age, clinical pregnancy, time to pregnancy, quality of life, and male factor infertility outcomes. We assessed the overall quality of evidence using GRADE criteria.\nMain results\nWe included in the review seven RCTs involving 2130 participants. Only one RCT included male partners. Three studies compared preconception lifestyle advice on a combination of topics with routine care or attention control. Four studies compared preconception lifestyle advice on one topic (weight, alcohol intake, or smoking) with routine care for women with infertility and specific lifestyle characteristics. The evidence was of low to very low-quality. The main limitations of the included studies were serious risk of bias due to lack of blinding, serious imprecision, and poor reporting of outcome measures.\nPreconception lifestyle advice on a combination of topics versus routine care or attention control \nPreconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.79 to 1.10; 1 RCT, 626 participants), but the quality of evidence was low. No studies reported on adverse events or miscarriage. Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice on a combination of topics affects lifestyle behavioural changes: body mass index (BMI) (mean difference (MD) -1.06 kg/m², 95% CI -2.33 to 0.21; 1 RCT, 180 participants), vegetable intake (MD 12.50 grams/d, 95% CI -8.43 to 33.43; 1 RCT, 264 participants), alcohol abstinence in men (RR 1.08, 95% CI 0.74 to 1.58; 1 RCT, 210 participants), or smoking cessation in men (RR 1.01, 95% CI 0.91 to 1.12; 1 RCT, 212 participants). Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of women with adequate folic acid supplement use (RR 0.98, 95% CI 0.95 to 1.01; 2 RCTs, 850 participants; I² = 4%), alcohol abstinence (RR 1.07, 95% CI 0.99 to 1.17; 1 RCT, 607 participants), and smoking cessation (RR 1.01, 95% CI 0.98 to 1.04; 1 RCT, 606 participants), on low quality evidence. No studies reported on other behavioural changes.\nPreconception lifestyle advice on weight versus routine care \nStudies on preconception lifestyle advice on weight were identified only in women with infertility and obesity. Compared to routine care, we are uncertain whether preconception lifestyle advice on weight affects the number of live births (RR 0.94, 95% CI 0.62 to 1.43; 2 RCTs, 707 participants; I² = 68%; very low-quality evidence), adverse events including gestational diabetes (RR 0.78, 95% CI 0.48 to 1.26; 1 RCT, 317 participants; very low-quality evidence), hypertension (RR 1.07, 95% CI 0.66 to 1.75; 1 RCT, 317 participants; very low-quality evidence), or miscarriage (RR 1.50, 95% CI 0.95 to 2.37; 1 RCT, 577 participants; very low-quality evidence). Regarding lifestyle behavioural changes for women with infertility and obesity, preconception lifestyle advice on weight may slightly reduce BMI (MD -1.30 kg/m², 95% CI -1.58 to -1.02; 1 RCT, 574 participants; low-quality evidence). Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice affects the percentage of weight loss, vegetable and fruit intake, alcohol abstinence, or physical activity. No studies reported on other behavioural changes.\nPreconception lifestyle advice on alcohol intake versus routine care \nStudies on preconception lifestyle advice on alcohol intake were identified only in at-risk drinking women with infertility. We are uncertain whether preconception lifestyle advice on alcohol intake affects the number of live births (RR 1.15, 95% CI 0.53 to 2.50; 1 RCT, 37 participants; very low-quality evidence) or miscarriages (RR 1.31, 95% CI 0.21 to 8.34; 1 RCT, 37 participants; very low-quality evidence). One study reported on behavioural changes for alcohol consumption but not as defined in the review methods. No studies reported on adverse events or other behavioural changes.\nPreconception lifestyle advice on smoking versus routine care \nStudies on preconception lifestyle advice on smoking were identified only in smoking women with infertility. No studies reported on live birth, ongoing pregnancy, adverse events, or miscarriage. One study reported on behavioural changes for smoking but not as defined in the review methods.\nAuthors' conclusions\nLow-quality evidence suggests that preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births. Evidence was insufficient to allow conclusions on the effects of preconception lifestyle advice on adverse events and miscarriage and on safety, as no studies were found that looked at these outcomes, or the studies were of very low quality. This review does not provide clear guidance for clinical practice in this area. However, it does highlight the need for high-quality RCTs to investigate preconception lifestyle advice on a combination of topics and to assess relevant effectiveness and safety outcomes in men and women with infertility.\n\nGiven the provided abstract, please respond to the following query: \"What we did\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for randomised controlled studies that compared preconception lifestyle advice for people with infertility with routine care or attention control.\nWe were interested in finding out what preconception lifestyle advice should be given to people with infertility; how well it works for improving lifestyle to increase their chance of having a baby; and whether it had any unwanted effects." } ]

[ { "role": "user", "content": "Abstract: Background\nRoot canal therapy is a sequence of treatments involving root canal cleaning, shaping, decontamination, and obturation. It is conventionally performed through a hole drilled into the crown of the affected tooth, namely orthograde root canal therapy. When it fails, retrograde filling, which seals the root canal from the root apex, is a good alternative. Many materials are used for retrograde filling. Since none meets all the criteria an ideal material should possess, selecting the most efficacious material is of utmost importance. This is an update of a Cochrane Review first published in 2016.\nObjectives\nTo determine the effects of different materials used for retrograde filling in children and adults for whom retrograde filling is necessary in order to save the tooth.\nSearch methods\nAn Information Specialist searched five bibliographic databases up to 21 April 2021 and used additional search methods to identify published, unpublished, and ongoing studies. We also searched four databases in the Chinese language.\nSelection criteria\nWe selected randomised controlled trials (RCTs) that compared different retrograde filling materials, with the reported success rate that was assessed by clinical or radiological methods for which the follow-up period was at least 12 months.\nData collection and analysis\nRecords were screened in duplicate by independent screeners. Two review authors extracted data independently and in duplicate. Original trial authors were contacted for any missing information. Two review authors independently assessed the risk of bias of the included studies. We followed Cochrane's statistical guidelines and assessed the certainty of the evidence using GRADE.\nMain results\nWe included eight studies, all at high risk of bias, involving 1399 participants with 1471 teeth, published between 1995 and 2019, and six comparisons of retrograde filling materials.\n- Mineral trioxide aggregate (MTA) versus intermediate restorative material (IRM): there may be little to no effect of MTA compared to IRM on success rate at one year, but the evidence is very uncertain (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.97 to 1.22; I2 = 0%; 2 studies; 222 teeth; very low-certainty evidence).\n- MTA versus super ethoxybenzoic acid (Super-EBA): there may be little to no effect of MTA compared to Super-EBA on success rate at one year, but the evidence is very uncertain (RR 1.03, 95% CI 0.96 to 1.10; 1 study; 192 teeth; very low-certainty evidence).\n- Super-EBA versus IRM: the evidence is very uncertain about the effect of Super-EBA compared with IRM on success rate at 1 year, with results indicating Super-EBA may reduce or have no effect on success rate (RR 0.90, 95% CI 0.80 to 1.01; 1 study; 194 teeth; very low-certainty evidence).\n- Dentine-bonded resin composite versus glass ionomer cement: compared to glass ionomer cement, dentine-bonded resin composite may increase the success rate of the treatment at 1 year, but the evidence is very uncertain (RR 2.39, 95% CI 1.60 to 3.59; 1 study; 122 teeth; very low-certainty evidence). Same result was obtained when considering the root as unit of analysis at one year (RR 1.59, 95% CI 1.20 to 2.09; 1 study; 127 roots; very low-certainty evidence).\n- Glass ionomer cement versus amalgam: the evidence is very uncertain about the effect of glass ionomer cement compared with amalgam on success rate at one year, with results indicating glass ionomer cement may reduce or have no effect on success rate (RR 0.98, 95% CI 0.86 to 1.12; 1 study; 105 teeth; very low-certainty evidence).\n- MTA versus root repair material (RRM): there may be little to no effect of MTA compared to RRM on success rate at one year, but the evidence is very uncertain (RR 1.00, 95% CI 0.94 to 1.07; I2 = 0%; 2 studies; 278 teeth; very low-certainty evidence).\nAdverse events were not assessed by any of the included studies.\nAuthors' conclusions\nBased on the present limited evidence, there is insufficient evidence to draw any conclusion as to the benefits of any one material over another for retrograde filling in root canal therapy. We conclude that more high-quality RCTs are required.\n\nGiven the provided abstract, please respond to the following query: \"What is retrograde filling in root canal therapy?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The living part of the tooth, also known as the tooth pulp, can become permanently swollen because of damage or bacterial infection due to tooth decay. To deal with this problem, the dentist has to drill a hole on the top of the crown of the tooth to access the inner space of the tooth, the root canal system. The dentist will then remove the infected tissue and bacteria by a combination of mechanical cleaning and irrigation.\nAfter this is done, the dentist fills the space with an inactive packing material and seals the opening. This treatment is known as root canal therapy. Although results are generally good, a small number of failures can happen. This can be because the root canal system is complex and it is not always easy to completely eliminate all bacteria. These can spread and the infection around the root can last indefinitely.\nWhen root canal therapy fails, a retreatment called retrograde filling is a good alternative to save the tooth. During retrograde filling the dentist cuts a flap in the gum and creates a hole in the bone to get access to the bottom tip of the root of the tooth. After cutting off the tip, followed by thorough preparation, the apex is sealed (the apical seal), and the hole made by the dentist filled with a dental material. This sealing process is considered the most important factor in achieving success in a retrograde root filling." } ]

[ { "role": "user", "content": "Abstract: Background\nIn vitro fertilisation (IVF) is a treatment for unexplained subfertility but is invasive, expensive, and associated with risks.\nObjectives\nTo evaluate the effectiveness and safety of IVF versus expectant management, unstimulated intrauterine insemination (IUI), and IUI with ovarian stimulation using gonadotropins, clomiphene citrate (CC), or letrozole in improving pregnancy outcomes.\nSearch methods\nWe searched following databases from inception to November 2021, with no language restriction: Cochrane Gynaecology and Fertility Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL. We searched reference lists of articles and conference abstracts.\nSelection criteria\nRandomised controlled trials (RCTs) comparing effectiveness of IVF for unexplained subfertility with expectant management, unstimulated IUI, and stimulated IUI.\nData collection and analysis\nWe followed standard Cochrane methods.\nMain results\nIVF versus expectant management (two RCTs)\nWe are uncertain whether IVF improves live birth rate (LBR) and clinical pregnancy rate (CPR) compared to expectant management (odds ratio (OR) 22.0, 95% confidence interval (CI) 2.56 to 189.37; 1 RCT; 51 women; very low-quality evidence; OR 3.24, 95% CI 1.07 to 9.8; 2 RCTs; 86 women; I2 = 80%; very low-quality evidence). Adverse effects were not reported. Assuming 4% LBR and 12% CPR with expectant management, these would be 8.8% to 9% and 13% to 58% with IVF.\nIVF versus unstimulated IUI (two RCTs)\nIVF may improve LBR compared to unstimulated IUI (OR 2.47, 95% CI 1.19 to 5.12; 2 RCTs; 156 women; I2 = 60%; low-quality evidence). We are uncertain whether there is a difference between IVF and IUI for multiple pregnancy rate (MPR) (OR 1.03, 95% CI 0.04 to 27.29; 1 RCT; 43 women; very low-quality evidence) and miscarriage rate (OR 1.72, 95% CI 0.14 to 21.25; 1 RCT; 43 women; very low-quality evidence). No study reported ovarian hyperstimulation syndrome (OHSS). Assuming 16% LBR, 3% MPR, and 6% miscarriage rate with unstimulated IUI, these outcomes would be 18.5% to 49%, 0.1% to 46%, and 0.9% to 58% with IVF.\nIVF versus IUI + ovarian stimulation with gonadotropins (6 RCTs), CC (1 RCT), or letrozole (no RCTs)\nStratified analysis was based on pretreatment status.\nTreatment-naive women\nThere may be little or no difference in LBR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.19, 95% CI 0.87 to 1.61; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 1.63, 95% CI 0.91 to 2.92; 2 RCTs; 221 women; I2 = 54%; low-quality evidence); or between IVF and IUI + CC (OR 2.51, 95% CI 0.96 to 6.55; 1 RCT; 103 women; low-quality evidence). Assuming 42% LBR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 26% LBR with IUI + gonadotropins (1 IVF to 1 IUI cycle), LBR would be 39% to 54% and 24% to 51% with IVF. Assuming 15% LBR with IUI + CC, LBR would be 15% to 54% with IVF.\nThere may be little or no difference in CPR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.17, 95% CI 0.85 to 1.59; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 4.59, 95% CI 1.86 to 11.35; 1 RCT; 103 women; low-quality evidence); or between IVF and IUI + CC (OR 3.58, 95% CI 1.51 to 8.49; 1 RCT; 103 women; low-quality evidence). Assuming 48% CPR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 17% with IUI + gonadotropins (1 IVF to 1 IUI cycle), CPR would be 44% to 60% and 28% to 70% with IVF. Assuming 21% CPR with IUI + CC, CPR would be 29% to 69% with IVF.\nThere may be little or no difference in multiple pregnancy rate (MPR) between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 0.82, 95% CI 0.38 to 1.77; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 0.76, 95% CI 0.36 to 1.58; 2 RCTs; 221 women; I2 = 0%; low-quality evidence); or between IVF and IUI + CC (OR 0.64, 95% CI 0.17 to 2.41; 1 RCT; 102 women; low-quality evidence).\nWe are uncertain if there is a difference in OHSS between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 6.86, 95% CI 0.35 to 134.59; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference in OHSS with 1 IVF to 1 IUI cycle (OR 1.22, 95% CI 0.36 to 4.16; 2 RCTs; 221 women; I2 = 0%; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.53, 95% CI 0.24 to 9.57; 1 RCT; 102 women; low-quality evidence).\nWe are uncertain if there is a difference in miscarriage rate between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 0.31, 95% CI 0.03 to 3.04; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference with 1 IVF to 1 IUI cycle (OR 1.16, 95% CI 0.44 to 3.02; 1 RCT; 103 women; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.48, 95% CI 0.54 to 4.05; 1 RCT; 102 women; low-quality evidence).\nIn women pretreated with IUI + CC\nIVF may improve LBR compared with IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57; 1 RCT; 280 women; low-quality evidence). Assuming 22% LBR with IUI + gonadotropins, LBR would be 39% to 65% with IVF.\nIVF may improve CPR compared with IUI + gonadotropins (OR 14.13, 95% CI 7.57 to 26.38; 1 RCT; 280 women; low-quality evidence). Assuming 30% CPR with IUI + gonadotropins, CPR would be 76% to 92% with IVF.\nAuthors' conclusions\nIVF may improve LBR over unstimulated IUI. Data should be interpreted with caution as overall evidence quality was low.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "IVF is frequently used for couples with unexplained subfertility, as it may bypass a variety of undiagnosed biological problems. However, it is expensive and invasive and can lead to complications. Other management options for unexplained subfertility include trying naturally for a pregnancy, introducing washed sperm within the womb (known as intrauterine insemination, or IUI), and performing IUI after the use of fertility drugs clomiphene citrate (CC) and gonadotropins to stimulate the ovaries." } ]

[ { "role": "user", "content": "Abstract: Background\nTuberculosis is an infectious bacterial disease that is spread via respiratory droplets from infected individuals to susceptible contacts. To eliminate this disease from low- and medium-incidence settings, people who are most likely to be infected (contacts) must be identified. Recently, study authors have examined alternate approaches to contact tracing methods that demonstrate improved detection and prioritization of contacts. The comparative benefit of these methods has not been established.\nObjectives\nTo assess the effectiveness of novel methods of contact tracing versus current standard of care to identify latent and active cases in low- to moderate-incidence settings.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, and CINAHL up to 15 July 2019. We also searched for clinical trials and examined reference lists and conference proceedings.\nSelection criteria\nRandomized controlled trials (RCTs) and cluster-RCTs of contact tracing strategies that included alternate approaches (other than standard practice).\nData collection and analysis\nTwo review authors independently assessed identified articles for eligibility and quality using prespecified criteria.\nMain results\nNo trials met the inclusion criteria of this review. Several study authors described an alternate method for examining contacts and performing social network analysis but did not compare this with the current contact tracing approach.\nAuthors' conclusions\nThis Cochrane Review highlights the lack of research in support of the current contact tracing method and the need for RCTs to compare new methods such as social network analysis to improve contact tracing processes.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Contact tracing is an important method to further reduce the rates of tuberculosis. Cochrane Review authors identified no studies addressing this question. Therefore further research is needed to determine whether alternate contact tracing approaches could produce a greater yield in the number of contacts detected and the proportion of individuals with disease." } ]

