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[ { "role": "user", "content": "Abstract: Background\nPoor growth and nutritional status are common in children with chronic diseases. Oral protein calorie supplements are used to improve nutritional status in these children. These expensive products may be associated with some adverse effects, e.g. the development of inappropriate eating behaviour patterns. This is a new update of a Cochrane review last updated in 2009.\nObjectives\nTo examine evidence that in children with chronic disease, oral protein calorie supplements alter daily nutrient intake, nutritional indices, survival and quality of life and are associated with adverse effects, e.g. diarrhoea, vomiting, reduced appetite, glucose intolerance, bloating and eating behaviour problems.\nSearch methods\nTrials of oral protein calorie supplements in children with chronic diseases were identified through comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Companies marketing these products were also contacted.\nMost recent search of the Group's Trials Register: 24 February 2015.\nSelection criteria\nRandomised or quasi-randomised controlled trials comparing oral protein calorie supplements for at least one month to increase calorie intake with existing conventional therapy (including advice on improving nutritional intake from food or no specific intervention) in children with chronic disease.\nData collection and analysis\nWe independently assessed the outcomes: indices of nutrition and growth; anthropometric measures of body composition; calorie and nutrient intake (total from oral protein calorie supplements and food); eating behaviour; compliance; quality of life; specific adverse effects; disease severity scores; and mortality; we also assessed the risk of bias in the included trials.\nMain results\nFour studies (187 children) met the inclusion criteria. Three studies were carried out in children with cystic fibrosis and one study included children with paediatric malignant disease. Overall there was a low risk of bias for blinding and incomplete outcome data.Two studies had a high risk of bias for allocation concealment. Few statistical differences were found in the outcomes we assessed between treatment and control groups, except change in total energy intake at six and 12 months, mean difference 304.86 kcal per day (95% confidence interval 5.62 to 604.10) and mean difference 265.70 kcal per day (95% confidence interval 42.94 to 485.46), respectively. However, these were based on the analysis of just 58 children in only one study. Only two chronic diseases were included in these analyses, cystic fibrosis and paediatric malignant disease. No other studies were identified which assessed the effectiveness of oral protein calorie supplements in children with other chronic diseases.\nAuthors' conclusions\nOral protein calorie supplements are widely used to improve the nutritional status of children with a number of chronic diseases. We identified a small number of studies assessing these products in children with cystic fibrosis and paediatric malignant disease, but were unable to draw any conclusions based on the limited data extracted. We recommend a series of large, randomised controlled trials be undertaken investigating the use of these products in children with different chronic diseases. Until further data are available, we suggest these products are used with caution.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We looked for trials of oral protein calorie supplements compared to usual treatment or no alternative treatment where the children took the supplements for at least one month. The review included four trials with 187 children; in three of these the children had cystic fibrosis and in one they had cancer. Studies lasted from three months to one year. We recorded the results and judged whether the trials were at risk of being biased based on the design or the way it was run. We looked at outcomes such as weight and height, calorie intake, behaviour and also side effects." } ]

[ { "role": "user", "content": "Abstract: Background\nSubfertility affects 15% to 20% of couples trying to conceive. In vitro fertilisation (IVF) is one of the assisted reproduction techniques developed to improve chances of achieving pregnancy. In the standard IVF method with controlled ovarian hyperstimulation (COH), growth and development of multiple follicles are stimulated by using gonadotrophins, often combined with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist. Although it is an established method of conception for subfertile couples, the treatment is expensive and has a high risk of adverse effects. Studies have shown that IVF in a natural cycle (NC) or a modified natural cycle (MNC) might be a promising low risk and low cost alternative to the standard stimulated IVF treatment since the available dominant follicle of each cycle is used. In this review, we included available randomised controlled studies comparing natural cycle IVF (NC and MNC) with standard IVF.\nObjectives\nTo compare the efficacy and safety of natural cycle IVF (including both NC-IVF and MNC-IVF) with controlled ovarian hyperstimulation IVF (COH-IVF) in subfertile couples.\nSearch methods\nAn extended search including of the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, conference abstracts in the Web of Knowledge, the World Health Organization International Trials Registry Platform search portal, LILACS database, PubMed and the OpenSIGLE database was conducted according to Cochrane guidelines. The last search was on 31st July 2013.\nSelection criteria\nAll randomised controlled trials (RCTs) comparing either natural cycle IVF or modified natural cycle IVF versus standard IVF in subfertile couples were included.\nData collection and analysis\nData selection and extraction and risk of bias assessment were carried out independently by two authors (TA and AC). The primary outcome measures were live birth rate and ovarian hyperstimulation syndrome (OHSS) rate per randomised woman. We calculated Mantel-Haenszel odds ratios for each dichotomous outcome and either the mean difference or the standardised mean difference (SMD) for continuous outcomes, with 95% confidence intervals (CIs). A fixed effect model was used unless there was substantial heterogeneity, in which case a random effects model was used.\nMain results\nSix randomised controlled trials with a total of 788 women were included. The largest of these trials included 396 women eligible for this review.\nNo evidence of a statistically significant difference was found between natural cycle and standard IVF in live birth rates (OR 0.68, 95% CI 0.46 to 1.01, two studies, 425 women, I2= 0%, moderate quality evidence). The evidence suggests that for a woman with a 53% chance of live birth using standard IVF, the chance using natural cycle IVF would range from 34% to 53%. There was no evidence of a statistically significant difference between natural cycle and standard IVF in rates of OHSS (OR 0.19, 95% CI 0.01 to 4.06, one study, 60 women, very low quality evidence), clinical pregnancy (OR 0.52 95% CI 0.17 to 1.61, 4 studies, 351 women, I2=63%, low quality evidence), ongoing pregnancy (OR 0.72, 95% CI 0.50 to 1.05, three studies, 485 women, I2=0%, moderate quality evidence), multiple pregnancy (OR 0.76, 95% CI 0.25 to 2.31, 2 studies, 527 women, I2=0%, very low quality evidence), gestational abnormalities (OR 0.44 95% CI 0.03 to 5.93, 1 study, 18 women, very low quality evidence) or cycle cancellations (OR 8.98, 95% CI 0.20 to 393.66, 2 studies, 159 women, I2=83%, very low quality evidence). One trial reported that the oocyte retrieval rate was significantly lower in the natural cycle group (MD -4.40, 95% CI -7.87 to -0.93, 60 women, very low quality evidence). There were insufficient data to draw any conclusions about rates of treatment cancellation. Findings on treatment costs were inconsistent and more data are awaited. The evidence was limited by imprecision. Findings for pregnancy rate and for cycle cancellation were sensitive to the choice of statistical model: for these outcomes, use of a fixed effect model suggested a benefit for the standard IVF group. Moreover the largest trial has not yet completed follow up, though data have been reported for over 95% of women.\nAuthors' conclusions\nFurther evidence from well conducted large trials is awaited on natural cycle IVF treatment. Future trials should compare natural cycle IVF with standard IVF. Outcomes should include cumulative live birth and pregnancy rates, the number of treatment cycles necessary to reach live birth, treatment costs and adverse effects.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Six trials were included, with a total of 788 women undergoing an IVF treatment. The evidence is current to 31st July 2013. The largest trial in the review (with 396 women) has not yet reported full results." } ]

[ { "role": "user", "content": "Abstract: Background\nSlow-release fluoride devices have been investigated as a potentially cost-effective method of reducing dental caries in people with high risk of disease. This is the second update of the Cochrane Review first published in 2006 and previously updated in 2014.\nObjectives\nTo evaluate the effectiveness and safety of different types of slow-release fluoride devices on preventing, arresting, or reversing the progression of carious lesions on all surface types of primary (deciduous) and permanent teeth.\nSearch methods\nCochrane Oral Health's Information Specialist searched the following electronic databases: Cochrane Oral Health's Trials Register (to 23 January 2018); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 12) in the Cochrane Library (searched 23 January 2018); MEDLINE Ovid (1946 to 23 January 2018); and Embase Ovid (1980 to 23 January 2018). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials (23 January 2018). We placed no restrictions on the language or date of publication when searching the electronic databases.\nSelection criteria\nParallel randomised controlled trials (RCTs) comparing slow-release fluoride devices with an alternative fluoride treatment, placebo, or no intervention in all age groups. The main outcome measures sought were changes in numbers of decayed, missing, and filled teeth or surfaces (DMFT/DMFS in permanent teeth or dmft/dmfs in primary teeth), and progression of carious lesions through enamel and into dentine.\nData collection and analysis\nWe conducted data collection and analysis using standard Cochrane review methods. At least two review authors independently performed all the key steps in the review such as screening of abstracts, application of inclusion criteria, data extraction, and risk of bias assessment. We resolved discrepancies through discussions or arbitration by a third or fourth review author.\nMain results\nWe found no evidence comparing slow-release fluoride devices against other types of fluoride therapy.\nWe found only one double-blind RCT involving 174 children comparing a slow-release fluoride device (glass beads with fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth) against control (glass beads without fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth). This study was assessed to be at high risk of bias. The study recruited children from seven schools in an area of deprivation that had low levels of fluoride in the water. The mean age at the beginning of the study was 8.8 years and at the termination was 10.9 years. DMFT in permanent teeth or dmft in primary teeth was greater than one at the start of the study and greater than one million colony-forming units of Streptococcus mutans per millilitre of saliva.\nAlthough 132 children were still included in the trial at the two-year completion point, examination and statistical analysis was performed on only the 63 children (31 in intervention group, 32 in control group) who had retained the beads (retention rate was 47.7% at 2 years). Among these 63 children, caries increment was reported to be statistically significantly lower in the intervention group than in the control group (DMFT: mean difference -0.72, 95% confidence interval (CI) -1.23 to -0.21; DMFS: mean difference -1.52, 95% CI -2.68 to -0.36 (very low-quality evidence)). Although this difference was clinically significant, it only holds true for those children who maintain the fluoride beads; over 50% of children did not retain the beads.\nHarms were not reported within the trial report. Evidence for other outcomes sought in this review (progression to of caries lesion, dental pain, healthcare utilisation data) were also not reported.\nAuthors' conclusions\nThere is insufficient evidence to determine the caries-inhibiting effect of slow-release fluoride glass beads. The body of evidence available is of very low quality and there is a potential overestimation of benefit to the average child. The applicability of the findings to the wider population is unclear; the study had included children from a deprived area that had low levels of fluoride in drinking water, and were considered at high risk of caries. In addition, the evidence was only obtained from children who still had the bead attached at 2 years (48% of all available children); children who had lost their slow-release fluoride devices earlier might not have benefited as much from the devices.\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 one study that randomised 174 children to either slow-dissolving, fluoride-releasing glass beads or placebo beads. The setting was an inner city school in an area served with low-fluoride water. Only 48% of children retained the beads and were available for analysis.\nThere is insufficient evidence to determine whether slow-release fluoride devices (such as glass beads) help reduce dental decay. Retention of the beads is a problem." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic spontaneous urticaria (CSU) is characterised by the development of crops of red, itchy, raised weals or hives with no identifiable external cause.\nObjectives\nTo assess the effects of H1-antihistamines for CSU.\nSearch methods\nWe searched the following databases up to June 2014: Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 5), MEDLINE (from 1946), EMBASE (from 1974) and PsycINFO (from 1806). We searched five trials registers and checked articles for references to relevant randomised controlled trials.\nSelection criteria\nWe included randomised controlled trials of H1-antihistamines for CSU. Interventions included single therapy or a combination of H1-antihistamines compared with no treatment (placebo) or another active pharmacological compound at any dose.\nData collection and analysis\nWe used standard methodological procedures as expected by The Cochrane Collaboration.\nOur primary outcome measures were proportion of participants with complete suppression of urticaria: 'good or excellent' response, 50% or greater improvement in quality of life measures, and adverse events. We present risk ratios (RR) with 95% confidence intervals (CIs).\nMain results\nWe identified 73 studies (9759 participants); 34 studies provided data for 23 comparisons. The duration of the intervention was up to two weeks (short-term) or longer than two weeks and up to three months (intermediate-term).\nCetirizine 10 mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). For this same outcome, comparison of desloratadine versus placebo in the intermediate term (5 mg) (RR 37.00, 95% CI 2.31 to 593.70) and in the short term (20 mg) (RR 15.97, 95% CI 1.04 to 245.04) favoured desloratadine, but no differences were seen between 5 mg and 10 mg for short-term treatment.\nLevocetirizine 20 mg per day (short-term) was more effective for complete suppression of urticaria compared with placebo (RR 20.87, 95% CI 1.37 to 317.60), and at 5 mg was effective in the intermediate term (RR 52.88, 95% CI 3.31 to 843.81) but not in the short term, nor was 10 mg effective in the short term.\nRupatadine at 10 mg and 20 mg in the intermediate term achieved a 'good or excellent response' compared with placebo (RR 1.35, 95% CI 1.03 to 1.77).\nLoratadine (10 mg) versus placebo (RR 1.86, 95% CI 0.91 to 3.79) and loratadine (10 mg) versus cetirizine (10 mg) (RR 1.05, 95% CI 0.76 to 1.43) over short-term and intermediate-term treatment showed no significant difference for 'good or excellent response' or for complete suppression of urticaria, respectively.\nLoratadine (10 mg) versus desloratadine (5 mg) (intermediate-term) showed no statistically significant difference for complete suppression of urticaria (RR 0.91, 95% CI 0.78 to 1.06) or for 'good or excellent response' (RR 1.04, 95% CI 0.64 to 1.71). For loratadine (10 mg) versus mizolastine (10 mg) (intermediate-term), no statistically significant difference was seen for complete suppression of urticaria (RR 0.86, 95% CI 0.64 to 1.16) or for 'good or excellent response' (RR 0.88, 95% CI 0.55 to 1.42).\nLoratadine (10 mg) versus emedastine (2 mg) (intermediate-term) showed no statistically significant difference for complete suppression (RR 1.04, 95% CI 0.78 to 1.39) or for 'good or excellent response' (RR 1.09, 95% CI 0.96 to 1.24); the quality of the evidence was moderate for this comparison.\nNo difference in short-term treatment was noted between loratadine (10 mg) and hydroxyzine (25 mg) in terms of complete suppression (RR 1.00, 95% CI 0.32 to 3.10).\nWhen desloratadine (5 to 20 mg) was compared with levocetirizine (5 to 20 mg), levocetirizine appeared to be the more effective (P value < 0.02).\nIn a comparison of fexofenadine versus cetirizine, more participants in the cetirizine group showed complete suppression of urticaria (P value < 0.001).\nAdverse events leading to withdrawals were not significantly different in the following comparisons: cetirizine versus placebo at 10 mg and 20 mg (RR 3.00, 95% CI 0.68 to 13.22); desloratadine 5 mg versus placebo (RR 1.46, 95% CI 0.42 to 5.10); loratadine 10 mg versus mizolastine 10 mg (RR 0.38, 95% CI 0.04 to 3.60); loratadine 10 mg versus emedastine 2 mg (RR 1.09, 95% CI 0.07 to 17.14); cetirizine 10 mg versus hydroxyzine 25 mg (RR 0.78, 95% CI 0.25 to 2.45); and hydroxyzine 25 mg versus placebo (RR 3.64, 95% CI 0.77 to 17.23), all intermediate term.\nNo difference was seen between loratadine 10 mg versus mizolastine 10 mg in the proportion of participants with at least 50% improvement in quality of life (RR 3.21, 95% CI 0.32 to 32.33).\nAuthors' conclusions\nAlthough the results of our review indicate that at standard doses of treatment, several antihistamines are effective when compared with placebo, all results were gathered from a few studies or, in some cases, from single-study estimates. The quality of the evidence was affected by the small number of studies in each comparison and the small sample size for many of the outcomes, prompting us to downgrade the quality of evidence for imprecision (unless stated for each comparison, the quality of the evidence was low).\nNo single H1-antihistamine stands out as most effective. Cetirizine at 10 mg once daily in the short term and in the intermediate term was found to be effective in completely suppressing urticaria. Evidence is limited for desloratadine given at 5 mg once daily in the intermediate term and at 20 mg in the short term. Levocetirizine at 5 mg in the intermediate but not short term was effective for complete suppression. Levocetirizine 20 mg was effective in the short term, but 10 mg was not. No difference in rates of withdrawal due to adverse events was noted between active and placebo groups. Evidence for improvement in quality of life was insufficient.\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": "Which H1-antihistamines are effective and safe for CSU?" } ]

[ { "role": "user", "content": "Abstract: Background\nSelf-harm (SH; intentional self-poisoning or self-injury regardless of degree of suicidal intent or other types of motivation) is a growing problem in most countries, often repeated, and associated with suicide. Evidence assessing the effectiveness of pharmacological agents and/or natural products in the treatment of SH is lacking, especially when compared with the evidence for psychosocial interventions. This review therefore updates a previous Cochrane Review (last published in 2015) on the role of pharmacological interventions for SH in adults.\nObjectives\nTo assess the effects of pharmacological agents or natural products for SH compared to comparison types of treatment (e.g. placebo or alternative pharmacological treatment) for adults (aged 18 years or older) who engage in SH.\nSearch methods\nWe searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials [CENTRAL] and Cochrane Database of Systematic Reviews [CDSR]), together with MEDLINE. Ovid Embase and PsycINFO (to 4 July 2020).\nSelection criteria\nWe included all randomised controlled trials (RCTs) comparing pharmacological agents or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months of trial entry) episode of SH resulting in presentation to hospital or clinical services. The primary outcome was the occurrence of a repeated episode of SH over a maximum follow-up period of two years. Secondary outcomes included treatment acceptability, treatment adherence, depression, hopelessness, general functioning, social functioning, suicidal ideation, and suicide.\nData collection and analysis\nWe independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence internals (CIs). For continuous outcomes we calculated the mean difference (MD) or standardised mean difference (SMD) and 95% CI. The overall certainty of evidence for the primary outcome (i.e. repetition of SH at post-intervention) was appraised for each intervention using the GRADE approach.\nMain results\nWe included data from seven trials with a total of 574 participants. Participants in these trials were predominately female (63.5%) with a mean age of 35.3 years (standard deviation (SD) 3.1 years). It is uncertain if newer generation antidepressants reduce repetition of SH compared to placebo (OR 0.59, 95% CI 0.29 to 1.19; N = 129; k = 2; very low-certainty evidence). There may be a lower rate of SH repetition for antipsychotics (21%) as compared to placebo (75%) (OR 0.09, 95% CI 0.02 to 0.50; N = 30; k = 1; low-certainty evidence). However, there was no evidence of a difference between antipsychotics compared to another comparator drug/dose for repetition of SH (OR 1.51, 95% CI 0.50 to 4.58; N = 53; k = 1; low-certainty evidence). There was also no evidence of a difference for mood stabilisers compared to placebo for repetition of SH (OR 0.99, 95% CI 0.33 to 2.95; N = 167; k = 1; very low-certainty evidence), or for natural products compared to placebo for repetition of SH (OR 1.33, 95% CI 0.38 to 4.62; N = 49; k = 1; lo- certainty) evidence.\nAuthors' conclusions\nGiven the low or very low quality of the available evidence, and the small number of trials identified, there is only uncertain evidence regarding pharmacological interventions in patients who engage in SH. More and larger trials of pharmacotherapy are required, preferably using newer agents. These might include evaluation of newer atypical antipsychotics. Further work should also include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment.\n\nGiven the provided abstract, please respond to the following query: \"Which studies were included in the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "To be included in the review, studies had to be randomised controlled trials of drug treatments for adults who had recently engaged in SH." } ]

[ { "role": "user", "content": "Abstract: Background\nPressure ulcers, also known as bedsores, pressure sores, or pressure injuries, are localised damage to the skin and underlying soft tissue, usually caused by intense or long-term pressure, shear, or friction. Negative pressure wound therapy (NPWT) has been widely used in the treatment of pressure ulcers, but its effect needs to be further clarified. This is an update of a Cochrane Review first published in 2015.\nObjectives\nTo evaluate the effectiveness of NPWT for treating adult with pressure ulcers in any care setting.\nSearch methods\nOn 13 January 2022, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase, and EBSCO CINAHL Plus. We also searched ClinicalTrials.gov and the WHO ICTRP Search Portal for ongoing and unpublished studies and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication, or study setting.\nSelection criteria\nWe included published and unpublished randomised controlled trials (RCTs) comparing the effects of NPWT with alternative treatments or different types of NPWT in the treatment of adults with pressure ulcers (stage II or above).\nData collection and analysis\nTwo review authors independently conducted study selection, data extraction, risk of bias assessment using the Cochrane risk of bias tool, and the certainty of the evidence assessment using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. Any disagreement was resolved by discussion with a third review author.\nMain results\nThis review included eight RCTs with a total of 327 randomised participants. Six of the eight included studies were deemed to be at a high risk of bias in one or more risk of bias domains, and evidence for all outcomes of interest was deemed to be of very low certainty. Most studies had small sample sizes (range: 12 to 96, median: 37 participants).\nFive studies compared NPWT with dressings, but only one study reported usable primary outcome data (complete wound healing and adverse events). This study had only 12 participants and there were very few events; only one participant was healed in the study (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.15 to 61.74, very low-certainly evidence). There was no evidence of a difference in the number of participants with adverse events in the NPWT group and the dressing group, but the evidence for this outcome was also assessed as very low certainty (RR 1.25, 95% CI 0.64 to 2.44, very low-certainty evidence). Changes in ulcer size, pressure ulcer severity, cost, and pressure ulcer scale for healing (PUSH) sores were also reported, but we were unable to draw conclusions due to the low certainly of the evidence.\nOne study compared NPWT with a series of gel treatments, but this study provided no usable data. Another study compared NPWT with 'moist wound healing',  which did not report primary outcome data. Changes in ulcer size and cost were reported in this study, but we assessed the evidence as being of very low certainty; One study compared NPWT combined with internet-plus home care with standard care, but no primary outcome data were reported. Changes in ulcer size, pain, and dressing change times were reported, but we also assessed the evidence as being of very low certainty.\nNone of the included studies reported time to complete healing, health-related quality of life, wound infection, or wound recurrence.\nAuthors' conclusions\nThe efficacy, safety, and acceptability of NPWT in treating pressure ulcers compared to usual care are uncertain due to the lack of key data on complete wound healing, adverse events, time to complete healing, and cost-effectiveness.\nCompared with usual care, using NPWT may speed up the reduction of pressure ulcer size and severity of pressure ulcer, reduce pain, and dressing change times. Still, trials were small, poorly described, had short follow-up times, and with a high risk of bias; any conclusions drawn from the current evidence should be interpreted with considerable caution. In the future, high-quality research with large sample sizes and low risk of bias is still needed to further verify the efficacy, safety, and cost-effectiveness of NPWT in the treatment of pressure ulcers. Future researchers need to recognise the importance of complete and accurate reporting of clinically important outcomes such as the complete healing rate, healing time, and adverse events.\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 the medical literature for published and unpublished robust medical studies (randomised controlled studies) that assessed NPWT for treating pressure ulcers, with no restrictions on language, date of publication, or study setting. We compared and summarised their results, and rated our confidence in the evidence according to research methods, scale, and other factors." } ]

[ { "role": "user", "content": "Abstract: Background\nMultiparametric magnetic resonance imaging (MRI), with or without MRI-targeted biopsy, is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision-making.\nObjectives\nTo determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, the MRI pathway (MRI with or without MRI-targeted biopsy) and systematic biopsy as compared to template-guided biopsy as the reference standard in detecting clinically significant prostate cancer as the target condition, defined as International Society of Urological Pathology (ISUP) grade 2 or higher. Secondary target conditions were the detection of grade 1 and grade 3 or higher-grade prostate cancer, and a potential change in the number of biopsy procedures.\nSearch methods\nWe performed a comprehensive systematic literature search up to 31 July 2018. We searched CENTRAL, MEDLINE, Embase, eight other databases and one trials register.\nSelection criteria\nWe considered for inclusion any cross-sectional study if it investigated one or more index tests verified by the reference standard, or if it investigated the agreement between the MRI pathway and systematic biopsy, both performed in the same men. We included only studies on men who were biopsy naïve or who previously had a negative biopsy (or a mix of both). Studies involving MRI had to report on both MRI-positive and MRI-negative men. All studies had to report on the primary target condition.\nData collection and analysis\nTwo reviewers independently extracted data and assessed the risk of bias using the QUADAS-2 tool. To estimate test accuracy, we calculated sensitivity and specificity using the bivariate model. To estimate agreement between the MRI pathway and systematic biopsy, we synthesised detection ratios by performing random-effects meta-analyses. To estimate the proportions of participants with prostate cancer detected by only one of the index tests, we used random-effects multinomial or binary logistic regression models. For the main comparisions, we assessed the certainty of evidence using GRADE.\nMain results\nThe test accuracy analyses included 18 studies overall.\nMRI compared to template-guided biopsy: Based on a pooled sensitivity of 0.91 (95% confidence interval (CI): 0.83 to 0.95; 12 studies; low certainty of evidence) and a pooled specificity of 0.37 (95% CI: 0.29 to 0.46; 12 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI may result in 273 (95% CI: 249 to 285) true positives, 441 false positives (95% CI: 378 to 497), 259 true negatives (95% CI: 203 to 322) and 27 (95% CI: 15 to 51) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.\nMRI-targeted biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.80 (95% CI: 0.69 to 0.87; 8 studies; low certainty of evidence) and a pooled specificity of 0.94 (95% CI: 0.90 to 0.97; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI-targeted biopsy may result in 240 (95% CI: 207 to 261) true positives, 42 (95% CI: 21 to 70) false positives, 658 (95% CI: 630 to 679) true negatives and 60 (95% CI: 39 to 93) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.\nThe MRI pathway compared to template-guided biopsy: Based on a pooled sensitivity of 0.72 (95% CI: 0.60 to 0.82; 8 studies; low certainty of evidence) and a pooled specificity of 0.96 (95% CI: 0.94 to 0.98; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, the MRI pathway may result in 216 (95% CI: 180 to 246) true positives, 28 (95% CI: 14 to 42) false positives, 672 (95% CI: 658 to 686) true negatives and 84 (95% CI: 54 to 120) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations, inconsistency and imprecision.\nSystemic biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.63 (95% CI: 0.19 to 0.93; 4 studies; low certainty of evidence) and a pooled specificity of 1.00 (95% CI: 0.91 to 1.00; 4 studies; low certainty of evidence) using a baseline prevalence of 30%, systematic biopsy may result in 189 (95% CI: 57 to 279) true positives, 0 (95% CI: 0 to 63) false positives, 700 (95% CI: 637 to 700) true negatives and 111 (95% CI: 21 to 243) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.\nAgreement analyses: In a mixed population of both biopsy-naïve and prior-negative biopsy men comparing the MRI pathway to systematic biopsy, we found a pooled detection ratio of 1.12 (95% CI: 1.02 to 1.23; 25 studies). We found pooled detection ratios of 1.44 (95% CI 1.19 to 1.75; 10 studies) in prior-negative biopsy men and 1.05 (95% CI: 0.95 to 1.16; 20 studies) in biopsy-naïve men.\nAuthors' conclusions\nAmong the diagnostic strategies considered, the MRI pathway has the most favourable diagnostic accuracy in clinically significant prostate cancer detection. Compared to systematic biopsy, it increases the number of significant cancer detected while reducing the number of insignificant cancer diagnosed. The certainty in our findings was reduced by study limitations, specifically issues surrounding selection bias, as well as inconsistency. Based on these findings, further improvement of prostate cancer diagnostic pathways should be pursued.\n\nGiven the provided abstract, please respond to the following query: \"How reliable is the evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We rated the quality of evidence for the main findings of this review as low. Additional high-quality research is likely to change these findings." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of a Cochrane Review previously published in 2019.\nCatamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses.\nCatamenial epilepsy and seizure exacerbation is common in women with epilepsy. Women may not receive appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aims to address these issues to inform clinical practice and future research.\nObjectives\nTo evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.\nSearch methods\nWe searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.\nSelection criteria\nWe included RCTs and quasi-RCTs of blinded or open-label design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. We included the following types of interventions: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.\nData collection and analysis\nWe extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.\nMain results\nFollowing title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone, and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses.\nMeta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group.\nThe results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I2 = 0%) or treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I2 = 0%). No treatment withdrawals were reported from the norethisterone RCTs. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life.\nWe judged the evidence for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.\nAuthors' conclusions\nThis review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out.\nOur review highlights an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those women who do not have regular menses. Further clinical trials are needed in this area.\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": "Catamenial (menstrual) epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. There are specific times within the menstrual cycle when women are most at risk: in the days leading up to a menstrual period and during a menstrual period (perimenstrual or catamenial type 1 pattern); at the time of ovulation (catamenial type 2 pattern); and in the second half of their cycle (luteal phase, or catamenial type 3 pattern). The reason for this increased risk may relate to changes in the levels of progesterone (a hormone released by the ovaries) around the time of a menstrual period and oestrogen (a female sex hormone) surge around ovulation. Studies in animals have demonstrated that lower progesterone may affect how the brain reacts to the brain chemical gamma-Aminobutyric acid (GABA), which is important in preventing seizures. The link between high levels of oestrogen and risk of seizures remains unclear.\nCurrent treatment of catamenial epilepsy depends on whether a woman has regular or irregular menstrual periods. If a woman has regular periods, hormonal (e.g. progesterone supplements) and non-hormonal treatments (e.g. clobazam or acetazolamide) taken prior to and during a period may be used. In women who do not have regular periods, and who therefore cannot predict their period days, stopping periods using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) are treatment options.\nCatamenial epilepsy is common in women with epilepsy, and may have a significant negative impact on quality of life. Women may not receive appropriate treatment for their catamenial seizures. There is uncertainty regarding which treatment works best and when in the menstrual cycle treatments should be taken. There are also concerns about the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aimed to address these issues in order to inform clinical practice and future research." } ]

[ { "role": "user", "content": "Abstract: Background\nIgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a Cochrane review first published in 2003 and updated in 2015.\nObjectives\nTo determine the benefits and harms of immunosuppression strategies for the treatment of IgA nephropathy.\nSearch methods\nWe searched the Cochrane Kidney and Transplant Register of Studies up to 9 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs of treatment for IgA nephropathy in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents.\nData collection and analysis\nTwo authors independently assessed study risk of bias and extracted data. Estimates of treatment effect were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Risks of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE methodology.\nMain results\nFifty-eight studies involving 3933 randomised participants were included. Six studies involving children were eligible. Disease characteristics (kidney function and level of proteinuria) were heterogeneous across studies. Studies evaluating steroid therapy generally included patients with protein excretion of 1 g/day or more. Risk of bias within the included studies was generally high or unclear for many of the assessed methodological domains.\nIn patients with IgA nephropathy and proteinuria > 1 g/day, steroid therapy given for generally two to four months with a tapering course probably prevents the progression to ESKD compared to placebo or standard care (8 studies; 741 participants: RR 0.39, 95% CI 0.23 to 0.65; moderate certainty evidence). Steroid therapy may induce complete remission (4 studies, 305 participants: RR 1.76, 95% CI 1.03 to 3.01; low certainty evidence), prevent doubling of serum creatinine (SCr) (7 studies, 404 participants: RR 0.43, 95% CI 0.29 to 0.65; low certainty evidence), and may lower urinary protein excretion (10 studies, 705 participants: MD -0.58 g/24 h, 95% CI -0.84 to -0.33;low certainty evidence). Steroid therapy had uncertain effects on glomerular filtration rate (GFR), death, infection and malignancy. The risk of adverse events with steroid therapy was uncertain due to heterogeneity in the type of steroid treatment used and the rarity of events.\nCytotoxic agents (azathioprine (AZA) or cyclophosphamide (CPA) alone or with concomitant steroid therapy had uncertain effects on ESKD (7 studies, 463 participants: RR 0.63, 95% CI 0.33 to 1.20; low certainty evidence), complete remission (5 studies; 381 participants: RR 1.47, 95% CI 0.94 to 2.30; very low certainty evidence), GFR (any measure), and protein excretion. Doubling of serum creatinine was not reported.\nMycophenolate mofetil (MMF) had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, infection, and malignancy. Death was not reported.\nCalcineurin inhibitors compared with placebo or standard care had uncertain effects on complete remission, SCr, GFR, protein excretion, infection, and malignancy. ESKD and death were not reported.\nMizoribine administered with renin-angiotensin system inhibitor treatment had uncertain effects on progression to ESKD, complete remission, GFR, protein excretion, infection, and malignancy. Death and SCr were not reported.\nLeflunomide followed by a tapering course with oral prednisone compared to prednisone had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, and infection. Death and malignancy were not reported.\nEffects of other immunosuppressive regimens (including steroid plus non-immunosuppressive agents or mTOR inhibitors) were inconclusive primarily due to insufficient data from the individual studies in low or very low certainty evidence. The effects of treatments on death, malignancy, reduction in GFR at least of 25% and adverse events were very uncertain. Subgroup analyses to determine the impact of specific patient characteristics such as ethnicity or disease severity on treatment effectiveness were not possible.\nAuthors' conclusions\nIn moderate certainty evidence, corticosteroid therapy probably prevents decline in GFR or doubling of SCr in adults and children with IgA nephropathy and proteinuria. Evidence for treatment effects of immunosuppressive agents on death, infection, and malignancy is generally sparse or low-quality. Steroid therapy has uncertain adverse effects due to a paucity of studies. Available studies are few, small, have high risk of bias and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible due to a lack of studies. There is no evidence that other immunosuppressive agents including CPA, AZA, or MMF improve clinical outcomes in IgA nephropathy.\n\nGiven the provided abstract, please respond to the following query: \"Conclusions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Steroid therapy may prevent kidney failure in IgA nephropathy but the risks of serious infections are uncertain with treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with neuromuscular disorders (NMDs) may have weak respiratory (breathing) muscles which makes it difficult for them to effectively cough and clear mucus from the lungs. This places them at risk of recurrent chest infections and chronic lung disease. Mechanical insufflation-exsufflation (MI-E) is one of a number of techniques available to improve cough efficacy and mucus clearance.\nObjectives\nTo determine the efficacy and safety of MI-E in people with NMDs.\nSearch methods\nOn 7 October 2013, we searched the following databases from inception: the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, and EMBASE. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for ongoing trials. We conducted handsearches of reference lists and conference proceedings.\nSelection criteria\nWe considered randomised or quasi-randomised clinical trials, and randomised cross-over trials of MI-E used to assist airway clearance in people with a NMD and respiratory insufficiency. We considered comparisons of MI-E with no treatment, or alternative cough augmentation techniques.\nData collection and analysis\nTwo authors independently assessed trial eligibility, extracted data, and assessed risk of bias in included studies according to standard Cochrane methodology. The primary outcome was mortality throughout follow-up or at six months follow-up.\nMain results\nFive studies with a total of 105 participants were found to be eligible for inclusion in this review. All included trials were short-term studies (two days or less), measuring immediate effects of the interventions. There was insufficient detail in the reports to assess methods of randomisation and allocation concealment. All five studies were at a high risk of bias from lack of blinding. The studies did not report on mortality, morbidity, quality of life, serious adverse events or any of the other prespecified outcomes. One study was a randomised cross-over trial conducted over two days, in which investigators applied two interventions twice daily in randomly assigned order, with a reverse cross-over the following day. Four studies applied multiple interventions for cough augmentation to each participant, in random order. One study reported fatigue as an adverse effect of MI-E, using a visual analogue scale. Peak cough expiratory flow (PCEF) was the most common outcome measure and was reported in four studies. Based on three studies, MI-E may improve PCEF compared to an unassisted cough. All interventions increased PCEF to the critical level necessary for mucus clearance. The included studies did not clearly show that MI-E improves cough expiratory flow more than other cough augmentation techniques. Based on one study, which was at risk of assessor bias, the addition of MI-E may reduce treatment time when added to a standard airway clearance regimen with manually assisted cough. MI-E appeared to be as well tolerated as other cough augmentation techniques, based on three studies which reported comfort visual analogue scores.\nAuthors' conclusions\nThe results of this review do not provide sufficient evidence on which to base clinical practice as we were unable to address important short- and long-term outcomes, including adverse effects of MI-E. There is currently insufficient evidence for or against the use of MI-E in people with NMDs. Further randomised controlled clinical trials are needed to test the safety and efficacy of MI-E.\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": "People with neuromuscular disorders (NMDs) sometimes have weak breathing muscles. This can make it difficult for them to cough and clear mucus from the lungs well, putting them at risk of repeated chest infections and ongoing lung disease. MI-E is one of a number of methods used to improve cough and mucus clearance. MI-E is given through a mask, mouthpiece, or via a tracheostomy (an opening in the neck into the windpipe). MI-E acts like a cough by first pushing air into the lungs when the person breathes in (insufflation), then sucking it out again (exsufflation)." } ]

[ { "role": "user", "content": "Abstract: Background\nThe detection and diagnosis of caries at the initial (non-cavitated) and moderate (enamel) levels of severity is fundamental to achieving and maintaining good oral health and prevention of oral diseases. An increasing array of methods of early caries detection have been proposed that could potentially support traditional methods of detection and diagnosis. Earlier identification of disease could afford patients the opportunity of less invasive treatment with less destruction of tooth tissue, reduce the need for treatment with aerosol-generating procedures, and potentially result in a reduced cost of care to the patient and to healthcare services.\nObjectives\nTo determine the diagnostic accuracy of different visual classification systems for the detection and diagnosis of non-cavitated coronal dental caries for different purposes (detection and diagnosis) and in different populations (children or adults).\nSearch methods\nCochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 30 April 2020); Embase Ovid (1980 to 30 April 2020); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 30 April 2020); and the World Health Organization International Clinical Trials Registry Platform (to 30 April 2020). We studied reference lists as well as published systematic review articles.\nSelection criteria\nWe included diagnostic accuracy study designs that compared a visual classification system (index test) with a reference standard (histology, excavation, radiographs). This included cross-sectional studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. Studies reporting at both the patient or tooth surface level were included. In vitro and in vivo studies were considered. Studies that explicitly recruited participants with caries into dentine or frank cavitation were excluded. We also excluded studies that artificially created carious lesions and those that used an index test during the excavation of dental caries to ascertain the optimum depth of excavation.\nData collection and analysis\nWe extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on QUADAS-2 specific to the review context. Estimates of diagnostic accuracy were determined using the bivariate hierarchical method to produce summary points of sensitivity and specificity with 95% confidence intervals (CIs) and regions, and 95% prediction regions. The comparative accuracy of different classification systems was conducted based on indirect comparisons. Potential sources of heterogeneity were pre-specified and explored visually and more formally through meta-regression.\nMain results\nWe included 71 datasets from 67 studies (48 completed in vitro) reporting a total of 19,590 tooth sites/surfaces. The most frequently reported classification systems were the International Caries Detection and Assessment System (ICDAS) (36 studies) and Ekstrand-Ricketts-Kidd (ERK) (15 studies). In reporting the results, no distinction was made between detection and diagnosis. Only two studies were at low risk of bias across all four domains, and 15 studies were at low concern for applicability across all three domains. The patient selection domain had the highest proportion of high risk of bias studies (49 studies). Four studies were assessed at high risk of bias for the index test domain, nine for the reference standard domain, and seven for the flow and timing domain. Due to the high number of studies on extracted teeth concerns regarding applicability were high for the patient selection and index test domains (49 and 46 studies respectively).\nStudies were synthesised using a hierarchical bivariate method for meta-analysis. There was substantial variability in the results of the individual studies: sensitivities ranged from 0.16 to 1.00 and specificities from 0 to 1.00. For all visual classification systems the estimated summary sensitivity and specificity point was 0.86 (95% CI 0.80 to 0.90) and 0.77 (95% CI 0.72 to 0.82) respectively, diagnostic odds ratio (DOR) 20.38 (95% CI 14.33 to 28.98). In a cohort of 1000 tooth surfaces with 28% prevalence of enamel caries, this would result in 40 being classified as disease free when enamel caries was truly present (false negatives), and 163 being classified as diseased in the absence of enamel caries (false positives). The addition of test type to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi2(4) = 3.78, P = 0.44), nor did the addition of primary or permanent dentition (Chi2(2) = 0.90, P = 0.64). The variability of results could not be explained by tooth surface (occlusal or approximal), prevalence of dentinal caries in the sample, nor reference standard. Only one study intentionally included restored teeth in its sample and no studies reported the inclusion of sealants.\nWe rated the certainty of the evidence as low, and downgraded two levels in total for risk of bias due to limitations in the design and conduct of the included studies, indirectness arising from the in vitro studies, and inconsistency of results.\nAuthors' conclusions\nWhilst the confidence intervals for the summary points of the different visual classification systems indicated reasonable performance, they do not reflect the confidence that one can have in the accuracy of assessment using these systems due to the considerable unexplained heterogeneity evident across the studies. The prediction regions in which the sensitivity and specificity of a future study should lie are very broad, an important consideration when interpreting the results of this review. Should treatment be provided as a consequence of a false-positive result then this would be non-invasive, typically the application of fluoride varnish where it was not required, with low potential for an adverse event but healthcare resource and finance costs.\nDespite the robust methodology applied in this comprehensive review, the results should be interpreted with some caution due to shortcomings in the design and execution of many of the included studies. Studies to determine the diagnostic accuracy of methods to detect and diagnose caries in situ are particularly challenging. Wherever possible future studies should be carried out in a clinical setting, to provide a realistic assessment of performance within the oral cavity with the challenges of plaque, tooth staining, and restorations, and consider methods to minimise bias arising from the use of imperfect reference standards in clinical studies.\n\nGiven the provided abstract, please respond to the following query: \"How up-to-date is this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Review authors searched for and used studies published up to 30 April 2020." } ]

[ { "role": "user", "content": "Abstract: Background\nHypothermia has been used in the treatment of brain injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials.\nObjectives\nTo determine the effect of mild hypothermia for traumatic brain injury (TBI) on mortality, long-term functional outcomes and complications.\nSearch methods\nWe ran and incorporated studies from database searches to 21 March 2016. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), PubMed, ISI Web of science (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registers, and screened reference lists. We also re-ran these searches pre-publication in June 2017; the result from this search is presented in 'Studies awaiting classification'.\nSelection criteria\nWe included randomised controlled trials of participants with closed TBI requiring hospitalisation who were treated with hypothermia to a maximum of 35 ºC for at least 12 consecutive hours. Treatment with hypothermia was compared to maintenance with normothermia (36.5 to 38 ºC).\nData collection and analysis\nTwo review authors assessed data on mortality, unfavourable outcomes according to the Glasgow Outcome Scale, and pneumonia.\nMain results\nWe included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re-assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification.\nStudies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty-three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability), and 14 studies reported pneumonia. Visual inspection of the results for these outcomes showed inconsistencies among studies, with differences in the direction of effect, and we did not pool these data for meta-analysis. We considered duration of hypothermia therapy and the length of follow-up in collected data for these subgroups; differences in study data remained such that we did not perform meta-analysis.\nStudies were generally poorly reported and we were unable to assess risk of bias adequately. Heterogeneity was evident both in the trial designs and participant inclusion. Inconsistencies in results may be explained by heterogeneity among study participants or bias introduced by individual study methodology but we did not explore this in detail in subgroup or sensitivity analyses. We used the GRADE approach to judge the quality of the evidence for each outcome and downgraded the evidence for mortality and unfavourable outcome to very low. We downgraded the evidence for the pneumonia outcome to low.\nAuthors' conclusions\nDespite a large number studies, there remains no high-quality evidence that hypothermia is beneficial in the treatment of people with TBI. Further research, which is methodologically robust, is required in this field to establish the effect of hypothermia for people with TBI.\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": "Hypothermia has been used for many years to treat people who have had a severe brain injury. This involves cooling the head or the whole body to a temperature below normal body temperature. We aimed to assess whether people treated with hypothermia after a brain injury are less likely to die or have a poor outcome (which we defined as death, coma or severe disability) and whether using hypothermia might increase the risk of a severe chest infection called pneumonia." } ]

[ { "role": "user", "content": "Abstract: Background\nAcupuncture has a history of traditional use in China for women's health conditions including premenstrual syndrome (PMS), but its effectiveness for this condition remains unclear. This review examined the available evidence supporting the use of acupuncture or acupressure to treat PMS.\nObjectives\nTo evaluate the effectiveness and safety of acupuncture or acupressure for women with PMS or premenstrual dysphoric disorder (PMDD).\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Specialised Register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, AMED, PsycINFO, CINAHL (from inception to 21 September 2017), two clinical trial databases (from their inception to 21 September 2017), and four electronic databases in China (from their inception to 15 October 2017): Chinese Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), VIP information/ Chinese Scientific Journals database and WANFANG. Reference lists from included articles were handsearched.\nSelection criteria\nWe included studies if they randomised women with PMS and associated disorders (PMDD and late luteal phase dysphoric disorder/LPDD) to receive acupuncture or acupressure versus sham, usual care/waiting-list control or pharmaceutical interventions mentioned by the International Society for Premenstrual Disorders (ISPMD). If acupuncture or acupressure were combined with another therapy, these studies were also included where the additional therapy was the same in both groups. Cross-over studies were eligible for inclusion, but only data from the first phase could be used.\nData collection and analysis\nTwo review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data from each study. Study authors were contacted for missing information. The quality of the evidence was assessed using GRADE. Our primary outcomes were overall premenstrual symptoms and adverse events. Secondary outcomes included specific PMS symptoms, response rate and quality of life.\nMain results\nFive trials (277 women) were included in this review. No trials compared acupuncture or acupressure versus other active treatments. The number of treatment sessions ranged from seven to 28. The quality of the evidence ranged from low to very low quality, the main limitations being imprecision due to small sample sizes and risk of bias related to detection bias and selective reporting.\nAcupuncture versus sham acupuncture\nAcupuncture may provide a greater reduction in mood-related PMS symptoms (mean difference (MD) -9.03, 95% confidence interval (CI) -10.71 to -7.35, one randomised controlled trial (RCT), n = 67, low-quality evidence) and in physical PMS symptoms (MD -9.11, 95% CI -10.82 to -7.40, one RCT, n = 67, low-quality evidence) than sham acupuncture, as measured by the Daily Record of Severity of Problems scale (DRSP). The evidence suggests that if women have a mood score of 51.91 points with sham acupuncture, their score with acupuncture would be between 10.71 and 7.35 points lower and if women have a physical score of 46.11 points, their score with acupuncture would be between 10.82 and 7.4 points lower.There was insufficient evidence to determine whether there was any difference between the groups in the rate of adverse events (risk ratio (RR) 1.74, 95% CI 0.39 to 7.76, three RCTs, n = 167, I2 = 0%, very low-quality evidence).\nSpecific PMS symptoms were not reported\nThere may be little or no difference between the groups in response rates. Use of a fixed-effect model suggested a higher response rate in the acupuncture group than in the sham group (RR 2.59, 95% CI 1.71 to 3.92; participants = 100; studies = 2; I2 = 82%), but owing to the high heterogeneity we tested the effect of using a random-effects model, which provided no clear evidence of benefit for acupuncture (RR 4.22, 95% CI 0.45 to 39.88, two RCTs, n = 100, I2 = 82%, very low-quality evidence).\nAcupuncture may improve quality of life (measured by the WHOQOL-BREF) compared to sham (MD 2.85, 95% CI 1.47 to 4.23, one RCT, n = 67, low-quality evidence).\nAcupuncture versus no treatment\nDue to the very low quality of the evidence, we are uncertain whether acupuncture reduces PMS symptoms compared to a no treatment control (MD -13.60, 95% CI -15.70 to -11.50, one RCT, n = 14).\nNo adverse events were reported in either group.\nNo data were available on specific PMS symptoms, response rate or quality of life outcomes.\nAcupressure versus sham acupressure\nWe found low-quality evidence that acupressure may reduce the number of women with moderate to severe PMS symptoms at the end of the trial compared to sham acupressure (RR 0.64 95% CI 0.52 to 0.79, one RCT, n = 90, low-quality evidence). The evidence suggests that if 97 women out of 100 in the sham acupressure group had moderate to severe PMS symptoms, the number of women in the acupressure group with moderate to severe symptoms would be 50 to 76 women.\nAcupressure may improve both physical (MD 24.3, 95% CI 17.18 to 31.42, one RCT, n = 90, low-quality evidence) and mental (MD 17.17, 95% CI 13.08 to 21.26, one RCT, n = 90, low-quality evidence) quality of life.\nNo data were available on adverse events, specific symptoms or response rates.\nAuthors' conclusions\nThe limited evidence available suggests that acupuncture and acupressure may improve both physical and psychological symptoms of PMS when compared to a sham control. There was insufficient evidence to determine whether there was a difference between the groups in rates of adverse events.There is no evidence comparing acupuncture or acupressure versus current ISPMD recommended treatments for PMS such as selective serotonin reuptake inhibitors (SSRIs). Further research is required, using validated outcome measures for PMS, adequate blinding and suitable comparator groups reflecting current best practice.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found five randomised controlled trials including 277 women that examined the effect of acupuncture or acupressure in women with PMS. The evidence is current to September 2017. We also ran a smaller search in November 2017 to see if we had missed any recently published studies. Three trials compared acupuncture with sham acupuncture, one compared acupuncture with no treatment and one compared acupressure with sham acupressure." } ]

[ { "role": "user", "content": "Abstract: Background\nScreening mammography can detect breast cancer at an early stage. Supporters of adding ultrasonography to the screening regimen consider it a safe and inexpensive approach to reduce false-negative rates during screening. However, those opposed to it argue that performing supplemental ultrasonography will also increase the rate of false-positive findings and can lead to unnecessary biopsies and treatments.\nObjectives\nTo assess the comparative effectiveness and safety of mammography in combination with breast ultrasonography versus mammography alone for breast cancer screening for women at average risk of breast cancer.\nSearch methods\nWe searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov up until 3 May 2021.\nSelection criteria\nFor efficacy and harms, we considered randomised controlled trials (RCTs) and controlled non-randomised studies enrolling at least 500 women at average risk for breast cancer between the ages of 40 and 75.\nWe also included studies where 80% of the population met our age and breast cancer risk inclusion criteria.\nData collection and analysis\nTwo review authors screened abstracts and full texts, assessed risk of bias, and applied the GRADE approach. We calculated the risk ratio (RR) with 95% confidence intervals (CI) based on available event rates. We conducted a random-effects meta-analysis.\nMain results\nWe included eight studies: one RCT, two prospective cohort studies, and five retrospective cohort studies, enrolling 209,207 women with a follow-up duration from one to three years. The proportion of women with dense breasts ranged from 48% to 100%. Five studies used digital mammography; one study used breast tomosynthesis; and two studies used automated breast ultrasonography (ABUS) in addition to mammography screening. One study used digital mammography alone or in combination with breast tomosynthesis and ABUS or handheld ultrasonography. Six of the eight studies evaluated the rate of cancer cases detected after one screening round, whilst two studies screened women once, twice, or more.\nNone of the studies assessed whether mammography screening in combination with ultrasonography led to lower mortality from breast cancer or all-cause mortality. High certainty evidence from one trial showed that screening with a combination of mammography and ultrasonography detects more breast cancer than mammography alone. The J-START (Japan Strategic Anti-cancer Randomised Trial), enrolling 72,717 asymptomatic women, had a low risk of bias and found that two additional breast cancers per 1000 women were detected over two years with one additional ultrasonography than with mammography alone (5 versus 3 per 1000; RR 1.54, 95% CI 1.22 to 1.94). Low certainty evidence showed that the percentage of invasive tumours was similar, with no statistically significant difference between the two groups (69.6% (128 of 184) versus 73.5% (86 of 117); RR 0.95, 95% CI 0.82 to 1.09). However, positive lymph node status was detected less frequently in women with invasive cancer who underwent mammography screening in combination with ultrasonography than in women who underwent mammography alone (18% (23 of 128) versus 34% (29 of 86); RR 0.53, 95% CI 0.33 to 0.86; moderate certainty evidence). Further, interval carcinomas occurred less frequently in the group screened by mammography and ultrasonography compared with mammography alone (5 versus 10 in 10,000 women; RR 0.50, 95% CI 0.29 to 0.89; 72,717 participants; high certainty evidence). False-negative results were less common when ultrasonography was used in addition to mammography than with mammography alone: 9% (18 of 202) versus 23% (35 of 152; RR 0.39, 95% CI 0.23 to 0.66; moderate certainty evidence). However, the number of false-positive results and necessary biopsies were higher in the group with additional ultrasonography screening. Amongst 1000 women who do not have cancer, 37 more received a false-positive result when they participated in screening with a combination of mammography and ultrasonography than with mammography alone (RR 1.43, 95% CI 1.37 to 1.50; high certainty evidence). Compared to mammography alone, for every 1000 women participating in screening with a combination of mammography and ultrasonography, 27 more women will have a biopsy (RR 2.49, 95% CI 2.28 to 2.72; high certainty evidence). Results from cohort studies with methodological limitations confirmed these findings.\nA secondary analysis of the J-START provided results from 19,213 women with dense and non-dense breasts. In women with dense breasts, the combination of mammography and ultrasonography detected three more cancer cases (0 fewer to 7 more) per 1000 women screened than mammography alone (RR 1.65, 95% CI 1.0 to 2.72; 11,390 participants; high certainty evidence). A meta-analysis of three cohort studies with data from 50,327 women with dense breasts supported this finding, showing that mammography and ultrasonography combined led to statistically significantly more diagnosed cancer cases compared to mammography alone (RR 1.78, 95% CI 1.23 to 2.56; 50,327 participants; moderate certainty evidence). For women with non-dense breasts, the secondary analysis of the J-START study demonstrated that more cancer cases were detected when adding ultrasound to mammography screening compared to mammography alone (RR 1.93, 95% CI 1.01 to 3.68; 7823 participants; moderate certainty evidence), whilst two cohort studies with data from 40,636 women found no statistically significant difference between the two screening methods (RR 1.13, 95% CI 0.85 to 1.49; low certainty evidence).\nAuthors' conclusions\nBased on one study in women at average risk of breast cancer, ultrasonography in addition to mammography leads to more screening-detected breast cancer cases. For women with dense breasts, cohort studies more in line with real-life clinical practice confirmed this finding, whilst cohort studies for women with non-dense breasts showed no statistically significant difference between the two screening interventions.\nHowever, the number of false-positive results and biopsy rates were higher in women receiving additional ultrasonography for breast cancer screening. None of the included studies analysed whether the higher number of screen-detected cancers in the intervention group resulted in a lower mortality rate compared to mammography alone. Randomised controlled trials or prospective cohort studies with a longer observation period are needed to assess the effects of the two screening interventions on morbidity and mortality.\n\nGiven the provided abstract, please respond to the following query: \"Gap in the evidence: no study examined the effect of additional ultrasonography screening on death\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "To determine whether routine screening with mammography and ultrasonography is beneficial, a study (ideally a randomised controlled trial (RCT), that is a study in which participants are randomly assigned to one of two or more treatment groups) comparing whether disease progression and death rates differ between methods is essential. None of the studies, which followed women for one to three years, lasted long enough to determine whether more cancer cases detected during screening with mammography and ultrasonography lead to reductions in disease and death." } ]

[ { "role": "user", "content": "Abstract: Background\nOccupational irritant hand dermatitis (OIHD) causes significant functional impairment, disruption of work, and discomfort in the working population. Different preventive measures such as protective gloves, barrier creams and moisturisers can be used, but it is not clear how effective these are. This is an update of a Cochrane review which was previously published in 2010.\nObjectives\nTo assess the effects of primary preventive interventions and strategies (physical and behavioural) for preventing OIHD in healthy people (who have no hand dermatitis) who work in occupations where the skin is at risk of damage due to contact with water, detergents, chemicals or other irritants, or from wearing gloves.\nSearch methods\nWe updated our searches of the following databases to January 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLlNE, and Embase. We also searched five trials registers and checked the bibliographies of included studies for further references to relevant trials. We handsearched two sets of conference proceedings.\nSelection criteria\nWe included parallel and cross-over randomised controlled trials (RCTs) which examined the effectiveness of barrier creams, moisturisers, gloves, or educational interventions compared to no intervention for the primary prevention of OIHD under field conditions.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. The primary outcomes were signs and symptoms of OIHD developed during the trials, and the frequency of treatment discontinuation due to adverse effects.\nMain results\nWe included nine RCTs involving 2888 participants without occupational irritant hand dermatitis (OIHD) at baseline. Six studies, including 1533 participants, investigated the effects of barrier creams, moisturisers, or both. Three studies, including 1355 participants, assessed the effectiveness of skin protection education on the prevention of OIHD. No studies were eligible that investigated the effects of protective gloves. Among each type of intervention, there was heterogeneity concerning the criteria for assessing signs and symptoms of OIHD, the products, and the occupations. Selection bias, performance bias, and reporting bias were generally unclear across all studies. The risk of detection bias was low in five studies and high in one study. The risk of other biases was low in four studies and high in two studies.\nThe eligible trials involved a variety of participants, including: metal workers exposed to cutting fluids, dye and print factory workers, gut cleaners in swine slaughterhouses, cleaners and kitchen workers, nurse apprentices, hospital employees handling irritants, and hairdressing apprentices. All studies were undertaken at the respective work places. Study duration ranged from four weeks to three years. The participants' ages ranged from 16 to 67 years.\nMeta-analyses for barrier creams, moisturisers, a combination of both barrier creams and moisturisers, or skin protection education showed imprecise effects favouring the intervention. Twenty-nine per cent of participants who applied barrier creams developed signs of OIHD, compared to 33% of the controls, so the risk may be slightly reduced with this measure (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.06; 999 participants; 4 studies; low-quality evidence). However, this risk reduction may not be clinically important. There may be a clinically important protective effect with the use of moisturisers: in the intervention groups, 13% of participants developed symptoms of OIHD compared to 19% of the controls (RR 0.71, 95% CI 0.46 to 1.09; 507 participants; 3 studies; low-quality evidence). Likewise, there may be a clinically important protective effect from using a combination of barrier creams and moisturisers: 8% of participants in the intervention group developed signs of OIHD, compared to 13% of the controls (RR 0.68, 95% CI 0.33 to 1.42; 474 participants; 2 studies; low-quality evidence). We are uncertain whether skin protection education reduces the risk of developing signs of OIHD (RR 0.76, 95% CI 0.54 to 1.08; 1355 participants; 3 studies; very low-quality evidence). Twenty-one per cent of participants who received skin protection education developed signs of OIHD, compared to 28% of the controls.\nNone of the studies addressed the frequency of treatment discontinuation due to adverse effects of the products directly. However, in three studies of barrier creams, the reasons for withdrawal from the studies were unrelated to adverse effects. Likewise, in one study of moisturisers plus barrier creams, and in one study of skin protection education, reasons for dropout were unrelated to adverse effects. The remaining studies (one to two in each comparison) reported dropouts without stating how many of them may have been due to adverse reactions to the interventions. We judged the quality of this evidence as moderate, due to the indirectness of the results. The investigated interventions to prevent OIHD probably cause few or no serious adverse effects.\nAuthors' conclusions\nMoisturisers used alone or in combination with barrier creams may result in a clinically important protective effect, either in the long- or short-term, for the primary prevention of OIHD. Barrier creams alone may have slight protective effect, but this does not appear to be clinically important. The results for all of these comparisons were imprecise, and the low quality of the evidence means that our confidence in the effect estimates is limited. For skin protection education, the results varied substantially across the trials, the effect was imprecise, and the pooled risk reduction was not large enough to be clinically important. The very low quality of the evidence means that we are unsure as to whether skin protection education reduces the risk of developing OIHD. The interventions probably cause few or no serious adverse effects.\nWe conclude that at present there is insufficient evidence to confidently assess the effectiveness of interventions used in the primary prevention of OIHD. This does not necessarily mean that current measures are ineffective. Even though the update of this review included larger studies of reasonable quality, there is still a need for trials which apply standardised measures for the detection of OIHD in order to determine the effectiveness of the different prevention strategies.\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": "Some of the preventive measures may reduce the risk of hand skin irritations. However, there were too few studies to be sure of this. The studies were too different from each other to combine in a meaningful way, and the results were too imprecise. Our results are therefore still debatable.\nVarious barrier creams, moisturisers, and skin protection education programs were investigated. It is possible that barrier creams may slightly reduce the risk of developing OIHD. This result was based on four studies. In these studies, 29% of people who applied barrier creams developed hand skin irritations. In the control group, who did not apply barrier creams, 33% developed hand skin irritations. The results of three studies showed that moisturisers may reduce the risk of developing OIHD by a useful amount. Thirteen per cent of the people who used moisturisers developed hand skin irritations, compared to 19% of those who did not use moisturisers. Two studies showed that using a combination of barrier creams and moisturisers may reduce the risk of developing OIHD by a useful amount. Eight per cent of the people who used moisturisers and barrier creams developed hand skin irritations, compared to 13% of the control group. Based on three studies, we are uncertain whether skin protection education reduces the risk of developing OIHD. In these studies, 21% of the people who received skin protection education developed hand skin irritations, compared to 28% of the people in the control group.\nThe safety and tolerability of these measures were not systematically addressed in these studies. However, no serious reactions to the treatments were reported. Mild reactions like itching or reddening of the skin were reported for only few people who applied the barrier creams or moisturisers. The measures to prevent hand skin irritations probably cause only few or no serious adverse effects." } ]