[ { "role": "user", "content": "Abstract: Background\nBronchiectasis is characterised by a widening of the airways, leading to excess mucus production and recurrent infection. It is more prevalent in women and those in middle age. Many patients with bronchiectasis do not adhere to treatments (medications, exercise and airway clearance) prescribed for their condition. The best methods to change these adherence behaviours have not been identified.\nObjectives\nTo assess the effects of interventions to enhance adherence to any aspect of treatment in adults with bronchiectasis in terms of adherence and health outcomes, such as pulmonary exacerbations, health-related quality of life and healthcare costs.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register (CAGR), which contains trial reports identified through systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, from inception to October 2015.\nSelection criteria\nWe planned to include randomised controlled trials (RCTs) of adults with bronchiectasis that compared any intervention aimed at enhancing adherence versus no intervention, usual care or another adherence intervention. We excluded studies of those who had bronchiectasis due to cystic fibrosis.\nData collection and analysis\nTwo review authors (AMcC and ET) independently screened titles, abstracts and full-texts of identified studies.\nMain results\nSearches retrieved 36 studies reported in 37 articles; no eligible studies were identified.\nAuthors' conclusions\nWe did not identify any studies that assessed the effect of interventions to enhance adherence to treatment in bronchiectasis. Adequately powered, well-designed trials of adherence interventions for bronchiectasis are needed.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We identified 37 reports but did not find any studies that tested ways to improve adherence to treatment. Properly-designed research studies that include an appropriate number of people with bronchiectasis are needed to answer this question." } ]

[ { "role": "user", "content": "Abstract: Background\nPostpartum constipation, with symptoms, such as pain or discomfort, straining, and hard stool, is a common condition affecting mothers. Haemorrhoids, pain at the episiotomy site, effects of pregnancy hormones, and haematinics used in pregnancy can increase the risk of postpartum constipation. Eating a high-fibre diet and increasing fluid intake are usually encouraged. Although laxatives are commonly used in relieving constipation, the effectiveness and safety of available interventions for preventing postpartum constipation should be ascertained. This is an update of a review first published in 2015.\nObjectives\nTo evaluate the effectiveness and safety of interventions for preventing postpartum constipation.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth’s Trials Register, and two trials registers ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 October 2019), and screened reference lists of retrieved trials.\nSelection criteria\nWe considered all randomised controlled trials (RCTs) comparing any intervention for preventing postpartum constipation versus another intervention, placebo, or no intervention in postpartum women. Interventions could include pharmacological (e.g. laxatives) and non-pharmacological interventions (e.g. acupuncture, educational and behavioural interventions). Quasi-randomised trials and cluster-RCTs were eligible for inclusion; none were identified. Trials using a cross-over design were not eligible.\nData collection and analysis\nTwo review authors independently screened the results of the search to select potentially relevant trials, extracted data, assessed risk of bias, and the certainty of the evidence, using the GRADE approach. We did not pool results in a meta-analysis, but reported them per study.\nMain results\nWe included five trials (1208 postpartum mothers); three RCTs and two quasi-RCTs. Four trials compared a laxative with placebo; one compared a laxative plus a bulking agent versus the same laxative alone, in women who underwent surgical repair of third degree perineal tears. Trials were poorly reported, and four of the five trials were published over 40 years ago. We judged the risk of bias to be unclear for most domains. Overall, we found a high risk of selection and attrition bias.\nLaxative versus placebo\nWe included four trials in this comparison. Two of the trials examined the effects of laxatives that are no longer used; one has been found to have carcinogenic properties (Danthron), and the other is not recommended for lactating women (Bisoxatin acetate); therefore, we did not include their results in our main findings.\nNone of the trials included in this comparison assessed our primary outcomes: pain or straining on defecation, incidence of postpartum constipation, or quality of life; or many of our secondary outcomes.\nA laxative (senna) may increase the number of women having their first bowel movement within 24 hours after delivery (risk ratio (RR) 2.90, 95% confidence interval (CI) 2.24 to 3.75; 1 trial, 471 women; low-certainty evidence); may have little or no effect on the number of women having their first bowel movement on day one after delivery (RR 0.94, 95% CI 0.72 to 1.22; 1 trial, 471 women; very low-certainty evidence); may reduce the number of women having their first bowel movement on day two (RR 0.23, 95% CI 0.11 to 0.45; 1 trial, 471 women; low-certainty evidence); and day three (RR 0.05, 95% CI 0.00 to 0.89; 1 trial, 471 women; low-certainty evidence); and may have little or no effect on the number of women having their first bowel movement on day four after delivery (RR 0.22, 95% CI 0.03 to 1.87; 1 trial, 471 women; very low-certainty evidence), but some of the evidence is very uncertain.\nAdverse effects were poorly reported. Low-certainty evidence suggests that the laxative (senna) may increase the number of women experiencing abdominal cramps (RR 4.23, 95% CI 1.75 to 10.19; 1 trial, 471 women). Very low-certainty evidence suggests that laxatives taken by the mother may have little or no effect on loose stools in the baby (RR 0.62, 95% CI 0.16 to 2.41; 1 trial, 281 babies); or diarrhoea (RR 2.46, 95% CI 0.23 to 26.82; 1 trial, 281 babies).\nLaxative plus bulking agent versus laxative only\nVery low-certainty evidence from one trial (147 women) suggests no evidence of a difference between these two groups of women who underwent surgical repair of third degree perineal tears; only median and range data were reported. The trial also reported no evidence of a difference in the incidence of postpartum constipation (data not reported), but did not report on quality of life. Time to first bowel movement was reported as a median (range); very low-certainty evidence suggests little or no difference between the two groups. A laxative plus bulking agent may increase the number of women having any episode of faecal incontinence during the first 10 days postpartum (RR 1.81, 95% CI 1.01 to 3.23; 1 trial, 147 women; very low-certainty evidence). The trial did not report on adverse effects of the intervention on babies, or many of our secondary outcomes.\nAuthors' conclusions\nThere is insufficient evidence to make general conclusions about the effectiveness and safety of laxatives for preventing postpartum constipation. The evidence in this review was assessed as low to very low-certainty evidence, with downgrading decisions based on limitations in study design, indirectness and imprecision.\nWe did not identify any trials assessing educational or behavioural interventions. We identified four trials that examined laxatives versus placebo, and one that examined laxatives versus laxatives plus stool bulking agents.\nFurther, rigorous trials are needed to assess the effectiveness and safety of laxatives during the postpartum period for preventing constipation. Trials should assess educational and behavioural interventions, and positions that enhance defecation. They should report on the primary outcomes from this review: pain or straining on defecation, incidence of postpartum constipation, quality of life, time to first bowel movement after delivery, and adverse effects caused by the intervention, such as: nausea or vomiting, pain, and flatus.\n\nGiven the provided abstract, please respond to the following query: \"What is the issue?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Constipation during the postpartum period is a bowel disorder, characterised by symptoms, such as pain or discomfort, straining, hard lumpy stool, and a sense of incomplete bowel evacuation. Administration of enemas before labour, the ability of women to eat during active labour, and irregular and altered eating habits during the first few days after delivery can each have an influence on bowel movements in the days after giving birth. This is an update of a review first published in 2015." } ]

[ { "role": "user", "content": "Abstract: Background\nBenign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one-third of women with fibroids will present with symptoms that are severe enough to warrant treatment. The standard treatment of symptomatic fibroids is hysterectomy (that is surgical removal of the uterus) for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus. Myomectomy, the surgical removal of myomas, can be associated with life-threatening bleeding. Excessive bleeding can necessitate emergency blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library (2011, Issue 11).\nObjectives\nTo assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy.\nSearch methods\nIn June 2014, we conducted electronic searches in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO, and trial registers for ongoing and registered trials.\nSelection criteria\nWe selected randomised controlled trials (RCTs) that compared potential interventions to reduce blood loss during myomectomy to placebo or no treatment.\nData collection and analysis\nThe two authors independently selected RCTs for inclusion, assessed the risk of bias and extracted data from the included RCTs. The primary review outcomes were blood loss and need for blood transfusion. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the quality of evidence using GRADE methods.\nMain results\nEighteen RCTs with 1250 participants met our inclusion criteria. The studies were conducted in hospital settings in low, middle and high income countries.\nBlood loss\nWe found significant reductions in blood loss with the following interventions:\nvaginal misoprostol (2 RCTs, 89 women: MD -97.88 ml, 95% CI -125.52 to -70.24; I2 = 43%; moderate-quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD -245.87 ml, 95% CI -434.58 to -57.16; I2 = 98%; moderate-quality evidence); intramyometrial bupivacaine plus epinephrine (1 RCT, 60 women: MD -68.60 ml, 95% CI -93.69 to -43.51; low-quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD -243 ml, 95% CI -460.02 to -25.98; low-quality evidence); gelatin-thrombin matrix (1 RCT, 50 women: MD -545.00 ml, 95% CI -593.26 to -496.74; low-quality evidence); intravenous ascorbic acid (1 RCT, 102 women: MD -411.46 ml, 95% CI -502.58 to -320.34; low-quality evidence); vaginal dinoprostone (1 RCT, 108 women: MD -131.60 ml, 95% CI -253.42 to -9.78; low-quality evidence); loop ligation of the myoma pseudocapsule (1 RCT, 70 women: MD -305.01 ml, 95% CI -354.83 to -255.19; low-quality evidence); a fibrin sealant patch (1 RCT, 70 women: MD -26.50 ml, 95% CI -44.47 to -8.53; low-quality evidence), a Foley catheter tied around the cervix (1 RCT, 93 women: MD -240.70 ml, 95% CI -359.61 to -121.79; low-quality evidence), and a polyglactin suture round both cervix and infundibulopelvic ligament (1 RCT, 28 women: MD -1870.0 ml, 95% CI -2547.16 to 1192.84; low-quality evidence). There was no good evidence of an effect on blood loss with oxytocin, morcellation or clipping of the uterine artery.\nNeed for blood transfusion\nWe found significant reductions in the need for blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I2 = 0%; moderate-quality evidence); tourniquet tied round the cervix (1 RCT, 98 women: OR 0.22, 95% CI 0.09 to 0.55; low-quality evidence); tourniquet tied round both cervix and infundibulopelvic ligament (1 RCT, 28 women: OR 0.02, 95% CI 0.00 to 0.23; low-quality evidence); gelatin-thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low-quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; low-quality evidence), but no evidence of effect on the need for blood transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop ligation of the myoma pseudocapsule and a fibrin sealant patch.\nThere were insufficient data on the adverse effects and costs of the different interventions.\nAuthors' conclusions\nAt present there is moderate-quality evidence that misoprostol or vasopressin may reduce bleeding during myomectomy, and low-quality evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin-thrombin matrix, ascorbic acid, dinoprostone, loop ligation, a fibrin sealant patch, a peri-cervical tourniquet or a tourniquet tied round both cervix and infundibulopelvic ligament may reduce bleeding during myomectomy. There is no evidence that oxytocin, morcellation and temporary clipping of the uterine artery reduce blood loss. Further well designed studies are required to establish the effectiveness, safety and costs of different interventions for reducing blood loss during myomectomy.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "There is moderate-quality evidence that misoprostol reduces blood loss by between 70.24 ml and 125.52 ml; with a laparotomy vasopressin reduces blood loss by between 392.51 and 507.49 ml during myomectomy, and by between 121.73 ml and 172.17 ml during laparoscopic myomectomy. There is low-quality evidence for the rest of the interventions (chemical dissection, dinoprostone, gelatin-thrombin matrix, tranexamic acid, vitamin C, mixture of bupivacaine and epinephrine, a fibrin sealant patch and the two types of tourniquet)." } ]

[ { "role": "user", "content": "Abstract: Background\nHigh altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres ( ˜ 8200 feet ). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions.\nObjectives\nTo assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), LILACS and trial registries in January 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text terms to search.\nSelection criteria\nWe included randomized-controlled and cross-over trials conducted in any setting where commonly-used classes of drugs were used to prevent acute HAI.\nData collection and analysis\nWe used standard methodological procedures as expected by Cochrane.\nMain results\nWe included 64 studies (78 references) and 4547 participants in this review, and classified 12 additional studies as ongoing. A further 12 studies await classification, as we were unable to obtain the full texts. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. Risks of bias were unclear for several domains, and a considerable number of studies did not report adverse events of the evaluated interventions. We found 26 comparisons, 15 of them comparing commonly-used drugs versus placebo. We report results for the three most important comparisons:\nAcetazolamide versus placebo (28 parallel studies; 2345 participants)\nThe risk of AMS was reduced with acetazolamide (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.56; I2 = 0%; 16 studies; 2301 participants; moderate quality of evidence). No events of HAPE were reported and only one event of HACE (RR 0.32, 95% CI 0.01 to 7.48; 6 parallel studies; 1126 participants; moderate quality of evidence). Few studies reported side effects for this comparison, and they showed an increase in the risk of paraesthesia with the intake of acetazolamide (RR 5.53, 95% CI 2.81 to 10.88, I2 = 60%; 5 studies, 789 participants; low quality of evidence).\nBudenoside versus placebo (2 parallel studies; 132 participants)\nData on budenoside showed a reduction in the incidence of AMS compared with placebo (RR 0.37, 95% CI 0.23 to 0.61; I2 = 0%; 2 studies, 132 participants; low quality of evidence). Studies included did not report events of HAPE or HACE, and they did not find side effects (low quality of evidence).\nDexamethasone versus placebo (7 parallel studies; 205 participants)\nFor dexamethasone, the data did not show benefits at any dosage (RR 0.60, 95% CI 0.36 to 1.00; I2 = 39%; 4 trials, 176 participants; low quality of evidence). Included studies did not report events of HAPE or HACE, and we rated the evidence about adverse events as of very low quality.\nAuthors' conclusions\nOur assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day. This information is based on evidence of moderate quality. Acetazolamide is associated with an increased risk of paraesthesia, although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for most of the pharmacological agents evaluated in this review, to evaluate their effectiveness and safety.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "High altitude illness (HAI) is a term used to describe a group of brain and breathing conditions that can occur while travelling to altitudes above 2500 metres ( ˜ 8200 feet ). HAI is generally characterized by headache, nausea, vomiting and tiredness (often called acute mountain sickness), but may affect the brain or the lungs in different individuals. In this review, we assessed the most commonly-used drugs to prevent the onset of this illness." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute cough due to upper respiratory tract infection (URTI) is a common symptom. Non-prescription, over-the-counter (OTC) medicines are frequently recommended as a first-line treatment, but there is little evidence as to whether these drugs are effective.\nObjectives\nTo assess the effects of oral OTC cough preparations for acute cough in children and adults in community settings.\nSearch methods\nWe searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3 2014), EMBASE (January 1974 to March 2014), CINAHL (January 2010 to March 2014), LILACS (January 2010 to March 2014), Web of Science (January 2010 to March 2014) and the UK Department of Health National Research Register (March 2010).\nSelection criteria\nRandomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in community settings. We considered all cough outcomes; secondary outcomes of interest were adverse effects.\nData collection and analysis\nTwo review authors independently screened potentially relevant citations, extracted data and assessed study quality. We performed quantitative analysis where appropriate.\nMain results\nDue to the small numbers of trials in each category, the limited quantitative data available and the marked differences between trials in terms of participants, interventions and outcome measurement, we felt that pooling of the results was inappropriate.\nWe included 29 trials (19 in adults, 10 in children) involving 4835 people (3799 adults and 1036 children). All studies were placebo-controlled RCTs. However, assessment of the risk of bias of the included studies was limited by poor reporting, particularly for the earlier studies.\nIn the adult studies, six trials compared antitussives with placebo and had variable results. Three trials compared the expectorant guaifenesin with placebo; one indicated significant benefit, whereas the other two did not. One trial found that a mucolytic reduced cough frequency and symptom scores. Two studies examined antihistamine-decongestant combinations and found conflicting results. Four studies compared other combinations of drugs with placebo and indicated some benefit in reducing cough symptoms. Three trials found that antihistamines were no more effective than placebo in relieving cough symptoms.\nIn the child studies, antitussives (data from three studies), antihistamines (data from three studies), antihistamine-decongestants (two studies) and antitussive/bronchodilator combinations (one study) were no more effective than placebo. No studies using expectorants met our inclusion criteria. The results of one trial favoured active treatment with mucolytics over placebo. One trial tested two paediatric cough syrups and both preparations showed a 'satisfactory response' in 46% and 56% of children compared to 21% of children in the placebo group. One new trial indicated that three types of honey were more effective than placebo over a three-day period.\nTwenty-one studies reported adverse effects. There was a wide range across studies, with higher numbers of adverse effects in participants taking preparations containing antihistamines and dextromethorphan.\nAuthors' conclusions\nThe results of this review have to be interpreted with caution because the number of studies in each category of cough preparations was small. Availability, dosing and duration of use of over-the-counter cough medicines vary significantly in different countries. Many studies were poorly reported making assessment of risk of bias difficult and studies were also very different from each other, making evaluation of overall efficacy difficult. There is no good evidence for or against the effectiveness of OTC medicines in acute cough. This should be taken into account when considering prescribing antihistamines and centrally active antitussive agents in children; drugs that are known to have the potential to cause serious harm.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Acute cough is a common and troublesome symptom in children and adults suffering from acute upper respiratory tract infection (URTI). Many people self prescribe over-the-counter (OTC) cough preparations, and health practitioners often recommend their use for the initial treatment of cough. There is substantial variation between countries in the availability and guidelines for use of many of these preparations." } ]