[ { "role": "user", "content": "Abstract: Background\nChoroidal neovascularisation (CNV) is a common complication of pathological myopia. Once developed, most eyes with myopic CNV (mCNV) experience a progression to macular atrophy, which leads to irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) therapy is used to treat diseases characterised by neovascularisation and is increasingly used to treat mCNV.\nObjectives\nTo assess the effects of anti-vascular endothelial growth factor (anti-VEGF) therapy for choroidal neovascularisation (CNV), compared with other treatments, sham treatment or no treatment, in people with pathological myopia.\nSearch methods\nWe searched a number of electronic databases including CENTRAL and Ovid MEDLINE, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP). We did not use any date or language restrictions in the electronic searches for trials. Electronic databases were last searched on 16 June 2016.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs comparing anti-VEGF therapy with another treatment (e.g. photodynamic therapy (PDT) with verteporfin, laser photocoagulation, macular surgery, another anti-VEGF), sham treatment or no treatment in participants with mCNV.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Two authors independently screened records, extracted data, and assessed risk of bias. We contacted trial authors for additional data. We analysed outcomes as risk ratios (RRs) or mean differences (MDs). We graded the certainty of the evidence using GRADE.\nMain results\nThe present review included six studies which provided data on the comparison between anti-VEGF with PDT, laser, sham treatment and another anti-VEGF treatment, with 594 participants with mCNV. Three trials compared bevacizumab or ranibizumab with PDT, one trial compared bevacizumab with laser, one trial compared aflibercept with sham treatment, and two trials compared bevacizumab with ranibizumab. Pharmaceutical companies conducted two trials. The trials were conducted at multiple clinical centres across three continents (Europe, Asia and North America). In all these six trials, one eye for each participant was included in the study.\nWhen compared with PDT, people treated with anti-VEGF agents (ranibizumab (one RCT), bevacizumab (two RCTs)), were more likely to regain vision. At one year of follow-up, the mean visual acuity (VA) in participants treated with anti-VEGFs was -0.14 logMAR better, equivalent of seven Early Treatment Diabetic Retinopathy Study (ETDRS) letters, compared with people treated with PDT (95% confidence interval (CI) -0.20 to -0.08, 3 RCTs, 263 people, low-certainty evidence). The RR for proportion of participants gaining 3+ lines of VA was 1.86 (95% CI 1.27 to 2.73, 2 RCTs, 226 people, moderate-certainty evidence). At two years, the mean VA in people treated with anti-VEGFs was -0.26 logMAR better, equivalent of 13 ETDRS letters, compared with people treated with PDT (95% CI -0.38 to -0.14, 2 RCTs, 92 people, low-certainty evidence). The RR for proportion of people gaining 3+ lines of VA at two years was 3.43 (95% CI 1.37 to 8.56, 2 RCTs, 92 people, low-certainty evidence). People treated with anti-VEGFs showed no obvious reduction (improvement) in central retinal thickness at one year compared with people treated with PDT (MD -17.84 μm, 95% CI -41.98 to 6.30, 2 RCTs, 226 people, moderate-certainty evidence). There was low-certainty evidence that people treated with anti-VEGF were more likely to have CNV angiographic closure at 1 year (RR 1.24, 95% CI 0.99 to 1.54, 2 RCTs, 208 people). One study allowed ranibizumab treatment as of month 3 in participants randomised to PDT, which may have led to an underestimate of the benefits of anti-VEGF treatment.\nWhen compared with laser photocoagulation, there was more improvement in VA among bevacizumab-treated people than among laser-treated people after one year (MD -0.22 logMAR, equivalent of 11 ETDRS letters, 95% CI -0.43 to -0.01, 1 RCT, 36 people, low-certainty evidence) and after two years (MD -0.29 logMAR, equivalent of 14 ETDRS letters, 95% CI -0.50 to -0.08, 1 RCT, 36 people, low-certainty evidence).\nWhen compared with sham treatment, people treated with aflibercept had better vision at one year (MD -0.19 logMAR, equivalent of 9 ETDRS letters, 95% CI -0.27 to -0.12, 1 RCT, 121 people, moderate-certainty evidence). The fact that this study allowed for aflibercept treatment at 6 months in the control group might cause an underestimation of the benefit with anti-VEGF.\nPeople treated with ranibizumab had similar improvement in VA recovery compared with people treated with bevacizumab after one year (MD -0.02 logMAR, equivalent of 1 ETDRS letter, 95% CI -0.11 to 0.06, 2 RCTs, 80 people, moderate-certainty evidence).\nOf the included six studies, two studies reported no adverse events in either group and two industry-sponsored studies reported both systemic and ocular adverse events. In the control group, there were no systemic or ocular adverse events reported in 149 participants. Fifteen people reported systemic serious adverse events among 359 people treated with anti-VEGF agents (15/359, 4.2%). Five people reported ocular adverse events among 359 people treated with anti-VEGF agents (5/359, 1.4%). The number of adverse events was low, and the estimate of RR was uncertain regarding systemic serious adverse events (4 RCTs, 15 events in 508 people, RR 4.50, 95% CI 0.60 to 33.99, very low-certainty evidence) and serious ocular adverse events (4 RCTs, 5 events in 508 people, RR 1.82, 95% CI 0.23 to 14.71, very low-certainty evidence). There were no reports of mortality or cases of endophthalmitis or retinal detachment.\nThere was sparse reporting of data for vision-related quality of life (in favour of anti-VEGF) in only one trial at one year of follow-up. The studies did not report data for other outcomes, such as percentage of participants with newly developed chorioretinal atrophy.\nAuthors' conclusions\nThere is low to moderate-certainty evidence from RCTs for the efficacy of anti-VEGF agents to treat mCNV at one year and two years. Moderate-certainty evidence suggests ranibizumab and bevacizumab are equivalent in terms of efficacy. Adverse effects occurred rarely and the trials included here were underpowered to assess these. Future research should be focused on the efficacy and safety of different drugs and treatment regimens, the efficacy on different location of mCNV, as well as the effects on practice in the real world.\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": "Myopia occurs when the eyeball becomes too long. If the myopia is severe, sometimes the retina (light-sensitive tissue at the back of the eye) becomes too thin and new blood vessels grow. These new blood vessels can leak and cause vision loss.\nAnti-vascular endothelial growth factor (anti-VEGF) is a drug that may slow down the growth of these new vessels. Doctors can inject anti-VEGF into the eye of people who have severe myopia and signs of new blood vessels growing at the back of the eye. This may prevent vision loss." } ]

[ { "role": "user", "content": "Abstract: Background\nOrthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.\nObjectives\nTo identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.\nSearch methods\nWe searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.\nSelection criteria\nWe included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.\nData collection and analysis\nWe used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.\nMain results\nWe included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs.\nWe found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants).\nFor orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal.\nObservational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.\nAuthors' conclusions\nThe evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.\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": "Orthostatic, or postural, hypotension is a condition in which blood pressure falls when moving from a seated or lying flat position to a standing position. Regular, reproducible symptomatic postural hypotension is an abnormal bodily response.\nOrthostatic hypotension can be due to the heart failing to supply enough blood to the brain after a change in position. It can also stem from failures in blood vessel response to a change in position, for which there are many causes. Medications, dehydration, poor physical health and age all contribute to the problem. It is more common among people older than 65 and increases with age.\nSymptoms include dizziness, lightheadedness and feeling faint. Some people have more general complaints such as weakness, fatigue, headache, visual blurring, trouble thinking, leg buckling, neck pain, breathlessness or chest pain. Some episodes of postural hypotension result in a faint, fall or 'black-out'. Symptoms decrease when blood pressure returns to normal, typically when the person sits, lies or, occasionally, falls down.\nFludrocortisone acetate is a man-made steroid that increases blood volume and improves the ability of blood vessels to respond to changes in position. Fludrocortisone is taken by mouth. It has also been associated with high blood pressure, swelling, congestive heart failure, low potassium (a blood salt), headache, sleeplessness and increased sweating. Other common medications for postural hypotension include midodrine and droxidopa.\nBecause postural hypotension results from many underlying diseases and conditions, it is important to understand the effect of fludrocortisone depending upon the underlying physical cause (heart pumping action or blood vessel reaction), by other underlying disease (Parkinson disease, diabetes, etc.) and by age. In this way, we can better understand whether different groups of people will be helped or harmed by using this medication.\nWe reviewed all the evidence about the effects of use of fludrocortisone in people with orthostatic hypotension." } ]

[ { "role": "user", "content": "Abstract: Background\nMaternal pushing during the second stage of labour is an important and indispensable contributor to the involuntary expulsive force developed by uterine contraction. There is no consensus on an ideal strategy to facilitate these expulsive efforts and there are contradictory results about the influence on the mother and fetus.\nObjectives\nTo evaluate the benefits and possible disadvantages of different kinds of techniques regarding maternal pushing/breathing during the expulsive stage of labour on maternal and fetal outcomes.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth's Trials Register (19 September 2016) and reference lists of retrieved studies.\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-RCTs assessing the effects of pushing/bearing down techniques (type and/or timing) performed during the second stage of labour on maternal and neonatal outcomes. Cluster-RCTs were eligible for inclusion, but none were identified. Studies using a cross-over design and those published in abstract form only were not eligible for inclusion in this review.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. Data were checked for accuracy.\nMain results\nIn this updated review, we included 21 studies in total, eight (884 women) comparing spontaneous pushing versus directed pushing, with or without epidural analgesia and 13 (2879 women) comparing delayed pushing versus immediate pushing with epidural analgesia. Our GRADE assessments of evidence ranged from moderate to very low quality; the main reasons for downgrading were study design limitations and imprecision of effect estimates. Overall, the included studies varied in their risk of bias; most were judged to be at unclear risk of bias.\nComparison 1: types of pushing: spontaneous pushing versus directed pushing\nThere was no clear difference in the duration of the second stage of labour (mean difference (MD) 10.26 minutes; 95% confidence interval (CI) -1.12 to 21.64 minutes, six studies, 667 women, random-effects, I² = 81%) (very low-quality evidence). There was no clear difference in 3rd or 4th degree perineal laceration (risk ratio (RR) 0.87; 95% CI 0.45 to 1.66, one study, 320 women) (low-quality evidence), episiotomy (average RR 1.05; 95% CI 0.60 to 1.85, two studies, 420 women, random-effects, I² = 81%), duration of pushing (MD -9.76 minutes, 95% CI -19.54 to 0.02; two studies; 169 women; I² = 88%) (very low-quality evidence), or rate of spontaneous vaginal delivery (RR 1.01, 95% CI 0.97 to 1.05; five studies; 688 women; I² = 2%) (moderate-quality evidence). For primary neonatal outcomes such as five-minute Apgar score less than seven, there was no clear difference between groups (RR 0.35; 95% CI 0.01 to 8.43, one study, 320 infants) (very low-quality evidence), and the number of admissions to neonatal intensive care (RR 1.08; 95% CI 0.30 to 3.79, two studies, 393 infants) (very low-quality evidence) also showed no clear difference between spontaneous and directed pushing. No data were available on hypoxic ischaemic encephalopathy.\nComparison 2: timing of pushing: delayed pushing versus immediate pushing (all women with epidural)\nFor the primary maternal outcomes, delayed pushing was associated with an increase of 56 minutes in the duration of the second stage of labour (MD 56.40, 95% CI 42.05 to 70.76; 11 studies; 3049 women; I² = 91%) (very low-quality evidence), but no clear difference in third or 4th degree perineal laceration (RR 0.94; 95% CI 0.78 to 1.14, seven studies. 2775 women) (moderate-quality evidence) or episiotomy (RR 0.95; 95% CI 0.87 to 1.04, five studies, 2320 women). Delayed pushing was also associated with a 19-minute decrease in the duration of pushing (MD -19.05, 95% CI -32.27 to -5.83; 11 studies; 2932 women; I² = 95%) (very low-quality evidence) and an increase in spontaneous vaginal delivery (RR 1.07; 95% CI 1.02 to 1.11, 12 studies, 3114 women) (moderate-quality evidence).\nFor the primary neonatal outcomes, there was no clear difference between groups in admission to neonatal intensive care (RR 0.98; 95% CI 0.67 to 1.41, three studies, n = 2197) (low-quality evidence) and five-minute Apgar score less than seven (RR 0.15; 95% CI 0.01 to 3.00; three studies; 413 infants) (very low-quality evidence). There were no data on hypoxic ischaemic encephalopathy. Delayed pushing was associated with a greater incidence of low umbilical cord blood pH (RR 2.24; 95% CI 1.37 to 3.68, 4 studies, 2145 infants) and increased the cost of intrapartum care by CDN$ 68.22 (MD 68.22, 95% CI 55.37, 81.07, one study, 1862 women).\nAuthors' conclusions\nThis updated review is based on 21 included studies of moderate to very low quality of evidence (with evidence mainly downgraded due to study design limitations and imprecision of effect estimates).\nTiming of pushing with epidural is consistent in that delayed pushing leads to a shortening of the actual time pushing and increase of spontaneous vaginal delivery at the expense of an overall longer duration of the second stage of labour and an increased risk of a low umbilical cord pH (based only on one study). Nevertheless, there was no clear difference in serious perineal laceration and episiotomy, and in other neonatal outcomes (admission to neonatal intensive care, five-minute Apgar score less than seven and delivery room resuscitation) between delayed and immediate pushing.\nTherefore, for the type of pushing, with or without epidural, there is no conclusive evidence to support or refute any specific style as part of routine clinical practice, and in the absence of strong evidence supporting a specific method or timing of pushing, the woman's preference and comfort and clinical context should guide decisions.\nFurther properly well-designed RCTs, addressing clinically important maternal and neonatal outcomes are required to add evidence-based information to the current knowledge. Such trials will provide more complete data to be incorporated into a future update of this review.\n\nGiven the provided abstract, please respond to the following query: \"Why is this important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We need to know the benefits and possible disadvantages of different kinds of techniques regarding maternal pushing/breathing during the expulsive stage of labour on maternal and fetal outcomes." } ]

[ { "role": "user", "content": "Abstract: Background\nPterygium, a growth of the conjunctiva over the cornea, is a progressive disease leading in advanced stages to visual impairment, restriction of ocular motility, chronic inflammation and cosmetic concerns. Surgical removal is the treatment of choice, but recurrence can be a problem. Currently the best surgical option in terms of recurrence is conjunctival autograft. To date the most common surgical methods of attaching conjunctival autografts to the sclera are through suturing or fibrin glue. Each method presents its own advantages and disadvantages. Sutures require considerable skill from the surgeon and can be associated with a prolonged operation time, postoperative discomfort and suture-related complications, whereas fibrin glue may give a decreased operation time, improve postoperative comfort and avoid suture-related problems.\nObjectives\nTo assess the effectiveness of fibrin glue compared to sutures in conjunctival autografting for the surgical treatment of pterygium.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2016), Embase (January 1980 to October 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 October 2016.\nSelection criteria\nWe included randomised controlled trials (RCTs) in any setting where fibrin glue was compared with sutures to treat people with pterygium.\nData collection and analysis\nTwo review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcome was recurrence of pterygium defined as any re-growth of tissue from the area of excision across the limbus onto the cornea. The secondary outcomes were surgical time and complication rate. We graded the certainty of the evidence using GRADE.\nMain results\nWe included 14 RCTs conducted in Brazil, China, Egypt, India, Malaysia, New Zealand, Philippines, Saudi Arabia, Sweden and Turkey. The trials were published between 2004 and 2016, and were assessed as a mixture of unclear and low risk of bias with three studies at high risk of attrition bias. Only adults were enrolled in these studies.\nUsing fibrin glue for the conjunctival autograft may result in less recurrence of pterygium compared with using sutures (risk ratio (RR) 0.47, 95% CI 0.27 to 0.82, 762 eyes, 12 RCTs; low-certainty evidence). If pterygium recurs after approximately 10 in every 100 surgeries with sutures, then using fibrin glue may result in approximately 5 fewer cases of recurrence in every 100 surgeries (95% CI 2 fewer to 7 fewer cases). Using fibrin glue may lead to more complications compared with sutures (RR 1.92; 95% CI 1.22 to 3.02, 11 RCTs, 673 eyes, low-certainty evidence). The most common complications reported were: graft dehiscence, graft retraction and granuloma. On average using fibrin glue may mean that surgery is quicker compared with suturing (mean difference (MD) -17.01 minutes 95% CI -20.56 to -13.46), 9 RCTs, 614 eyes, low-certainty evidence).\nAuthors' conclusions\nThe meta-analyses, conducted on people with pterygium in a hospital or outpatient setting, show fibrin glue may result in less recurrence and may take less time than sutures for fixing the conjunctival graft in place during pterygium surgery. There was low-certainty evidence to suggest a higher proportion of complications in the fibrin glue group.\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": "Using fibrin glue when doing the graft may result in a lower chance of recurrence of the pterygium. The operation may take less time as well. Fibrin glue may be associated with more complications such as a rupture of the graft, the graft shrinking and the development of an area of inflammation (granuloma)." } ]

[ { "role": "user", "content": "Abstract: Background\nMalaria remains an important public health problem. Research in 1900 suggested house modifications may reduce malaria transmission. A previous version of this review concluded that house screening may be effective in reducing malaria. This update includes data from five new studies.\nObjectives\nTo assess the effects of house modifications that aim to reduce exposure to mosquitoes on malaria disease and transmission.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS) up to 25 May 2022. We also searched the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry to identify ongoing trials up to 25 May 2022.\nSelection criteria\nRandomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies.\nWe sought studies investigating primary construction and house modifications to existing homes reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We extracted any entomological outcomes that were also reported in these studies.\nData collection and analysis\nTwo review authors independently selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach.\nMain results\nOne RCT and six cRCTs met our inclusion criteria, with an additional six ongoing RCTs. We did not identify any eligible non-randomized studies. All included trials were conducted in sub-Saharan Africa since 2009; two randomized by household and four at the block or village level. All trials assessed screening of windows, doors, eaves, ceilings, or any combination of these; this was either alone, or in combination with roof modification or eave tube installation (an insecticidal \"lure and kill\" device that reduces mosquito entry whilst maintaining some airflow). In one trial, the screening material was treated with 2% permethrin insecticide. In five trials, the researchers implemented the interventions. A community-based approach was adopted in the other trial.\nOverall, the implementation of house modifications probably reduced malaria parasite prevalence (RR 0.68, 95% CI 0.57 to 0.82; 5 trials, 5183 participants; moderate-certainty evidence), although an inconsistent effect was observed in a subpopulation of children in one study. House modifications reduced moderate to severe anaemia prevalence (RR 0.70, 95% CI 0.55 to 0.89; 3 trials, 3643 participants; high-certainty evidence). There was no consistent effect on clinical malaria incidence, with rate ratios ranging from 0.38 to 1.62 (3 trials, 3365 participants, 4126.6 person-years). House modifications may reduce indoor mosquito density (rate ratio 0.63, 95% CI 0.30 to 1.30; 4 trials, 9894 household-nights; low-certainty evidence), although two studies showed little effect on this parameter.\nAuthors' conclusions\nHouse modifications – largely screening, sometimes combined with insecticide and lure and kill devices – were associated with a reduction in malaria parasite prevalence and a reduction in people with anaemia. Findings on malaria incidence were mixed. Modifications were also associated with lower indoor adult mosquito density, but this effect was not present in some studies.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The seven included trials all assessed either the number of cases of malaria identified during specific time periods in people living in the house, the proportion of people with malaria parasites in their blood, or both. Overall, the studies showed that people living in modified houses were around 32% less likely to have malaria parasites in their blood, and were 30% less likely to experience moderate or severe anaemia. Our confidence in these results was moderate to high. The studies demonstrated 37% reduction in the number of mosquitoes trapped indoors at night in modified houses, although this result varied between trials. The trials showed mixed results for the likelihood of experiencing an episode of clinical malaria (caused by Plasmodium falciparum parasites), ranging from a 62% lower rate to a 68% higher rate of malaria for people living in modified houses. Due to the high inconsistency between these results, we have very low confidence in this evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nAntisocial personality disorder (AsPD) is associated with poor mental health, criminality, substance use and relationship difficulties. This review updates Gibbon 2010 (previous version of the review).\nObjectives\nTo evaluate the potential benefits and adverse effects of psychological interventions for adults with AsPD.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also searched reference lists and contacted study authors to identify studies.\nSelection criteria\nRandomised controlled trials of adults, where participants with an AsPD or dissocial personality disorder diagnosis comprised at least 75% of the sample randomly allocated to receive a psychological intervention, treatment-as-usual (TAU), waiting list or no treatment. The primary outcomes were aggression, reconviction, global state/functioning, social functioning and adverse events.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nThis review includes 19 studies (eight new to this update), comparing a psychological intervention against TAU (also called 'standard Maintenance'(SM) in some studies). Eight of the 18 psychological interventions reported data on our primary outcomes.\nFour studies focussed exclusively on participants with AsPD, and 15 on subgroups of participants with AsPD. Data were available from only 10 studies involving 605 participants.\nEight studies were conducted in the UK and North America, and one each in Iran, Denmark and the Netherlands. Study duration ranged from 4 to 156 weeks (median = 26 weeks). Most participants (75%) were male; the mean age was 35.5 years. Eleven studies (58%) were funded by research councils. Risk of bias was high for 13% of criteria, unclear for 54% and low for 33%.\nCognitive behaviour therapy (CBT) + TAUversus TAU\nOne study (52 participants) found no evidence of a difference between CBT + TAU and TAU for physical aggression (odds ratio (OR) 0.92, 95% CI 0.28 to 3.07; low-certainty evidence) for outpatients at 12 months post-intervention.\nOne study (39 participants) found no evidence of a difference between CBT + TAU and TAU for social functioning (mean difference (MD) −1.60 points, 95% CI −5.21 to 2.01; very low-certainty evidence), measured by the Social Functioning Questionnaire (SFQ; range = 0-24), for outpatients at 12 months post-intervention.\nImpulsive lifestyle counselling (ILC) + TAU versus TAU\nOne study (118 participants) found no evidence of a difference between ILC + TAU and TAU for trait aggression (assessed with Buss-Perry Aggression Questionnaire-Short Form) for outpatients at nine months (MD 0.07, CI −0.35 to 0.49; very low-certainty evidence).\nOne study (142 participants) found no evidence of a difference between ILC + TAU and TAU alone for the adverse event of death (OR 0.40, 95% CI 0.04 to 4.54; very low-certainty evidence) or incarceration (OR 0.70, 95% CI 0.27 to 1.86; very low-certainty evidence) for outpatients between three and nine months follow-up.\nContingency management (CM) + SM versus SM\nOne study (83 participants) found evidence that, compared to SM alone, CM + SM may improve social functioning measured by family/social scores on the Addiction Severity Index (ASI; range = 0 (no problems) to 1 (severe problems); MD −0.08, 95% CI −0.14 to −0.02; low-certainty evidence) for outpatients at six months.\n‘Driving whilst intoxicated' programme (DWI) + incarcerationversus incarceration\nOne study (52 participants) found no evidence of a difference between DWI + incarceration and incarceration alone on reconviction rates (hazard ratio 0.56, CI −0.19 to 1.31; very low-certainty evidence) for prisoner participants at 24 months.\nSchema therapy (ST) versus TAU\nOne study (30 participants in a secure psychiatric hospital, 87% had AsPD diagnosis) found no evidence of a difference between ST and TAU for the number of participants who were reconvicted (OR 2.81, 95% CI 0.11 to 74.56, P = 0.54) at three years. The same study found that ST may be more likely to improve social functioning (assessed by the mean number of days until patients gain unsupervised leave (MD −137.33, 95% CI −271.31 to −3.35) compared to TAU, and no evidence of a difference between the groups for overall adverse events, classified as the number of people experiencing a global negative outcome over a three-year period (OR 0.42, 95% CI 0.08 to 2.19). The certainty of the evidence for all outcomes was very low.\nSocial problem-solving (SPS) + psychoeducation (PE) versus TAU\nOne study (17 participants) found no evidence of a difference between SPS + PE and TAU for participants’ level of social functioning (MD −1.60 points, 95% CI −5.43 to 2.23; very low-certainty evidence) assessed with the SFQ at six months post-intervention.\nDialectical behaviour therapy versus TAU\nOne study (skewed data, 14 participants) provided very low-certainty, narrative evidence that DBT may reduce the number of self-harm days for outpatients at two months post-intervention compared to TAU.\nPsychosocial risk management (PSRM; 'Resettle') versus TAU\nOne study (skewed data, 35 participants) found no evidence of a difference between PSRM and TAU for a number of officially recorded offences at one year after release from prison. It also found no evidence of difference between the PSRM and TAU for the adverse event of death during the study period (OR 0.89, 95% CI 0.05 to 14.83, P = 0.94, 72 participants (90% had AsPD), 1 study, very low-certainty evidence).\nAuthors' conclusions\nThere is very limited evidence available on psychological interventions for adults with AsPD. Few interventions addressed the primary outcomes of this review and, of the eight that did, only three (CM + SM, ST and DBT) showed evidence that the intervention may be more effective than the control condition. No intervention reported compelling evidence of change in antisocial behaviour. Overall, the certainty of the evidence was low or very low, meaning that we have little confidence in the effect estimates reported.\nThe conclusions of this update have not changed from those of the original review, despite the addition of eight new studies. This highlights the ongoing need for further methodologically rigorous studies to yield further data to guide the development and application of psychological interventions for AsPD and may suggest that a new approach is required.\n\nGiven the provided abstract, please respond to the following query: \"Conclusions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The review shows that there is not enough good quality evidence to recommend or reject any psychological treatment for people with a diagnosis of AsPD." } ]

[ { "role": "user", "content": "Abstract: Background\nOral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.\nObjectives\nTo determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.\nSearch methods\nAn information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.\nData collection and analysis\nFor this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment).\nWe contacted trial authors for additional information or clarification when necessary.\nMain results\nWe included 100 studies with 18,813 participants. None of the included trials were at low risk of bias.\nFor induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence).\nThere is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence).\nPrimary treatment with CRT, as compared to radiotherapy alone,  was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence).\nAuthors' conclusions\nThe results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The  evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.\n\nGiven the provided abstract, please respond to the following query: \"What were the main results?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found no clear evidence that chemotherapy given before surgery or radiotherapy improved survival. Similarly, chemotherapy given after surgery did not seem to lead to an improvement in survival.\nWe found treatment with radiotherapy and chemotherapy together after surgery, as compared to radiotherapy alone following surgery, may increase the likelihood of survival. Also, in patients who are not eligible for surgery, it may improve survival if chemotherapy is added to radiotherapy, as compared to radiotherapy treatment alone. There was not enough evidence to judge which chemotherapy drug is best to use." } ]

[ { "role": "user", "content": "Abstract: Background\nPressure ulcers, which are a localised injury to the skin, or underlying tissue, or both, occur when people are unable to reposition themselves to relieve pressure on bony prominences. Pressure ulcers are often difficult to heal, painful, expensive to manage and have a negative impact on quality of life. While individual patient safety and quality care stem largely from direct healthcare practitioner-patient interactions, each practitioner-patient wound-care contact may be constrained or enhanced by healthcare organisation of services. Research is needed to demonstrate clearly the effect of different provider-orientated approaches to pressure ulcer prevention and treatment.\nObjectives\nTo assess the effects of different provider-orientated interventions targeted at the organisation of health services, on the prevention and treatment of pressure ulcers.\nSearch methods\nIn April 2018 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched three clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.\nSelection criteria\nRandomised controlled trials (RCTs), cluster-RCTs, non-RCTs, controlled before-and-after studies and interrupted time series, which enrolled people at risk of, or people with existing pressure ulcers, were eligible for inclusion in the review.\nData collection and analysis\nTwo review authors independently performed study selection, risk of bias assessment, data extraction and GRADE assessment of the certainty of evidence.\nMain results\nThe search yielded a total of 3172 citations and, following screening and application of the inclusion and exclusion criteria, we deemed four studies eligible for inclusion. These studies reported the primary outcome of pressure ulcer incidence or pressure ulcer healing, or both.\nOne controlled before-and-after study explored the impact of transmural care (a care model that provided activities to support patients and their family/partners and activities to promote continuity of care), among 62 participants with spinal cord injury. It is unclear whether transmural care leads to a difference in pressure ulcer incidence compared with usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.53 to 1.64; very low-certainty evidence, downgraded twice for very serious study limitations and twice for very serious imprecision).\nOne RCT explored the impact of hospital-in-the-home care, among 100 older adults. It is unclear whether hospital-in-the-home care leads to a difference in pressure ulcer incidence risk compared with hospital admission (RR 0.32, 95% CI 0.03 to 2.98; very low-certainty evidence, downgraded twice for very serious study limitations and twice for very serious imprecision).\nA third study (cluster-randomised stepped-wedge trial), explored the impact of being cared for by enhanced multidisciplinary teams (EMDT), among 161 long-term-care residents. The analyses of the primary outcome used measurements of 201 pressure ulcers from 119 residents. It is unclear if EMDT reduces the pressure ulcer incidence rate compared with usual care (hazard ratio (HR) 1.12, 95% CI 0.74 to 1.68; very low-certainty evidence, downgraded twice for very serious study limitations and twice for very serious imprecision). It is unclear whether there is a difference in the number of wounds healed (RR 1.69, 95% CI 1.00 to 2.87; very low-certainty evidence, downgraded twice for very serious study limitations and twice for very serious imprecision). It is unclear whether there is a difference in the reduction in surface area, with and without EMDT, (healing rate 1.006; 95% CI 0.99 to 1.03; very low-certainty evidence, downgraded twice for very serious study limitations and twice for very serious imprecision). It is unclear if EMDT leads to a difference in time to complete healing (HR 1.48, 95% CI 0.79 to 2.78, very low-certainty evidence, downgraded twice for very serious study limitations and twice for very serious imprecision).\nThe final study (quasi-experimental cluster trial), explored the impact of multidisciplinary wound care among 176 nursing home residents. It is unclear whether there is a difference in the number of pressure ulcers healed between multidisciplinary care, or usual care (RR 1.18, 95% CI 0.98 to 1.42; very low-certainty evidence, downgraded twice for very serious study limitations and twice for very serious imprecision). It is unclear if this type of care leads to a difference in time to complete healing compared with usual care (HR 1.73, 95% CI 1.20 to 2.50; very low-certainty evidence; downgraded twice for very serious study limitations and twice for very serious imprecision).\nIn all studies the certainty of the evidence is very low due to high risk of bias and imprecision. We downgraded the evidence due to study limitations, which included selection and attrition bias, and sample size. Secondary outcomes, such as adverse events were not reported in all studies. Where they were reported it was unclear if there was a difference as the certainty of evidence was very low.\nAuthors' conclusions\nEvidence for the impact of organisation of health services for preventing and treating pressure ulcers remains unclear. Overall, GRADE assessments of the evidence resulted in judgements of very low-certainty evidence. The studies were at high risk of bias, and outcome measures were imprecise due to wide confidence intervals and small sample sizes, meaning that additional research is required to confirm these results. The secondary outcomes reported varied across the studies and some were not reported. We judged the evidence from those that were reported (including adverse events), to be of very low certainty.\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": "We cannot be certain whether transmural care (a way of providing care that delivers activities to support patients and their family/partners, and activities to promote continuity of care), hospital-in-the-home care, care provided by a team of different disciplines or care that is usually provided, make any difference to whether people develop pressure ulcers, how fast existing ulcers heal, or whether people with ulcers are admitted or readmitted to hospital." } ]