[ { "role": "user", "content": "Abstract: Background\nTuberculosis causes more deaths than any other infectious disease globally. Bacillus Calmette-Guérin (BCG) is the only available vaccine, but protection is incomplete and variable. The modified Vaccinia Ankara virus expressing antigen 85A (MVA85A) is a viral vector vaccine produced to prevent tuberculosis.\nObjectives\nTo assess and summarize the effects of the MVA85A vaccine boosting BCG in humans.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and four other databases. We searched the WHO ICTRP and ClinicalTrials.gov. All searches were run up to 10 May 2018.\nSelection criteria\nWe evaluated randomized controlled trials of MVA85A vaccine given with BCG in people regardless of age or HIV status.\nData collection and analysis\nTwo review authors independently assessed the eligibility and risk of bias of trials, and extracted and analyzed data. The primary outcome was active tuberculosis disease. We summarized dichotomous outcomes using risk ratios (RR) and risk differences (RD), with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses. Where meta-analysis was inappropriate, we summarized results narratively.\nMain results\nThe search identified six studies relating to four Phase 2 randomized controlled trials enrolling 3838 participants. Funding was by government bodies, charities, and philanthropic donors. Five studies included infants, one of them infants born to HIV-positive mothers. One study included adults living with HIV. All trials included authors from Oxford University who led the laboratory development of the vaccine. Participants received intradermal MVA85A after BCG in some studies, and before selective deferred BCG in HIV-exposed infants.\nThe largest trial in 2797 African children was well conducted with low risk of bias for most parameters. Risk of bias was uncertain for selective reporting because there were no precise case definition endpoints for active tuberculosis published prior to the trial analysis.\nMVA85A added to BCG compared to BCG alone probably has no effect on the risk of developing microbiologically confirmed tuberculosis (RR 0.97, 95% CI 0.58 to 1.62; 3439 participants, 2 trials; moderate-certainty evidence), or the risk of starting on tuberculosis treatment (RR 1.10, 95% CI 0.92 to 1.33; 3687 participants, 3 trials; moderate-certainty evidence). MVA85A probably has no effect on the risk of developing latent tuberculosis (RR 1.01, 95% CI 0.85 to 1.21; 3831 participants, 4 trials; moderate-certainty evidence). Vaccinating people with MVA85A in addition to BCG did not cause life-threatening serious adverse effects (RD 0.00, 95% CI –0.00 to 0.00; 3692 participants, 3 trials; high-certainty evidence). Vaccination with MVA85A is probably associated with an increased risk of local skin adverse effects (3187 participants, 3 trials; moderate-certainty evidence), but not systemic adverse effect related to vaccination (144 participants, 1 trial; low-certainty evidence). This safety profile is consistent with Phase 1 studies which outlined a transient, superficial reaction local to the injection site and mild short-lived symptoms such as malaise and fever.\nAuthors' conclusions\nMVA85A delivered by intradermal injection in addition to BCG is safe but not effective in reducing the risk of developing tuberculosis.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "After examining the research published up to 10 May 2018, we included six study findings from four randomized controlled trials (clinical trials where people are randomly put into one of two or more treatment groups), enrolling 3838 children and adults. Based on these studies of mostly children and adults living in Africa, MVA85A added to BCG compared to BCG alone probably has no effect on the risk of developing active tuberculosis defined as microbiologically confirmed tuberculosis (moderate-certainty evidence) or the risk of starting on tuberculosis treatment (moderate-certainty evidence). MVA85A has no effect on the risk of developing latent tuberculosis (moderate-certainty evidence). MVA85A does not cause any life-threatening serious side effects (highly-certainty evidence). There were more local skin reactions in people vaccinated with MVA85A, however, there was no increase in overall side effects in people given MVA85A." } ]

[ { "role": "user", "content": "Abstract: Background\nStudies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review.\nObjectives\nTo determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of last search: 01 April 2020.\nWe also searched online study registries and contacted authors. Date of last search: 12 February 2020.\nSelection criteria\nRandomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo.\nData collection and analysis\nTwo authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The quality of the evidence was assessed using GRADE.\nMain results\nThe searches identified 23 studies; five studies with 106 participants (children and adults) were included; duration of studies and interventions differed. Two studies compared omega-3 fatty acids to olive oil for six weeks; one study compared omega-3 fatty acids and omega-6 fatty acids to control capsules (customised fatty acid blends) for three months; one study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months; and one study compared omega-3 fatty acids to a placebo for 12 months. Three studies had a low risk of bias for randomisation, but the risk was unclear in the remaining two studies; all studies had an unclear risk of bias for allocation concealment. Three of the studies adequately blinded participants; the risk of bias for selective reporting was high in one study and unclear for four studies.\nTwo studies reported the number of respiratory exacerbations. At three months, one study (43 participants) reported no change in antibiotic usage. At 12 months the second study (15 participants) reported a reduction in the number of pulmonary exacerbations and cumulative antibiotic days in the supplement group compared to the previous year (no data for the control group); very low-quality evidence means we are unsure whether supplementation has any effect on this outcome.\nWith regards to adverse events, one six-week study (12 participants) reported no difference in diarrhoea between omega-3 or placebo capsules; the very low-quality evidence means we are unsure if supplementation has any effect on this outcome. Additionally, one study reported an increase in steatorrhoea requiring participants to increase their daily dose of pancreatic enzymes, but three studies had already increased pancreatic enzyme dose at study begin so as to reduce the incidence of steatorrhoea. One study (43 participants) reported stomach pains at three months (treatment or control group not specified). One six-week study (19 participants) reported three asthma exacerbations leading to exclusion of participants since corticosteroid treatment could affect affect essential fatty acid metabolism.\nFour studies reported lung function. One six-week study (19 participants) reported an increase in forced expiratory volume in one second (FEV1) (L) and forced vital capacity (FVC) (L), but the very low-quality evidence means we are unsure if supplementation has any effect on lung function. The remaining studies did not report any difference in lung function at three months (unit of measurement not specified) or at six months and one year (FEV1 % predicted and FVC % predicted).\nNo deaths were reported in any of the five studies. Four studies reported clinical variables. One study reported an increase in Schwachman score and weight alongside a reduction in sputum volume with supplementation compared to placebo at three months (data not analysable). However, three studies reported no differences in either weight at six weeks, in body mass index (BMI) standard deviation (SD) score at six months (very low-quality evidence) or BMI Z score at 12 months.\nThree studies reported biochemical markers of fatty acid status. One study showed an increase from baseline in both EPA and DHA content of serum phospholipids in the omega-3 group compared to placebo at three months and also a significant decrease in n-6/n-3 ratio in the supplement group compared to placebo; since the quality of the evidence is very low we are not certain that these changes are due to supplementation. One six-month cross-over study showed a higher EPA content of the neutrophil membrane in the supplement group compared to the placebo group, but, no difference in DHA membrane concentration. Furthermore, the leukotriene B4 to leukotriene B5 ratio was lower at six months in the omega-3 group compared to placebo. A one-year study reported a greater increase in the essential fatty acid profile and a decrease in AA levels in the treatment arm compared to placebo.\nAuthors' conclusions\nThis review found that regular omega-3 supplements may provide some limited benefits for people with cystic fibrosis with relatively few adverse effects: however, the quality of the evidence across all outcomes was very low. The current evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes when providing omega-3 supplementation or olive oil placebo capsules. More research is required to determine the exact dose of pancreatic enzyme required.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In people with cystic fibrosis recurring cycles of infection and inflammation are thought to worsen lung function. Studies suggest that omega-3 fatty acids, such as those derived from fish oils, may work to counter the inflammation and may be of benefit in chronic inflammatory diseases including cystic fibrosis. This is an updated version of the review." } ]

[ { "role": "user", "content": "Abstract: Background\nThromboangiitis obliterans, also known as Buerger's disease, is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small- and medium-sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Stem cell therapy is an option for patients with severe complications, such as ischemic ulcers or rest pain.\nObjectives\nTo assess the effectiveness and safety of stem cell therapy in individuals with thromboangiitis obliterans (Buerger's disease).\nSearch methods\nThe Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 October 2017. The review authors searched the European grey literature OpenGrey Database, screened reference lists of relevant studies and contacted study authors.\nSelection criteria\nRandomized controlled trials (RCTs) or quasi-RCTs of stem cell therapy in thromboangiitis obliterans (Buerger's disease).\nData collection and analysis\nThe review authors (DC, DM, FN) independently assessed the studies, extracted data and performed data analysis.\nMain results\nWe only included one RCT (18 participants with thromboangiitis obliterans) comparing the implantation of stem cell derived from bone marrow with placebo and standard wound dressing care in this review. We identified no studies that compared stem cell therapy (bone marrow source) versus stem cell therapy (umbilical cord source), stem cell therapy (any source) versus pharmacological treatment and stem cell therapy (any source) versus sympathectomy. Ulcer healing was assessed in the form of ulcer size. The mean ulcer area decreased more in the stem cell implantation group: from 5.04 cm2 (standard deviation (SD) 0.70) to 1.48 cm2 (SD 0.56) compared with the control group: mean ulcer size area decreased from 4.68 cm2 (SD 0.62) to 3.59 cm2 (SD 0.14); mean difference (MD) -2.11 cm2, 95% confidence interval (CI) -2.49 to -1.73; 1 study, 18 participants; very low-quality evidence. Pain-free walking distance showed more of an improvement in the stem cell implantation group: from mean of 38.33 meters (SD 17.68) to 284.44 meters (SD 212.12) compared with the control group: mean walking distance increased from 35.66 meters (SD 19.79) to 78.22 meters (SD 35.35); MD 206.22 meters, 95% CI 65.73 to 346.71; 1 study; 18 participants; very low-quality evidence.\nOutcomes such as rate of amputation, pain, amputation-free survival and adverse effects were not assessed.\nThe quality of evidence was classified as very low, with only one study, small numbers of participants, high risk of bias in many domains and missing information regarding tobacco exposure status.\nAuthors' conclusions\nVery low-quality evidence suggests there may be an effect of the use of bone marrow-derived stem cells in the healing of ulcers and improvement in the pain-free walking distance in patients with Buerger's disease. High-quality trials assessing the effectiveness of stem cell therapy for treatment of patients with thromboangiitis obliterans (Buerger's disease) are needed.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Thromboangiitis obliterans, also known as Buerger's disease, is a condition characterized by recurring progressive inflammation and clotting in small- and medium-sized arteries and veins of the hands and feet. Its cause is unknown, but it is most common in men with a history of tobacco use. It is responsible for ulcers and extreme pain in the limbs of young smokers. In many cases, mainly in patients with the most severe form, there is no possibility of improving the condition with surgery, and therefore, alternative treatments are used. Stem cell therapy is an experimental treatment performed through the implantation of cells (from bone marrow, umbilical cord, peripheral blood etc.) which are capable of becoming new blood vessels, improving local circulation and contributing to the healing of ulcers and relieving rest pain. This review assessed the effectiveness of stem cell therapy in the treatment of patients with thromboangiitis obliterans (Buerger's disease)." } ]

[ { "role": "user", "content": "Abstract: Background\nGenerally, before being operated on, patients will be given informal information by the healthcare providers involved in the care of the patients (doctors, nurses, ward clerks, or healthcare assistants). This information can also be provided formally in different formats including written information, formal lectures, or audio-visual recorded information.\nObjectives\nTo compare the benefits and harms of formal preoperative patient education for patients undergoing laparoscopic cholecystectomy.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to March 2013.\nSelection criteria\nWe included only randomised clinical trials irrespective of language and publication status.\nData collection and analysis\nTwo review authors independently extracted the data. We planned to calculate the risk ratio with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) with 95% CI for continuous outcomes based on intention-to-treat analyses when data were available.\nMain results\nA total of 431 participants undergoing elective laparoscopic cholecystectomy were randomised to formal patient education (215 participants) versus standard care (216 participants) in four trials. The patient education included verbal education, multimedia DVD programme, computer-based multimedia programme, and PowerPoint presentation in the four trials. All the trials were of high risk of bias. One trial including 212 patients reported mortality. There was no mortality in either group in this trial. None of the trials reported surgery-related morbidity, quality of life, proportion of patients discharged as day-procedure laparoscopic cholecystectomy, the length of hospital stay, return to work, or the number of unplanned visits to the doctor. There were insufficient details to calculate the mean difference and 95% CI for the difference in pain scores at 9 to 24 hours (1 trial; 93 patients); and we did not identify clear evidence of an effect on patient knowledge (3 trials; 338 participants; SMD 0.19; 95% CI -0.02 to 0.41; very low quality evidence), patient satisfaction (2 trials; 305 patients; SMD 0.48; 95% CI -0.42 to 1.37; very low quality evidence), or patient anxiety (1 trial; 76 participants; SMD -0.37; 95% CI -0.82 to 0.09; very low quality evidence) between the two groups.\nA total of 173 participants undergoing elective laparoscopic cholecystectomy were randomised to electronic consent with repeat-back (patients repeating back the information provided) (92 participants) versus electronic consent without repeat-back (81 participants) in one trial of high risk of bias. The only outcome reported in this trial was patient knowledge. The effect on patient knowledge between the patient education with repeat-back versus patient education without repeat-back groups was imprecise and based on 1 trial of 173 participants; SMD 0.07; 95% CI -0.22 to 0.37; very low quality evidence).\nAuthors' conclusions\nDue to the very low quality of the current evidence, the effects of formal patient education provided in addition to the standard information provided by doctors to patients compared with standard care remain uncertain. Further well-designed randomised clinical trials of low risk of bias are necessary.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found four trials including 431 patients undergoing elective laparoscopic cholecystectomy who received either formal patient education (215 participants) or standard care (216 participants). The choice of whether the patient received formal patient education or standard care was determined by a method similar to the toss of a coin in order to create comparable groups of patients. The patient education included providing information by just talking to the patient but in a more formal way or by using various method of presentation. All the trials were of high risk of bias (faults in study design that can result in erroneous conclusions). Only one trial including 212 participants reported deaths after surgery. There were no deaths in either group in this trial. There was no clear evidence of an effect on pain scores at 9 to 24 hours, patient knowledge, patient satisfaction, or patient anxiety associated with education. None of the trials reported surgical complications, quality of life, percentage of patients discharged as day-procedure laparoscopic cholecystectomy, length of hospital stay, return to work, or the number of unplanned visits to the doctor.\nA total of 173 participants undergoing elective laparoscopic cholecystectomy underwent patient education with repeat-back (patients repeating back the information provided) (92 participants) or patient education without repeat-back (81 participants) in one trial of high risk of bias. The only outcome reported in this trial was patient knowledge. The results we found for the effect onpatient knowledge between the patient education with repeat-back and patient education without repeat-back groups were uncertain and we could not exclude possible benefits of either education or control.\nDue to the very low quality of the current evidence, we are uncertain as to whether formal patient education provided in addition to the standard information provided by doctors has any benefit to patients. Further well-designed randomised clinical trials are necessary." } ]

[ { "role": "user", "content": "Abstract: Background\nPatients with a low platelet count (thrombocytopenia) often require the insertion of central lines (central venous catheters (CVCs)). CVCs have a number of uses; these include: administration of chemotherapy; intensive monitoring and treatment of critically-ill patients; administration of total parenteral nutrition; and long-term intermittent intravenous access for patients requiring repeated treatments. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to CVC insertion, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to CVC insertion varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding after a central line insertion appears to be low if an ultrasound-guided technique is used. Patients may therefore be exposed to the risks of a platelet transfusion without any obvious clinical benefit.\nObjectives\nTo assess the effects of different platelet transfusion thresholds prior to the insertion of a central line in patients with thrombocytopenia (low platelet count).\nSearch methods\nWe searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2015, Issue 2), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 February 2015.\nSelection criteria\nWe included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients of any age with thrombocytopenia requiring insertion of a CVC.\nData collection and analysis\nWe used standard methodological procedures expected by The Cochrane Collaboration.\nMain results\nOne RCT was identified that compared different platelet transfusion thresholds prior to insertion of a CVC in people with chronic liver disease. This study is still recruiting participants (expected recruitment: up to 165 participants) and is due to be completed in December 2017. There were no completed studies. There were no studies that compared no platelet transfusions to a platelet transfusion threshold.\nAuthors' conclusions\nThere is no evidence from RCTs to determine whether platelet transfusions are required prior to central line insertion in patients with thrombocytopenia, and, if a platelet transfusion is required, what is the correct platelet transfusion threshold. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients. The one ongoing RCT involving people with cirrhosis will not be able to answer this review's questions, because it is a small study that assesses one patient group and does not address all of the comparisons included in this review. To detect an increase in the proportion of participants who had major bleeding from 1 in 100 to 2 in 100 would require a study containing at least 4634 participants (80% power, 5% significance).\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We evaluated the evidence about whether people with a low platelet count require a platelet transfusion prior to insertion of a central line (central venous catheter (CVC)), and if so what is the platelet count level at which a platelet transfusion is required." } ]

[ { "role": "user", "content": "Abstract: Background\nChanges to the method of payment for healthcare providers, including pay-for-performance schemes, are increasingly being used by governments, health insurers, and employers to help align financial incentives with health system goals. In this review we focused on changes to the method and level of payment for all types of healthcare providers in outpatient healthcare settings. Outpatient healthcare settings, broadly defined as 'out of hospital' care including primary care, are important for health systems in reducing the use of more expensive hospital services.\nObjectives\nTo assess the impact of different payment methods for healthcare providers working in outpatient healthcare settings on the quantity and quality of health service provision, patient outcomes, healthcare provider outcomes, cost of service provision, and adverse effects.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase (searched 5 March 2019), and several other databases. In addition, we searched clinical trials platforms, grey literature, screened reference lists of included studies, did a cited reference search for included studies, and contacted study authors to identify additional studies. We screened records from an updated search in August 2020, with any potentially relevant studies categorised as awaiting classification.\nSelection criteria\nRandomised trials, non-randomised trials, controlled before-after studies, interrupted time series, and repeated measures studies that compared different payment methods for healthcare providers working in outpatient care settings.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We conducted a structured synthesis. We first categorised the payment methods comparisons and outcomes, and then described the effects of different types of payment methods on different outcome categories. Where feasible, we used meta-analysis to synthesise the effects of payment interventions under the same category. Where it was not possible to perform meta-analysis, we have reported means/medians and full ranges of the available point estimates. We have reported the risk ratio (RR) for dichotomous outcomes and the relative difference (as per cent change or mean difference (MD)) for continuous outcomes.\nMain results\nWe included 27 studies in the review: 12 randomised trials, 13 controlled before-and-after studies, one interrupted time series, and one repeated measure study. Most healthcare providers were primary care physicians. Most of the payment methods were implemented by health insurance schemes in high-income countries, with only one study from a low- or middle-income country. The included studies were categorised into four groups based on comparisons of different payment methods.\n(1) Pay for performance (P4P) plus existing payment methods comparedwith existing payment methods for healthcare providers working in outpatient healthcare settings\nP4P incentives probably improve child immunisation status (RR 1.27, 95% confidence interval (CI) 1.19 to 1.36; 3760 patients; moderate-certainty evidence) and may slightly increase the number of patients who are asked more detailed questions on their disease by their pharmacist (MD 1.24, 95% CI 0.93 to 1.54; 454 patients; low-certainty evidence). P4P may slightly improve primary care physicians' prescribing of guideline-recommended antihypertensive medicines compared with an existing payment method (RR 1.07, 95% CI 1.02 to 1.12; 362 patients; low-certainty evidence). We are uncertain about the effects of extra P4P incentives on mean blood pressure reduction for patients and costs for providing services compared with an existing payment method (very low-certainty evidence). Outcomes related to workload or other health professional outcomes were not reported in the included studies. One randomised trial found that compared to the control group, the performance of incentivised professionals was not sustained after the P4P intervention had ended.\n(2) Fee for service (FFS) comparedwith existing payment methods for healthcare providers working in outpatient healthcare settings\nWe are uncertain about the effect of FFS on the quantity of health services delivered (outpatient visits and hospitalisations), patient health outcomes, and total drugs cost compared to an existing payment method due to very low-certainty evidence. The quality of service provision and health professional outcomes were not reported in the included studies. One randomised trial reported that physicians paid via FFS may see more well patients than salaried physicians (low-certainty evidence), possibly implying that more unnecessary services were delivered through FFS.\n(3) FFS mixed with existing payment methods compared with existing payment methods for healthcare providers working in outpatient healthcare settings\nFFS mixed payment method may increase the quantity of health services provided compared with an existing payment method (RR 1.37, 95% CI 1.07 to 1.76; low-certainty evidence). We are uncertain about the effect of FFS mixed payment on quality of services provided, patient health outcomes, and health professional outcomes compared with an existing payment method due to very low-certainty evidence. Cost outcomes and adverse effects were not reported in the included studies.\n(4) Enhanced FFS compared with FFS for healthcare providers working in outpatient healthcare settings\nEnhanced FFS (higher FFS payment) probably increases child immunisation rates (RR 1.25, 95% CI 1.06 to 1.48; moderate-certainty evidence). We are uncertain whether higher FFS payment results in more primary care visits and about the effect of enhanced FFS on the net expenditure per year on covered children with regular FFS (very low-certainty evidence). Quality of service provision, patient outcomes, health professional outcomes, and adverse effects were not reported in the included studies.\nAuthors' conclusions\nFor healthcare providers working in outpatient healthcare settings, P4P or an increase in FFS payment level probably increases the quantity of health service provision (moderate-certainty evidence), and P4P may slightly improve the quality of service provision for targeted conditions (low-certainty evidence). The effects of changes in payment methods on health outcomes is uncertain due to very low-certainty evidence. Information to explore the influence of specific payment method design features, such as the size of incentives and type of performance measures, was insufficient. Furthermore, due to limited and very low-certainty evidence, it is uncertain if changing payment models without including additional funding for professionals would have similar effects.\nThere is a need for further well-conducted research on payment methods for healthcare providers working in outpatient healthcare settings in low- and middle-income countries; more studies comparing the impacts of different designs of the same payment method; and studies that consider the unintended consequences of payment interventions.\n\nGiven the provided abstract, please respond to the following query: \"What was studied in the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Healthcare providers may be paid in different ways. Different payment methods can encourage healthcare providers to give patients the treatment they need in the best and most cost-efficient way, but they can also encourage healthcare providers to offer poor-quality, expensive, and unnecessary care, and to avoid certain treatments or certain types of patients. Different payment methods can also influence healthcare providers’ work morale and workload. And they can cost more or less for the healthcare system.\nThe review authors searched for studies on the effects of different payment methods for healthcare providers working in outpatient care. Outpatient care is where patients get health care from healthcare providers outside of hospitals and where there is no need for a bed. Healthcare centres, family planning centres, and dental clinics are all examples of outpatient facilities.\nThe payment methods the review authors were interested in were as follows.\n- Pay-for-performance: healthcare providers are paid for carrying out certain tasks or reaching certain targets.\n- Fee-for-service: healthcare providers are paid for each service they provide to the patient.\n- Salary: healthcare providers are paid based on the time they spend at work.\n- Capitation: healthcare providers are paid according to how many patients they have.\n- A mix of these different approaches." } ]

[ { "role": "user", "content": "Abstract: Background\nAbout 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5-hydroxytryptamine-3 (5-HT₃) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK₁) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head-to-head comparisons do not allow comparison of all treatments versus another.\nObjectives\n• In adults with solid cancer or haematological malignancy receiving HEC\n- To compare the effects of antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting in network meta-analysis (NMA)\n- To generate a clinically meaningful treatment ranking according to treatment safety and efficacy\n• In adults with solid cancer or haematological malignancy receiving MEC\n- To compare whether antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting to treatment combinations including 5-HT₃ receptor antagonists and corticosteroids solely, in network meta-analysis\n- To generate a clinically meaningful treatment ranking according to treatment safety and efficacy\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs).\nSelection criteria\nWe included RCTs including adults with any cancer receiving HEC or MEC (according to the latest definition) and comparing combination therapies of NK₁ and 5-HT₃ inhibitors and corticosteroids for prevention of CINV.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nWe expressed treatment effects as risk ratios (RRs). Prioritised outcomes were complete control of vomiting during delayed and overall phases, complete control of nausea during the overall phase, quality of life, serious adverse events (SAEs), and on-study mortality. We assessed GRADE and developed 12 'Summary of findings' tables. We report results of most crucial outcomes in the abstract, that is, complete control of vomiting during the overall phase and SAEs. For a comprehensive illustration of results, we randomly chose aprepitant plus granisetron as exemplary reference treatment for HEC, and granisetron as exemplary reference treatment for MEC.\nMain results\nHighly emetogenic chemotherapy (HEC)\nWe included 73 studies reporting on 25,275 participants and comparing 14 treatment combinations with NK₁ and 5-HT₃ inhibitors. All treatment combinations included corticosteroids.\nComplete control of vomiting during the overall phase\nWe estimated that 704 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with aprepitant + granisetron. Evidence from NMA (39 RCTs, 21,642 participants; 12 treatment combinations with NK₁ and 5-HT₃ inhibitors) suggests that the following drug combinations are more efficacious than aprepitant + granisetron for completely controlling vomiting during the overall treatment phase (one to five days): fosnetupitant + palonosetron (810 of 1000; RR 1.15, 95% confidence interval (CI) 0.97 to 1.37; moderate certainty), aprepitant + palonosetron (753 of 1000; RR 1.07, 95% CI 1.98  to 1.18; low-certainty), aprepitant + ramosetron (753 of 1000; RR 1.07, 95% CI 0.95 to 1.21; low certainty), and fosaprepitant + palonosetron (746 of 1000; RR 1.06, 95% CI 0.96 to 1.19; low certainty).\nNetupitant + palonosetron (704 of 1000; RR 1.00, 95% CI 0.93 to 1.08; high-certainty) and fosaprepitant + granisetron (697 of 1000; RR 0.99, 95% CI 0.93 to 1.06; high-certainty) have little to no impact on complete control of vomiting during the overall treatment phase (one to five days) when compared to aprepitant + granisetron, respectively.\nEvidence further suggests that the following drug combinations are less efficacious than aprepitant + granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): aprepitant + ondansetron (676 of 1000; RR 0.96, 95% CI 0.88 to 1.05; low certainty), fosaprepitant + ondansetron (662 of 1000; RR 0.94, 95% CI 0.85 to 1.04; low certainty), casopitant + ondansetron (634 of 1000; RR 0.90, 95% CI 0.79 to 1.03; low certainty), rolapitant + granisetron (627 of 1000; RR 0.89, 95% CI 0.78 to 1.01; moderate certainty), and rolapitant + ondansetron (598 of 1000; RR 0.85, 95% CI 0.65 to 1.12; low certainty).\nWe could not include two treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron) in NMA for this outcome because of missing direct comparisons.\nSerious adverse events\nWe estimated that 35 of 1000 participants experience any SAEs when treated with aprepitant + granisetron. Evidence from NMA (23 RCTs, 16,065 participants; 11 treatment combinations) suggests that fewer participants may experience SAEs when treated with the following drug combinations than with aprepitant + granisetron: fosaprepitant + ondansetron (8 of 1000; RR 0.23, 95% CI 0.05 to 1.07; low certainty), casopitant + ondansetron (8 of 1000; RR 0.24, 95% CI 0.04 to 1.39; low certainty), netupitant + palonosetron (9 of 1000; RR 0.27, 95% CI 0.05 to 1.58; low certainty), fosaprepitant + granisetron (13 of 1000; RR 0.37, 95% CI 0.09 to 1.50; low certainty), and rolapitant + granisetron (20 of 1000; RR 0.57, 95% CI 0.19 to 1.70; low certainty).\nEvidence is very uncertain about the effects of aprepitant + ondansetron (8 of 1000; RR 0.22, 95% CI 0.04 to 1.14; very low certainty), aprepitant + ramosetron (11 of 1000; RR 0.31, 95% CI 0.05 to 1.90; very low certainty), fosaprepitant + palonosetron (12 of 1000; RR 0.35, 95% CI 0.04 to 2.95; very low certainty), fosnetupitant + palonosetron (13 of 1000; RR 0.36, 95% CI 0.06 to 2.16; very low certainty), and aprepitant + palonosetron (17 of 1000; RR 0.48, 95% CI 0.05 to 4.78; very low certainty) on the risk of SAEs when compared to aprepitant + granisetron, respectively.\nWe could not include three treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron, rolapitant + ondansetron) in NMA for this outcome because of missing direct comparisons.\nModerately emetogenic chemotherapy (MEC)\nWe included 38 studies reporting on 12,038 participants and comparing 15 treatment combinations with NK₁ and 5-HT₃ inhibitors, or 5-HT₃ inhibitors solely. All treatment combinations included corticosteroids.\nComplete control of vomiting during the overall phase\nWe estimated that 555 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with granisetron. Evidence from NMA (22 RCTs, 7800 participants; 11 treatment combinations) suggests that the following drug combinations are more efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days): aprepitant + palonosetron (716 of 1000; RR 1.29, 95% CI 1.00 to 1.66; low certainty), netupitant + palonosetron (694 of 1000; RR 1.25, 95% CI 0.92 to 1.70; low certainty), and rolapitant + granisetron (660 of 1000; RR 1.19, 95% CI 1.06 to 1.33; high certainty).\nPalonosetron (588 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) and aprepitant + granisetron (577 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) may or may not increase complete response in the overall treatment phase (one to five days) when compared to granisetron, respectively. Azasetron (560 of 1000; RR 1.01, 95% CI 0.76 to 1.34; low certainty) may result in little to no difference in complete response in the overall treatment phase (one to five days) when compared to granisetron.\nEvidence further suggests that the following drug combinations are less efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): fosaprepitant + ondansetron (500 of 1000; RR 0.90, 95% CI 0.66 to 1.22; low certainty), aprepitant + ondansetron (477 of 1000; RR 0.86, 95% CI 0.64 to 1.17; low certainty), casopitant + ondansetron (461 of 1000; RR 0.83, 95% CI 0.62 to 1.12; low certainty), and ondansetron (433 of 1000; RR 0.78, 95% CI 0.59 to 1.04; low certainty).\nWe could not include five treatment combinations (fosaprepitant + granisetron, azasetron, dolasetron, ramosetron, tropisetron) in NMA for this outcome because of missing direct comparisons.\nSerious adverse events\nWe estimated that 153 of 1000 participants experience any SAEs when treated with granisetron. Evidence from pair-wise comparison (1 RCT, 1344 participants) suggests that more participants may experience SAEs when treated with rolapitant + granisetron (176 of 1000; RR 1.15, 95% CI 0.88 to 1.50; low certainty). NMA was not feasible for this outcome because of missing direct comparisons.\nCertainty of evidence\nOur main reason for downgrading was serious or very serious imprecision (e.g. due to wide 95% CIs crossing or including unity, few events leading to wide 95% CIs, or small information size). Additional reasons for downgrading some comparisons or whole networks were serious study limitations due to high risk of bias or moderate inconsistency within networks.\nAuthors' conclusions\nThis field of supportive cancer care is very well researched. However, new drugs or drug combinations are continuously emerging and need to be systematically researched and assessed.\nFor people receiving HEC, synthesised evidence does not suggest one superior treatment for prevention and control of chemotherapy-induced nausea and vomiting.\nFor people receiving MEC, synthesised evidence does not suggest superiority for treatments including both NK₁ and 5-HT₃ inhibitors when compared to treatments including 5-HT₃ inhibitors only. Rather, the results of our NMA suggest that the choice of 5-HT₃ inhibitor may have an impact on treatment efficacy in preventing CINV.\nWhen interpreting the results of this systematic review, it is important for the reader to understand that NMAs are no substitute for direct head-to-head comparisons, and that results of our NMA do not necessarily rule out differences that could be clinically relevant for some individuals.\n\nGiven the provided abstract, please respond to the following query: \"...for people receiving HEC\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found 73 studies that reported on the experience of 25,275 participants and compared 14 treatment combinations of our interest." } ]