[ { "role": "user", "content": "Abstract: Background\nGender dysphoria is described as a mismatch between an individual's experienced or expressed gender and their assigned gender, based on primary or secondary sexual characteristics. Gender dysphoria can be associated with clinically significant psychological distress and may result in a desire to change sexual characteristics. The process of adapting a person's sexual characteristics to their desired sex is called ‘transition.'\nCurrent guidelines suggest hormonal and, if needed, surgical intervention to aid transition in transgender women, i.e. persons who aim to transition from male to female. In adults, hormone therapy aims to reverse the body's male attributes and to support the development of female attributes. It usually includes estradiol, antiandrogens, or a combination of both. Many individuals first receive hormone therapy alone, without surgical interventions. However, this is not always sufficient to change such attributes as facial bone structure, breasts, and genitalia, as desired. For these transgender women, surgery may then be used to support transition.\nObjectives\nWe aimed to assess the efficacy and safety of hormone therapy with antiandrogens, estradiol, or both, compared to each other or placebo, in transgender women in transition.\nSearch methods\nWe searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Biosis Preview, PsycINFO, and PSYNDEX. We carried out our final searches on 19 December 2019.\nSelection criteria\nWe aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cohort studies that enrolled transgender women, age 16 years and over, in transition from male to female. Eligible studies investigated antiandrogen and estradiol hormone therapies alone or in combination, in comparison to another form of the active intervention, or placebo control.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane to establish study eligibility.\nMain results\nOur database searches identified 1057 references, and after removing duplicates we screened 787 of these. We checked 13 studies for eligibility at the full text screening stage. We excluded 12 studies and identified one as an ongoing study. We did not identify any completed studies that met our inclusion criteria. The single ongoing study is an RCT conducted in Thailand, comparing estradiol valerate plus cyproterone treatment with estradiol valerate plus spironolactone treatment. The primary outcome will be testosterone level at three month follow-up.\nAuthors' conclusions\nWe found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition. This lack of studies shows a gap between current clinical practice and clinical research. Robust RCTs and controlled cohort studies are needed to assess the benefits and harms of hormone therapy (used alone or in combination) for transgender women in transition. Studies should specifically focus on short-, medium-, and long-term adverse effects, quality of life, and participant satisfaction with the change in male to female body characteristics of antiandrogen and estradiol therapy alone, and in combination. They should also focus on the relative effects of these hormones when administered orally, transdermally, and intramuscularly. We will include non-controlled cohort studies in the next iteration of this review, as our review has shown that such studies provide the highest quality evidence currently available in the field. We will take into account methodological limitations when doing so.\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 searched for studies up to 19 December 2019. We were unable to find any relevant completed studies that we could include. We did find one ongoing study that aimed to recruit all of the people taking part in the study by the end of 2020. This study is comparing the effects of estradiol valerate plus cyproterone treatment with estradiol valerate plus spironolactone treatment in transitioning transgender women in Thailand." } ]

[ { "role": "user", "content": "Abstract: Background\nMarfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural and pulmonary systems. Aortic root dilatation is the most frequent cardiovascular manifestation and its complications, including aortic regurgitation, dissection and rupture are the main cause of morbidity and mortality.\nObjectives\nTo assess the long-term efficacy and safety of beta-blocker therapy as compared to placebo, no treatment or surveillance only in people with Marfan syndrome.\nSearch methods\nWe searched the following databases on 28 June 2017; CENTRAL, MEDLINE, Embase, Science Citation Index Expanded and the Conference Proceeding Citation Index - Science in the Web of Science Core Collection. We also searched the Online Metabolic and Molecular Bases of Inherited Disease (OMMBID), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 June 2017. We did not impose any restriction on language of publication.\nSelection criteria\nAll randomised controlled trials (RCTs) of at least one year in duration assessing the effects of beta-blocker monotherapy compared with placebo, no treatment or surveillance only, in people of all ages with a confirmed diagnosis of Marfan syndrome were eligible for inclusion.\nData collection and analysis\nTwo review authors independently screened titles and abstracts for inclusion, extracted data and assessed trial quality. Trial authors were contacted to obtain missing data. Dichotomous outcomes will be reported as relative risk and continuous outcomes as mean differences with 95% confidence intervals. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.\nMain results\nOne open-label, randomised, single-centre trial including 70 participants with Marfan syndrome (aged 12 to 50 years old) met the inclusion criteria. Participants were randomly assigned to propranolol (N = 32) or no treatment (N = 38) for an average duration of 9.3 years in the control group and 10.7 years in the treatment group. The initial dose of propranolol was 10 mg four times daily and the optimal dose was reached when the heart rate remained below 100 beats per minute during exercise or the systolic time interval increased by 30%. The mean (± standard error (SE)) optimal dose of propranolol was 212 ± 68 mg given in four divided doses daily.\nBeta-blocker therapy did not reduce the incidence of all-cause mortality (RR 0.24, 95% CI 0.01 to 4.75; participants = 70; low-quality evidence). Mortality attributed to Marfan syndrome was not reported. Non-fatal serious adverse events were also not reported. However, study authors report on pre-defined, non-fatal clinical endpoints, which include aortic dissection, aortic regurgitation, cardiovascular surgery and congestive heart failure. Their analysis showed no difference between the treatment and control groups in these outcomes (RR 0.79, 95% CI 0.37 to 1.69; participants = 70; low-quality evidence).\nBeta-blocker therapy did not reduce the incidence of aortic dissection (RR 0.59, 95% CI 0.12 to 3.03), aortic regurgitation (RR 1.19, 95% CI 0.18 to 7.96), congestive heart failure (RR 1.19, 95% CI 0.18 to 7.96) or cardiovascular surgery, (RR 0.59, 95% CI 0.12 to 3.03); participants = 70; low-quality evidence.\nThe study reports a reduced rate of aortic dilatation measured by M-mode echocardiography in the treatment group (aortic ratio mean slope: 0.084 (control) vs 0.023 (treatment), P < 0.001). The change in systolic and diastolic blood pressure, total adverse events and withdrawal due to adverse events were not reported in the treatment or control group at study end point.\nWe judged this study to be at high risk of selection (allocation concealment) bias, performance bias, detection bias, attrition bias and selective reporting bias. The overall quality of evidence was low. We do not know whether a statistically significant reduced rate of aortic dilatation translates into clinical benefit in terms of aortic dissection or mortality.\nAuthors' conclusions\nBased on only one, low-quality RCT comparing long-term propranolol to no treatment in people with Marfan syndrome, we could draw no definitive conclusions for clinical practice. High-quality, randomised trials are needed to evaluate the long-term efficacy of beta-blocker treatment in people with Marfan syndrome. Future trials should report on all clinically relevant end points and adverse events to evaluate benefit versus harm of therapy.\n\nGiven the provided abstract, please respond to the following query: \"Study funding source\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This study was supported by grants from the National Institute of Health, the US Food and Drug Administration, and the National Marfan Foundation." } ]

[ { "role": "user", "content": "Abstract: Background\nWhen a woman has had a previous caesarean birth and requires induction of labour for a subsequent pregnancy, two options are available for her care: an elective repeat caesarean and planned induction of labour. Although risks and benefits are associated with both elective repeat caesarean birth and planned induction of labour, current sources of information are limited to non-randomised cohort studies, and studies designed in this way have significant potential for bias. Consequently, any conclusions based on results of these studies are limited in their reliability and should be interpreted with caution.\nObjectives\nTo assess, using the best available evidence, the benefits and harms of a policy of planned elective repeat caesarean section versus a policy of induction of labour for women with a previous caesarean birth who require induction of labour for a subsequent pregnancy. Primary outcomes include success of induction of labour, need for caesarean section, maternal and neonatal mortality, and maternal and neonatal morbidity.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Trials Register (31 May 2017) and planned to search reference lists of retrieved studies.\nSelection criteria\nRandomised controlled trials with reported data on comparison of outcomes in mothers and babies between women who planned an elective repeat caesarean section and women who planned induction of labour when a previous birth was performed by caesarean. Cluster trials and quasi-randomised trials were also eligible for inclusion. We would consider trials published only as abstracts if they provided enough information to meet review inclusion criteria.\nData collection and analysis\nWe performed no data extraction. For future updates, if randomised controlled trials are identified, two review authors will independently assess trials for inclusion and risk of bias, and will extract data and check extracted data for accuracy. Review authors will assess the quality of the evidence using the GRADE approach.\nMain results\nReview authors identified no randomised controlled trials.\nAuthors' conclusions\nBoth planned elective repeat caesarean section and planned induction of labour for women with a prior caesarean birth are associated with benefits and harms. Evidence for these care practices has been drawn from non-randomised studies, which are associated with potential bias. Therefore, any results and conclusions presented must be interpreted with caution. Randomised controlled trials are required to provide the most reliable evidence regarding the benefits and harms of both planned elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth.\n\nGiven the provided abstract, please respond to the following query: \"What does this mean?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Caregivers and women faced with making a decision about labour and birth after a previous caesarean section cannot be informed by randomised trial evidence. A woman should discuss with her caregivers the benefits and risks of both courses of action. She and her caregivers should come to a shared decision for action that is based on the woman’s wishes and priorities." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of a Cochrane review first published in 2002. Osteoarthritis is a disease that affects the synovial joints, causing degeneration and destruction of hyaline cartilage and subchondral bone. Electromagnetic field therapy is currently used by physiotherapists and may promote growth and repair of bone and cartilage. It is based on principles of physics which include Wolff's law, the piezoelectric effect and the concept of streaming potentials.\nObjectives\nTo assess the benefits and harms of electromagnetic fields for the treatment of osteoarthritis as compared to placebo or sham.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), PreMEDLINE for trials published before 1966, MEDLINE from 1966 to October 2013, CINAHL and PEDro up to and including October 2013. Electronic searches were complemented by handsearches.\nSelection criteria\nRandomised controlled trials of electromagnetic fields in osteoarthritis, with four or more weeks treatment duration. We included papers in any language.\nData collection and analysis\nTwo review authors independently assessed studies for inclusion in the review and resolved differences by consensus with a third review author. We extracted data using pre-developed data extraction forms. The same review authors assessed the risk of bias of the trials independently using the Cochrane 'Risk of bias' tool. We extracted outcomes for osteoarthritis from the publications according to Outcome Measures in Rheumatology Clinical Trials (OMERACT) guidelines. We expressed results for continuous outcome measures as mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI). We pooled dichotomous outcome measures using risk ratio (RR) and calculated the number needed to treat (NNT).\nMain results\nNine studies with a total of 636 participants with osteoarthritis were included, six of which were added in this update of the review. Selective outcome reporting was unclear in all nine included studies due to inadequate reporting of study design and conduct, and there was high risk of bias for incomplete outcome data in three studies. The overall risk of bias across the nine studies was low for the other domains.\nParticipants who were randomised to electromagnetic field treatment rated their pain relief 15.10 points more on a scale of 0 to 100 (MD 15.10, 95% CI 9.08 to 21.13; absolute improvement 15%) after 4 to 26 weeks' treatment compared with placebo. Electromagnetic field treatment had no statistically significant effect on physical function (MD 4.55, 95% CI -2.23 to 11.32; absolute improvement 4.55%) based on the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scale from 0 to 100 after 12 to 26 weeks' treatment. We also found no statistically significant difference in quality of life on a scale from 0 to 100 (SMD 0.09, 95% CI -0.36 to 0.54; absolute improvement 0.09%) after four to six weeks' treatment, based on the SF-36. No data were available for analysis of radiographic changes. Safety was evaluated in four trials including up to 288 participants: there was no difference in the experience of any adverse event after 4 to 12 weeks of treatment compared with placebo (RR 1.17, 95% CI 0.72 to 1.92). There was no difference in participants who withdrew because of adverse events (measured in one trial) after four weeks of treatment (RR 0.90, 95% CI 0.06 to 13.92). No participants experienced any serious adverse events.\nAuthors' conclusions\nCurrent evidence suggests that electromagnetic field treatment may provide moderate benefit for osteoarthritis sufferers in terms of pain relief. Further studies are required to confirm whether this treatment confers clinically important benefits in terms of physical function and quality of life. Our conclusions are unchanged from the previous review conducted in 2002.\n\nGiven the provided abstract, please respond to the following query: \"Overall health and well-being\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "- Electromagnetic fields probably make no difference to overall health and well-being." } ]

[ { "role": "user", "content": "Abstract: Background\nInfective endocarditis is a severe infection arising in the lining of the chambers of the heart. It can be caused by fungi, but most often is caused by bacteria. Many dental procedures cause bacteraemia, which could lead to bacterial endocarditis in a small proportion of people. The incidence of bacterial endocarditis is low, but it has a high mortality rate.\nGuidelines in many countries have recommended that antibiotics be administered to people at high risk of endocarditis prior to invasive dental procedures. However, guidance by the National Institute for Health and Care Excellence (NICE) in England and Wales states that antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures. This is an update of a review that we first conducted in 2004 and last updated in 2013.\nObjectives\nPrimary objective\nTo determine whether prophylactic antibiotic administration, compared to no antibiotic administration or placebo, before invasive dental procedures in people at risk or at high risk of bacterial endocarditis, influences mortality, serious illness or the incidence of endocarditis.\nSecondary objectives\nTo determine whether the effect of dental antibiotic prophylaxis differs in people with different cardiac conditions predisposing them to increased risk of endocarditis, and in people undergoing different high risk dental procedures.\nHarms\nHad we foundno evidence from randomised controlled trials or cohort studies on whether prophylactic antibiotics affected mortality or serious illness, and we had found evidence from these or case-control studies suggesting that prophylaxis with antibiotics reduced the incidence of endocarditis, then we would also have assessed whether the harms of prophylaxis with single antibiotic doses, such as with penicillin (amoxicillin 2 g or 3 g) before invasive dental procedures, compared with no antibiotic or placebo, equalled the benefits in prevention of endocarditis in people at high risk of this disease.\nSearch methods\nAn information specialist searched four bibliographic databases up to 10 May 2021 and used additional search methods to identify published, unpublished and ongoing studies\nSelection criteria\nDue to the low incidence of bacterial endocarditis, we anticipated that few if any trials would be located. For this reason, we included cohort and case-control studies with suitably matched control or comparison groups. The intervention was antibiotic prophylaxis, compared to no antibiotic prophylaxis or placebo, before a dental procedure in people with an increased risk of bacterial endocarditis. Cohort studies would need to follow at-risk individuals and assess outcomes following any invasive dental procedures, grouping participants according to whether or not they had received prophylaxis. Case-control studies would need to match people who had developed endocarditis after undergoing an invasive dental procedure (and who were known to be at increased risk before undergoing the procedure) with those at similar risk who had not developed endocarditis.\nOur outcomes of interest were mortality or serious adverse events requiring hospital admission; development of endocarditis following any dental procedure in a defined time period; development of endocarditis due to other non-dental causes; any recorded adverse effects of the antibiotics; and the cost of antibiotic provision compared to that of caring for patients who developed endocarditis.\nData collection and analysis\nTwo review authors independently screened search records, selected studies for inclusion, assessed the risk of bias in the included study and extracted data from the included study. As an author team, we judged the certainty of the evidence identified for the main comparison and key outcomes using GRADE criteria. We presented the main results in a summary of findings table.\nMain results\nOur new search did not find any new studies for inclusion since the last version of the review in 2013.\nNo randomised controlled trials (RCTs), controlled clinical trials (CCTs) or cohort studies were included in the previous versions of the review, but one case-control study met the inclusion criteria. The trial authors collected information on 48 people who had contracted bacterial endocarditis over a specific two-year period and had undergone a medical or dental procedure with an indication for prophylaxis within the past 180 days. These people were matched to a similar group of people who had not contracted bacterial endocarditis. All study participants had undergone an invasive medical or dental procedure. The two groups were compared to establish whether those who had received preventive antibiotics (penicillin) were less likely to have developed endocarditis. The authors found no significant effect of penicillin prophylaxis on the incidence of endocarditis. No data on other outcomes were reported.\nThe level of certainty we have about the evidence is very low.\nAuthors' conclusions\nThere remains no clear evidence about whether antibiotic prophylaxis is effective or ineffective against bacterial endocarditis in at-risk people who are about to undergo an invasive dental procedure. We cannot determine whether the potential harms and costs of antibiotic administration outweigh any beneficial effect. Ethically, practitioners should discuss the potential benefits and harms of antibiotic prophylaxis with their patients before a decision is made about administration.\n\nGiven the provided abstract, please respond to the following query: \"Date of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review updates one carried out originally in 2004 and last revised in 2013. It is now up to date to 10 May 2021." } ]

[ { "role": "user", "content": "Abstract: Background\nMechanical ventilation is a life-saving intervention for critically ill newborn infants with respiratory failure admitted to a neonatal intensive care unit (NICU). Ventilating newborn infants can be challenging due to small tidal volumes, high breathing frequencies, and the use of uncuffed endotracheal tubes. Mechanical ventilation has several short-term, as well as long-term complications. To prevent complications, weaning from the ventilator is started as soon as possible. Weaning aims to support the transfer from full mechanical ventilation support to spontaneous breathing activity.\nObjectives\nTo assess the efficacy of protocolized versus non-protocolized ventilator weaning for newborn infants in reducing the duration of invasive mechanical ventilation, the duration of weaning, and shortening the NICU and hospital length of stay. To determine efficacy in predefined subgroups including: gestational age and birth weight; type of protocol; and type of protocol delivery. To establish whether protocolized weaning is safe and clinically effective in reducing the duration of mechanical ventilation without increasing the risk of adverse events.\nSearch methods\nWe searched the Cochrane Central Register of Controlled trials (CENTRAL; the Cochrane Library; 2015, Issue 7); MEDLINE In-Process and other Non-Indexed Citations and OVID MEDLINE (1950 to 31 July 2015); CINAHL (1982 to 31 July 2015); EMBASE (1988 to 31 July 2015); and Web of Science (1990 to 15 July 2015). We did not restrict language of publication. We contacted authors of studies with a subgroup of newborn infants in their study, and experts in the field regarding this subject. In addition, we searched abstracts from conference proceedings, theses, dissertations, and reference lists of all identified studies for further relevant studies.\nSelection criteria\nRandomized, quasi-randomized or cluster-randomized controlled trials that compared protocolized with non-protocolized ventilator weaning practices in newborn infants with a gestational age of 24 weeks or more, who were enrolled in the study before the postnatal age of 28 completed days after the expected date of birth.\nData collection and analysis\nFour authors, in pairs, independently reviewed titles and abstracts identified by electronic searches. We retrieved full-text versions of potentially relevant studies.\nMain results\nOur search yielded 1752 records. We removed duplicates (1062) and irrelevant studies (843). We did not find any randomized, quasi-randomized or cluster-randomized controlled trials conducted on weaning from mechanical ventilation in newborn infants. Two randomized controlled trials met the inclusion criteria on type of study and type of intervention, but only included a proportion of newborns. The study authors could not provide data needed for subgroup analysis; we excluded both studies.\nAuthors' conclusions\nBased on the results of this review, there is no evidence to support or refute the superiority or inferiority of weaning by protocol over non-protocol weaning on duration of invasive mechanical ventilation in newborn infants.\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": "Key resultsWe found no studies that involved newborn infants before the 28thday of life. We found two studies with a subpopulation of newborns, but we were not able to extract the data from this subgroup out of the total group studied.Quality of evidence\nThere is currently no evidence comparing protocolized and non-protocolized weaning in newborn infants in the neonatal intensive care unit." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with hemophilia A or B with inhibitors are at high risk of bleeding complications. Infusion of bypassing agents, such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrate, are suggested as alternative therapies to factor VIII (haemophilia A) or IX (haemophilia B) for individuals who no longer respond to these treatments because they develop inhibitory antibodies. The ultimate goal of treatment is to preserve the individual's joints, otherwise destroyed by recurrent bleeds.\nObjectives\nTo assess the effects of bypassing agent prophylaxis to prevent bleeding in people with hemophilia A or B and inhibitors.\nSearch methods\nWe searched for relevant studies from the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries (16 February 2017) and bibliographic references of retrieved studies were reviewed for potential articles to be included in the review.\nDate of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register: 12 December 2016.\nSelection criteria\nWe included randomized and quasi-randomized controlled studies (cross-over or parallel design) evaluating the effect of prophylaxis treatment with bypassing agents compared with on-demand treatment, or studies evaluating the effects of high-dose compared with low-dose prophylaxis in males of any age with hemophilia with inhibitors.\nData collection and analysis\nTwo authors independently selected studies and extracted data and assessed the risk of bias according to standard Cochrane criteria. They assessed the quality of the evidence using the GRADE criteria.\nMain results\nWe included four randomized studies (duration 7 to 15 months) involving 116 males. Risk of bias was judged to be high in two studies due to the open-label study design and in one study due to attrition bias.\nTwo studies compared on-demand treatment to prophylaxis with bypassing agents. In one study (34 males) prophylaxis significantly reduced mean overall bleeding rates, MD - 7.27 (95% CI -9.92 to -4.62) (low quality evidence), mean number of overall bleeding events per month, MD -1.10 (95% CI -1.54 to -0.66), mean number of hemarthrosis, MD -6.60 (95% CI -9.32 to -3.88) (low quality evidence) and mean number of joints that had hemarthrosis, MD -0.90 (95% CI -1.36 to -0.44). The meta-analysis did not conclusively demonstrate significant benefit of prophylaxis on health-related quality of life as measured by Haem-A-QoL score, EQ-5D total score and utility score, EQ-5D VAS and SF-36 physical summary and mental summary score (low quality evidence for all health-related quality of life analyses).\nThe remaining two studies compared dose regimens. The results from one study (22 males) did not conclusively demonstrate benefit or harm of high-dose versus low-dose recombinant activated factor VIIa (rFVIIa) as a prophylaxis for overall bleeding rate, MD -0.82 (95% CI -2.27 to 0.63) (moderate quality evidence), target joint bleeding rate, MD -3.20 (95% CI -7.23 to 0.83) (moderate quality evidence) and serious adverse events, RR 9.00 (95% CI, 0.54 to 149.50) (moderate quality evidence).\nThe overall quality of evidence was moderate to low due to imprecision from limited information provided by studies with small sample sizes and incomplete outcome data in one study.\nAuthors' conclusions\nThe evidence suggests that prophylaxis with bypassing agents may be effective in reducing bleeding in males with hemophilia with inhibitors. However, there is a lack of evidence for the superiority of one agent over the other or for the optimum dosage regimen. Further studies are needed to evaluate the benefits and harms of prophylaxis treatment on health-related quality of life, as well as the effects of dose of bypassing agents on the outcomes.\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": "The overall quality of evidence of these studies was moderate to low as the included studies were small and provided limited information. Also, in one of the studies, up to 24% of the men recruited were not included in the analysis of the results, which further increases imprecision of results." } ]

[ { "role": "user", "content": "Abstract: Background\nIn people with sickle cell disease, sickled red blood cells cause the occlusion of small blood vessels, which presents as episodes of severe pain known as pain crises or vaso-occlusive crises. The pain can occur in the bones, chest, or other parts of the body, and may last several hours to days. Pain relief during crises includes both pharmacologic and non-pharmacologic treatments. The efficacy of inhaled nitric oxide in pain crises has been a subject of controversy; hypotheses have been made suggesting a beneficial response due to its vasodilator properties, yet no conclusive evidence has been presented. This review aimed to evaluate the available randomised controlled studies addressing this topic.\nObjectives\nTo capture the body of evidence evaluating the efficacy and safety of the use of inhaled nitric oxide in treating pain crises in people with sickle cell disease, and to assess the relevance, robustness, and validity of the treatment to better guide medical practice in the fields of haematology and palliative care (since the recent literature seems to favour the involvement of palliative care for such people).\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register. We searched for unpublished work in the abstract books of the European Haematology Association conference, the American Society of Hematology conference, the British Society for Haematology Annual Scientific Meeting, the Caribbean Health Research Council Meetings, and the National Sickle Cell Disease Program Annual Meeting. The most recent search was conducted on 1 September 2021. We also searched ongoing study registries on 19 November 2021.\nSelection criteria\nRandomised and quasi-randomised trials comparing inhaled nitric oxide with placebo for treating pain crises in people with sickle cell disease.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data (including adverse event data), with any disagreements resolved by consulting a third review author. When the data were not reported in the text, we attempted to extract the data from available tables or figures. We contacted trial authors for additional information. We assessed the certainty of the evidence using the GRADE criteria.\nMain results\nWe included three trials involving a total of 188 participants in the review. There were equal numbers of males and females. Most participants were adults, although one small trial was conducted in a children's hospital and recruited children over the age of 10 years. All three parallel trials compared inhaled nitric oxygen (80 parts per million (ppm)) to placebo (nitrogen gas mixed with oxygen or room air) for four hours; one trial continued administering nitric oxide (40 ppm) for a further four hours. This extended trial had an overall low risk of bias; however, we had concerns about risk of bias for the remaining two trials due to their small sample size, and additionally a high risk of bias due to financial conflicts of interest in one of these smaller trials. We were only able to analyse some limited data from the eight-hour trial, reporting the remaining results narratively.\nEvidence from one trial (150 participants) suggested that inhaled nitric oxide may not reduce the time to pain resolution: inhaled nitric oxide median 73.0 hours (95% confidence interval (CI) 46.0 to 91.0) and with placebo median 65.5 hours (95% CI 48.1 to 84.0) (low-certainty evidence). No trial reported on the duration of the initial pain crisis. Only one large trial reported on the frequency of pain crises in the follow-up period and found there may be little or no difference between the inhaled nitric oxide and placebo groups for return to the emergency department (risk ratio (RR) 0.73, 95% CI 0.31 to 1.71) and rehospitalisation (RR 0.53, 95% CI 0.25 to 1.11) (150 participants; low-certainty evidence).\nThere may be little or no difference between treatment and placebo in terms of reduction in pain score at any time point up to eight hours (150 participants). The two smaller trials reported a beneficial effect of inhaled nitric oxide in reducing the visual analogue pain score after four hours of the intervention.\nAnalgesic use was reported not to differ greatly between the inhaled nitric oxide group and placebo group in any of the three trials, but no analysable data were provided. Two trials reported the median duration of hospitalisation: in the largest trial the placebo group had the shorter duration, whilst in the second smaller (paediatric) trial hospitalisation was shorter in the treatment group.\nOnly the largest trial (150 participants) reported serious adverse events, with no increase in the inhaled nitric oxide group during or after the intervention compared to the control group (acute chest syndrome occurred in 5 out of 75 participants from each group, pyrexia in 1 out of 75 participants from each group, and dysphagia and a drop in haemoglobin were each reported in 1 out of 75 participants in the inhaled nitric oxide group) (low-certainty evidence).\nAuthors' conclusions\nThe currently available evidence is insufficient to determine the effects (benefits or harms) of using inhaled nitric oxide to treat pain (vaso-occlusive) crises in people with sickle cell disease. Large-scale, long-term trials are needed to provide more robust data in this area. Patient-important outcomes (e.g. measures of pain and time to pain resolution and amounts of analgesics used), as well as use of healthcare services, should be measured and reported in a standardised manner.\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": "Only one large trial (150 participants) reported time until the pain stopped, finding no difference between nitric oxide or room air. This trial was also the only trial to report on the frequency of pain crises in the follow-up period, and we found little or no difference between inhaled nitric oxide and room air for a return to the emergency department or for readmission to hospital. All three trials reported pain scores: the larger trial found no difference between nitric oxide or room air at each time point up to eight hours, but the two smaller trials (38 participants) reported a benefit of inhaled nitric oxide in relieving the pain after four hours; however, these trials were small and limited compared to the first trial.\nAll three trials reported that inhaled nitric oxide had no effect on decreasing the use of painkillers, but there were no data that could be analysed. Two trials reported the average duration of stay in hospital: in the large trial those who were given room air had a shorter stay, whilst the smaller trial conducted at the children's hospital reported a shorter stay in those treated with inhaled nitric oxide. Only the larger trial reported on harmful effects of nitric oxide, finding little or no difference between treatment groups.\nWe could not combine the available data from the three included trials due to differences in the reporting of outcomes. As a result, the currently available evidence is not enough to give a clear answer about the use of inhaled nitric oxide for people with sickle cell disease experiencing a pain crisis.\nFuture trials, preferably large-scale and long term, should be carried out to provide strong evidence in this area. Investigators should measure and report outcomes important to patients (e.g. measures of pain and time to pain resolution and amounts of analgesics used), as well as use of healthcare services in a standardised way." } ]