[ { "role": "user", "content": "Abstract: Background\nMoxibustion, a common treatment in traditional Chinese medicine, involves burning herbal preparations containing Artemisia vulgaris on or above the skin at acupuncture points. Its intended effect is to enhance body function, and it could reduce the side effects of chemotherapy or radiotherapy and improve quality of life (QoL) in people with cancer.\nObjectives\nTo assess the effects of moxibustion for alleviating side effects associated with chemotherapy, radiotherapy or both in people with cancer.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid and AMED (Allied and Complementary Medicine Database) from their inception to February 2018. We also searched databases in China including the Chinese BioMedical Literature Database (CBM), Chinese Medical Current Contents (CMCC), TCMonline, Chinese Dissertation Database (CDDB), China Medical Academic Conference (CMAC) and Index to Chinese Periodical Literature from inception to August 2017. Registries for clinical trials and other resources were also searched.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing moxibustion treatment, including moxa cone and moxa stick, versus sham, no treatment or conventional treatment.\nData collection and analysis\nTwo review authors (HWZ and FC) independently extracted data on study design, participants, treatment and control intervention, and outcome measures, and they also assessed risk of bias in the included studies. We performed meta-analyses, expressing dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), with 95% confidence intervals (CI).\nMain results\nWe included 29 RCTs involving 2569 participants. Five RCTs compared moxibustion versus no treatment, 15 compared moxibustion plus conventional treatment versus conventional treatment, one compared moxibustion versus sham moxibustion, and eight compared moxibustion versus conventional medicine. The overall risk of bias was high in 18 studies and unclear in 11 studies. Studies measured outcomes in various ways, and we could rarely pool data.\nMoxibustion versus no treatment: low-certainty evidence from single small studies suggested that moxibustion was associated with higher white blood cell counts (MD 1.77 × 109/L; 95% CI 0.76 to 2.78; 80 participants, low-certainty evidence) and higher serum haemoglobin concentrations (MD 1.33 g/L; 95% CI 0.59 to 2.07; 66 participants, low-certainty evidence) in people with cancer, during or after chemotherapy/radiotherapy, compared with no treatment. There was no evidence of an effect on leukopenia (RR 0.50, 95% CI 0.10 to 2.56; 72 participants, low-certainty evidence) between study groups. The effects on immune function (CD3, CD4, and CD8 counts) were inconsistent.\nMoxibustion versus sham moxibustion: low-certainty evidence from one study (50 participants) suggested that moxibustion improved QoL (measured as the score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)) compared with sham treatment (MD 14.88 points; 95% CI 4.83 to 24.93). Low-certainty evidence from this study also showed reductions in symptom scores for nausea and vomiting (MD −38.57 points, 95% CI −48.67 to −28.47) and diarrhoea (MD −13.81, 95% CI −27.52 to −0.10), and higher mean white blood cell count (MD 1.72 × 109/L, 95% CI 0.97 to 2.47), serum haemoglobin (MD 2.06 g/L, 95% CI 1.26 to 2.86) and platelets (MD 210.79 × 109/L, 95% CI 167.02 to 254.56) when compared with sham moxibustion.\nMoxibustion versus conventional medicines: low-certainty evidence from one study (90 participants) suggested that moxibustion improved WBC count eight days after treatment ended compared with conventional medicines (MD 0.40 × 109/L; 95% CI 0.15 to 0.65). Low-certainty evidence from two studies (235 participants) suggested moxibustion improved serum haemoglobin concentrations compared with conventional medicines (MD 10.28 g/L; 95% CI 4.51 to 16.05).\nMoxibustion plus conventional treatment versus conventional treatment alone: low-certainty evidence showed that moxibustion plus conventional treatment was associated with lower incidence and severity of leukopenia (WHO grade 3 to 4) (RR 0.14, 95% CI 0.01 to 2.64; 1 study, 56 participants), higher QoL scores on the EORTC QLQ-C30 (MD 8.85 points, 95% CI 4.25 to 13.46; 3 studies, 134 participants, I² = 26%), lower symptom scores for nausea and vomiting (RR 0.43, 95% CI 0.25 to 0.74; 7 studies, 801participants; I² = 19%), higher white blood cell counts (data not pooled due to heterogeneity), higher serum haemoglobin (MD 3.97 g/L, 95% CI 1.40 to 6.53; 2 studies, 142 participants, I² = 0%). There was no difference in platelet counts between the two groups (MD 13.48 × 109/L; 95% CI −16.00 to 42.95; 2 studies, 142 participants; I² = 34%).\nMost included studies did not report related adverse events, such as burning or allergic reactions.\nAuthors' conclusions\nLimited, low-certainty evidence suggests that moxibustion treatment may help to reduce the haematological and gastrointestinal toxicities of chemotherapy or radiotherapy, improving QoL in people with cancer; however, the evidence is not conclusive, and we cannot rule out benefits or risks with this treatment. High-quality studies that report adverse effects are needed.\n\nGiven the provided abstract, please respond to the following query: \"The issue\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Moxibustion is used in traditional Chinese medicine to enhance quality of life and relieve the side effects of conventional treatments for a variety of diseases. As its application involves the burning of a herbal preparation, it can also cause some undesirable side effects itself, such as allergic reactions, burns and infection." } ]

[ { "role": "user", "content": "Abstract: Background\nAbout one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have previously been considered to be ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, recent studies suggest benefit from recanalisation therapies in selected patients.\nObjectives\nTo assess the effects of intravenous thrombolysis and endovascular thrombectomy versus control in people with acute ischaemic stroke presenting on awakening from sleep.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (last search 24 of May 2021). In addition, we searched the following electronic databases in May 2021: Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 4 of 12, April 2021) in the Cochrane Library, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We searched the Stroke Trials Registry (last search 7 December 2017, as the site is currently inactive). We also screened references lists of relevant trials, contacted trialists, and undertook forward tracking of relevant references.\nSelection criteria\nRandomised controlled trials (RCTs) of intravenous thrombolytic drugs or endovascular thrombectomy treatments in people with acute ischaemic stroke presenting upon awakening.\nData collection and analysis\nTwo review authors applied the inclusion criteria, extracted data, and assessed risk of bias and the certainty of the evidence using the GRADE approach. We obtained both published and unpublished data for participants with wake-up strokes. We excluded participants with strokes of unknown onset if the symptoms did not begin upon awakening.\nMain results\nWe included seven trials with a total of 980 participants, of which five trials with 775 participants investigated intravenous thrombolytic treatment and two trials with 205 participants investigated endovascular thrombectomy in large vessel occlusion in the anterior intracranial circulation. All trials used advanced imaging for selecting patients to treat.\nFor intravenous thrombolytic treatment, good functional outcome (defined as modified Rankin Scale score 0 to 2) at 90 days follow-up was observed in 66% of participants randomised to thrombolytic treatment and 58% of participants randomised to control (risk ratio (RR) 1.13, 95% confidence interval (CI) 1.01 to 1.26; P = 0.03; 763 participants, 5 RCTs; high-certainty evidence). Seven per cent of participants randomised to intravenous thrombolytic treatment and 10% of participants randomised to control had died at 90 days follow-up (RR 0.68, 95% CI 0.43 to 1.07; P = 0.09; 763 participants, 5 RCTs; high-certainty evidence). Symptomatic intracranial haemorrhage occurred in 3% of participants randomised to intravenous thrombolytic treatment and 1% of participants randomised to control (RR 3.47, 95% CI 0.98 to 12.26; P = 0.05; 754 participants, 4 RCTs; high-certainty evidence).\nFor endovascular thrombectomy of large vessel occlusion, good functional outcome at 90 days follow-up was observed in 46% of participants randomised to endovascular thrombectomy and 9% of participants randomised to control (RR 5.12, 95% CI 2.57 to 10.17; P < 0.001; 205 participants, 2 RCTs; high-certainty evidence). Twenty-two per cent of participants randomised to endovascular thrombectomy and 33% of participants randomised to control had died at 90 days follow-up (RR 0.68, 95% CI 0.43 to 1.07; P = 0.10; 205 participants, 2 RCTs; high-certainty evidence).\nAuthors' conclusions\nIn selected patients with acute ischaemic wake-up stroke, both intravenous thrombolytic treatment and endovascular thrombectomy of large vessel occlusion improved functional outcome without increasing the risk of death. However, a possible increased risk of symptomatic intracranial haemorrhage associated with thrombolytic treatment cannot be ruled out. The criteria used for selecting patients to treatment differed between the trials. All studies were relatively small, and six of the seven studies were terminated early. More studies are warranted in order to determine the optimal criteria for selecting patients for treatment.\n\nGiven the provided abstract, please respond to the following query: \"Quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We judged the included trials to be at low or unclear risk of bias, and the overall certainty of the evidence as high." } ]

[ { "role": "user", "content": "Abstract: Background\nGroin dissection is commonly performed for the treatment of a variety of cancers, including melanoma, and squamous cell carcinoma of the skin, penis or vulva. It is uncertain whether insertion of a drain reduces complication rates, and, if used, the optimum time for drain removal after surgery is also unknown.\nObjectives\nTo assess the current level of evidence to determine whether placement of a drain is beneficial after groin dissection in terms of reducing seroma, haematoma, wound dehiscence and wound infection rates, and to determine the optimal type and duration of drainage following groin dissection if it is shown to be beneficial.\nSearch methods\nIn September 2014 we searched the following electronic databases using a pre-designed search strategy: the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library). In November 2013 we searched Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We did not restrict the search and study selection with respect to language, date of publication or study setting.\nSelection criteria\nWe considered all randomised controlled trials (RCTs) comparing wound drainage with no wound drainage in individuals undergoing groin dissection, where the most superior node excised was Cloquet's node (the most superior inguinal lymph node). No limits were applied to language of publication or trial location. Two review authors independently determined the eligibility of each trial.\nData collection and analysis\nTwo review authors, working independently, screened studies identified from the search; there were no disagreements.\nMain results\nWe did not identify any RCTs that met the inclusion criteria for the review.\nAuthors' conclusions\nThere is a need for high quality RCTs to guide clinical practice in this under-researched area.\n\nGiven the provided abstract, please respond to the following query: \"The purpose of this review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The aim of this review was to review all randomised clinical trials (RCTs) that have compared what happens to patients who had a drain inserted after removal of the inguinal lymph nodes with patients who did not have a drain. We also looked for RCTs that examined the effect of removing drains at different times. We searched the medical literature up to September 2014 to gather all the available evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of the Cochrane review published in 2013, Issue 10.\nImmunosuppressed cancer patients are at increased risk of serious influenza-related complications. Guidelines, therefore, recommend influenza vaccination for these patients. However, data on vaccine effectiveness in this population are lacking, and the value of vaccination in this population remains unclear.\nObjectives\nTo assess the effectiveness of influenza vaccine in immunosuppressed adults with malignancies. The primary review outcome is all-cause mortality, preferably at the end of the influenza season. Influenza-like illness (ILI, a clinical definition), confirmed influenza, pneumonia, any hospitalisations, influenza-related mortality and immunogenicity were defined as secondary outcomes.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and LILACS databases up to May 2017. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (haematological), and ASCO (oncological) between the years 2006 to 2017. In addition, we scanned the references of all identified studies and pertinent reviews. We searched the websites of the manufacturers of influenza vaccine. Finally, we searched for ongoing or unpublished trials in clinical trial registry databases.\nSelection criteria\nRandomised controlled trials (RCTs), prospective and retrospective cohort studies and case-control studies were considered, comparing inactivated influenza vaccines versus placebo, no vaccination or a different vaccine, in adults (16 years and over) with cancer. We considered solid malignancies treated with chemotherapy, haematological cancer patients treated or not treated with chemotherapy, cancer patients post-autologous (up to six months after transplantation) or allogeneic (at any time) haematopoietic stem cell transplantation (HSCT).\nData collection and analysis\nTwo review authors independently assessed the risk of bias and extracted data from included studies adhering to Cochrane methodology. Meta-analysis could not be performed because of different outcome and denominator definitions in the included studies.\nMain results\nWe identified six studies with a total of 2275 participants: five studies comparing vaccination with no vaccination, and one comparing adjuvanted vaccine with non-adjuvanted vaccine. Three studies were RCTs, one was a prospective observational cohort study and two were retrospective cohort studies.\nFor the comparison of vaccination with no vaccination we included two RCTs and three observational studies, including 2202 participants. One study reported results in person-years while the others reported results per person. The five studies were performed between 1993 and 2015 and included adults with haematological diseases (three studies), patients following bone marrow transplantation (BMT) (two studies) and solid malignancies (three studies).\nOne RCT and two observational studies reported all-cause mortality; the RCT showed similar mortality rates in both arms (odds ratio (OR) 1.25 (95% CI 0.43 to 3.62; 1 study, 78 participants, low-certainty evidence)); and the observational studies demonstrated a significant association between vaccine receipt and lower risk of death, adjusted hazard ratio 0.88 (95% CI 0.78 to 1; 1 study, 1577 participants, very low-certainty evidence) in one study and OR 0.42 (95% CI 0.24 to 0.75; 1 study, 806 participants, very low-certainty evidence) in the other. One RCT reported a reduction in ILI with vaccination, while no difference was observed in one observational study. Confirmed influenza rates were lower with vaccination in one RCT and the three observational studies, the difference reaching statistical significance in one. Pneumonia was observed significantly less frequently with vaccination in one observational study, but no difference was detected in another or in the RCT. One RCT showed a reduction in hospitalisations following vaccination, while an observational study found no difference. No life-threatening or persistent adverse effects from vaccination were reported. The strength of evidence was limited by the low number of included studies and by their low methodological quality and the certainty of the evidence for the mortality outcome according to GRADE was low to very low.\nFor the comparison of adjuvanted vaccine with non-adjuvanted vaccine, we identified one RCT, including 73 patients. No differences were found for the primary and all secondary outcomes assessed. Mortality risk ratio was 0.54 (95% CI 0.05 to 5.73; low-certainty evidence) in the adjuvanted vaccine group. The quality of evidence was low due to the small sample size and the large confidence intervals for all outcomes.\nAuthors' conclusions\nObservational data suggest lower mortality and infection-related outcomes with influenza vaccination. The strength of evidence is limited by the small number of studies and low grade of evidence. It seems that the evidence, although weak, shows that the benefits overweigh the potential risks when vaccinating adults with cancer against influenza. However, additional placebo or no-treatment controlled RCTs of influenza vaccination among adults with cancer is ethically questionable.There is no conclusive evidence regarding the use of adjuvanted versus non-adjuvanted influenza vaccine in this population.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Adults with cancer are prone to serious complications from influenza, more than healthy adults. The influenza vaccine protects against influenza and its complications. However, its effectiveness among people with cancer is unclear, as immune dysfunction that accompanies cancer as a result of chemotherapy might lower immune response to the vaccine. People with cancer, therefore, do not have clear information on the importance and effectiveness of the vaccine." } ]

[ { "role": "user", "content": "Abstract: Background\nVascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion.\nObjectives\nTo assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss.\nSearch methods\nWe searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status.\nSelection criteria\nWe included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence.\nMain results\nWe included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs.\nWe were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review.\nSystemic drug treatments\nWe identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants).\nNeither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding.\nTranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision).\nThere is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE).\nTopical drug treatments\nMost trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants).\nThe five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies.\nNone of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days.\nThe other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days.\nWe identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes.\nAuthors' conclusions\nBecause of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days.\nThere may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased.\nTrials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.\n\nGiven the provided abstract, please respond to the following query: \"• What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched electronic libraries for reports of the most reliable studies (called randomised controlled trials) of drugs to prevent bleeding after surgery on blood vessels." } ]