[ { "role": "user", "content": "Abstract: Background\nOpportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and therapeutically in these patients.\nObjectives\nTo compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.\nSearch methods\nCochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were accepted. Contact was made with trial authors and industry.\nSelection criteria\nRandomised clinical trials comparing voriconazole with amphotericin B or fluconazole.\nData collection and analysis\nData on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted independently by two review authors.\nMain results\nThree trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infection) in neutropenic cancer patients (849 patients, 58 deaths). The second trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). The third trial compared fluconazole to voriconazole for prophylaxis of fungal infections in patients receiving allogeneic stem cell transplantation (600 patients, number of deaths not stated). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the trial authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from the analysis by the trial authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication to counter side effects and replacement of electrolytes or use of salt water. This choice of comparator resulted in a marked difference in the duration of treatment on the trial drugs (77 days with voriconazole versus 10 days with amphotericin B) and precluded meaningful comparisons of the benefits and harms of the two drugs. The third trial failed to find a difference in fungal free survival or invasive fungal infections at 180 days when voriconazole was compared to fluconazole.\nAuthors' conclusions\nLiposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of fungal infections in neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions. For prophylactic fungal treatment in patients receiving allogeneic stem cell transplantation, there was no difference between voriconazole and fluconazole regarding fungal free survival or invasive fungal infections.\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": "Patients with cancer who are treated with chemotherapy or receive a bone marrow transplant have an increased risk of fungal infections. Such infections can be life-threatening. Antifungal drugs are therefore often given to prevent fungal infections in such patients, either when these patients are known to have a fungal infection or when such an infection is suspected. We reviewed the evidence about the effect of voriconazole compared to amphotericin B or fluconazole to prevent or treat fungal infections in cancer patients with a poor immune system to provide defence." } ]

[ { "role": "user", "content": "Abstract: Background\nThymic carcinoma or advanced thymoma is a rare cancer of the thymus gland that tends to be aggressive and infiltrate neighbouring organs, making total resection very difficult. Induction or adjuvant chemotherapy, or both, are often used in a multimodality approach to treat people affected by this condition, but the effectiveness of chemotherapy for thymic carcinoma or advanced thymoma remains uncertain.\nObjectives\nTo assess the role of chemotherapy in adults with thymic carcinoma or advanced thymoma.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 7), MEDLINE (accessed via Ovid from 1966 to July 2012), EMBASE (accessed via Ovid, from 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS), the Chinese Biological Medicine Database (CBM, 1978 to July 2012), China National Knowledge Infrastructure (CNKI, 1980 to July 2012) and the Chinese scientific periodical database VIP Information (VIP, 1989 to July 2012). There was no language restriction in searching for studies.\nSelection criteria\nWe planned to include randomised controlled trials (RCTs) of  trials using chemotherapy (either single-agent or combination chemotherapy plus surgery, radiotherapy or not) for thymic carcinoma and/or advanced thymoma. We planned to include all adults (aged 18 years and over) diagnosed with thymic carcinoma and/or with Masaoka stage III or IV thymic tumours. The intended primary outcomes were overall survival (OS) and progression-free survival (PFS).\nData collection and analysis\nTwo review authors independently evaluated the search results according to the inclusion and exclusion criteria. There were no studies identified for inclusion and therefore no data extraction was completed.\nMain results\nNo RCTs were eligible for inclusion in this review. We report details of excluded prospective studies in an additional table and try to provide some useful evidence regarding current practice.\nAuthors' conclusions\nThere were no RCTs eligible for inclusion in this review. In current practice the most common regimen for adult patients with thymic carcinoma or advanced thymoma is cisplatin-based chemotherapy. Considering the condition is rare, it is suggested that an international group is set up to organise and evaluate prospective collection of data from cohorts of patients to inform current clinical practice.\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": "Thymic cancers are rare tumours arising in the thymus gland behind the breastbone in the chest cavity. For people with advanced-stage thymic tumours complete surgical resection is normally not possible and the only treatment option is combined chemotherapy. This review aimed to assess the role of chemotherapy in people with advanced thymic tumours." } ]

[ { "role": "user", "content": "Abstract: Background\nAn abdominal aortic aneurysm (AAA) (pathological enlargement of the aorta) is a condition that can occur as a person ages. It is most commonly seen in men older than 65 years of age. Progressive aneurysm enlargement can lead to rupture and massive internal bleeding, which is fatal unless timely repair can be achieved. Despite improvements in perioperative care, mortality remains high (approximately 50%) after conventional open surgical repair. Endovascular aneurysm repair (EVAR), a minimally invasive technique, has been shown to reduce early morbidity and mortality as compared to conventional open surgery for planned AAA repair. More recently emergency endovascular aneurysm repair (eEVAR) has been used successfully to treat ruptured abdominal aortic aneurysm (RAAA), proving that it is feasible in select patients; however, it is unclear if eEVAR will lead to significant improvements in outcomes for these patients or if indeed it can replace conventional open repair as the preferred treatment for this lethal condition. This is an update of the review first published in 2006.\nObjectives\nTo assess the advantages and disadvantages of emergency endovascular aneurysm repair (eEVAR) in comparison with conventional open surgical repair for the treatment of ruptured abdominal aortic aneurysm (RAAA). This will be determined by comparing the effects of eEVAR and conventional open surgical repair on short-term mortality, major complication rates, aneurysm exclusion (specifically endoleaks in the eEVAR treatment group), and late complications.\nSearch methods\nFor this update the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (last searched June 2016), CENTRAL (2016, Issue 5), and trials registries. We also checked reference lists of relevant publications.\nSelection criteria\nRandomised controlled trials in which participants with a clinically or radiologically diagnosed RAAA were randomly allocated to eEVAR or conventional open surgical repair.\nData collection and analysis\nTwo review authors independently assessed studies identified for potential inclusion for eligibility. Two review authors also independently completed data extraction and quality assessment. Disagreements were resolved through discussion. We performed meta-analysis using fixed-effect models with odds ratios (ORs) and 95% confidence intervals (CIs) for dichotomous data and mean differences with 95% CIs for continuous data.\nMain results\nWe included four randomised controlled trials in this review. A total of 868 participants with a clinical or radiological diagnosis of RAAA were randomised to receive either eEVAR or open surgical repair. Overall risk of bias was low, but we considered one study that performed randomisation in blocks by week and performed no allocation concealment and no blinding to be at high risk of selection bias. Another study did not adequately report random sequence generation, putting it at risk of selection bias, and two studies were underpowered. There was no clear evidence to support a difference between the two interventions for 30-day (or in-hospital) mortality (OR 0.88, 95% CI 0.66 to 1.16; moderate-quality evidence). There were a total of 44 endoleak events in 128 participants from three studies (low-quality evidence). Thirty-day complication outcomes (myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation, and respiratory failure) were reported in between one and three studies, therefore we were unable to draw a robust conclusion. We downgraded the quality of the evidence for myocardial infarction, renal complications, and respiratory failure due to imprecision, inconsistency, and risk of bias. Odds ratios for complications outcomes were OR 2.38 (95% CI 0.34 to 16.53; 139 participants; 2 studies; low-quality evidence) for myocardial infarction; OR 1.07 (95% CI 0.21 to 5.42; 255 participants; 3 studies; low-quality evidence) for renal complications; and OR 3.62 (95% CI 0.14 to 95.78; 32 participants; 1 study; low-quality evidence) for respiratory failure. There was low-quality evidence of a reduction in bowel ischaemia in the eEVAR treatment group, but very few events were reported (OR 0.37, 95% CI 0.14 to 0.94), and we downgraded the evidence due to imprecision and risk of bias. Six-month and one-year outcomes were evaluated in three studies, but only results from a single study could be used for each outcome, which showed no clear evidence of a difference between the interventions. We rated six-month mortality evidence as of moderate quality due to imprecision (OR 0.89, 95% CI 0.40 to 1.98; 116 participants).\nAuthors' conclusions\nThe conclusions of this review are currently limited by the paucity of data. We found from the data available moderate-quality evidence suggesting there is no difference in 30-day mortality between eEVAR and open repair. Not enough information was provided for complications for us to make a well-informed conclusion, although it is possible that eEVAR is associated with a reduction in bowel ischaemia. Long-term data were lacking for both survival and late complications. More high-quality randomised controlled trials comparing eEVAR and open repair for the treatment of RAAA are needed to better understand if one method is superior to the other, or if there is no difference between the methods on relevant outcomes.\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": "The abdominal aorta is the main artery supplying blood to the lower part of the body. An abnormal ballooning and weakening of the wall of the aorta (aortic aneurysm) can occur with age, particularly in older men. An aneurysm may progressively enlarge without obvious symptoms, yet it is potentially lethal as it can burst (rupture), causing massive internal bleeding. Death is inevitable unless the bleeding can be stopped and blood flow to the lower body promptly restored. Until recently this required an open operation (laparotomy) to clamp the abdominal aorta and replace the segment of the aorta with a synthetic artery tube-graft. Many patients do not survive this major operation due to the effects of massive bleeding or failure of vital organs, such as the heart, lungs, and kidneys, despite improvements in the surgical technique and care of the critically ill patient.\nEndovascular treatment, a minimally invasive technique, allows the surgeon to pass a stent graft through the blood vessels from the groin to the site of rupture, where it is positioned and attached to the healthy artery above and below the aneurysm to stop bleeding and form a new channel for blood flow. This technique is successful in suitable patients for the planned treatment of non-ruptured aneurysms and can reduce early postoperative complications and deaths." } ]

[ { "role": "user", "content": "Abstract: Background\nMind-body interventions are based on the holistic principle that mind, body and behaviour are all interconnected. Mind-body interventions incorporate strategies that are thought to improve psychological and physical well-being, aim to allow patients to take an active role in their treatment, and promote people's ability to cope. Mind-body interventions are widely used by people with fibromyalgia to help manage their symptoms and improve well-being. Examples of mind-body therapies include psychological therapies, biofeedback, mindfulness, movement therapies and relaxation strategies.\nObjectives\nTo review the benefits and harms of mind-body therapies in comparison to standard care and attention placebo control groups for adults with fibromyalgia, post-intervention and at three and six month follow-up.\nSearch methods\nElectronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), AMED (EBSCO) and CINAHL (Ovid) were conducted up to 30 October 2013. Searches of reference lists were conducted and authors in the field were contacted to identify additional relevant articles.\nSelection criteria\nAll relevant randomised controlled trials (RCTs) of mind-body interventions for adults with fibromyalgia were included.\nData collection and analysis\nTwo authors independently selected studies, extracted the data and assessed trials for low, unclear or high risk of bias. Any discrepancy was resolved through discussion and consensus. Continuous outcomes were analysed using mean difference (MD) where the same outcome measure and scoring method was used and standardised mean difference (SMD) where different outcome measures were used. For binary data standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was used.\nMain results\nSeventy-four papers describing 61 trials were identified, with 4234 predominantly female participants. The nature of fibromyalgia varied from mild to severe across the study populations. Twenty-six studies were classified as having a low risk of bias for all domains assessed. The findings of mind-body therapies compared with usual care were prioritised.\nThere is low quality evidence that in comparison to usual care controls psychological therapies have favourable effects on physical functioning (SMD -0.4, 95% CI -0.6 to -0.3, -7.5% absolute change, 2 point shift on a 0 to 100 scale), pain (SMD -0.3, 95% CI -0.5 to -0.2, -3.5% absolute change, 2 point shift on a 0 to 100 scale) and mood (SMD -0.5, 95% CI -0.6 to -0.3, -4.8% absolute change, 3 point shift on a 20 to 80 scale). There is very low quality evidence of more withdrawals in the psychological therapy group in comparison to usual care controls (RR 1.38, 95% CI 1.12 to 1.69, 6% absolute risk difference). There is lack of evidence of a difference between the number of adverse events in the psychological therapy and control groups (RR 0.38, 95% CI 0.06 to 2.50, 4% absolute risk difference).\nThere was very low quality evidence that biofeedback in comparison to usual care controls had an effect on physical functioning (SMD -0.1, 95% CI -0.4 to 0.3, -1.2% absolute change, 1 point shift on a 0 to 100 scale), pain (SMD -2.6, 95% CI -91.3 to 86.1, -2.6% absolute change) and mood (SMD 0.1, 95% CI -0.3 to 0.5, 1.9% absolute change, less than 1 point shift on a 0 to 90 scale) post-intervention. In view of the quality of evidence we cannot be certain that biofeedback has a little or no effect on these outcomes. There was very low quality evidence that biofeedback led to more withdrawals from the study (RR 4.08, 95% CI 1.43 to 11.62, 20% absolute risk difference). No adverse events were reported.\nThere was no advantage observed for mindfulness in comparison to usual care for physical functioning (SMD -0.3, 95% CI -0.6 to 0.1, -4.8% absolute change, 4 point shift on a scale 0 to 100), pain (SMD -0.1, CI -0.4 to 0.3, -1.3% absolute change, less than 1 point shift on a 0 to 10 scale), mood (SMD -0.2, 95% CI -0.5 to 0.0, -3.7% absolute change, 2 point shift on a 20 to 80 scale) or withdrawals (RR 1.07, 95% CI 0.67 to 1.72, 2% absolute risk difference) between the two groups post-intervention. However, the quality of the evidence was very low for pain and moderate for mood and number of withdrawals. No studies reported any adverse events.\nVery low quality evidence revealed that movement therapies in comparison to usual care controls improved pain (MD -2.3, CI -4.2 to -0.4, -23% absolute change) and mood (MD -9.8, 95% CI -18.5 to -1.2, -16.4% absolute change) post-intervention. There was no advantage for physical functioning (SMD -0.2, 95% CI -0.5 to 0.2, -3.4% absolute change, 2 point shift on a 0 to 100 scale), participant withdrawals (RR 1.95, 95% CI 1.13 to 3.38, 11% absolute difference) or adverse events (RR 4.62, 95% CI 0.23 to 93.92, 4% absolute risk difference) between the two groups, however rare adverse events may include worsening of pain.\nLow quality evidence revealed that relaxation based therapies in comparison to usual care controls showed an advantage for physical functioning (MD -8.3, 95% CI -10.1 to -6.5, -10.4% absolute change) and pain (SMD -1.0, 95% CI -1.6 to -0.5, -3.5% absolute change, 2 point shift on a 0 to 78 scale) but not for mood (SMD -4.4, CI -14.5 to 5.6, -7.4% absolute change) post-intervention. There was no difference between the groups for number of withdrawals (RR 4.40, 95% CI 0.59 to 33.07, 31% absolute risk difference) and no adverse events were reported.\nAuthors' conclusions\nPsychological interventions therapies may be effective in improving physical functioning, pain and low mood for adults with fibromyalgia in comparison to usual care controls but the quality of the evidence is low. Further research on the outcomes of therapies is needed to determine if positive effects identified post-intervention are sustained. The effectiveness of biofeedback, mindfulness, movement therapies and relaxation based therapies remains unclear as the quality of the evidence was very low or low. The small number of trials and inconsistency in the use of outcome measures across the trials restricted the analysis.\n\nGiven the provided abstract, please respond to the following query: \"What are mind-body interventions?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Mind-body interventions include treatments such as biofeedback, mindfulness, movement therapies, psychological therapy and relaxation therapies. Biofeedback is when you are connected to electrical sensors that help you receive information about your body to make subtle changes in your body, such as relaxing. Mindfulness means having awareness of thoughts, feelings and bodily sensations. All mind-body therapies make the link between thoughts, behaviour and feelings to help people to cope with their symptoms." } ]

[ { "role": "user", "content": "Abstract: Background\nInvasive fungal infections are important causes of morbidity and mortality among critically ill patients. Early institution of antifungal therapy is pivotal for mortality reduction. Starting a targeted antifungal therapy after culture positivity and fungi identification requires a long time. Therefore, alternative strategies (globally defined as 'untargeted antifungal treatments') for antifungal therapy institution in patients without proven microbiological evidence of fungal infections have been discussed by international guidelines. This review was originally published in 2006 and updated in 2016. This updated review provides additional evidence for the clinician dealing with suspicion of fungal infection in critically ill, non-neutropenic patients, taking into account recent findings in this field.\nObjectives\nTo assess the effects of untargeted treatment with any antifungal drug (either systemic or nonabsorbable) compared to placebo or no antifungal or any other antifungal drug (either systemic or nonabsorbable) in non-neutropenic, critically ill adults and children. We assessed effectiveness in terms of total (all-cause) mortality and incidence of proven invasive fungal infections as primary outcomes.\nSearch methods\nWe searched the following databases to February 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), and EMBASE (OVID). We also searched reference lists of identified studies and major reviews, abstracts of conference proceedings, scientific meetings and clinical trials registries. We contacted experts in the field, study authors and pharmaceutical companies as part of the search strategy.\nSelection criteria\nWe included randomized controlled trials (RCTs) (irrespective of language or publication status) comparing the use of untargeted treatment with any antifungal drug (either systemic or nonabsorbable) to placebo, no antifungal, or another antifungal agent in non-neutropenic critically ill participants.\nData collection and analysis\nThree authors independently applied selection criteria, extracted data and assessed the risk of bias. We resolved any discrepancies by discussion. We synthesized data using the random-effects model and expressed the results as risk ratios (RR) with 95% confidence intervals. We assessed overall evidence quality using the GRADE approach.\nMain results\nWe included 22 studies (total of 2761 participants). Of those 22 studies, 12 were included in the original published review and 10 were newly identified. Eleven trials compared the use of fluconazole to placebo or no antifungal treatment. Three trials compared ketoconazole versus placebo. One trial compared anidulafungin with placebo. One trial compared caspofungin to placebo. Two trials compared micafungin to placebo. One trial compared amphotericin B to placebo. Two trials compared nystatin to placebo and one trial compared the effect of clotrimazole, ketoconazole, nystatin and no treatment. We found two new ongoing studies and four new studies awaiting classification. The RCTs included participants of both genders with wide age range, severity of critical illness and clinical characteristics. Funding sources from pharmaceutical companies were reported in 11 trials and one trial reported funding from a government agency. Most of the studies had an overall unclear risk of bias for key domains of this review (random sequence generation, allocation concealment, incomplete outcome data). Two studies had a high risk of bias for key domains. Regarding the other domains (blinding of participants and personnel, outcome assessment, selective reporting, other bias), most of the studies had a low or unclear risk but four studies had a high risk of bias.\nThere was moderate grade evidence that untargeted antifungal treatment did not significantly reduce or increase total (all-cause) mortality (RR 0.93, 95% CI 0.79 to 1.09, P value = 0.36; participants = 2374; studies = 19). With regard to the outcome of proven invasive fungal infection, there was low grade evidence that untargeted antifungal treatment significantly reduced the risk (RR 0.57, 95% CI 0.39 to 0.83, P value = 0.0001; participants = 2024; studies = 17). The risk of fungal colonization was significantly reduced (RR 0.71, 95% CI 0.52 to 0.97, P value = 0.03; participants = 1030; studies = 12) but the quality of evidence was low. There was no difference in the risk of developing superficial fungal infection (RR 0.69, 95% CI 0.37 to 1.29, P value = 0.24; participants = 662; studies = 5; low grade of evidence) or in adverse events requiring cessation of treatment between the untargeted treatment group and the other group (RR 0.89, 95% CI 0.62 to 1.27, P value = 0.51; participants = 1691; studies = 11; low quality of evidence). The quality of evidence for the outcome of total (all-cause) mortality was moderate due to limitations in study design. The quality of evidence for the outcome of invasive fungal infection, superficial fungal infection, fungal colonization and adverse events requiring cessation of therapy was low due to limitations in study design, non-optimal total population size, risk of publication bias, and heterogeneity across studies.\nAuthors' conclusions\nThere is moderate quality evidence that the use of untargeted antifungal treatment is not associated with a significant reduction in total (all-cause) mortality among critically ill, non-neutropenic adults and children compared to no antifungal treatment or placebo. The untargeted antifungal treatment may be associated with a reduction of invasive fungal infections but the quality of evidence is low, and both the heterogeneity and risk of publication bias is high.\nFurther high-quality RCTs are needed to improve the strength of the evidence, especially for more recent and less studied drugs (e.g. echinocandins). Future trials should adopt standardized definitions for microbiological outcomes (e.g. invasive fungal infection, colonization) to reduce heterogeneity. Emergence of resistance to antifungal drugs should be considered as outcome in studies investigating the effects of untargeted antifungal treatment to balance risks and benefit.\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": "The quality of evidence for the outcome of mortality (all-cause) was moderate due to limitations in study design. The quality of evidence for the outcome of invasive fungal infection, superficial fungal infection, fungal colonization and adverse events requiring cessation of therapy was low due to limitations in study design, non-optimal total number of patients studied and results inconsistent across studies." } ]

[ { "role": "user", "content": "Abstract: Background\nIn some people with asthma, expiratory airflow limitation, premature closure of small airways, activity of inspiratory muscles at the end of expiration and reduced pulmonary compliance may lead to lung hyperinflation. With the increase in lung volume, chest wall geometry is modified, shortening the inspiratory muscles and leaving them at a sub-optimal position in their length-tension relationship. Thus, the capacity of these muscles to generate tension is reduced. An increase in cross-sectional area of the inspiratory muscles caused by hypertrophy could offset the functional weakening induced by hyperinflation. Previous studies have shown that inspiratory muscle training promotes diaphragm hypertrophy in healthy people and patients with chronic heart failure, and increases the proportion of type I fibres and the size of type II fibres of the external intercostal muscles in patients with chronic obstructive pulmonary disease. However, its effects on clinical outcomes in patients with asthma are unclear.\nObjectives\nTo evaluate the efficacy of inspiratory muscle training with either an external resistive device or threshold loading in people with asthma.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and reference lists of included studies. The latest search was performed in November 2012.\nSelection criteria\nWe included randomised controlled trials that involved the use of an external inspiratory muscle training device versus a control (sham or no inspiratory training device) in people with stable asthma.\nData collection and analysis\nWe used standard methodological procedures expected by The Cochrane Collaboration.\nMain results\nWe included five studies involving 113 adults. Participants in four studies had mild to moderate asthma and the fifth study included participants independent of their asthma severity. There were substantial differences between the studies, including the training protocol, duration of training sessions (10 to 30 minutes) and duration of the intervention (3 to 25 weeks). Three clinical trials were produced by the same research group. Risk of bias in the included studies was difficult to ascertain accurately due to poor reporting of methods.\nThe included studies showed a statistically significant increase in inspiratory muscle strength, measured by maximal inspiratory pressure (PImax) (mean difference (MD) 13.34 cmH2O, 95% CI 4.70 to 21.98, 4 studies, 84 participants, low quality evidence). Our other primary outcome, exacerbations requiring a course of oral or inhaled corticosteroids or emergency department visits, was not reported. For the secondary outcomes, results from one trial showed no statistically significant difference between the inspiratory muscle training group and the control group for maximal expiratory pressure, peak expiratory flow rate, forced expiratory volume in one second, forced vital capacity, sensation of dyspnoea and use of beta2-agonist. There were no studies describing inspiratory muscle endurance, hospital admissions or days off work or school.\nAuthors' conclusions\nThere is no conclusive evidence in this review to support or refute inspiratory muscle training for asthma. The evidence was limited by the small number of trials with few participants together with the risk of bias. More well conducted randomised controlled trials are needed. Future trials should investigate the following outcomes: lung function, exacerbation rate, asthma symptoms, hospital admissions, use of medications and days off work or school. Inspiratory muscle training should also be assessed in people with more severe asthma and conducted in children with asthma.\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": "Asthma is the most common chronic disease found in children and young adults. Clinically, asthma is characterized by symptoms of shortness of breath, wheeze and cough, and episodes of worsening of symptoms. The objective of asthma treatment is to achieve and maintain control of the disease and to reduce symptoms. In most cases the symptoms can be controlled with inhalers, but IMT may assist treatment. For people with other chronic respiratory diseases, IMT significantly increases the strength of the inspiratory muscles, reduces dyspnoea and improves quality of life. It is unclear whether inspiratory muscle training has similar benefits in individuals with asthma." } ]

[ { "role": "user", "content": "Abstract: Background\nFetal compromise in the term pregnancy is suspected when the following clinical indicators are present: intrauterine growth restriction (IUGR), decreased fetal movement (DFM), or when investigations such as cardiotocography (CTG) and ultrasound reveal results inconsistent with standard measurements. Pathological results would necessitate the need for immediate delivery, but the management for ‘suspicious’ results remains unclear and varies widely across clinical centres. There is clinical uncertainty as to how to best manage women presenting with a suspected term compromised baby in an otherwise healthy pregnancy.\nObjectives\nTo assess, using the best available evidence, the effects of immediate delivery versus expectant management of the term suspected compromised baby on neonatal, maternal and long-term outcomes.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies.\nSelection criteria\nRandomised or quasi-randomised controlled trials comparing expectant management versus planned early delivery for women with a suspected compromised fetus from 37 weeks' gestation or more.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and assessed trial quality. Two review authors independently extracted data. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.\nMain results\nOf the 20 reports identified by the search strategy, we included three trials (546 participants: 269 to early delivery and 277 to expectant management), which met our inclusion criteria. Two of the trials compared outcomes in 492 pregnancies with IUGR of the fetus, and one in 54 pregnancies with oligohydramnios. All three trials were of reasonable quality and at low risk of bias. The level of evidence was graded moderate, low or very low, downgrading mostly for imprecision and for some indirectness. Overall, there was no difference in the primary neonatal outcomes of perinatal mortality (no deaths in either group, one trial, 459 women, evidence graded moderate), major neonatal morbidity (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.01 to 2.81, one trial, 459 women, evidence graded low), or neurodevelopmental disability/impairment at two years of age (RR 2.04, 95% CI 0.62 to 6.69,one trial, 459 women, evidence graded low). There was no difference in the risk of necrotising enterocolitis (one trial, 333 infants) or meconium aspiration (one trial, 459 infants), There was also no difference in the reported primary maternal outcomes: maternal mortality (RR 3.07, 95% CI 0.13 to 74.87, one trial, 459 women, evidence graded low), and significant maternal morbidity (RR 0.92, 95% CI 0.38 to 2.22, one trial, 459 women, evidence graded low).\nThe gestational age at birth was on average 10 days earlier in women randomised to early delivery (mean difference (MD) -9.50, 95% CI -10.82 to -8.18, one trial, 459 women) and women in the early delivery group were significantly less likely to have a baby beyond 40 weeks' gestation (RR 0.10, 95% CI 0.01 to 0.67, one trial, 33 women). Significantly more infants in the planned early delivery group were admitted to intermediate care nursery (RR 1.28, 95% CI 1.02 to 1.61, two trials, 491 infants). There was no difference in the risk of respiratory distress syndrome, (one trial, 333 infants), Apgar score less than seven at five minutes (three trials, 546 infants), resuscitation required (one trial, 459 infants), mechanical ventilation (one trial, 337 infants), admission to neonatal intensive care unit (NICU) (RR 0.88, 95% CI 0.35 to 2.23, three trials, 545 infants, evidence graded very low), length of stay in NICU/SCN (one trial, 459 infants), and sepsis (two trials, 366 infants).\nBabies in the expectant management group were more likely to be < 2.3rd centile for birthweight (RR 0.51, 95% CI 0.36 to 0.73, two trials, 491 infants), however there was no difference in the proportion of babies with birthweight < 10th centile (RR 0.98, 95% CI 0.88 to 1.10). There was no difference in any of the reported maternal secondary outcomes including: caesarean section rates (RR 1.02, 95% CI 0.65 to 1.59, three trials, 546 women, evidence graded low), placental abruption (one trial, 459 women), pre-eclampsia (one trial, 459 women), vaginal birth (three trials 546 women), assisted vaginal birth (three trials 546 women), breastfeeding rates (one trial, 218 women), and number of weeks of breastfeeding after delivery one trial, 124 women). There was an expected increase in induction in the early delivery group (RR 2.05, 95% CI 1.78 to 2.37, one trial, 459 women).\nNo data were reported for the pre-specified secondary neonatal outcomes of the number of days of mechanical ventilation, moderate-severe hypoxic ischaemic encephalopathy or need for therapeutic hypothermia. Likewise, no data were reported for secondary maternal outcomes of postnatal infection, maternal satisfaction or views of care.\nAuthors' conclusions\nA policy for planned early delivery versus expectant management for a suspected compromised fetus at term does not demonstrate any differences in major outcomes of perinatal mortality, significant neonatal or maternal morbidity or neurodevelopmental disability. In women randomised to planned early delivery, the gestational age at birth was on average 10 days earlier, women were less likely to have a baby beyond 40 weeks' gestation, they were more likely to be induced and infants were more likely to be admitted to intermediate care nursery. There was also a significant difference in the proportion of babies with a birthweight centile < 2.3rd, however this did not translate into a reduction in morbidity. The review is informed by only one large trial and two smaller trials assessing fetuses with IUGR or oligohydramnios and therefore cannot be generalised to all term pregnancies with suspected fetal compromise. There are other indications for suspecting compromise in a fetus at or near term such as maternal perception of DFM, and ultrasound and/or CTG abnormalities. Future randomised trials need to assess effectiveness of timing of delivery for these indications.\n\nGiven the provided abstract, please respond to the following query: \"What evidence did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found three trials involving 546 pregnant women and their babies at term (search – 31 May 2015). All three trials looked at using induction of labour for an early birth. Two trials looked at babies thought to have growth restriction and one trial looked at babies thought to have a small volume of amniotic fluid (oligohydramnios). All three trials were of reasonable quality and most of the evidence comes from the largest trial which compared babies who were growth restricted. There is no information about funding sources for these trials.\nOverall, we found no major differences between these two strategies in terms of the babies’ survival, the numbers of very sick babies nor in the numbers of babies with problems in development.\nWe looked at many other outcomes, too, including how many caesarean sections there were, and how many operative vaginal births (with forceps or ventouse). However, we cannot be sure there are no real major differences because the numbers of women and babies included were too small. There were more inductions of labour in the early birth group." } ]