[ { "role": "user", "content": "Abstract: Background\nThe consequences of influenza in adults are mainly time off work. Vaccination of pregnant women is recommended internationally. This is an update of a review published in 2014. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated due to their lack of influence on the review conclusions.\nObjectives\nTo assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy adults, including pregnant women.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE (January 1966 to 31 December 2016), Embase (1990 to 31 December 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017), as well as checking the bibliographies of retrieved articles.\nSelection criteria\nRandomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy individuals aged 16 to 65 years. Previous versions of this review included observational comparative studies assessing serious and rare harms cohort and case-control studies. Due to the uncertain quality of observational (i.e. non-randomised) studies and their lack of influence on the review conclusions, we decided to update only randomised evidence. The searches for observational comparative studies are no longer updated.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data. We rated certainty of evidence for key outcomes (influenza, influenza-like illness (ILI), hospitalisation, and adverse effects) using GRADE.\nMain results\nWe included 52 clinical trials of over 80,000 people assessing the safety and effectiveness of influenza vaccines. We have presented findings from 25 studies comparing inactivated parenteral influenza vaccine against placebo or do-nothing control groups as the most relevant to decision-making. The studies were conducted over single influenza seasons in North America, South America, and Europe between 1969 and 2009. We did not consider studies at high risk of bias to influence the results of our outcomes except for hospitalisation.\nInactivated influenza vaccines probably reduce influenza in healthy adults from 2.3% without vaccination to 0.9% (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.36 to 0.47; 71,221 participants; moderate-certainty evidence), and they probably reduce ILI from 21.5% to 18.1% (RR 0.84, 95% CI 0.75 to 0.95; 25,795 participants; moderate-certainty evidence; 71 healthy adults need to be vaccinated to prevent one of them experiencing influenza, and 29 healthy adults need to be vaccinated to prevent one of them experiencing an ILI). The difference between the two number needed to vaccinate (NNV) values depends on the different incidence of ILI and confirmed influenza among the study populations. Vaccination may lead to a small reduction in the risk of hospitalisation in healthy adults, from 14.7% to 14.1%, but the CI is wide and does not rule out a large benefit (RR 0.96, 95% CI 0.85 to 1.08; 11,924 participants; low-certainty evidence). Vaccines may lead to little or no small reduction in days off work (-0.04 days, 95% CI -0.14 days to 0.06; low-certainty evidence). Inactivated vaccines cause an increase in fever from 1.5% to 2.3%.\nWe identified one RCT and one controlled clinical trial assessing the effects of vaccination in pregnant women. The efficacy of inactivated vaccine containing pH1N1 against influenza was 50% (95% CI 14% to 71%) in mothers (NNV 55), and 49% (95% CI 12% to 70%) in infants up to 24 weeks (NNV 56). No data were available on efficacy against seasonal influenza during pregnancy. Evidence from observational studies showed effectiveness of influenza vaccines against ILI in pregnant women to be 24% (95% CI 11% to 36%, NNV 94), and against influenza in newborns from vaccinated women to be 41% (95% CI 6% to 63%, NNV 27).\nLive aerosol vaccines have an overall effectiveness corresponding to an NNV of 46. The performance of one- or two-dose whole-virion 1968 to 1969 pandemic vaccines was higher (NNV 16) against ILI and (NNV 35) against influenza. There was limited impact on hospitalisations in the 1968 to 1969 pandemic (NNV 94). The administration of both seasonal and 2009 pandemic vaccines during pregnancy had no significant effect on abortion or neonatal death, but this was based on observational data sets.\nAuthors' conclusions\nHealthy adults who receive inactivated parenteral influenza vaccine rather than no vaccine probably experience less influenza, from just over 2% to just under 1% (moderate-certainty evidence). They also probably experience less ILI following vaccination, but the degree of benefit when expressed in absolute terms varied across different settings. Variation in protection against ILI may be due in part to inconsistent symptom classification. Certainty of evidence for the small reductions in hospitalisations and time off work is low. Protection against influenza and ILI in mothers and newborns was smaller than the effects seen in other populations considered in this review.\nVaccines increase the risk of a number of adverse events, including a small increase in fever, but rates of nausea and vomiting are uncertain. The protective effect of vaccination in pregnant women and newborns is also very modest. We did not find any evidence of an association between influenza vaccination and serious adverse events in the comparative studies considered in this review. Fifteen included RCTs were industry funded (29%).\n\nGiven the provided abstract, please respond to the following query: \"Review aim\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The aim of this Cochrane Review, first published in 1999, was to summarise research that looks at the effects of immunising healthy adults with influenza vaccines during influenza seasons. We used information from randomised trials comparing vaccines with dummy vaccines or nothing. We focused on the results of studies looking at vaccines based on inactivated influenza viruses, which are developed by killing the influenza virus with a chemical and are given by injection through the skin. We evaluated the effects of vaccines on reducing the number of adults with confirmed influenza and the number of adults who had influenza-like symptoms such as headache, high temperature, cough, and muscle pain (influenza-like illness, or ILI). We also evaluated hospital admission and harms arising from the vaccines. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated due to their lack of influence on the review conclusions." } ]

[ { "role": "user", "content": "Abstract: Background\nThe effective control of moisture and microbes is necessary for the success of restoration procedures. The rubber dam, as an isolation method, has been widely used in dental restorative treatments. The effects of rubber dam usage on the longevity and quality of dental restorations still require evidence-based discussion. This review compares the effects of rubber dam with other isolation methods in dental restorative treatments. This is an update of the Cochrane Review first published in 2016.\nObjectives\nTo assess the effects of rubber dam isolation compared with other types of isolation used for direct and indirect restorative treatments in dental patients.\nSearch methods\nCochrane Oral Health's Information specialist searched the following electronic databases: Cochrane Oral Health's Trials Register (searched 13 January 2021), Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 12) in the Cochrane Library (searched 13 January 2021), MEDLINE Ovid (1946 to 13 January 2021), Embase Ovid (1980 to 13 January 2021), LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 13 January 2021), and SciELO BIREME Virtual Health Library (1998 to 13 January 2021). We also searched Chinese BioMedical Literature Database (CBM, in Chinese) (1978 to 13 January 2021), VIP database (in Chinese) (1989 to 13 January 2021), and China National Knowledge Infrastructure (CNKI, in Chinese) (1994 to 13 January 2021). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform, OpenGrey, and Sciencepaper Online (in Chinese) for ongoing trials. There were no restrictions on the language or date of publication when searching the electronic databases.\nSelection criteria\nWe included randomised controlled trials (including split-mouth trials) over one month in length assessing the effects of rubber dam compared with alternative isolation methods for dental restorative treatments.\nData collection and analysis\nTwo review authors independently screened the results of the electronic searches, extracted data, and assessed the risk of bias of the included studies. Disagreement was resolved by discussion. We strictly followed Cochrane's statistical guidelines and assessed the certainty of the evidence using GRADE.\nMain results\nWe included six studies conducted worldwide between 2010 and 2015 involving a total of 1342 participants (of which 233 participants were lost to follow-up). All the included studies were at high risk of bias.\nFive studies compared rubber dam with traditional cotton rolls isolation. One study was excluded from the analysis due to inconsistencies in the presented data. Of the four remaining trials, three reported survival rates of the restorations with a minimum follow-up of six months. Pooled results from two studies involving 192 participants indicated that the use of rubber dam isolation may increase the survival rates of direct composite restorations of non-carious cervical lesions (NCCLs) at six months (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.05 to 4.99; low-certainty evidence). However, the use of rubber dam in NCCLs composite restorations may have little to no effect on the survival rates of the restorations compared to cotton rolls at 12 months (OR 1.38, 95% CI 0.45 to 4.28; 1 study, 30 participants; very low-certainty evidence) and at 18 months (OR 1.00, 95% CI 0.45 to 2.25; 1 study, 30 participants; very low-certainty evidence) but the evidence is very uncertain. At 24 months, the use of rubber dam may decrease the risk of failure of the restorations in children undergoing proximal atraumatic restorative treatment in primary molars but the evidence is very uncertain (hazard ratio (HR) 0.80, 95% CI 0.66 to 0.97; 1 study, 559 participants; very low-certainty evidence).\nNone of the included studies mentioned adverse effects or reported the direct cost of the treatment.\nAuthors' conclusions\nThis review found some low-certainty evidence that the use of rubber dam in dental direct restorative treatments may lead to a lower failure rate of the restorations compared with cotton roll usage after six months. At other time points, the evidence is very uncertain. Further high-quality research evaluating the effects of rubber dam usage on different types of restorative treatments is required.\n\nGiven the provided abstract, please respond to the following query: \"What do dental practitioners use to isolate teeth?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "A common method for isolating teeth from the rest of the mouth is to use cotton rolls and a straw-like tube that sucks up saliva. This technique uses simple, inexpensive equipment, but requires frequent replacement of sodden cotton rolls.\nAn alternative option is to use a thin sheet of rubber (rubber dam). First, the dental practitioner makes a small hole in the sheet. They then place it over the tooth to be treated, creating a barrier around it. The sheet can be held in place with several methods, such as clasps placed over the tooth or a small piece of rubber wedged between teeth." } ]

[ { "role": "user", "content": "Abstract: Background\nShift work is often associated with sleepiness and sleep disorders. Person-directed, non-pharmacological interventions may positively influence the impact of shift work on sleep, thereby improving workers’ well-being, safety, and health.\nObjectives\nTo assess the effects of person-directed, non-pharmacological interventions for reducing sleepiness at work and improving the length and quality of sleep between shifts for shift workers.\nSearch methods\nWe searched CENTRAL, MEDLINE Ovid, Embase, Web of Knowledge, ProQuest, PsycINFO, OpenGrey, and OSH-UPDATE from inception to August 2015. We also screened reference lists and conference proceedings and searched the World Health Organization (WHO) Trial register. We contacted experts to obtain unpublished data.\nSelection criteria\nRandomised controlled trials (RCTs) (including cross-over designs) that investigated the effect of any person-directed, non-pharmacological intervention on sleepiness on-shift or sleep length and sleep quality off-shift in shift workers who also work nights.\nData collection and analysis\nAt least two authors screened titles and abstracts for relevant studies, extracted data, and assessed risk of bias. We contacted authors to obtain missing information. We conducted meta-analyses when pooling of studies was possible.\nMain results\nWe included 17 relevant trials (with 556 review-relevant participants) which we categorised into three types of interventions: (1) various exposures to bright light (n = 10); (2) various opportunities for napping (n = 4); and (3) other interventions, such as physical exercise or sleep education (n = 3). In most instances, the studies were too heterogeneous to pool. Most of the comparisons yielded low to very low quality evidence. Only one comparison provided moderate quality evidence. Overall, the included studies’ results were inconclusive. We present the results regarding sleepiness below.\nBright light\nCombining two comparable studies (with 184 participants altogether) that investigated the effect of bright light during the night on sleepiness during a shift, revealed a mean reduction 0.83 score points of sleepiness (measured via the Stanford Sleepiness Scale (SSS) (95% confidence interval (CI) -1.3 to -0.36, very low quality evidence). Another trial did not find a significant difference in overall sleepiness on another sleepiness scale (16 participants, low quality evidence).\nBright light during the night plus sunglasses at dawn did not significantly influence sleepiness compared to normal light (1 study, 17 participants, assessment via reaction time, very low quality evidence).\nBright light during the day shift did not significantly reduce sleepiness during the day compared to normal light (1 trial, 61 participants, subjective assessment, low quality evidence) or compared to normal light plus placebo capsule (1 trial, 12 participants, assessment via reaction time, very low quality evidence).\nNapping during the night shift\nA meta-analysis on a single nap opportunity and the effect on the mean reaction time as a surrogate for sleepiness, resulted in a 11.87 ms reduction (95% CI 31.94 to -8.2, very low quality evidence). Two other studies also reported statistically non-significant decreases in reaction time (1 study seven participants; 1 study 49 participants, very low quality evidence).\nA two-nap opportunity resulted in a statistically non-significant increase of sleepiness (subjective assessment) in one study (mean difference (MD) 2.32, 95% CI -24.74 to 29.38, 1 study, 15 participants, low quality evidence).\nOther interventions\nPhysical exercise and sleep education interventions showed promise, but sufficient data to draw conclusions are lacking.\nAuthors' conclusions\nGiven the methodological diversity of the included studies, in terms of interventions, settings, and assessment tools, their limited reporting and the very low to low quality of the evidence they present, it is not possible to determine whether shift workers' sleepiness can be reduced or if their sleep length or quality can be improved with these interventions.\nWe need better and adequately powered RCTs of the effect of bright light, and naps, either on their own or together and other non-pharmacological interventions that also consider shift workers’ chronobiology on the investigated sleep parameters.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Bright light\nAlmost all of the bright light studies we looked at had some problem with the way they were designed. This problem made it difficult to know if any differences in sleepiness and sleep between those receiving bright light and those not receiving bright light were truly because of the bright light intervention. The studies were also too different in the types of bright light they used and types of light that the control groups received to compare them to one another.\nNapping\nThe studies in the napping group did not report enough information for us to be certain whether napping helps shift workers feel more awake. The studies were very short, with each study lasting only a single night.\nOthers\nThis group of studies, which included, for example, physical exercise and sleep education, also reported too little information for us to say whether these interventions can make shift workers less sleepy on-shift or help them sleep longer and better after their shift." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of the original Cochrane review, last published in 2009 (Huertas-Ceballos 2009). Recurrent abdominal pain (RAP), including children with irritable bowel syndrome, is a common problem affecting between 4% and 25% of school-aged children. For the majority of such children, no organic cause for their pain can be found on physical examination or investigation. Many dietary inventions have been suggested to improve the symptoms of RAP. These may involve either excluding ingredients from the diet or adding supplements such as fibre or probiotics.\nObjectives\nTo examine the effectiveness of dietary interventions in improving pain in children of school age with RAP.\nSearch methods\nWe searched CENTRAL, Ovid MEDLINE, Embase, eight other databases, and two trials registers, together with reference checking, citation searching and contact with study authors, in June 2016.\nSelection criteria\nRandomised controlled trials (RCTs) comparing dietary interventions with placebo or no treatment in children aged five to 18 years with RAP or an abdominal pain-related, functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006).\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We grouped dietary interventions together by category for analysis. We contacted study authors to ask for missing information and clarification, when needed. We assessed the quality of the evidence for each outcome using the GRADE approach.\nMain results\nWe included 19 RCTs, reported in 27 papers with a total of 1453 participants. Fifteen of these studies were not included in the previous review. All 19 RCTs had follow-up ranging from one to five months. Participants were aged between four and 18 years from eight different countries and were recruited largely from paediatric gastroenterology clinics. The mean age at recruitment ranged from 6.3 years to 13.1 years. Girls outnumbered boys in most trials. Fourteen trials recruited children with a diagnosis under the broad umbrella of RAP or functional gastrointestinal disorders; five trials specifically recruited only children with irritable bowel syndrome. The studies fell into four categories: trials of probiotic-based interventions (13 studies), trials of fibre-based interventions (four studies), trials of low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets (one study), and trials of fructose-restricted diets (one study).\nWe found that children treated with probiotics reported a greater reduction in pain frequency at zero to three months postintervention than those given placebo (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.98 to -0.12; 6 trials; 523 children). There was also a decrease in pain intensity in the intervention group at the same time point (SMD -0.50, 95% CI -0.85 to -0.15; 7 studies; 575 children). However, we judged the evidence for these outcomes to be of low quality using GRADE due to an unclear risk of bias from incomplete outcome data and significant heterogeneity.\nWe found that children treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (odds ratio (OR) 1.63, 95% CI 1.07 to 2.47; 7 studies; 722 children). The estimated number needed to treat for an additional beneficial outcome (NNTB) was eight, meaning that eight children would need to receive probiotics for one to experience improvement in pain in this timescale. We judged the evidence for this outcome to be of moderate quality due to significant heterogeneity.\nChildren with a symptom profile defined as irritable bowel syndrome treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (OR 3.01, 95% CI 1.77 to 5.13; 4 studies; 344 children). Children treated with probiotics were more likely to experience improvement in pain at three to six months postintervention compared to those receiving placebo (OR 1.94, 95% CI 1.10 to 3.43; 2 studies; 224 children). We judged the evidence for these two outcomes to be of moderate quality due to small numbers of participants included in the studies.\nWe found that children treated with fibre-based interventions were not more likely to experience an improvement in pain at zero to three months postintervention than children given placebo (OR 1.83, 95% CI 0.92 to 3.65; 2 studies; 136 children). There was also no reduction in pain intensity compared to placebo at the same time point (SMD -1.24, 95% CI -3.41 to 0.94; 2 studies; 135 children). We judged the evidence for these outcomes to be of low quality due to an unclear risk of bias, imprecision, and significant heterogeneity.\nWe found only one study of low FODMAP diets and only one trial of fructose-restricted diets, meaning no pooled analyses were possible.\nWe were unable to perform any meta-analyses for the secondary outcomes of school performance, social or psychological functioning, or quality of daily life, as not enough studies included these outcomes or used comparable measures to assess them.\nWith the exception of one study, all studies reported monitoring children for adverse events; no major adverse events were reported.\nAuthors' conclusions\nOverall, we found moderate- to low-quality evidence suggesting that probiotics may be effective in improving pain in children with RAP. Clinicians may therefore consider probiotic interventions as part of a holistic management strategy. However, further trials are needed to examine longer-term outcomes and to improve confidence in estimating the size of the effect, as well as to determine the optimal strain and dosage. Future research should also explore the effectiveness of probiotics in children with different symptom profiles, such as those with irritable bowel syndrome.\nWe found only a small number of trials of fibre-based interventions, with overall low-quality evidence for the outcomes. There was therefore no convincing evidence that fibre-based interventions improve pain in children with RAP. Further high-quality RCTs of fibre supplements involving larger numbers of participants are required. Future trials of low FODMAP diets and other dietary interventions are also required to facilitate evidence-based recommendations.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Recurrent abdominal pain, or RAP, is a term used for unexplained episodes of stomachache or abdominal pain in children. Recurrent abdominal pain is a common condition, and most children are likely to be helped by simple measures. However, a range of treatments have been recommended to relieve abdominal pain, including making changes to the child's eating habits by adding supplements or excluding certain foods." } ]