[ { "role": "user", "content": "Abstract: Background\nFibromyalgia (FM) is a clinically well-defined chronic condition of unknown aetiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. Patients often report high disability levels and negative mood. Psychotherapies focus on reducing key symptoms, improving daily functioning, mood and sense of personal control over pain.\nObjectives\nTo assess the benefits and harms of cognitive behavioural therapies (CBTs) for treating FM at end of treatment and at long-term (at least six months) follow-up.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE (1966 to 28 August 2013), PsycINFO (1966 to 28 August 2013) and SCOPUS (1980 to 28 August 2013). We searched http://www.clinicaltrials.gov (web site of the US National Institutes of Health) and the World Health Organization Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/) for ongoing trials (last search 28 August,2013), and the reference lists of reviewed articles.\nSelection criteria\nWe selected randomised controlled trials of CBTs with children, adolescents and adults diagnosed with FM.\nData collection and analysis\nThe data of all included studies were extracted and the risks of bias of the studies were assessed independently by two review authors. Discrepancies were resolved by discussion.\nMain results\nTwenty-three studies with 24 study arms with CBTs were included. A total of 2031 patients were included; 1073 patients in CBT groups and 958 patients in control groups. Only two studies were without any risk of bias. The GRADE quality of evidence of the studies was low. CBTs were superior to controls in reducing pain at end of treatment by 0.5 points on a scale of 0 to 10 (standardised mean difference (SMD) - 0.29; 95% confidence interval (CI) -0.49 to -0.17) and by 0.6 points at long-term follow-up (median 6 months) (SMD -0.40; 95% CI -0.62 to -0.17); in reducing negative mood at end of treatment by 0.7 points on a scale of 0 to 10 (SMD - 0.33; 95% CI -0.49 to -0.17) and by 1.3 points at long-term follow-up (median 6 months) (SMD -0.43; 95% CI -0.75 to -0.11); and in reducing disability at end of treatment by 0.7 points on a scale of 0 to 10 (SMD - 0.30; 95% CI -0.51 to -0.08) and at long-term follow-up (median 6 months) by 1.2 points (SMD -0.52; 95% CI -0.86 to -0.18). There was no statistically significant difference in dropout rates for any reasons between CBTs and controls (risk ratio (RR) 0.94; 95% CI 0.65 to 1.35).\nAuthors' conclusions\nCBTs provided a small incremental benefit over control interventions in reducing pain, negative mood and disability at the end of treatment and at long-term follow-up. The dropout rates due to any reason did not differ between CBTs and controls.\n\nGiven the provided abstract, please respond to the following query: \"Withdrawing from treatment\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "\n- The number of people who withdrew from CBTs compared to control interventions due to any reason was equal.\n- 15 people out of 100 who used CBTs withdrew from treatment due to any reason;\n- 15 people out of 100 who used control interventions withdrew from treatment due to any reason." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review.\nObjectives\nTo assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis.\nSearch methods\nWe searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.\nDate of the most recent search: 31 January 2019.\nWe also searched online trial registries. Date of latest search: 25 February 2019.\nSelection criteria\nAll randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis.\nData collection and analysis\nThe two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies.\nMain results\nWe identified 15 studies for possible inclusion in the review. Five studies reporting results from a total of 354 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One cross-over trial had 26 participants who received the first-arm treatment but only 15 received the second arm. One study had a low risk of bias for all criteria assessed; the remaining included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.\nThere was little or no difference between treatment groups in: forced expiratory volume in one second, mean difference (MD) 0.33 (95% confidence interval (CI) -2.81 to 3.48, moderate-quality evidence); forced vital capacity, MD 0.29 (95% CI -6.58 to 7.16, low-quality evidence); % weight for height, MD -0.82 (95% CI -3.77 to 2.13, low-quality evidence); body mass index, MD 0.00 (95% CI -0.42 to 0.42, low-quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% CI 0.04 to 7.96, moderate-quality evidence). Once-daily treatment in children probably improved the percentage change in creatinine, MD -8.20 (95% CI -15.32 to -1.08, moderate-quality evidence), but showed no difference in adults, MD 3.25 (95% CI -1.82 to 8.33, moderate-quality evidence). The included trials did not report antibiotic resistance patterns or quality of life.\nAuthors' conclusions\nOnce- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.\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": "Most people with cystic fibrosis develop persistent lung infections and they may receive frequent courses of intravenous antibiotics to treat pulmonary exacerbations. Giving the antibiotics just once per day rather than several doses per day reduces the cost of treatment and the time involved." } ]

[ { "role": "user", "content": "Abstract: Background\nCutaneous melanoma is amongst the most aggressive of all skin cancers. Neoadjuvant treatment is a form of induction therapy, given to shrink a cancerous tumour prior to the main treatment (usually surgery). The purpose is to improve survival and surgical outcomes. This review systematically appraises the literature investigating the use of neoadjuvant treatment for stage III and IV cutaneous melanoma.\nObjectives\nTo assess the effects of neoadjuvant treatment in adults with stage III or stage IV melanoma according to the seventh edition American Joint Committee on Cancer (AJCC) staging system.\nSearch methods\nWe searched the following databases up to 10 August 2021 inclusive: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and four trials registers, together with reference checking and contact with study authors to identify additional studies. We also handsearched proceedings from specific conferences from 2016 to 2020 inclusive.\nSelection criteria\nRandomised controlled trials (RCTs) of people with stage III and IV melanoma, comparing neoadjuvant treatment strategies (using targeted treatments, immunotherapies, radiotherapy, topical treatments or chemotherapy) with any of these agents or current standard of care (SOC), were eligible for inclusion.\nData collection and analysis\nWe used standard Cochrane methods. Primary outcomes were overall survival (OS) and adverse effects (AEs). Secondary outcomes included time to recurrence (TTR), quality of life (QOL), and overall response rate (ORR). We used GRADE to evaluate the certainty of the evidence.\nMain results\nWe included eight RCTs involving 402 participants. Studies enrolled adults, mostly with stage III melanoma, investigated immunotherapies, chemotherapy, or targeted treatments, and compared these with surgical excision with or without adjuvant treatment. Duration of follow-up and therapeutic regimens varied, which, combined with heterogeneity in the population and definitions of the endpoints, precluded meta-analysis of all identified studies. We performed a meta-analysis including three studies.\nWe are very uncertain if neoadjuvant treatment increases OS when compared to no neoadjuvant treatment (hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.15 to 1.21; 2 studies, 171 participants; very low-certainty evidence). Neoadjuvant treatment may increase the rate of AEs, but the evidence is very uncertain (26% versus 16%, risk ratio (RR) 1.58, 95% CI 0.97 to 2.55; 2 studies, 162 participants; very low-certainty evidence). We are very uncertain if neoadjuvant treatment increases TTR (HR 0.51, 95% CI 0.22 to 1.17; 2 studies, 171 participants; very low-certainty evidence). Studies did not report ORR as a comparative outcome or measure QOL data.\nWe are very uncertain whether neoadjuvant targeted treatment with dabrafenib and trametinib increases OS (HR 0.28, 95% CI 0.03 to 2.25; 1 study, 21 participants; very low-certainty evidence) or TTR (HR 0.02, 95% CI 0.00 to 0.22; 1 study, 21 participants; very low-certainty evidence) when compared to surgery. The study did not report comparative rates of AEs and overall response, and did not measure QOL.\nWe are very uncertain if neoadjuvant immunotherapy with talimogene laherparepvec increases OS when compared to no neoadjuvant treatment (HR 0.49, 95% CI 0.15 to 1.64; 1 study, 150 participants, very low-certainty evidence). It may have a higher rate of AEs, but the evidence is very uncertain (16.5% versus 5.8%, RR 2.84, 95% CI 0.96 to 8.37; 1 study, 142 participants; very low-certainty evidence). We are very uncertain if it increases TTR (HR 0.75, 95% CI 0.31 to 1.79; 1 study, 150 participants; very low-certainty evidence). The study did not report comparative ORRs or measure QOL.\nOS was not reported for neoadjuvant immunotherapy (combined ipilimumab and nivolumab) when compared to the combination of ipilimumab and nivolumab as adjuvant treatment. There may be little or no difference in the rate of AEs between these treatments (9%, RR 1.0, 95% CI 0.75 to 1.34; 1 study, 20 participants; low-certainty evidence). The study did not report comparative ORRs or measure TTR and QOL.\nNeoadjuvant immunotherapy (combined ipilimumab and nivolumab) likely results in little to no difference in OS when compared to neoadjuvant nivolumab monotherapy (P = 0.18; 1 study, 23 participants; moderate-certainty evidence). It may increase the rate of AEs, but the certainty of this evidence is very low (72.8% versus 8.3%, RR 8.73, 95% CI 1.29 to 59; 1 study, 23 participants); this trial was halted early due to observation of disease progression preventing surgical resection in the monotherapy arm and the high rate of treatment-related AEs in the combination arm. Neoadjuvant combination treatment may lead to higher ORR, but the evidence is very uncertain (72.8% versus 25%, RR 2.91, 95% CI 1.02 to 8.27; 1 study, 23 participants; very low-certainty evidence). It likely results in little to no difference in TTR (P = 0.19; 1 study, 23 participants; low-certainty evidence). The study did not measure QOL.\nOS was not reported for neoadjuvant immunotherapy (combined ipilimumab and nivolumab) when compared to neoadjuvant sequential immunotherapy (ipilimumab then nivolumab). Only Grade 3 to 4 immune-related AEs were reported; fewer were reported with combination treatment, and the sequential treatment arm closed early due to a high incidence of severe AEs. The neoadjuvant combination likely results in a higher ORR compared to sequential neoadjuvant treatment (60.1% versus 42.3%, RR 1.42, 95% CI 0.87 to 2.32; 1 study, 86 participants; low-certainty evidence). The study did not measure TTR and QOL.\nNo data were reported on OS, AEs, TTR, or QOL for the comparison of neoadjuvant interferon (HDI) plus chemotherapy versus neoadjuvant chemotherapy. Neoadjuvant HDI plus chemotherapy may have little to no effect on ORR, but the evidence is very uncertain (33% versus 22%, RR 1.75, 95% CI 0.62 to 4.95; 1 study, 36 participants; very low-certainty evidence).\nAuthors' conclusions\nWe are uncertain if neoadjuvant treatment increases OS or TTR compared with no neoadjuvant treatment, and it may be associated with a slightly higher rate of AEs. There is insufficient evidence to support the use of neoadjuvant treatment in clinical practice. Priorities for research include the development of a core outcome set for neoadjuvant trials that are adequately powered, with validation of pathological and radiological responses as intermediate endpoints, to investigate the relative benefits of neoadjuvant treatment compared with adjuvant treatment with immunotherapies or targeted therapies.\n\nGiven the provided abstract, please respond to the following query: \"What does this mean?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We are uncertain if neoadjuvant treatment of stage III or IV melanoma will help people to live longer, or to have more time before the disease recurs. We are also uncertain if the benefits of neoadjuvant treatment outweigh the risks of adverse events." } ]

[ { "role": "user", "content": "Abstract: Background\nGastric cancer is the third most common cause of cancer-related mortality in the world. Currently there are two surgical options for potentially curable patients (i.e. people with non-metastatic gastric cancer), laparoscopic and open gastrectomy. However, it is not clear whether one of these options is superior.\nObjectives\nTo assess the benefits and harms of laparoscopic gastrectomy or laparoscopy-assisted gastrectomy versus open gastrectomy for people with gastric cancer. In particular, we planned to investigate the effects by patient groups, such as cancer stage, anaesthetic risk, and body mass index (BMI), and by intervention methods, such as method of anastomosis, type of gastrectomy and laparoscopic or laparoscopically-assisted gastrectomy.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov and the WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) until September 2015. We also screened reference lists from included trials.\nSelection criteria\nTwo review authors independently selected references for further assessment by going through all titles and abstracts. Further selection was based on review of full text articles for selected references.\nData collection and analysis\nTwo review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes, the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes and the hazard ratio (HR) for time-to-event outcomes. We performed meta-analyses where it was meaningful.\nMain results\nIn total, 2794 participants were randomised in 13 trials included in this review. All the trials were at unclear or high risk of bias. One trial (which included 53 participants) did not contribute any data to this review. A total of 213 participants were excluded in the remaining trials after randomisation, leaving a total of 2528 randomised participants for analysis, with 1288 undergoing laparoscopic gastrectomy and 1240 undergoing open gastrectomy. All the participants were suitable for major surgery.\nThere was no difference in the proportion of participants who died within thirty days of treatment between laparoscopic gastrectomy (7/1188: adjusted proportion = 0.6% (based on meta-analysis)) and open gastrectomy (4/1447: 0.3%) (RR 1.60, 95% CI 0.50 to 5.10; risk difference 0.00, 95% CI -0.01 to 0.01; participants = 2335; studies = 11; I2 = 0%; low quality evidence). There were no events in either group for short-term recurrence (participants = 103; studies = 3), proportion requiring blood transfusion (participants = 66; studies = 2), and proportion with positive margins at histopathology (participants = 28; studies = 1). None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term mortality (HR 0.94, 95% CI 0.70 to 1.25; participants = 195; studies = 3; I2 = 0%; very low quality evidence), serious adverse events within three months (laparoscopic gastrectomy (7/216: adjusted proportion = 3.6%) versus open gastrectomy (13/216: 6%) (RR 0.60, 95% CI 0.27 to 1.34; participants = 432; studies = 8; I2 = 0%; very low quality evidence), long-term recurrence (HR 0.95, 95% CI 0.70 to 1.30; participants = 162; studies = 4; very low quality evidence), adverse events within three months (laparoscopic gastrectomy (204/268: adjusted proportion = 16.1%) versus open gastrectomy (253/1222: 20.7%) (RR 0.78, 95% CI 0.60 to 1.01; participants = 2490; studies = 11; I2 = 38%; very low quality evidence), quantity of perioperative blood transfused (SMD 0.05, 95% CI -0.27 to 0.38; participants = 143; studies = 2; I2 = 0%; very low quality evidence), length of hospital stay (MD -1.82 days, 95% CI -3.72 to 0.07; participants = 319; studies = 6; I2 = 83%; very low quality evidence), and number of lymph nodes harvested (MD -0.63, 95% CI -1.51 to 0.25; participants = 472; studies = 9; I2 = 40%; very low quality evidence) were imprecise. There was no alteration in the interpretation of the results in any of the subgroups.\nAuthors' conclusions\nBased on low quality evidence, there is no difference in short-term mortality between laparoscopic and open gastrectomy. Based on very low quality evidence, there is no evidence for any differences in short-term or long-term outcomes between laparoscopic and open gastrectomy. However, the data are sparse, and the confidence intervals were wide, suggesting that significant benefits or harms of laparoscopic gastrectomy cannot be ruled out. Several trials are currently being conducted and interim results of these trials have been included in this review. These trials need to perform intention-to-treat analysis to ensure that the results are reliable and report the results according to the CONSORT Statement.\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": "Stomach cancer is the third most frequent cause of cancer-related death in the world. If cancer has not spread to other areas of the body, and if the person can withstand a major operation, depending upon the part of the stomach involved, removal of part of the stomach, or the entire stomach (gastrectomy), is the only treatment that offers long-term cure of cancer. Gastrectomy can be performed by laparoscopic (key hole) operation, or by open operation, which involves a large cut. While the cut is smaller with key hole surgery, it is not clear whether key hole surgery is as safe as open surgery, and whether it offers any advantages in terms of quicker recovery of people undergoing gastrectomy. We sought to resolve this issue by searching the medical literature for studies reported until September 2015 that compared laparoscopic and open gastrectomy in people with stomach cancer." } ]

[ { "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 find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Fourteen studies investigated different red flags used to identify spinal fractures, and most of the red flags were not accurate or useful. Overall, the four best red flags found were corticosteroid use (e.g. medicines that can weaken bones), person's age (e.g. aged above 70 years), trauma (e.g. a fall), and a contusion (bruising) or abrasion (cuts and grazes).\nIn the primary healthcare setting (e.g. general practitioners), 'trauma' as a red flag was best to screen for 'unspecified spinal fracture' and 'osteoporotic spinal fracture'. 'Older age' as a red flag was best to screen for 'unspecified spinal fracture' in primary care. 'Corticosteroid use' may be useful as a red flag in primary care to screen for 'unspecified spinal fracture' and 'osteoporotic spinal fracture'. Red flags as part of a combination of index tests such as 'older age and female gender' as a red flag in primary care is best to screen for 'unspecified spinal fracture'.\nIn the secondary healthcare setting (e.g. specialists and consultants), 'trauma' as a red flag is best to screen for 'unspecified spinal fracture' and 'older age' for 'osteoporotic spinal fracture'. Red flags as part of a combination of index tests such as 'older age and trauma' in secondary care as a red flag is best to screen for 'unspecified spinal fracture'. When 'four of five tests' are positive in secondary care as a red flag, it may be used to screen for 'osteoporotic spinal fracture'.\nIn the tertiary care setting (e.g. specialised care in a hospital setting), the 'presence of contusion/abrasion' as a red flag was best to screen for 'spinal compression fracture'." } ]

[ { "role": "user", "content": "Abstract: Background\nOrgan injury is a common and severe complication of cardiac surgery that contributes to the majority of deaths. There are no effective treatment or prevention strategies. It has been suggested that innate immune system activation may have a causal role in organ injury. A wide range of organ protection interventions targeting the innate immune response have been evaluated in randomised controlled trials (RCTs) in adult cardiac surgery patients, with inconsistent results in terms of effectiveness.\nObjectives\nThe aim of the review was to summarise the results of RCTs of organ protection interventions targeting the innate immune response in adult cardiac surgery. The review considered whether the interventions had a treatment effect on inflammation, important clinical outcomes, or both.\nSearch methods\nCENTRAL, MEDLINE, Embase, conference proceedings and two trial registers were searched on October 2022 together with reference checking to identify additional studies.\nSelection criteria\nRCTs comparing organ protection interventions targeting the innate immune response versus placebo or no treatment in adult patients undergoing cardiac surgery where the treatment effect on innate immune activation and on clinical outcomes of interest were reported.\nData collection and analysis\nSearches, study selection, quality assessment, and data extractions were performed independently by pairs of authors. The primary inflammation outcomes were peak IL-6 and IL-8 concentrations in blood post-surgery. The primary clinical outcome was in-hospital or 30-day mortality. Treatment effects were expressed as risk ratios (RR) and standardised mean difference (SMD) with 95% confidence intervals (CI). Meta-analyses were performed using random effects models, and heterogeneity was assessed using I2.\nMain results\nA total of 40,255 participants from 328 RCTs were included in the synthesis. The effects of treatments on IL-6 (SMD -0.77, 95% CI -0.97 to -0.58, I2 = 92%) and IL-8 (SMD -0.92, 95% CI -1.20 to -0.65, I2 = 91%) were unclear due to heterogeneity. Heterogeneity for inflammation outcomes persisted across multiple sensitivity and moderator analyses. The pooled treatment effect for in-hospital or 30-day mortality was RR 0.78, 95% CI 0.68 to 0.91, I2 = 0%, suggesting a significant clinical benefit. There was little or no treatment effect on mortality when analyses were restricted to studies at low risk of bias. Post hoc analyses failed to demonstrate consistent treatment effects on inflammation and clinical outcomes. Levels of certainty for pooled treatment effects on the primary outcomes were very low.\nAuthors' conclusions\nA systematic review of RCTs of organ protection interventions targeting innate immune system activation did not resolve uncertainty as to the effectiveness of these treatments, or the role of innate immunity in organ injury following cardiac surgery.\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 understand if reducing the inflammatory response after cardiac surgery had a clinical benefit." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic health conditions in children and adolescents can have profound impacts on education, well-being and health. They are described as non-communicable illnesses that are prolonged in duration, do not resolve spontaneously, and rarely cured completely. Due to variations in the definition of chronic health conditions and how they are measured prevalence estimates vary considerably and have been reported to be as high as 44% in children and adolescents. Of young people with a chronic health condition, an estimated 5% are affected by severe conditions characterised by limitations to daily activities impacting their ability to attend school. School attendance is important for academic and social skill development as well as well-being. When children and adolescents are absent from school due to a chronic health condition, school engagement can be affected. Disengagement from school is associated with poorer academic achievement, social-emotional functioning and career choices. Education support services for children and adolescents with chronic health conditions aim to prevent disengagement from school, education and learning during periods where their illness caused them to miss school. However, there is limited evidence on the effectiveness of educational support interventions at improving school engagement and educational/learning outcomes for children and adolescents with chronic health conditions.\nObjectives\nTo describe the nature of educational support interventions for children and adolescents with a chronic health condition, and to examine the effectiveness of these interventions on school engagement and academic achievement.\nSearch methods\nWe searched eight electronic databases which span the health/medical, social sciences and education disciplines between 18 and 25 January 2021: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid). CINAHL (EBSCO), PsycINFO (EBSCO), ERIC (Education Resources Information Center), Applied Social Sciences Index and Abstracts: ASSIA (ProQuest), and PubMed (from 2019). We also searched five grey literature trials registers and databases between 8 and 12 February 2021 to identify additional published and unpublished studies, theses and conference abstracts, as well as snowballing reference lists of included studies.\nSelection criteria\nRandomised controlled trials (RCTs), controlled before-and-after studies and interrupted time series studies that met the inclusion criteria were selected. Other inclusion criteria were: participants - must include children or adolescents (aged four to 18 years) with a chronic health condition, intervention - must include educational support, outcomes - must report the primary outcomes (i.e. school engagement or academic achievement) or secondary outcomes (i.e. quality of life, transition to school/school re-entry, mental health or adverse outcomes).\nData collection and analysis\nTwo people independently screened titles and abstracts, and full-text articles, to identify included studies. Where disagreements arose between reviewers, the two reviewers discussed the discrepancy. If resolution was unable to be achieved, the issues were discussed with a senior reviewer to resolve the matter. We extracted study characteristic data and risk of bias data from the full texts of included studies using a data extraction form before entering the information into Review Manager 5.4.1. Two people independently extracted data, assessed risk of bias of individual studies and undertook GRADE assessments of the quality of the evidence.\nMeta-analysis was not possible due to the small number of studies for each outcome. Our synthesis, therefore, used vote-counting based on the direction of the effect/impact of the intervention.\nMain results\nThe database searches identified 14,202 titles and abstracts. Grey literature and reference list searches did not identify any additional studies that met the inclusion criteria. One hundred and twelve full-text studies were assessed for eligibility, of which four studies met the eligibility criteria for inclusion in the review. All studies were randomised controlled studies with a combined total of 359 participants. All included studies were disease-specific; three studies focused on children with cancer, and one study focused on children with Attention Deficit Hyperactivity Disorder (ADHD).\nThere was evidence that education support improved school engagement with three of four studies favouring the intervention. Three studies measured academic achievement but only two studies provided effect estimates. Based on the vote-counting method, we found contradictory results from the studies: one study showed a positive direction of effect and the other study showed a negative direction of effect. One study measured transition back to school and found a positive impact of education support favouring the intervention (SMD 0.18, 95% CI -0.46 to 0.96, no P value reported). The result came from a single study with a small sample size (n = 30), and produced a confidence interval that indicated the possibility of a very small or no effect. The overall certainty of evidence for these three outcomes was judged to be 'very low'.\nTwo of four studies measured mental health (measured as self-esteem). Both studies reported a positive impact of education support interventions on mental health; this was the only outcome for which the overall certainty of evidence was judged to be 'low' rather than 'very low'.\nNo studies measured or reported quality of life or adverse effects.\nRisk of bias (selection, performance, detection, attrition, reporting and other bias) was assessed using the Cochrane risk of bias tool for randomised trials (version 1). Overall risk of bias for all studies was assessed as 'high risk' because all studies had at least one domain at high risk of bias.\nAuthors' conclusions\nThis review has demonstrated the infancy of quality research on the effectiveness of education support interventions for children and adolescents with chronic health conditions. At best, we can say that we are uncertain whether education support interventions improve either academic achievement or school engagement. Of the secondary outcomes, we are also uncertain whether education support interventions improve transition back to school, or school re-entry. However, we suggest there is some evidence that education support may slightly improve mental health, measured as self-esteem. Given the current state of the evidence of the effectiveness of education support interventions for children and adolescents with chronic health conditions, we highlight some important implications for future research in this field to strengthen the evidence that can inform effective practice and policy.\n\nGiven the provided abstract, please respond to the following query: \"What are the limitations of the evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Overall, the certainty of the evidence was judged to be low for the mental health outcome and very low for academic achievement, school engagement and return to school. The main reasons for this were that there were different types of education support programmes trialed, conflicting results, different types and sometimes indirect measures of the outcomes across studies, a large amount of missing data and there was not enough information in the reporting of outcome data. These problems, and the small number of studies included, means we cannot make clear statements about the effects of these programmes." } ]

[ { "role": "user", "content": "Abstract: Background\nSeveral comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review.\nObjectives\nTo assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy.\nSearch methods\nWe performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020.\nSelection criteria\nWe included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI-based targeted therapy.\nData collection and analysis\nTwo review authors independently assessed the included studies and extracted data for the primary outcomes: progression-free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health-related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach.\nMain results\nWe included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons.\n1. Pazopanib versus sunitinib\nPazopanib may result in little to no difference in PFS as compared to sunitinib (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.90 to 1.23; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 420 per 1000 in this trial at 12 months, this corresponds to 18 fewer participants experiencing PFS (95% CI 76 fewer to 38 more) per 1000 participants. Pazopanib may result in little to no difference in OS compared to sunitinib (HR 0.92, 95% CI 0.80 to 1.06; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 27 more OSs (95% CI 19 fewer to 70 more) per 1000 participants. Pazopanib may result in little to no difference in SAEs as compared to sunitinib (risk ratio (RR) 1.01, 95% CI 0.94 to 1.09; 1 study, 1102 participants; low-certainty evidence). Based on the control event risk of 734 per 1000 in this trial, this corresponds to 7 more participants experiencing SAEs (95% CI 44 fewer to 66 more) per 1000 participants.\n2. Sunitinib versus avelumab and axitinib\nSunitinib probably reduces PFS as compared to avelumab plus axitinib (HR 1.45, 95% CI 1.17 to 1.80; 1 study, 886 participants; moderate-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 130 fewer participants experiencing PFS (95% CI 209 fewer to 53 fewer) per 1000 participants. Sunitinib may result in little to no difference in OS (HR 1.28, 95% CI 0.92 to 1.79; 1 study, 886 participants; low-certainty evidence). Based on the control event risk of 890 per 1000 in this trial at 12 months, this would result in 29 fewer OSs (95% CI 78 fewer to 8 more) per 1000 participants. Sunitinib may result in little to no difference in SAEs (RR 1.01, 95% CI 0.93 to 1.10; 1 study, 873 participants; low-certainty evidence). Based on the control event risk of 705 per 1000 in this trial, this corresponds to 7 more SAEs (95% CI 49 fewer to 71 more) per 1000 participants.\n3. Sunitinib versus pembrolizumab and axitinib\nSunitinib probably reduces PFS as compared to pembrolizumab plus axitinib (HR 1.45, 95% CI 1.19 to 1.76; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 590 per 1000 in this trial at 12 months, this corresponds to 125 fewer participants experiencing PFS (95% CI 195 fewer to 56 fewer) per 1000 participants. Sunitinib probably reduces OS (HR 1.90, 95% CI 1.36 to 2.65; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 880 per 1000 in this trial at 12 months, this would result in 96 fewer OSs (95% CI 167 fewer to 40 fewer) per 1000 participants. Sunitinib may reduce SAEs as compared to pembrolizumab plus axitinib (RR 0.90, 95% CI 0.81 to 1.02; 1 study, 854 participants; low-certainty evidence) although the CI includes the possibility of no effect. Based on the control event risk of 604 per 1000 in this trial, this corresponds to 60 fewer SAEs (95% CI 115 fewer to 12 more) per 1000 participants.\n4. Sunitinib versus nivolumab and ipilimumab\nSunitinib may reduce PFS as compared to nivolumab plus ipilimumab (HR 1.30, 95% CI 1.11 to 1.52; 1 study, 847 participants; low-certainty evidence). Based on the control event risk of 280 per 1000 in this trial at 30 months' follow-up, this corresponds to 89 fewer PFSs (95% CI 136 fewer to 37 fewer) per 1000 participants. Sunitinib reduces OS (HR 1.52, 95% CI 1.23 to 1.89; 1 study, 847 participants; high-certainty evidence). Based on the control event risk 600 per 1000 in this trial at 30 months, this would result in 140 fewer OSs (95% CI 219 fewer to 67 fewer) per 1000 participants. Sunitinib probably increases SAEs (RR 1.37, 95% CI 1.22 to 1.53; 1 study, 1082 participants; moderate-certainty evidence). Based on the control event risk of 457 per 1000 in this trial, this corresponds to 169 more SAEs (95% CI 101 more to 242 more) per 1000 participants.\nAuthors' conclusions\nBased on the low to high certainty of evidence, several combinations of immune checkpoint inhibitors appear to be superior to single-agent targeted therapy in terms of PFS and OS, and with a favourable AE profile. Some single-agent targeted therapies demonstrated a similar or improved oncological outcome compared to others; minor differences were observed for AE within this group. The certainty of evidence was variable ranging from high to very low and all comparisons were based on single trials.\n\nGiven the provided abstract, please respond to the following query: \"1. Pazopanib versus sunitinib (targeted therapy versus targeted therapy)\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Pazopanib may make little to no difference in progression, survival, and serious unwanted effects compared to sunitinib." } ]