[ { "role": "user", "content": "Abstract: Background\nAcquired haemophilia A is a rare bleeding disorder caused by the development of specific autoantibodies against coagulation factor VIII. Standard treatment, usually steroids alone, or in combination with cyclophosphamide, aims to stop acute bleeds by using haemostatic agents to promote clotting. Rituximab may be an alternative approach to the treatment of acquired haemophilia by eradicating FVIII autoantibodies. This is an update of a previously published Cochrane Review.\nObjectives\nTo assess the efficacy and adverse effects of rituximab for treating people with acquired haemophilia A.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's trials registers, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings (January 2021). We also undertook searches of CENTRAL, MEDLINE and online trial registries (January 2021).\nSelection criteria\nRandomised and quasi-randomised controlled trials of rituximab for people with acquired haemophilia A, with no restrictions on gender, age or ethnicity.\nData collection and analysis\nNo trials matching the selection criteria were eligible for inclusion.\nMain results\nNo trials matching the selection criteria were eligible for inclusion.\nAuthors' conclusions\nWe found no randomised clinical trials of rituximab for acquired haemophilia A. Thus, we are not able to draw any conclusions or make any recommendations on rituximab for eradicating inhibitors in people with acquired haemophilia A based on the highest quality evidence. Given that undertaking randomised controlled trials in this field is a complex task, we suggest that, while planning such trials, clinicians treating the disease continue to base their choices on alternative, lower-quality sources of evidence. In a future update of this review, we plan to appraise and incorporate eligible randomised controlled trials, as well as other high-quality, non-randomised studies.\n\nGiven the provided abstract, please respond to the following query: \"Background\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Acquired haemophilia A is a rare but severe bleeding disorder. It is caused by an autoantibody directed against factor VIII (FVIII, a blood clotting protein) in people with no previous history of a bleeding disorder. This bleeding disorder occurs more often in the elderly and may be associated with several other conditions (e.g. solid tumours and autoimmune diseases), or with medication. It sometimes happens in pregnancy. However, in about half of cases, the causes are unknown. Bleeding occurs in the skin, mucous membranes, and muscles. Bleeds into the joints are unusual.\nDoctors looking after people with acquired haemophilia A aim to stop acute bleeding episodes and to remove factor VIII autoantibodies. Most doctors regard medicines which suppress the body's immune system (in particular, the corticosteroid prednisone, sometimes in combination with another medicine, cyclophosphamide) as the most effective inital treatment option for acquired haemophilia A. However, up to one-third of people do not respond to this treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life expectancy. Apart from smoking cessation, no other treatments that slow lung function decline are available. Roflumilast and cilomilast are oral phosphodiesterase-4 (PDE₄) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This Cochrane Review was first published in 2011, and was updated in 2017 and 2020.\nObjectives\nTo evaluate the efficacy and safety of oral PDE₄ inhibitors for management of stable COPD.\nSearch methods\nWe identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 9 March 2020). We found other trials at web-based clinical trials registers.\nSelection criteria\nWe included RCTs if they compared oral PDE₄ inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy.\nData collection and analysis\nWe used standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were change in lung function (minimally important difference (MID) = 100 mL) and quality of life (scale 0 to 100; higher score indicates more limitations).\nMain results\nWe found 42 RCTs that met the inclusion criteria and were included in the analyses for roflumilast (28 trials with 18,046 participants) or cilomilast (14 trials with 6457 participants) or tetomilast (1 trial with 84 participants), with a duration between six weeks and one year or longer. These trials included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II to IV), with mean age of 64 years.\nWe judged risks of selection bias, performance bias, and attrition bias as low overall amongst the 39 published and unpublished trials.\nLung function\nTreatment with a PDE₄ inhibitor was associated with a small, clinically insignificant improvement in forced expiratory volume in one second (FEV₁) over a mean of 40 weeks compared with placebo (mean difference (MD) 49.33 mL, 95% confidence interval (CI) 44.17 to 54.49; participants = 20,815; studies = 29; moderate-certainty evidence). Forced vital capacity (FVC) and peak expiratory flow (PEF) were also improved over 40 weeks (FVC: MD 86.98 mL, 95% CI 74.65 to 99.31; participants = 22,108; studies = 17; high-certainty evidence; PEF: MD 6.54 L/min, 95% CI 3.95 to 9.13; participants = 4245; studies = 6; low-certainty evidence).\nQuality of life\nTrials reported improvements in quality of life over a mean of 33 weeks (St George's Respiratory Questionnaire (SGRQ) MD -1.06 units, 95% CI -1.68 to -0.43; participants = 7645 ; moderate-certainty evidence).\nIncidence of exacerbations\nTreatment with a PDE₄ inhibitor was associated with a reduced likelihood of COPD exacerbation over a mean of 40 weeks (odds ratio (OR) 0.78, 95% CI 0.73 to 0.84; participants = 20,382; studies = 27; high-certainty evidence), that is, for every 100 people treated with PDE₄ inhibitors, five more remained exacerbation-free during the study period compared with those given placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 27). No change in COPD-related symptoms nor in exercise tolerance was found.\nAdverse events\nMore participants in the treatment groups experienced an adverse effect compared with control participants over a mean of 39 weeks (OR 1.30, 95% CI 1.22 to 1.38; participants = 21,310; studies = 30; low-certainty evidence). Participants experienced a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting, or dyspepsia. Diarrhoea was more commonly reported with PDE₄ inhibitor treatment (OR 3.20, 95% CI 2.74 to 3.50; participants = 20,623; studies = 29; high-certainty evidence), that is, for every 100 people treated with PDE₄ inhibitors, seven more suffered from diarrhoea during the study period compared with those given placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). The likelihood of psychiatric adverse events was higher with roflumilast 500 µg than with placebo (OR 2.13, 95% CI 1.79 to 2.54; participants = 11,168; studies = 15 (COPD pool data); moderate-certainty evidence). Roflumilast in particular was associated with weight loss during the trial period and with an increase in insomnia and depressive mood symptoms.\nParticipants treated with PDE₄ inhibitors were more likely to withdraw from trial participation; on average, 14% in the treatment groups withdrew compared with 8% in the control groups.\nMortality\nNo effect on mortality was found (OR 0.98, 95% CI 0.77 to 1.24; participants = 19,786; studies = 27; moderate-certainty evidence), although mortality was a rare event during these trials.\nAuthors' conclusions\nFor this current update, five new studies from the 2020 search contributed to existing findings but made little impact on outcomes described in earlier versions of this review.\nPDE₄ inhibitors offered a small benefit over placebo in improving lung function and reducing the likelihood of exacerbations in people with COPD; however, they had little impact on quality of life or on symptoms. Gastrointestinal adverse effects and weight loss were common, and the likelihood of psychiatric symptoms was higher, with roflumilast 500 µg.\nThe findings of this review provide cautious support for the use of PDE₄ inhibitors in COPD. In accordance with GOLD 2020 guidelines, they may have a place as add-on therapy for a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management (e.g. people whose condition is not controlled by fixed-dose long-acting beta₂-agonist (LABA) and inhaled corticosteroid (ICS) combinations). More longer-term trials are needed to determine whether or not PDE₄ inhibitors modify FEV₁ decline, hospitalisation, or mortality in COPD.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Data analysis included 42 studies in 24,587 adults with moderate to very severe disease who discontinued other regular COPD medications. Some trials allowed people to carry on using their usual COPD medicines. Most trials were funded by manufacturers of PDE₄ inhibitors.\nPDE₄ inhibitors provided a small benefit in improving lung function measurements (forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and peak expiratory flow (PEF)). PDE₄ inhibitors also reduced the likelihood of COPD-related exacerbations. We found that 28 out of 100 people taking PDE₄ inhibitors every day for a year would experience at least one exacerbation, which was five fewer than for people who did not receive these medicines.\nPDE₄ inhibitors provided a small benefit in reducing breathlessness and improving quality of life. Around 5% to 10% of people who received roflumilast or cilomilast reported side effects such as diarrhoea, nausea, and vomiting. We expected that 11 out of 100 people taking PDE₄ inhibitors every day for 39 weeks would experience an episode of diarrhoea, which was seven more than for those not receiving PDE₄ inhibitors. We found that 7 people out of 100 were likely to experience a psychiatric event with roflumilast 500 µg. A two- to three-fold increase in risk of sleep or mood disturbance was found with roflumilast 500 μg, although overall the total number of reported incidents was low. There was no effect on death rates. Effects were the same regardless of the severity of COPD, or whether other medicines for COPD were being taken." } ]

[ { "role": "user", "content": "Abstract: Background\nBrexpiprazole is the newest antipsychotic drug approved as an adjunctive for treatment-resistant depression. This systematic review provides comprehensive, high-quality evidence for the effects of brexpiprazole in major depressive disorder (MDD) based on existing and emerging randomised controlled trials (RCTs).\nObjectives\nTo evaluate the benefits and harms of brexpiprazole as monotherapy or adjunct treatment in the acute and longer-term treatment of MDD compared to placebo or other antidepressive agents.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was November 2021.\nSelection criteria\nWe included RCTs in people with a history of non-response to one or more antidepressant monotherapies comparing brexpiprazole as monotherapy or adjunct treatment with placebo or other antidepressive agents.\nData collection and analysis\nWe used standard Cochrane methods. Primary outcomes were 1. response to treatment, measured as number of participants who achieved 50% or more reduction of the score on a validated scale for depression, 2. dropouts due to any reason, and 3. dropouts due to adverse effects, all measured at eight weeks (acute treatment). Our secondary outcomes were 4. number of participants who responded to treatment after two and 18 weeks, number of participants who achieved remission after eight weeks, 5. total number of participants with any adverse events, 6. social functioning or adjustment, and 7. health-related quality of life. We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe retrieved nine studies with 3424 participants with treatment-resistant depression, defined as lack of response to at least two trials of antidepressant monotherapy. The age of participants was 18 to 65 years in seven studies, 18 to 75 years in one study, and older than 65 years in one study. Inclusion criteria for all studies required a diagnosis of MDD with a current major depressive episode per Diagnostic and Statistical Manual of Mental Disorders Text Revision Fourth Edition criteria and additional criteria on minimal scores on Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale which varied across studies. Eight studies compared brexpiprazole as adjunctive treatment to an antidepressant versus placebo as adjunctive treatment to an antidepressant. One study added brexpiprazole or placebo to a combination of antidepressant and ketamine. Four studies used fixed dosages and five studies used flexible dosages of brexpiprazole. The manufacturer sponsored eight studies and one study was independently funded.\nBrexpiprazole was superior in achieving response at eight weeks (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.23 to 1.75; 8 studies, 3409 participants; high-certainty evidence). More participants randomised to brexpiprazole dropped out due to any cause at eight weeks (OR 1.37, 95% CI 1.02 to 1.83; 7 studies, 2523 participants; high-certainty evidence) or due to adverse effects (OR 2.88, 95% CI 1.37 to 6.05; 6 studies, 2472 participants; high-certainty evidence). Brexpiprazole was superior to placebo when added to an antidepressant for achieving remission at eight weeks (OR 1.46, 95% CI 1.19 to 1.79; 7 studies, 3358 participants; high-certainty evidence). When response was defined based on a change in the score on MADRS, brexpiprazole also demonstrated better efficacy than placebo (mean difference (MD) –1.39, 95% CI –1.96 to –0.82; 8 studies, 3263 participants; high-certainty evidence). Compared to placebo, add-on brexpiprazole is probably more likely to result in akathisia (OR 2.95, 95% CI 2.06 to 4.21; 7 studies, 3358 participants; moderate-certainty evidence) and weight gain (OR 3.14, 95% CI 2.19 to 4.49; 9 studies, 3424 participants; moderate-certainty evidence).\nThe risk of bias varied between low and unclear for most studies. Only one study was at high risk of selective reporting bias and other bias; however, this study had a small sample size and its impact on overall risk of bias was not considered significant. The certainty of the evidence on five of the main outcomes (response to treatment, measured as number of participants who achieved response and change in depressive symptoms, remission, dropouts due to any cause, dropouts due to adverse effects) was high. The certainty of evidence for akathisia and weight gain was downgraded one level to moderate due to indirectness.\nAuthors' conclusions\nOur review supports the superior efficacy of add-on brexpiprazole in comparison to placebo in adults with treatment-resistant depression for the short-term and acute treatment of depression. Our findings were limited by the small number of studies and the moderate-certainty evidence for the most common adverse effects (akathisia and weight gain). There was insufficient evidence for the effects of brexpiprazole for depression in older people or children. In addition, we found no studies that compared brexpiprazole to other antidepressants or where brexpiprazole was added after lack of response to only one antidepressant. We also lacked sufficient data to establish the long-term efficacy of brexpiprazole as adjunctive treatment. Active comparators, long-term studies in different age groups and cost-effect analyses are needed to more precisely establish the clinical role of brexpiprazole in the treatment of MDD.\n\nGiven the provided abstract, please respond to the following query: \"How is the condition treated?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Unless the symptoms of depression are mild, the first option for treatment is an antidepressant medication, but antidepressants only help in half of cases when prescribed for the first time. When an antidepressant is not enough to treat depression, one available option is to add another medication to help the effects of the antidepressant. Other options include changing the antidepressant to another antidepressant, talking therapy or stimulation of the brain through electrical pulses. Brexpiprazole is a new medication which can be added to an antidepressant that has not worked by itself. Brexpiprazole can be prescribed in doses from 0.5 mg to 3 mg for the treatment of depression. It has also been approved for the treatment of schizophrenia." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent.\nObjectives\nTo determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD.\nSearch methods\nWe searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions.\nSelection criteria\nRandomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors.\nData collection and analysis\nTwo review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias.\nMain results\nWe included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.\nThe composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.\nThe evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.\nFour studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding.\nAuthors' conclusions\nCurrently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Eight trials fulfilled our inclusion criteria. One large trial looked at the effects of vitamin C supplements on the risk of major CVD events (fatal and non-fatal) and found no beneficial effects. This trial was however conducted in middle-aged and older male doctors in the USA and so its not certain that the effects are the same in other groups of people. Seven trials looked at the effects of vitamin C supplements on CVD risk factors. We could not combine these trials as there was lots of missing information and differences between the trials in terms of the participants recruited, the dose of vitamin C and the duration of trials. Overall, there were inconsistent effects of vitamin C supplements on lipid levels and blood pressure and more research is needed. Four of the included studies did not mention sources of funding of the study, two had non-commercial (grants) funding and two had both commercial (industries) and non-commercial funding (grants)." } ]