[ { "role": "user", "content": "Abstract: Background\nThe diagnosis of Alzheimer's disease dementia and other dementias relies on clinical assessment. There is a high prevalence of cognitive disorders, including undiagnosed dementia in secondary care settings. Short cognitive tests can be helpful in identifying those who require further specialist diagnostic assessment; however, there is a lack of consensus around the optimal tools to use in clinical practice. The Mini-Cog is a short cognitive test comprising three-item recall and a clock-drawing test that is used in secondary care settings.\nObjectives\nThe primary objective was to determine the accuracy of the Mini-Cog for detecting dementia in a secondary care setting. The secondary objectives were to investigate the heterogeneity of test accuracy in the included studies and potential sources of heterogeneity. These potential sources of heterogeneity will include the baseline prevalence of dementia in study samples, thresholds used to determine positive test results, the type of dementia (Alzheimer's disease dementia or all causes of dementia), and aspects of study design related to study quality.\nSearch methods\nWe searched the following sources in September 2012, with an update to 12 March 2019: Cochrane Dementia Group Register of Diagnostic Test Accuracy Studies, MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We made no exclusions with regard to language of Mini-Cog administration or language of publication, using translation services where necessary.\nSelection criteria\nWe included cross-sectional studies and excluded case-control designs, due to the risk of bias. We selected those studies that included the Mini-Cog as an index test to diagnose dementia where dementia diagnosis was confirmed with reference standard clinical assessment using standardised dementia diagnostic criteria. We only included studies in secondary care settings (including inpatient and outpatient hospital participants).\nData collection and analysis\nWe screened all titles and abstracts generated by the electronic database searches. Two review authors independently checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool. We extracted data into two-by-two tables to allow calculation of accuracy metrics for individual studies, reporting the sensitivity, specificity, and 95% confidence intervals of these measures, summarising them graphically using forest plots.\nMain results\nThree studies with a total of 2560 participants fulfilled the inclusion criteria, set in neuropsychology outpatient referrals, outpatients attending a general medicine clinic, and referrals to a memory clinic. Only n = 1415 (55.3%) of participants were included in the analysis to inform evaluation of Mini-Cog test accuracy, due to the selective use of available data by study authors. There were concerns related to high risk of bias with respect to patient selection, and unclear risk of bias and high concerns related to index test conduct and applicability. In all studies, the Mini-Cog was retrospectively derived from historic data sets. No studies included acute general hospital inpatients. The prevalence of dementia ranged from 32.2% to 87.3%. The sensitivities of the Mini-Cog in the individual studies were reported as 0.67 (95% confidence interval (CI) 0.63 to 0.71), 0.60 (95% CI 0.48 to 0.72), and 0.87 (95% CI 0.83 to 0.90). The specificity of the Mini-Cog for each individual study was 0.87 (95% CI 0.81 to 0.92), 0.65 (95% CI 0.57 to 0.73), and 1.00 (95% CI 0.94 to 1.00). We did not perform meta-analysis due to concerns related to risk of bias and heterogeneity.\nAuthors' conclusions\nThis review identified only a limited number of diagnostic test accuracy studies using Mini-Cog in secondary care settings. Those identified were at high risk of bias related to patient selection and high concerns related to index test conduct and applicability. The evidence was indirect, as all studies evaluated Mini-Cog differently from the review question, where it was anticipated that studies would conduct Mini-Cog and independently but contemporaneously perform a reference standard assessment to diagnose dementia. The pattern of test accuracy varied across the three studies. Future research should evaluate Mini-Cog as a test in itself, rather than derived from other neuropsychological assessments. There is also a need for evaluation of the feasibility of the Mini-Cog for the detection of dementia to help adequately determine its role in the clinical pathway.\n\nGiven the provided abstract, please respond to the following query: \"What was the aim of the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The aim of this Cochrane Review was to find out how accurate the Mini-Cog test is for detecting dementia among patients in inpatient and outpatient hospital settings. The researchers included three studies to answer this question." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is the first update of a Cochrane Review first published in 2015. Renin angiotensin system (RAS) inhibitors include angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin inhibitors. They are widely prescribed for treatment of hypertension, especially for people with diabetes because of postulated advantages for reducing diabetic nephropathy and cardiovascular morbidity and mortality. Despite widespread use for hypertension, the efficacy and safety of RAS inhibitors compared to other antihypertensive drug classes remains unclear.\nObjectives\nTo evaluate the benefits and harms of first-line RAS inhibitors compared to other first-line antihypertensive drugs in people with hypertension.\nSearch methods\nThe Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.\nSelection criteria\nWe included randomized, active-controlled, double-blinded studies (RCTs) with at least six months follow-up in people with elevated blood pressure (≥ 130/85 mmHg), which compared first-line RAS inhibitors with other first-line antihypertensive drug classes and reported morbidity and mortality or blood pressure outcomes. We excluded people with proven secondary hypertension.\nData collection and analysis\nTwo authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis.\nMain results\nThis update includes three new RCTs, totaling 45 in all, involving 66,625 participants, with a mean age of 66 years. Much of the evidence for our key outcomes is dominated by a small number of large RCTs at low risk for most sources of bias. Imbalances in the added second-line antihypertensive drugs in some of the studies were important enough for us to downgrade the quality of the evidence.\nPrimary outcomes were all-cause death, fatal and non-fatal stroke, fatal and non-fatal myocardial infarction (MI), fatal and non-fatal congestive heart failure (CHF) requiring hospitalizations, total cardiovascular (CV) events (fatal and non-fatal stroke, fatal and non-fatal MI and fatal and non-fatal CHF requiring hospitalization), and end-stage renal failure (ESRF). Secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR).\nCompared with first-line calcium channel blockers (CCBs), we found moderate-certainty evidence that first-line RAS inhibitors decreased heart failure (HF) (35,143 participants in 5 RCTs, risk ratio (RR) 0.83, 95% confidence interval (CI) 0.77 to 0.90, absolute risk reduction (ARR) 1.2%), and that they increased stroke (34,673 participants in 4 RCTs, RR 1.19, 95% CI 1.08 to 1.32, absolute risk increase (ARI) 0.7%). Moderate-certainty evidence showed that first-line RAS inhibitors and first-line CCBs did not differ for all-cause death (35,226 participants in 5 RCTs, RR 1.03, 95% CI 0.98 to 1.09); total CV events (35,223 participants in 6 RCTs, RR 0.98, 95% CI 0.93 to 1.02); and total MI (35,043 participants in 5 RCTs, RR 1.01, 95% CI 0.93 to 1.09). Low-certainty evidence suggests they did not differ for ESRF (19,551 participants in 4 RCTs, RR 0.88, 95% CI 0.74 to 1.05).\nCompared with first-line thiazides, we found moderate-certainty evidence that first-line RAS inhibitors increased HF (24,309 participants in 1 RCT, RR 1.19, 95% CI 1.07 to 1.31, ARI 1.0%), and increased stroke (24,309 participants in 1 RCT, RR 1.14, 95% CI 1.02 to 1.28, ARI 0.6%). Moderate-certainty evidence showed that first-line RAS inhibitors and first-line thiazides did not differ for all-cause death (24,309 participants in 1 RCT, RR 1.00, 95% CI 0.94 to 1.07); total CV events (24,379 participants in 2 RCTs, RR 1.05, 95% CI 1.00 to 1.11); and total MI (24,379 participants in 2 RCTs, RR 0.93, 95% CI 0.86 to 1.01). Low-certainty evidence suggests they did not differ for ESRF (24,309 participants in 1 RCT, RR 1.10, 95% CI 0.88 to 1.37).\nCompared with first-line beta-blockers, low-certainty evidence suggests that first-line RAS inhibitors decreased total CV events (9239 participants in 2 RCTs, RR 0.88, 95% CI 0.80 to 0.98, ARR 1.7%), and decreased stroke (9193 participants in 1 RCT, RR 0.75, 95% CI 0.63 to 0.88, ARR 1.7% ). Low-certainty evidence suggests that first-line RAS inhibitors and first-line beta-blockers did not differ for all-cause death (9193 participants in 1 RCT, RR 0.89, 95% CI 0.78 to 1.01); HF (9193 participants in 1 RCT, RR 0.95, 95% CI 0.76 to 1.18); and total MI (9239 participants in 2 RCTs, RR 1.05, 95% CI 0.86 to 1.27).\nBlood pressure comparisons between first-line RAS inhibitors and other first-line classes showed either no differences or small differences that did not necessarily correlate with the differences in the morbidity outcomes.\nThere is no information about non-fatal serious adverse events, as none of the trials reported this outcome.\nAuthors' conclusions\nAll-cause death is similar for first-line RAS inhibitors and first-line CCBs, thiazides and beta-blockers. There are, however, differences for some morbidity outcomes. First-line thiazides caused less HF and stroke than first-line RAS inhibitors. First-line CCBs increased HF but decreased stroke compared to first-line RAS inhibitors. The magnitude of the increase in HF exceeded the decrease in stroke. Low-quality evidence suggests that first-line RAS inhibitors reduced stroke and total CV events compared to first-line beta-blockers. The small differences in effect on blood pressure between the different classes of drugs did not correlate with the differences in the morbidity outcomes.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included randomized, double-blind, parallel design RCTs for the present review. 45 trials with 66,625 participants who were followed-up for between 0.5 year and 5.6 years were included. The participants had an average age of 66 years." } ]

[ { "role": "user", "content": "Abstract: Background\nFunctional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found. Acid suppressive therapy, including proton pump inhibitors (PPIs), has been proposed as a therapeutic option in FD, but its efficacy remains controversial. While PPIs are generally considered safe and well tolerated, they have been associated with adverse events, especially in the long term. For this reason, decisions on whether to initiate or continue PPI therapy should be made based on an appropriate clinical indication. Therefore, we conducted a systematic review to evaluate whether PPI therapy provides symptomatic relief in FD.\nObjectives\nTo determine the efficacy of proton pump inhibitors in the improvement of global symptoms of dyspepsia and quality of life compared to placebo, H2 receptor antagonists or prokinetics, in people with functional dyspepsia.\nSearch methods\nWe searched in the following electronic databases: the Cochrane Library (to May 2017), MEDLINE (OvidSP; to May 2017), Embase (OvidSP; to May 2017), and SIGLE grey literature (up to May 2017) and clinical trial registries; we handsearched abstracts from conferences up to May 2017. We screened non-systematic reviews, systematic reviews and guidelines to identify any additional trials. We contacted trialists to obtain missing information.\nSelection criteria\nAll randomized controlled trials (RCTs) comparing any PPI with placebo, H2 receptor antagonists (H2RAs) or prokinetics for the treatment of FD of at least two weeks' duration. Participants were adults (aged 16 years or greater) with an adequate diagnosis of FD (any validated criteria such as Rome I, II, III or Lancet Working Group).\nData collection and analysis\nTwo review authors independently assessed eligibility and trial quality, and extracted data. We collected data on dyspeptic symptoms, quality of life and number of overall adverse events. Specific adverse events were beyond the scope of this review.\nMain results\nWe identified 25 RCTs from 27 papers (with 8453 participants) studying the effect of PPIs versus placebo, H2RAs or prokinetics for improvement of global symptoms of dyspepsia and quality of life in people with FD. Low-dose PPIs had similar efficacy as standard-dose PPIs, therefore we combined these subgroups for the analysis. PPI was more effective than placebo at relieving overall dyspepsia symptoms in people with FD (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.94; participants = 6172; studies = 18; number needed to treat for an additional beneficial outcome (NNTB) 11; moderate quality evidence). PPIs may have little or no effect compared with H2RAs (RR 0.88, 95% CI 0.74 to 1.04; participants = 740; studies = 2; low quality evidence), and may be slightly more effective than prokinetics (RR 0.89, 95% CI 0.81 to 0.99; participants = 1033; studies = 5; NNTB 16; low quality evidence) at relieving overall dyspepsia symptoms in people with FD. PPIs plus prokinetics have probably little or no effect compared with PPIs alone at relieving overall dyspepsia symptoms (RR 0.85, 95% CI 0.68 to 1.08; participants = 407; studies = 2; moderate quality evidence).\nThere was no difference when subgrouped by Helicobacter pylori status, country of origin, or presence of reflux or Rome III subtypes. There were no differences in the number of adverse events observed between PPIs and any of the other treatments. There were fewer adverse events in the combination of PPI plus prokinetics compared to prokinetics alone (RR 0.60, 95% CI 0.39 to 0.93; participants = 407; studies = 2; moderate quality evidence).\nAuthors' conclusions\nThere is evidence that PPIs are effective for the treatment of FD, independent of the dose and duration of treatment compared with placebo. PPIs may be slightly more effective than prokinetics for the treatment of FD; however, the evidence is scarce. The trials evaluating PPIs versus prokinetics are difficult to interpret as they are at risk of bias. Although the effect of these drugs seems to be small, the drugs are well tolerated.\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": "Acid suppression is a possible treatment for functional dyspepsia (indigestion), which is recurring pain over the stomach, bloating, burping or the feeling of being full. Several medicines are used to treat functional dyspepsia; proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) reduce stomach acid, and prokinetics accelerate stomach emptying. There is no clear evidence that one medicine is more effective than another. Although these are considered safe, a few people have side effects. The most common side effects are headache, tummy (abdominal) pain, bloating, diarrhoea and feeling sick (nausea). Long-term use of PPIs has been associated with infectious diarrhoea (inflammation of the stomach and small intestine), bone fracture and bacterial overgrowth. Therefore, we need to know whether these medications are effective and safe for people with indigestion." } ]

[ { "role": "user", "content": "Abstract: Background\nAttention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can persist into adulthood and can affects individuals' social and occupational functioning, as well as their quality of life and health. ADHD is frequently associated with other mental disorders such as substance use disorders and anxiety and affective disorders. Amphetamines are used to treat adults with ADHD, but uncertainties about their efficacy and safety remain.\nObjectives\nTo examine the efficacy and safety of amphetamines for adults with ADHD.\nSearch methods\nIn August 2017, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and two trials registers, and we ran citation searches for included studies. We also contacted the corresponding authors of all included studies, other experts in the field, and the pharmaceutical company, Shire, and we searched the reference lists of retrieved studies and reviews for other published, unpublished, or ongoing studies. For each included study, we performed a citation search in Web of Science to identify any later studies that may have cited it.\nSelection criteria\nWe searched for randomised controlled trials comparing the efficacy of amphetamines (at any dose) for ADHD in adults aged 18 years and over against placebo or an active intervention.\nData collection and analysis\nTwo review authors extracted data from each included study. We used the standardised mean difference (SMD) and the risk ratio (RR) to assess continuous and dichotomous outcomes, respectively. We conducted a stratified analysis to determine the influence of moderating variables. We assessed trials for risk of bias and drew a funnel plot to investigate the possibility of publication bias. We rated the quality of the evidence using the GRADE approach, which yielded high, moderate, low, or very low quality ratings based on evaluation of within-trial risk of bias, directness of evidence, heterogeneity of data; precision of effect estimates, and risk of publication bias.\nMain results\nWe included 19 studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD (78.8%). Eighteen studies were conducted in the USA, and one study was conducted in both Canada and the USA. Ten were multi-site studies. All studies were placebo-controlled, and three also included an active comparator: guanfacine, modafinil, or paroxetine. Most studies had short-term follow-up and a mean study length of 5.3 weeks.\nWe found no studies that had low risk of bias in all domains of the Cochrane 'Risk of bias’ tool, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment, but also because we noted attrition bias, and because we could not rule out the possibility of a carry-over effect in studies that used a cross-over design.\nSixteen studies were funded by the pharmaceutical industry, one study was publicly funded, and two studies did not report their funding sources.\nAmphetamines versus placebo\nSeverity of ADHD symptoms: we found low- to very low-quality evidence suggesting that amphetamines reduced the severity of ADHD symptoms as rated by clinicians (SMD −0.90, 95% confidence interval (CI) −1.04 to −0.75; 13 studies, 2028 participants) and patients (SMD −0.51, 95% CI −0.75 to −0.28; six studies, 120 participants).\nRetention: overall, we found low-quality evidence suggesting that amphetamines did not improve retention in treatment (risk ratio (RR) 1.06, 95% CI 0.99 to 1.13; 17 studies, 2323 participants).\nAdverse events: we found that amphetamines were associated with an increased proportion of patients who withdrew because of adverse events (RR 2.69, 95% CI 1.63 to 4.45; 17 studies, 2409 participants).\nType of amphetamine: we found differences between amphetamines for the severity of ADHD symptoms as rated by clinicians. Both lisdexamfetamine (SMD −1.06, 95% CI −1.26 to −0.85; seven studies, 896 participants; low-quality evidence) and MAS (SMD −0.80, 95% CI −0.93 to −0.66; five studies, 1083 participants; low-quality evidence) reduced the severity of ADHD symptoms. In contrast, we found no evidence to suggest that dexamphetamine reduced the severity of ADHD symptoms (SMD −0.24, 95% CI −0.80 to 0.32; one study, 49 participants; very low-quality evidence). In addition, all amphetamines were efficacious in reducing the severity of ADHD symptoms as rated by patients (dexamphetamine: SMD −0.77, 95% CI −1.14 to −0.40; two studies, 35 participants; low-quality evidence; lisdexamfetamine: SMD −0.33, 95% CI −0.65 to −0.01; three studies, 67 participants; low-quality evidence; MAS: SMD −0.45, 95% CI −1.02 to 0.12; one study, 18 participants; very low-quality evidence).\nDose at study completion: different doses of amphetamines did not appear to be associated with differences in efficacy.\nType of drug-release formulation: we investigated immediate- and sustained-release formulations but found no differences between them for any outcome.\nAmphetamines versus other drugs\nWe found no evidence that amphetamines improved ADHD symptom severity compared to other drug interventions.\nAuthors' conclusions\nAmphetamines improved the severity of ADHD symptoms, as assessed by clinicians or patients, in the short term but did not improve retention to treatment. Amphetamines were associated with higher attrition due to adverse events. The short duration of studies coupled with their restrictive inclusion criteria limits the external validity of these findings. Furthermore, none of the included studies had an overall low risk of bias. Overall, the evidence generated by this review is of low or very low quality.\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": "Attention deficit hyperactivity disorder (ADHD) is a childhood-onset psychiatric disorder that can persist into adulthood in up to 50% of patients. From a clinical point of view, ADHD is characterised by hyperactivity, mood instability, irritability, difficulties in maintaining attention, lack of organisation, and impulsive behaviours. Occurrence of other disorders at the the same time is common, especially mood disorders and substance abuse. Amphetamines (a type of stimulant) are thought to improve ADHD symptoms, but there are concerns about how safe they are for regular use by patients with ADHD." } ]

[ { "role": "user", "content": "Abstract: Background\nPneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011.\nObjectives\nTo assess the efficacy and safety of corticosteroids in the treatment of pneumonia.\nSearch methods\nWe searched the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3 March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials.\nSelection criteria\nWe included randomised controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel–Haenszel fixed-effect model when possible.\nMain results\nWe included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.\nAll trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.\nCorticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.\nAmong children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.\nHyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93).\nAuthors' conclusions\nCorticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.\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 looked at the effects of treating people with pneumonia using corticosteroids (also called steroids or glucocorticoids) on numbers of deaths, response to treatment, treatment complications, and side effects. We compared treatment with corticosteroids in addition to antibiotics with placebo or no treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nSickle cell disease is a group of genetic diseases which is especially prevalent in tropical and subtropical regions; however, forced migration and ongoing population movement have spread it throughout the world, with estimated birth rates reaching 0.49 per 1000 in the Americas, 0.07 per 1000 in Europe, 0.68 per 1000 in South and Southeast Asia, and 10.68 per 1000 in Africa. Life for individuals with sickle cell disease can be affected by repeated acute complications and compounded by progressive organ damage. Studies reveal that when people with chronic illness learn self-management, their clinical outcomes and quality of life improves; and they show lower dependence on healthcare services. There are, however, no reviews identifying which interventions improve knowledge and little is known about the impact of patient or care-giver knowledge on clinical and psychosocial outcomes in people with sickle cell disease.\nObjectives\n1. To determine the effectiveness of patient- and caregiver-centred educational interventions for changing knowledge and understanding of sickle cell disease among patients as well as caregivers of people with the disease.\n2. To assess the effectiveness and safety of patient- and caregiver-centred educational interventions and programs for the recognition of signs and symptoms of disease-related morbidity, adherence to treatment and healthcare utilization in patients with sickle cell disease.\nSearch methods\nThe authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.\nDate of last search: 11 April 2016.\nSelection criteria\nRandomized and quasi-randomized controlled trials which evaluate the effectiveness of individual- and group-based interventions for either the patient with sickle cell disease or their caregivers, or both. Eligible interventions will aim to change knowledge, attitudes or skills, improve psychosocial aspects of the disease as well as treatment adherence and healthcare utilization. Trials evaluating the intervention versus no program, comparing two interventions and those which are part of a multi-faceted intervention to improve a range of sickle cell-related health outcomes are all eligible for inclusion.\nData collection and analysis\nTwo review authors independently selected trials based on stated inclusion criteria and thereafter examined each selected report to extract data using a prepared, piloted, data collection form. A third author assisted in reaching consensus if there were any discrepancies. Similarly, risk of bias was assessed by two authors and verified by a third author.\nMain results\nA total of 12 trials (11 randomized controlled trials and one quasi-randomized trial) of 563 people with HbSS, HbSC or HbSβthal, aged six to 35 years old, were included in the review; the majority of participants were African-American. Interventions ranged from a total of one hour to weekly sessions for eight weeks and the post-intervention assessments ranged from the end of the intervention period to 12 months after completion. The heterogeneity of the included trials, which encompasses setting, inclusion and exclusion criteria, interventional method and time of assessment, ranged from 'not important' to 'moderate to substantial' for different review outcomes. The overall risk of bias was low for selective reporting, unclear for random sequence generation, allocation concealment, blinding of participants and blinding of outcome assessment. Incomplete outcome reporting and blinding of personnel showed mixed bias representations.\nPatient knowledge was assessed by four trials (160 participants) with moderate to substantial heterogeneity. There was evidence that educational programs improved patient knowledge, standardised mean difference 0.87 points (95% confidence interval 0.28 to 1.45, moderate quality evidence), which improved further when a trial with high bias was removed in a sensitivity analysis. Caregiver knowledge, reported in a single trial of 20 families, also showed an improvement, standardised mean difference 0.52 points (95% confidence interval 0.03 to 1.00, moderate quality evidence). The effect on patient knowledge was sustained at longer follow-up periods, whereas the effect on caregiver knowledge was not sustained.\nThere were two primary outcomes related to the effectiveness of educational programs on the recognition of signs and symptoms of disease-related morbidity. No comparative data were reported for patients or caregivers (or both) recognising signs and symptoms leading to self-management. Data from two trials were analysed for the utilization of health services and showed no evidence of an effect, mean difference 0.33 (95% confidence interval -0.57 to 1.23, moderate quality evidence).\nWith regard to the review's secondary outcomes, depression showed a statistically significant decline in intervention groups, standardised mean difference -0.66 points (95% confidence interval -1.18, to -0.14, moderate quality evidence). Adherence to treatment was not assessed in any of the identified trials. No effects of interventions were seen on coping, family relationships or health-related quality of life of patients.\nThe quality of evidence was low for positive coping and moderate for child knowledge, healthcare utilization and depression. This suggests that further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimates.\nAuthors' conclusions\nThis review identifies important positive effects of educational interventions on improving patient knowledge of sickle cell disease and depression. Effects on patients' knowledge were maintained for longer than for caregivers. The effect on knowledge was significant but small and whether it offers any clinical benefit is uncertain. Significant factors limiting these effects could be trials being under powered as well as attrition rates. Effects were not statistically significant in assessments of secondary outcomes, possibly due to the paucity of the number of trials and patients and caregivers. Trials showed moderate to high heterogeneity which might impact the results. To better study effects on outcomes, further controlled trials are needed with rigorous attention given to improve recruitment and retention and to decrease bias. Predetermined protocols using similar measurements should be used across multiple sites.\n\nGiven the provided abstract, please respond to the following query: \"Search date\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence is current to 11 April 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nGeneral health checks are common elements of health care in some countries. They aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used individual screening tests offered in general health checks have been incompletely studied. Also, screening leads to increased use of diagnostic and therapeutic interventions, which can be harmful as well as beneficial. It is therefore important to assess whether general health checks do more good than harm. This is the first update of the review published in 2012.\nObjectives\nTo quantify the benefits and harms of general health checks.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, two other databases and two trials registers on 31 January 2018. Two review authors independently screened titles and abstracts, assessed papers for eligibility and read reference lists. One review author used citation tracking (Web of Knowledge) and asked trial authors about additional studies.\nSelection criteria\nWe included randomised trials comparing health checks with no health checks in adults unselected for disease or risk factors. We did not include geriatric trials. We defined health checks as screening for more than one disease or risk factor in more than one organ system.\nData collection and analysis\nTwo review authors independently extracted data and assessed the risk of bias in the trials. We contacted trial authors for additional outcomes or trial details when necessary. When possible, we analysed the results with a random-effects model meta-analysis; otherwise, we did a narrative synthesis.\nMain results\nWe included 17 trials, 15 of which reported outcome data (251,891 participants). Risk of bias was generally low for our primary outcomes. Health checks have little or no effect on total mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.97 to 1.03; 11 trials; 233,298 participants and 21,535 deaths; high-certainty evidence, I2 = 0%), or cancer mortality (RR 1.01, 95% CI 0.92 to 1.12; 8 trials; 139,290 participants and 3663 deaths; high-certainty evidence, I2 = 33%), and probably have little or no effect on cardiovascular mortality (RR 1.05, 95% CI 0.94 to 1.16; 9 trials; 170,227 participants and 6237 deaths; moderate-certainty evidence; I2 = 65%). Health checks have little or no effect on fatal and non-fatal ischaemic heart disease (RR 0.98, 95% CI 0.94 to 1.03; 4 trials; 164,881 persons, 10,325 events; high-certainty evidence; I2 = 11%), and probably have little or no effect on fatal and non-fatal stroke (RR 1.05 95% CI 0.95 to 1.17; 3 trials; 107,421 persons, 4543 events; moderate-certainty evidence, I2 = 53%).\nAuthors' conclusions\nGeneral health checks are unlikely to be beneficial.\n\nGiven the provided abstract, please respond to the following query: \"What is the aim of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The aim of this Cochrane Review was to find out if general health checks reduce illness and deaths. This is an update of a previous Cochrane Review." } ]

[ { "role": "user", "content": "Abstract: Background\nMultiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance – including the respiratory muscles, affecting functional performance and exercise capacity. Respiratory muscle weakness can also lead to diminished performance on coughing, which may result in (aspiration) pneumonia or even acute ventilatory failure, complications that frequently cause death in MS. Training of the respiratory muscles might improve respiratory function and cough efficacy.\nObjectives\nTo assess the effects of respiratory muscle training versus any other type of training or no training for respiratory muscle function, pulmonary function and clinical outcomes in people with MS.\nSearch methods\nWe searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (3 February 2017), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. Two authors independently screened records yielded by the search, handsearched reference lists of review articles and primary studies, checked trial registers for protocols, and contacted experts in the field to identify further published or unpublished trials.\nSelection criteria\nWe included randomized controlled trials (RCTs) that investigated the efficacy of respiratory muscle training versus any control in people with MS.\nData collection and analysis\nOne reviewer extracted study characteristics and study data from included RCTs, and two other reviewers independently cross-checked all extracted data. Two review authors independently assessed risk of bias with the Cochrane 'Risk of bias' assessment tool. When at least two RCTs provided data for the same type of outcome, we performed meta-analyses. We assessed the certainty of the evidence according to the GRADE approach.\nMain results\nWe included six RCTs, comprising 195 participants with MS. Two RCTs investigated inspiratory muscle training with a threshold device; three RCTs, expiratory muscle training with a threshold device; and one RCT, regular breathing exercises. Eighteen participants (˜ 10%) dropped out; trials reported no serious adverse events.\nWe pooled and analyzed data of 5 trials (N=137) for both inspiratory and expiratory muscle training, using a fixed-effect model for all but one outcome. Compared to no active control, meta-analysis showed that inspiratory muscle training resulted in no significant difference in maximal inspiratory pressure (mean difference (MD) 6.50 cmH2O, 95% confidence interval (CI) −7.39 to 20.38, P = 0.36, I2 = 0%) or maximal expiratory pressure (MD −8.22 cmH2O, 95% CI −26.20 to 9.77, P = 0.37, I2 = 0%), but there was a significant benefit on the predicted maximal inspiratory pressure (MD 20.92 cmH2O, 95% CI 6.03 to 35.81, P = 0.006, I2 = 18%). Meta-analysis with a random-effects model failed to show a significant difference in predicted maximal expiratory pressure (MD 5.86 cmH2O, 95% CI −10.63 to 22.35, P = 0.49, I2 = 55%). These studies did not report outcomes for health-related quality of life.\nThree RCTS compared expiratory muscle training versus no active control or sham training. Under a fixed-effect model, meta-analysis failed to show a significant difference between groups with regard to maximal expiratory pressure (MD 8.33 cmH2O, 95% CI −0.93 to 17.59, P = 0.18, I2 = 42%) or maximal inspiratory pressure (MD 3.54 cmH2O, 95% CI −5.04 to 12.12, P = 0.42, I2 = 41%). One trial assessed quality of life, finding no differences between groups.\nFor all predetermined secondary outcomes, such as forced expiratory volume, forced vital capacity and peak flow pooling was not possible. However, two trials on inspiratory muscle training assessed fatigue using the Fatigue Severity Scale (range of scores 0-56 ), finding no difference between groups (MD, −0.28 points, 95% CI−0.95 to 0.39, P = 0.42, I2 = 0%). Due to the low number of studies included, we could not perform cumulative meta-analysis or subgroup analyses. It was not possible to perform a meta-analysis for adverse events, no serious adverse were mentioned in any of the included trials.\nThe quality of evidence was low for all outcomes because of limitations in design and implementation as well as imprecision of results.\nAuthors' conclusions\nThis review provides low-quality evidence that resistive inspiratory muscle training with a resistive threshold device is moderately effective postintervention for improving predicted maximal inspiratory pressure in people with mild to moderate MS, whereas expiratory muscle training showed no significant effects. The sustainability of the favourable effect of inspiratory muscle training is unclear, as is the impact of the observed effects on quality of life.\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": "The six trials that were eligible for inclusion in this review were small, so statistical power was low, making analyses less precise. In addition, studies were heterogeneous in terms of the type of respiratory muscle training, dosing/intensity, and the severity of MS. In addition, we could not analyze the effects of training on, for example, cough efficacy, pneumonia, and quality of life, as the included trials did not report on these outcomes even though they are important for patients, caregivers and healthcare professionals. Altogether, this review provides low-quality evidence that resistive inspiratory muscle training improves predicted inspiratory muscle strength in people with MS. We did not find any effects for resistive expiratory muscle training. More high-quality research in respiratory muscle training in MS is needed." } ]