[ { "role": "user", "content": "Abstract: Background\nCataract is the leading cause of blindness in the world, and clinically significant astigmatism may affect up to approximately 20% of people undergoing cataract surgery. Pre-existing astigmatism in people undergoing cataract surgery may be treated, among other techniques, by placing corneal incisions near the limbus (limbal relaxing incisions or LRIs) or by toric intraocular lens (IOLs) specially designed to reduce or treat the effect of corneal astigmatism on unaided visual acuity.\nObjectives\nTo assess the effects of toric IOLs compared with LRIs in the management of astigmatism during phacoemulsification cataract surgery.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2019, Issue 9); Ovid MEDLINE; Ovid Embase and four other databases. The date of the search was 27 September 2019.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing toric IOLs with LRIs during phacoemulsification cataract surgery.\nData collection and analysis\nWe used standard methods expected by Cochrane. We graded the certainty of the evidence using GRADE. Our primary outcome was the proportion of participants with postoperative residual refractive astigmatism of less than 0.50 dioptres (D) six months or more after surgery. We also collected data on mean residual refractive astigmatism. Secondary outcomes included: uncorrected distance visual acuity, vision-related quality of life, spectacle independence and adverse effects including postoperative lens rotation requiring re-alignment. To supplement the main systematic review assessing the effects of toric IOLs compared with LRIs in the management of astigmatism during phacoemulsification cataract surgery, we sought to identify economic evaluations on the subject.\nMain results\nWe identified 10 relevant studies including 517 people (626 eyes). These studies took place in China (three studies), UK (three), Brazil (one), India (one), Italy (one) and Spain (one). The median age of participants was 71 years. The level of corneal astigmatism specified in the inclusion criteria of these studies ranged from 0.75 D to 3 D. A variety of toric IOLs were used in these studies, in all but one study, these were monofocal. Studies used three different nomograms to determine the size and placement of the LRI. Two studies did not specify this. None of the studies were at low risk of bias in all domains, but two studies were at low risk of bias in all domains except selective outcome reporting, which was unclear. The remaining studies were at a mixture of low, unclear or high risk of bias.\nPeople receiving toric IOLs were probably more likely to achieve a postoperative residual refractive astigmatism of less than 0.5 D six months or more after surgery (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.10 to 1.78; 5 RCTs, 262 eyes). We judged this to be moderate-certainty evidence, downgrading for risk of bias. In the included studies, approximately 500 eyes per 1000 achieved postoperative astigmatism less than 0.5 D in the LRI group compared with 700 per 1000 in the toric IOLs group. There was a small difference in residual astigmatism between the two groups, favouring toric IOLs (mean difference (MD) –0.32 D, 95% CI –0.48 to –0.15 D; 10 RCTs, 620 eyes). Although all studies favoured toric IOLs, the results of individual studies were inconsistent (range of effects –0.02 D to –0.71 D; I² = 89%). We considered this to be low-certainty evidence, downgrading for risk of bias and inconsistency. People receiving a toric IOL probably have a small improvement in visual acuity at six months or more after surgery compared to people receiving LRI, but the difference is small and probably clinically insignificant (MD –0.04 logMAR, 95% CI –0.07 to –0.02; 8 RCTs, 474 eyes; moderate-certainty evidence). Low-certainty evidence from one study of 40 people suggested little difference in vision-related quality of life measured using the Visual Function Index (VF-14) (MD –3.01, 95% CI –8.56 to 2.54). Two studies reported spectacle independence and suggested that people receiving toric IOLs may be more likely to be spectacle independent (RR 1.56, 95% CI 1.14 to 2.15; 100 people; low-certainty evidence). There were no cases of lens rotation requiring surgery (very low-certainty evidence). Five studies (320 eyes) commented on a range of other adverse effects including corneal oedema, endophthalmitis and corneal ectasia. All these studies reported that there were no adverse events with the exception of one study (40 eyes) where one participant in the LRI group had a central de-epithelisation which recovered over 10 days.\nWe found no economic studies that compared toric IOLs with LRIs.\nAuthors' conclusions\nToric IOLs probably provide a higher chance of achieving astigmatism within 0.5 D after cataract surgery compared with LRIs. There may be a small mean difference in postoperative astigmatism, favouring toric IOLs, but this difference is likely to be clinically unimportant. There was no evidence of an important difference in postoperative visual acuity or quality of life between the techniques. Evidence on adverse effects was uncertain. The apparent shortage of relevant economic evaluations indicates that economic evidence regarding the costs and consequence of these two procedures is currently lacking.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review shows that toric IOLs probably provide a higher chance of a good outcome with respect to astigmatism after cataract surgery compared with LRIs. The difference in average astigmatism may be small and there may be little or no difference in vision or quality of life. There was a lack of evidence on which of these techniques represents best value for money." } ]

[ { "role": "user", "content": "Abstract: Background\nCommunity-acquired pneumonia (CAP) is a lung infection that can be acquired during day-to-day activities in the community (not while receiving care in a hospital). Community-acquired pneumonia poses a significant public health burden in terms of mortality, morbidity, and costs. Shorter antibiotic courses for CAP may limit treatment costs and adverse effects, but the optimal duration of antibiotic treatment is uncertain.\nObjectives\nTo evaluate the efficacy and safety of short-course versus longer-course treatment with the same antibiotic at the same daily dosage for CAP in non-hospitalised adolescents and adults (outpatients). We planned to investigate non-inferiority of short-course versus longer-term course treatment for efficacy outcomes, and superiority of short-course treatment for safety outcomes.\nSearch methods\nWe searched CENTRAL, which contains the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, five other databases, and three trials registers on 28 September 2017 together with conference proceedings, reference checking, and contact with experts and pharmaceutical companies.\nSelection criteria\nRandomised controlled trials (RCTs) comparing short- and long-courses of the same antibiotic for CAP in adolescent and adult outpatients.\nData collection and analysis\nWe planned to use standard Cochrane methods.\nMain results\nOur searches identified 5260 records. We did not identify any RCTs that compared short- and longer-courses of the same antibiotic for the treatment of adolescents and adult outpatients with CAP.\nWe excluded two RCTs that compared short courses (five compared to seven days) of the same antibiotic at the same daily dose because they evaluated antibiotics (gemifloxacin and telithromycin) not commonly used in practice for the treatment of CAP. In particular, gemifloxacin is no longer approved for the treatment of mild-to-moderate CAP due to its questionable risk-benefit balance, and reported adverse effects. Moreover, the safety profile of telithromycin is also cause for concern.\nWe found one ongoing study that we will assess for inclusion in future updates of the review.\nAuthors' conclusions\nWe found no eligible RCTs that studied a short-course of antibiotic compared to a longer-course (with the same antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients. The effects of antibiotic therapy duration for CAP in adolescent and adult outpatients remains unclear.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Our searches identified 5260 records, but no completed studies compared short- and longer-courses of the same antibiotic for treatment of adolescents and adults in the community with CAP. The effect of length of antibiotic therapy on adolescents and adults with CAP who are treated in the community remains unclear.\nWe excluded two studies that compared short courses (five versus seven days) of the same antibiotic at the same daily dose because they evaluated antibiotics (gemifloxacin and telithromycin) that are not commonly used for people with CAP. Gemifloxacin is no longer used because its risks do not appear be balanced with treatment benefit, and adverse treatment effects have been reported. The safety of telithromycin has also raised concerns.\nWe found one ongoing study that we will assess for inclusion in future updates of the review." } ]

[ { "role": "user", "content": "Abstract: Background\nLow back pain is a common presentation across different healthcare settings. Clinicians need to confidently be able to screen and identify people presenting with low back pain with a high suspicion of serious or specific pathology (e.g. vertebral fracture). Patients identified with an increased likelihood of having a serious pathology will likely require additional investigations and specific treatment. Guidelines recommend a thorough history and clinical assessment to screen for serious pathology as a cause of low back pain. However, the diagnostic accuracy of recommended red flags (e.g. older age, trauma, corticosteroid use) remains unclear, particularly those used to screen for vertebral fracture.\nObjectives\nTo assess the diagnostic accuracy of red flags used to screen for vertebral fracture in people presenting with low back pain. Where possible, we reported results of red flags separately for different types of vertebral fracture (i.e. acute osteoporotic vertebral compression fracture, vertebral traumatic fracture, vertebral stress fracture, unspecified vertebral fracture).\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 26 July 2022.\nSelection criteria\nWe considered primary diagnostic studies if they compared results of history taking or physical examination (or both) findings (index test) with a reference standard test (e.g. X-ray, magnetic resonance imaging (MRI), computed tomography (CT), single-photon emission computerised tomography (SPECT)) for the identification of vertebral fracture in people presenting with low back pain. We included index tests that were presented individually or as part of a combination of tests.\nData collection and analysis\nTwo review authors independently extracted data for diagnostic two-by-two tables from the publications or reconstructed them using information from relevant parameters to calculate sensitivity, specificity, and positive (+LR) and negative (−LR) likelihood ratios with 95% confidence intervals (CIs). We extracted aspects of study design, characteristics of the population, index test, reference standard, and type of vertebral fracture. Meta-analysis was not possible due to heterogeneity of studies and index tests, therefore the analysis was descriptive. We calculated sensitivity, specificity, and LRs for each test and used these as an indication of clinical usefulness. Two review authors independently conducted risk of bias and applicability assessment using the QUADAS-2 tool.\nMain results\nThis review is an update of a previous Cochrane Review of red flags to screen for vertebral fracture in people with low back pain. We included 14 studies in this review, six based in primary care, five in secondary care, and three in tertiary care. Four studies reported on 'osteoporotic vertebral fractures', two studies reported on 'vertebral compression fracture', one study reported on 'osteoporotic and traumatic vertebral fracture', two studies reported on 'vertebral stress fracture', and five studies reported on 'unspecified vertebral fracture'. Risk of bias was only rated as low in one study for the domains reference standard and flow and timing. The domain patient selection had three studies and the domain index test had six studies rated at low risk of bias. Meta-analysis was not possible due to heterogeneity of the data. Results from single studies suggest only a small number of the red flags investigated may be informative.\nIn the primary healthcare setting, results from single studies suggest 'trauma' demonstrated informative +LRs (range: 1.93 to 12.85) for 'unspecified vertebral fracture' and 'osteoporotic vertebral fracture' (+LR: 6.42, 95% CI 2.94 to 14.02). Results from single studies suggest 'older age' demonstrated informative +LRs for studies in primary care for 'unspecified vertebral fracture' (older age greater than 70 years: 11.19, 95% CI 5.33 to 23.51). Results from single studies suggest 'corticosteroid use' may be an informative red flag in primary care for 'unspecified vertebral fracture' (+LR range: 3.97, 95% CI 0.20 to 79.15 to 48.50, 95% CI 11.48 to 204.98) and 'osteoporotic vertebral fracture' (+LR: 2.46, 95% CI 1.13 to 5.34); however, diagnostic values varied and CIs were imprecise. Results from a single study suggest red flags as part of a combination of index tests such as 'older age and female gender' in primary care demonstrated informative +LRs for 'unspecified vertebral fracture' (16.17, 95% CI 4.47 to 58.43).\nIn the secondary healthcare setting, results from a single study suggest 'trauma' demonstrated informative +LRs for 'unspecified vertebral fracture' (+LR: 2.18, 95% CI 1.86 to 2.54) and 'older age' demonstrated informative +LRs for 'osteoporotic vertebral fracture' (older age greater than 75 years: 2.51, 95% CI 1.48 to 4.27). Results from a single study suggest red flags as part of a combination of index tests such as 'older age and trauma' in secondary care demonstrated informative +LRs for 'unspecified vertebral fracture' (+LR: 4.35, 95% CI 2.92 to 6.48). Results from a single study suggest when '4 of 5 tests' were positive in secondary care, they demonstrated informative +LRs for 'osteoporotic vertebral fracture' (+LR: 9.62, 95% CI 5.88 to 15.73).\nIn the tertiary care setting, results from a single study suggest 'presence of contusion/abrasion' was informative for 'vertebral compression fracture' (+LR: 31.09, 95% CI 18.25 to 52.96).\nAuthors' conclusions\nThe available evidence suggests that only a few red flags are potentially useful in guiding clinical decisions to further investigate people suspected to have a vertebral fracture. Most red flags were not useful as screening tools to identify vertebral fracture in people with low back pain. In primary care, 'older age' was informative for 'unspecified vertebral fracture', and 'trauma' and 'corticosteroid use' were both informative for 'unspecified vertebral fracture' and 'osteoporotic vertebral fracture'. In secondary care, 'older age' was informative for 'osteoporotic vertebral fracture' and 'trauma' was informative for 'unspecified vertebral fracture'. In tertiary care, 'presence of contusion/abrasion' was informative for 'vertebral compression fracture'. Combinations of red flags were also informative and may be more useful than individual tests alone. Unfortunately, the challenge to provide clear guidance on which red flags should be used routinely in clinical practice remains. Further research with primary studies is needed to improve and consolidate our current recommendations for screening for vertebral fractures to guide clinical care.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We wanted to assess how accurate the red flags used to screen for spinal fracture are in people presenting with low back pain. Where possible, we reported results of red flags separately for the different types of spinal fracture, such as osteoporotic vertebral compression fractures (e.g. fractures due to osteoporosis), vertebral traumatic fracture (e.g. due to falls), vertebral stress fracture (e.g. rapid increase in load on the spine), or unspecified vertebral fracture (e.g. no specific cause reported)." } ]

[ { "role": "user", "content": "Abstract: Background\nCerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain, which has potential neuroprotective properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. This is an update of a review first published in 2010 and last updated in 2020.\nObjectives\nTo assess the benefits and harms of Cerebrolysin or Cerebrolysin-like agents for treating acute ischaemic stroke.\nSearch methods\nWe searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, and LILACS in May 2022 and a number of Russian databases in June 2022. We also searched reference lists, ongoing trials registers, and conference proceedings.\nSelection criteria\nRandomised controlled trials (RCTs) comparing Cerebrolysin or Cerebrolysin-like agents started within 48 hours of stroke onset and continued for any length of time, with placebo or no treatment in people with acute ischaemic stroke.\nData collection and analysis\nThree review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, extracted data, and applied GRADE criteria to the evidence.\nMain results\nSeven RCTs (1773 participants) met the inclusion criteria of the review. In this update we added one RCT of Cerebrolysin-like agent Cortexin, which contributed 272 participants.\nWe used the same approach for risk of bias assessment that was re-evaluated for the previous update: we added consideration of the public availability of study protocols and reported outcomes to the selective outcome reporting judgement, through identification, examination, and evaluation of study protocols.\nFor the Cerebrolysin studies, we judged the risk of bias for selective outcome reporting to be unclear across all studies; for blinding of participants and personnel to be low in three studies and unclear in the remaining four; and for blinding of outcome assessors to be low in three studies and unclear in four studies. We judged the risk of bias for generation of allocation sequence to be low in one study and unclear in the remaining six studies; for allocation concealment to be low in one study and unclear in six studies; and for incomplete outcome data to be low in three studies and high in the remaining four studies. The manufacturer of Cerebrolysin supported three multicentre studies, either totally, or by providing Cerebrolysin and placebo, randomisation codes, research grants, or statisticians. We judged two studies to be at high risk of other bias and the remaining five studies to be at unclear risk of other bias. We judged the study of Cortexin to be at low risk of bias for incomplete outcome data and at unclear risk of bias for all other domains.\nAll-cause death: Cerebrolysin or Cortexin probably result in little to no difference in all-cause death (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.41; 6 trials, 1689 participants; moderate-certainty evidence).\nNone of the included studies reported on poor functional outcome, defined as death or dependence at the end of the follow-up period, early death (within two weeks of stroke onset), quality of life, or time to restoration of capacity for work.\nOnly one study clearly reported on the cause of death: cerebral infarct (four in the Cerebrolysin and two in the placebo group), heart failure (two in the Cerebrolysin and one in the placebo group), pulmonary embolism (two in the placebo group), and pneumonia (one in the placebo group).\nNon-death attrition (secondary outcome): Cerebrolysin or similar peptide mixtures may result in little to no difference in non-death attrition, but the evidence is very uncertain, with a considerable level of heterogeneity (RR 0.72, 95% CI 0.38 to 1.39; 6 trials, 1689 participants; very low-certainty evidence).\nSerious adverse events (SAEs): Cerebrolysin probably results in little to no difference in the total number of people with SAEs (RR 1.16, 95% CI 0.81 to 1.66; 3 trials, 1335 participants; moderate-certainty evidence). This comprised fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38; 3 trials, 1335 participants; moderate-certainty evidence) and an increase in the total number of people with non-fatal SAEs (RR 2.39, 95% CI 1.10 to 5.23; 3 trials, 1335 participants; moderate-certainty evidence). In the subgroup of dosing schedule 30 mL for 10 days (cumulative dose 300 mL), the increase was more prominent (RR 2.87, 95% CI 1.24 to 6.69; 2 trials, 1189 participants).\nTotal number of people with adverse events: Cerebrolysin or similar peptide mixtures may result in little to no difference in the total number of people with adverse events (RR 1.03, 95% CI 0.92 to 1.14; 4 trials, 1607 participants; low-certainty evidence).\nAuthors' conclusions\nModerate-certainty evidence indicates that Cerebrolysin or Cerebrolysin-like peptide mixtures derived from cattle brain probably have no beneficial effect on preventing all-cause death in acute ischaemic stroke. Moderate-certainty evidence suggests that Cerebrolysin probably has no beneficial effect on the total number of people with serious adverse events. Moderate-certainty evidence also indicates a potential increase in non-fatal serious adverse events with Cerebrolysin use.\n\nGiven the provided abstract, please respond to the following query: \"Results of our review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Adding Cerebrolysin or a Cerebrolysin-like agent, Cortexin, to standard therapy probably adds no benefit to the risk of dying from any cause after a stroke (6 studies, 1689 people).\nWe did not find enough evidence about how Cerebrolysin or the Cerebrolysin-like agent Cortexin affected:\n• the risk of dying or needing continuing care at the end of the study;\n• the risk of dying within two weeks of having a stroke;\n• the time taken for people to be able to go back to work; or\n• people's well-being (quality of life).\nWe are uncertain whether adding Cerebrolysin to standard therapy made any difference to the numbers of people who dropped out of studies (6 studies, 1689 people).\nCerebrolysin added to standard therapy probably made little or no difference to:\n• the total number of people who had serious unwanted effects (life-threatening effects that could result in death, disability, or a longer hospital stay) (3 studies, 1335 people);\n• the number of serious unwanted effects that caused death (3 studies, 1335 people).\nHowever, more people given Cerebrolysin plus standard therapy probably had serious unwanted effects that did not kill them than those who were given standard therapy (alone or with placebo) (3 studies, 1335 people).\nCerebrolysin or the Cerebrolysin-like agent Cortexin may make little or no difference to the total number of people who had any unwanted effects (4 studies, 1607 people)." } ]