[ { "role": "user", "content": "Abstract: Background\nIt is well known that poverty is associated with ill health and that ill health can result in direct and indirect costs that can perpetuate poverty. Social protection, which includes policies and programmes intended to prevent and reduce poverty in times of ill health, could be one way to break this vicious cycle. Social protection, particularly cash transfers, also has the potential to promote healthier behaviours, including healthcare seeking. Although social protection, particularly conditional and unconditional cash transfers, has been widely studied, it is not well known how recipients experience social protection interventions, and what unintended effects such interventions can cause.\nObjectives\nThe aim of this review was to explore how conditional and unconditional cash transfer social protection interventions with a health outcome are experienced and perceived by their recipients.\nSearch methods\nWe searched Epistemonikos, MEDLINE, CINAHL, Social Services Abstracts, Global Index Medicus, Scopus, AnthroSource and EconLit from the start of the database to 5 June 2020. We combined this with reference checking, citation searching, grey literature and contact with authors to identify additional studies. We reran all strategies in July 2022, and the new studies are awaiting classification.\nSelection criteria\nWe included primary studies, using qualitative methods or mixed-methods studies with qualitative research reporting on recipients’ experiences of cash transfer interventions where health outcomes were evaluated. Recipients could be adult patients of healthcare services, the general adult population as recipients of cash targeted at themselves or directed at children. Studies could be evaluated on any mental or physical health condition or cash transfer mechanism. Studies could come from any country and be in any language. Two authors independently selected studies.\nData collection and analysis\nWe used a multistep purposive sampling framework for selecting studies, starting with geographical representation, followed by health condition, and richness of data. Key data were extracted by the authors into Excel. Methodological limitations were assessed independently using the Critical Appraisal Skills Programme (CASP) criteria by two authors. Data were synthesised using meta-ethnography, and confidence in findings was assessed using the Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach.\nMain results\nWe included 127 studies in the review and sampled 41 of these studies for our analysis. Thirty-two further studies were found after the updated search on 5 July 2022 and are awaiting classification. The sampled studies were from 24 different countries: 17 studies were from the African region, seven were from the region of the Americas, seven were from the European region, six were from the South-East Asian region, three from the Western Pacific region and one study was multiregional, covering both the African and the Eastern Mediterranean regions. These studies primarily explored the views and experiences of cash transfer recipients with different health conditions, such as infectious diseases, disabilities and long-term illnesses, sexual and reproductive health, and maternal and child health. Our GRADE-CERQual assessment indicated we had mainly moderate- and high-confidence findings. We found that recipients perceived the cash transfers as necessary and helpful for immediate needs and, in some cases, helpful for longer-term benefits. However, across conditional and unconditional programmes, recipients often felt that the amount given was too little in relation to their total needs. They also felt that the cash alone was not enough to change their behaviour and, to change behaviour, additional types of support would be required. The cash transfer was reported to have important effects on empowerment, autonomy and agency, but also in some settings, recipients experienced pressure from family or programme staff on cash usage. The cash transfer was reported to improve social cohesion and reduce intrahousehold tension. However, in settings where some received the cash and others did not, the lack of an equal approach caused tension, suspicion and conflict. Recipients also reported stigma in terms of cash transfer programme assessment processes and eligibility, as well as inappropriate eligibility processes. Across settings, recipients experienced barriers in accessing the cash transfer programme, and some refused or were hesitant to receive the cash. Some recipients found cash transfer programmes more acceptable when they agreed with the programme's goals and processes.\nAuthors' conclusions\nOur findings highlight the impact of the sociocultural context on the functioning and interaction between the individual, family and cash transfer programmes. Even where the goals of a cash transfer programme are explicitly health-related, the outcomes may be far broader than health alone and may include, for example, reduced stigma, empowerment and increased agency of the individual. When measuring programme outcomes, therefore, these broader impacts could be considered for understanding the health and well-being benefits of cash transfers.\n\nGiven the provided abstract, please respond to the following query: \"What was studied in this synthesis?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Conditional and unconditional cash transfer programmes are found across the world. A conditional cash transfer is money (cash) that is given to people if they behave in a certain way. For example, parents could receive cash if they take their children to a health centre. An unconditional cash transfer is money that is given without any conditions or rules about its use. In some settings, people receive cash transfers through government programmes. In other settings, cash transfers are mainly given through non-governmental organisations or research projects. Many of these programmes aim to improve people’s health, but research measuring the effect of these programmes on health shows mixed results. We, therefore, wanted to explore how people experienced these programmes." } ]

[ { "role": "user", "content": "Abstract: Background\nZinc is a vital micronutrient for humans and is essential for protein synthesis, cell growth, and differentiation. Severe zinc deficiency can lead to slower physical, cognitive and sexual growth, cause skin disorders, decrease immunity, increase incidence of acute illnesses in infants and children and contribute to childhood stunting. By estimation, 17.3% of the world population is at risk of inadequate zinc intake. Such nutritional impairment increases the risk of diarrhoea and pneumonia by 20%, as well as leads to a global loss of more than 16 million disability-adjusted life years in children less than five years of age. Not only does zinc deficiency affect lives, it adds to the considerable financial burden on depleted resources in countries that are most affected. By preventing or curing this deficiency, we can improve childhood mortality, morbidity and growth.\nObjectives\nTo assess the effectiveness of zinc supplementation for the promotion of growth, reduction in mortality, and the prevention of infections in infants less than six months of age.\nSearch methods\nWe used the standard search strategy of the Cochrane Neonatal Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 4), MEDLINE via PubMed (1966 to 18 May 2018), Embase (1980 to 18 May 2018), and CINAHL (1982 to 18 May 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. An updated search from 1 January 2018 to 29 January 2020 was run in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost.\nSelection criteria\nAll randomised controlled (individual and cluster randomised) and quasi-randomised trials of zinc supplementation in healthy, term infants, less than six months of age comparing infant mortality, incidence of diarrhoea or respiratory illnesses, growth and/or serum zinc levels were eligible.\nData collection and analysis\nTwo review authors screened search results (title and abstracts) and relevant full texts. Studies fulfilling prespecified inclusion criteria were included with any disagreements resolved by consensus. Extraction and analysis were then conducted. We used the GRADE approach to assess the quality of evidence as indicated by certainty in effect estimates.\nMain results\nEight studies (with 85,629 infants) were included and five studies were meta-analysed, out of which four studies compared zinc with placebo, and one compared zinc plus riboflavin versus riboflavin. Certain growth outcomes after six months of intervention (Weight for Age Z-scores (WAZ) (standardised mean difference) (SMD) 0.16, 95% CI 0.03 to 0.29; three studies, n = 955; fixed-effect; heterogeneity Chi² P = 0.96); I² = 0%); change in WAZ (SMD 0.16, 95% CI 0.07 to 0.25; one study, n = 386; fixed-effect); (Weight-for-Length Z-score (WLZ) (SMD 0.15, 95% CI 0.02 to 0.28; three studies, n = 955; fixed-effect; heterogeneity: Chi² P = 0.81); I² = 0%); (change in WLZ (SMD 0.17, 95% CI 0.06 to 0.28; one study, n = 386; fixed-effect)) were positively affected by zinc supplementation compared to placebo. A single study reported no difference in the incidence of diarrhoea and lower respiratory tract infection with zinc supplementation. Zinc had no effect on mortality in children younger than 12 months.\nWhen zinc plus riboflavin was compared to riboflavin only, significant improvement was observed in the incidence of wasting at 24 months (risk ratio (RR) 0.59, 95% CI 0.37 to 0.96; one study, n = 296; fixed-effect), but significant worsening of incidence of stunting was present at 21 months (RR 1.53, 95% CI 1.09 to 2.16; one study, n = 298; fixed-effect).\nAuthors' conclusions\nThere was a significant positive impact of zinc supplementation on WAZ and WLZ after six months of intervention in infants compared to placebo. When a combined supplement of zinc and riboflavin was compared to riboflavin, there was a significant reduction in wasting at 24 months, but stunting at 21 months was negatively affected. Although included trials were of good-to-moderate quality, evidence that could be meta-analysed was based on a few studies which affected the overall quality of results. Regardless, there is a need for strong trials conducted in infants younger than six months before a strong recommendation can be made supporting zinc supplementation in this age group.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "we searched for studies through January 2020 that enrolled healthy infants aged less than six months old and provided at least six months of zinc supplementation. We included eight studies that covered zinc supplementation compared with placebo, zinc and riboflavin compared with riboflavin only, zinc, riboflavin and B complex vitamins compared with riboflavin and B complex vitamins." } ]

[ { "role": "user", "content": "Abstract: Background\nAttention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood. The psychostimulant methylphenidate is the most frequently used medication to treat it. Several studies have investigated the benefits of methylphenidate, showing possible favourable effects on ADHD symptoms, but the true magnitude of the effect is unknown. Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non-serious adverse events.\nObjectives\nTo assess the adverse events associated with methylphenidate treatment for children and adolescents with ADHD in non-randomised studies.\nSearch methods\nIn January 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 12 other databases and two trials registers. We also checked reference lists and contacted authors and pharmaceutical companies to identify additional studies.\nSelection criteria\nWe included non-randomised study designs. These comprised comparative and non-comparative cohort studies, patient-control studies, patient reports/series and cross-sectional studies of methylphenidate administered at any dosage or formulation. We also included methylphenidate groups from RCTs assessing methylphenidate versus other interventions for ADHD as well as data from follow-up periods in RCTs. Participants had to have an ADHD diagnosis (from the 3rd to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders or the 9th or 10th edition of theInternational Classification of Diseases, with or without comorbid diagnoses. We required that at least 75% of participants had a normal intellectual capacity (intelligence quotient of more than 70 points) and were aged below 20 years. We excluded studies that used another ADHD drug as a co-intervention.\nData collection and analysis\nFourteen review authors selected studies independently. Two review authors assessed risk of bias independently using the ROBINS-I tool for assessing risk of bias in non-randomised studies of interventions. All review authors extracted data. We defined serious adverse events according to the International Committee of Harmonization as any lethal, life-threatening or life-changing event. We considered all other adverse events to be non-serious adverse events and conducted meta-analyses of data from comparative studies. We calculated meta-analytic estimates of prevalence from non-comparative cohorts studies and synthesised data from patient reports/series qualitatively. We investigated heterogeneity by conducting subgroup analyses, and we also conducted sensitivity analyses.\nMain results\nWe included a total of 260 studies: 7 comparative cohort studies, 6 of which compared 968 patients who were exposed to methylphenidate to 166 controls, and 1 which assessed 1224 patients that were exposed or not exposed to methylphenidate during different time periods; 4 patient-control studies (53,192 exposed to methylphenidate and 19,906 controls); 177 non-comparative cohort studies (2,207,751 participants); 2 cross-sectional studies (96 participants) and 70 patient reports/series (206 participants). Participants' ages ranged from 3 years to 20 years. Risk of bias in the included comparative studies ranged from moderate to critical, with most studies showing critical risk of bias. We evaluated all non-comparative studies at critical risk of bias. The GRADE quality rating of the evidence was very low.\nPrimary outcomes\nIn the comparative studies, methylphenidate increased the risk ratio (RR) of serious adverse events (RR 1.36, 95% confidence interval (CI) 1.17 to 1.57; 2 studies, 72,005 participants); any psychotic disorder (RR 1.36, 95% CI 1.17 to 1.57; 1 study, 71,771 participants); and arrhythmia (RR 1.61, 95% CI 1.48 to 1.74; 1 study, 1224 participants) compared to no intervention.\nIn the non-comparative cohort studies, the proportion of participants on methylphenidate experiencing any serious adverse event was 1.20% (95% CI 0.70% to 2.00%; 50 studies, 162,422 participants). Withdrawal from methylphenidate due to any serious adverse events occurred in 1.20% (95% CI 0.60% to 2.30%; 7 studies, 1173 participants) and adverse events of unknown severity led to withdrawal in 7.30% of participants (95% CI 5.30% to 10.0%; 22 studies, 3708 participants).\nSecondary outcomes\nIn the comparative studies, methylphenidate, compared to no intervention, increased the RR of insomnia and sleep problems (RR 2.58, 95% CI 1.24 to 5.34; 3 studies, 425 participants) and decreased appetite (RR 15.06, 95% CI 2.12 to 106.83; 1 study, 335 participants).\nWith non-comparative cohort studies, the proportion of participants on methylphenidate with any non-serious adverse events was 51.2% (95% CI 41.2% to 61.1%; 49 studies, 13,978 participants). These included difficulty falling asleep, 17.9% (95% CI 14.7% to 21.6%; 82 studies, 11,507 participants); headache, 14.4% (95% CI 11.3% to 18.3%; 90 studies, 13,469 participants); abdominal pain, 10.7% (95% CI 8.60% to 13.3%; 79 studies, 11,750 participants); and decreased appetite, 31.1% (95% CI 26.5% to 36.2%; 84 studies, 11,594 participants). Withdrawal of methylphenidate due to non-serious adverse events occurred in 6.20% (95% CI 4.80% to 7.90%; 37 studies, 7142 participants), and 16.2% were withdrawn for unknown reasons (95% CI 13.0% to 19.9%; 57 studies, 8340 participants).\nAuthors' conclusions\nOur findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children and adolescents, which often lead to withdrawal of methylphenidate. Our certainty in the evidence is very low, and accordingly, it is not possible to accurately estimate the actual risk of adverse events. It might be higher than reported here.\nGiven the possible association between methylphenidate and the adverse events identified, it may be important to identify people who are most susceptible to adverse events. To do this we must undertake large-scale, high-quality RCTs, along with studies aimed at identifying responders and non-responders.\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": "The quality of the evidence and hence the certainty or reliability of the evidence for the comparative studies is very low. The reliability of the evidence for the non-comparative studies is low due to weaknesses in study design. Accordingly, it is not possible to accurately estimate the risks of adverse events in children and adolescents prescribed methylphenidate." } ]

[ { "role": "user", "content": "Abstract: Background\nOcrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. In November 2017, the European Medicines Agency (EMA) also approved ocrelizumab as the first drug for people with early PPMS. Therefore, it is important to evaluate the benefits, harms, and tolerability of ocrelizumab in people with MS.\nObjectives\nTo assess the benefits, harms, and tolerability of ocrelizumab in people with RRMS and PPMS.\nSearch methods\nWe searched MEDLINE, Embase, CENTRAL, and two trials registers on 8 October 2021. We screened reference lists, contacted experts, and contacted the main authors of studies.\nSelection criteria\nAll randomised controlled trials (RCTs) involving adults diagnosed with RRMS or PPMS according to the McDonald criteria, comparing ocrelizumab alone or associated with other medications, at the approved dose of 600 mg every 24 weeks for any duration, versus placebo or any other active drug therapy.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nFour RCTs met our selection criteria. The overall population included 2551 participants; 1370 treated with ocrelizumab 600 mg and 1181 controls. Among the controls, 298 participants received placebo and 883 received interferon beta-1a. The treatment duration was 24 weeks in one study, 96 weeks in two studies, and at least 120 weeks in one study. One study was at high risk of allocation concealment and blinding of participants and personnel; all four studies were at high risk of bias for incomplete outcome data.\nFor RRMS, compared with interferon beta-1a, ocrelizumab was associated with: 1. lower relapse rate (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.73; 2 studies, 1656 participants; moderate-certainty evidence); 2. a lower number of participants with disability progression (hazard ratio (HR) 0.60, 95% CI 0.43 to 0.84; 2 studies, 1656 participants; low-certainty evidence); 3. little to no difference in the number of participants with any adverse event (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 1651 participants; moderate-certainty evidence); 4. little to no difference in the number of participants with any serious adverse event (RR 0.79, 95% CI 0.57 to 1.11; 2 studies, 1651 participants; low-certainty evidence); 5. a lower number of participants experiencing treatment discontinuation caused by adverse events (RR 0.58, 95% CI 0.37 to 0.91; 2 studies, 1651 participants; low-certainty evidence); 6. a lower number of participants with gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) (RR 0.27, 95% CI 0.22 to 0.35; 2 studies, 1656 participants; low-certainty evidence); 7. a lower number of participants with new or enlarging T2-hyperintense lesions on MRI (RR 0.63, 95% CI 0.57 to 0.69; 2 studies, 1656 participants; low-certainty evidence) at 96 weeks.\nFor PPMS, compared with placebo, ocrelizumab was associated with: 1. a lower number of participants with disability progression (HR 0.75, 95% CI 0.58 to 0.98; 1 study, 731 participants; low-certainty evidence); 2. a higher number of participants with any adverse events (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 725 participants; moderate-certainty evidence); 3. little to no difference in the number of participants with any serious adverse event (RR 0.92, 95% CI 0.68 to 1.23; 1 study, 725 participants; low-certainty evidence); 4. little to no difference in the number of participants experiencing treatment discontinuation caused by adverse events (RR 1.23, 95% CI 0.55 to 2.75; 1 study, 725 participants; low-certainty evidence) for at least 120 weeks. There were no data for number of participants with gadolinium-enhancing T1 lesions on MRI and number of participants with new or enlarging T2-hyperintense lesions on MRI.\nAuthors' conclusions\nFor people with RRMS, ocrelizumab probably results in a large reduction in relapse rate and little to no difference in adverse events when compared with interferon beta-1a at 96 weeks (moderate-certainty evidence). Ocrelizumab may result in a large reduction in disability progression, treatment discontinuation caused by adverse events, number of participants with gadolinium-enhancing T1 lesions on MRI, and number of participants with new or enlarging T2-hyperintense lesions on MRI, and may result in little to no difference in serious adverse events (low-certainty evidence).\nFor people with PPMS, ocrelizumab probably results in a higher rate of adverse events when compared with placebo for at least 120 weeks (moderate-certainty evidence). Ocrelizumab may result in a reduction in disability progression and little to no difference in serious adverse events and treatment discontinuation caused by adverse events (low-certainty evidence).\nOcrelizumab was well tolerated clinically; the most common adverse events were infusion-related reactions and nasopharyngitis, and urinary tract and upper respiratory tract infections.\n\nGiven the provided abstract, please respond to the following query: \"What is ocrelizumab?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Ocrelizumab is a medicine that has been recently approved to treat relapsing-remitting MS and primary progressive MS. It is a disease-modifying therapy, which is a type of medicine that treats the underlying symptoms of MS. Ocrelizumab targets white blood cells in the body's immune system. It sticks to a type of these cells called B cells, and stops them attacking the central nervous system. This prevents inflammation and nerve damage, reducing the number and severity of relapses and slowing the worsening of symptoms." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia, and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition.\nObjectives\nTo compare the efficacy, safety, and tolerability of BtA versus placebo, in people with cervical dystonia.\nSearch methods\nWe searched Cochrane Movement Disorders' Trials Register, CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. All elements of the search, with no language restrictions, were last run in July 2020.\nSelection criteria\nDouble-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with cervical dystonia.\nData collection and analysis\nTwo review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third review author. We performed meta-analyses using a random-effects model, for the comparison of BtA versus placebo, to estimate pooled effects and corresponding 95% confidence intervals (95% CI). We performed preplanned subgroup analyses according to BtA dose used, the BtA formulation used, and the use (or not) of guidance for BtA injections. The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event.\nMain results\nWe included nine RCTs, with moderate, overall risk of bias, that included 1144 participants with cervical dystonia. Seven studies excluded participants with poorer responses to BtA treatment, therefore, including an enriched population with a higher probability of benefiting from this therapy. Only one trial was independently funded. All RCTs evaluated the effect of a single BtA treatment session, using doses from 150 U to 500 U of onabotulinumtoxinA (Botox), 120 U to 240 U of incobotulinumtoxinA (Xeomin), and 250 U to 1000 U of abobotulinumtoxinA (Dysport).\nBtA resulted in a moderate to large improvement from the participant's baseline clinical status, assessed by the investigators, with a mean reduction of 8.09 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score) at week four after injection (95% CI 6.22 to 9.96; I² = 0%) compared to placebo. This corresponded, on average, to a 18.4% improvement from baseline. The mean difference (MD) in TWSTRS pain subscore at week four was 2.11 (95% CI 1.38 to 2.83; I² = 0%) compared to placebo. Overall, both participants and clinicians reported an improvement of subjective clinical status. It was unclear if dropouts due to adverse events differed (risk ratio (RR) 2.51; 95% CI 0.42 to 14.94; I² = 0%) However, BtA treatment increased the risk of experiencing an adverse event (RR) 1.23; 95% CI 1.05 to 1.43; I² = 28%). Neck weakness (14%; RR 3.40; 95% CI 1.19 to 9.71; I² = 15%), dysphagia (11%; RR 3.19; 95% CI 1.79 to 5.70; I² = 0%), and diffuse weakness or tiredness (8%; RR 1.80; 95% CI 1.10 to 2.95; I² = 0%) were the most common treatment-related adverse events. Treatment with BtA resulted in a decreased risk of dropouts. We have moderate certainty in the evidence across all of the aforementioned outcomes, with the exception of subjective assessment and tolerability, in which we have high confidence in the evidence.\nWe found no evidence supporting the existence of a clear dose-response relationship between BtA and improvement in cervical dystonia-specific impairment, a destinction between BtA formulations, or a variation with use of EMG-guided injection for efficacy outcomes.\nDue to clinical heterogeneity, we did not pool health-related quality of life data, duration of clinical effect, or the development of secondary non-responsiveness.\nAuthors' conclusions\nWe are moderately certain in the evidence that a single BtA treatment session resulted in a clinically relevant reduction of cervical dystonia-specific impairment, and pain, and highly certain that it is well tolerated, compared with placebo. There is moderate-certainty evidence that people treated with BtA are at an increased risk of developing adverse events, most notably, dysphagia, neckweakness and diffuse weakness or tiredness. There are no data from RCTs evaluating the effectiveness and safety of repeated BtA injection cycles. There is no evidence from RCTs to allow us to draw definitive conclusions on the optimal treatment intervals and doses, the usefulness of guidance techniques for injection, the impact on quality of life, or the duration of treatment effect.\n\nGiven the provided abstract, please respond to the following query: \"The review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This is an update of a Cochrane Review, We assessed the effectiveness (reduction in severity, disability, and pain) and safety of botulinum toxin type A (BtA) versus placebo (a pretend medicine) in people with involuntary positioning of the head, or cervical dystonia" } ]

[ { "role": "user", "content": "Abstract: Background\nDespite local therapies, commonly transurethral resection (TUR) followed by adjuvant treatments, non-muscle-invasive bladder cancer (NMIBC) has a high rate of recurrence and progression. Intravesical Bacillus Calmette-Guérin (BCG) has been shown to reduce recurrence and progression in people with NMIBC following TUR, however many people do not respond to treatment, have recurrence shortly after, or cannot tolerate standard-dose therapy. The potential for synergistic antitumour activity of interferon (IFN)-alpha (α) and BCG provides some rationale for combination therapy for people who do not tolerate or respond to standard-dose BCG therapy.\nObjectives\nTo assess the effects of intravesically administered BCG plus IFN-α compared with BCG alone for treating non-muscle-invasive bladder cancer.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2016), MEDLINE (OvidSP) (1946 to 2016), Embase (OvidSP) (1974 to 2016), ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) as well as reference lists of retrieved articles and handsearched abstract proceedings of relevant conferences for the past three years. We applied no language restrictions. The date of last search of all databases was 25 August 2016.\nSelection criteria\nWe included randomised controlled trials (RCTs) and pseudo-randomised trials assessing intravesically administered BCG plus IFN-α versus BCG alone in adults of either gender with histologically confirmed Ta and T1 superficial bladder cancer, with or without carcinoma in situ, treated with TUR.\nData collection and analysis\nTwo review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of included studies. We used Review Manager 5 for data synthesis and employed the random-effects model for meta-analyses. For prespecified outcomes, where we were unable to derive time-to-event information (e.g. time-to-recurrence), we assessed dichotomous outcomes (e.g. recurrence) instead. We assessed the quality of the evidence for the main comparisons using the GRADE approach.\nMain results\nWe included five RCTs involving a total of 1231 participants with NMIBC in this review. Due to poor reporting, the risk of bias in the included studies was often unclear. We assessed the studies under two main comparisons: intravesical BCG plus IFN-α versus intravesical BCG alone (four RCTs), and intravesical BCG alternating with IFN-α versus intravesical BCG alone (one RCT).\nIntravesical BCG plus IFN-α versus intravesical BCG alone (four RCTs): We observed no clear difference between BCG plus IFN-α and BCG alone for recurrence (average risk ratio (RR) 0.76, 95% confidence interval (CI) 0.44 to 1.32; 4 RCTs; 925 participants; very low-quality evidence) or progression (average RR 0.26, 95% CI 0.04 to 1.87; 2 RCTs; 219 participants; low-quality evidence). The included RCTs did not report on the other primary outcome of this review, discontinuation of therapy due to adverse events. Regarding secondary outcomes, we observed no clear difference for disease-specific mortality (RR 0.38, 95% CI 0.05 to 3.05; 1 RCT; 99 participants; very low-quality evidence). Two RCTs reporting contradictory findings for adverse events could not be pooled due to variation in definitions. There were no data from the included RCTs on time-to-death or disease-specific quality of life.\nIntravesical BCG alternating with IFN-α versus intravesical BCG alone (one RCT): We observed shorter time-to-recurrence for participants in the BCG alternating with IFN-α group compared with the BCG alone group (hazard ratio (HR) 2.86, 95% CI 1.98 to 4.13; 1 RCT; 205 participants; low-quality evidence), but no clear differences in time-to-progression (HR 2.39, 95% CI 0.92 to 6.21; 1 RCT; 205 participants; low-quality evidence) and discontinuation of therapy due to adverse events (RR 2.97, 95% CI 0.31 to 28.09; 1 RCT; 205 participants; low-quality evidence). Regarding secondary outcomes, there were no clear differences between the BCG alternating with IFN-α and BCG alone groups for disease-specific mortality (HR 2.74, 95% CI 0.73 to 10.28; 1 RCT; 205 participants; low-quality evidence), time-to-death (overall survival) (HR 1.00, 95% CI 0.68 to 1.47; 1 RCT; 205 participants; low-quality evidence), or systemic or local adverse events (RR 1.65, 95% CI 0.41 to 6.73; 1 RCT; 205 participants; low-quality evidence). There were no data on disease-specific quality of life.\nAuthors' conclusions\nWe found low- to very low-quality evidence suggesting no clear differences in recurrence or progression with BCG plus IFN-α compared with BCG alone for people with NMIBC; there was no information to determine the effect on discontinuation of therapy due to adverse events. Low-quality evidence suggests BCG alternating with IFN-α compared with BCG alone may increase time-to-recurrence, however low-quality evidence also suggests no clear differences for time-to-progression or discontinuation of therapy due to adverse events.\nAdditional high-quality, adequately powered trials using standardised instillation regimens and doses of both BCG and IFN-α, reporting outcomes in subgroups stratified by patient and tumour characteristics, and on long-term outcomes related not only to recurrence but also to progression, discontinuation due to adverse events, and mortality may help to clarify the ideal treatment strategy and provide a more definitive result.\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 reviewed the evidence on the effects of local treatment of the bladder with Bacillus Calmette-Guérin (BCG) and interferon (IFN)-alpha (α) for cancer of the superficial layers of the bladder (known as non-muscle-invasive bladder cancer)." } ]

[ { "role": "user", "content": "Abstract: Background\nAcne vulgaris, a chronic inflammatory disease of the pilosebaceous unit associated with socialisation and mental health problems, may affect more than 80% of teenagers. Isotretinoin is widely recognised as a very effective treatment for severe acne; however, it may cause adverse effects.\nObjectives\nTo assess efficacy and safety of oral isotretinoin for acne vulgaris.\nSearch methods\nWe searched the following databases up to July 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and LILACS. We updated this search in March 2018, but these results have not yet been incorporated in the review. We also searched five trial registries, checked the reference lists of retrieved studies for further references to relevant trials, and handsearched dermatology conference proceedings. A separate search for adverse effects of oral isotretinoin was undertaken in MEDLINE and Embase up to September 2013.\nSelection criteria\nRandomised clinical trials (RCTs) of oral isotretinoin in participants with clinically diagnosed acne compared against placebo, any other systemic or topical active therapy, and itself in different formulation, doses, regimens, or course duration.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included 31 RCTs, involving 3836 participants (12 to 55 years) with mild to severe acne. There were twice as many male participants as females.\nMost studies were undertaken in Asia, Europe, and North America. Outcomes were generally measured between eight to 32 weeks (mean 19.7) of therapy.\nAssessed comparisons included oral isotretinoin versus placebo or other treatments such as antibiotics. In addition, different doses, regimens, or formulations of oral isotretinoin were assessed, as well as oral isotretinoin with the addition of topical agents.\nPharmaceutical companies funded 12 included trials. All, except three studies, had high risk of bias in at least one domain. Attrition bias was high in 20 trials, selective reporting bias was high in 12 trials, and performance bias was high in 11 trials.\nOral isotretinoin compared with oral antibiotics plus topical agents\nThese studies included participants with moderate or severe acne and assessed outcomes immediately after 20 to 24 weeks of treatment (short-term). Three studies (400 participants) showed no evidence that isotretinoin decreases trial investigator-assessed inflammatory lesion count more than antibiotics (RR 1.01 95% CI 0.96 to 1.06), with only one serious adverse effect found, which was Stevens-Johnson syndrome in the isotretinoin group (RR 3.00, 95% CI 0.12 to 72.98). However, we are uncertain about these results as they were based on very low-quality evidence.\nIsotretinoin may slightly improve (by 15%) acne severity, assessed by physician's global evaluation (RR 1.15, 95% CI 1.00 to 1.32; 351 participants; 2 studies), but resulted in more less serious adverse effects (67% higher risk) (RR 1.67, 95% CI 1.42 to 1.98; 351 participants; 2 studies), such as dry lips/skin, cheilitis, vomiting, nausea (both outcomes, low-quality evidence).\nDifferent doses/therapeutic regimens of oral isotretinoin\nFor our primary efficacy outcome, we found three RCTs, but heterogeneity precluded meta-analysis. One study (154 participants) reported 79%, 80% and 84% decrease in total inflammatory lesion count after 20 weeks of 0.05, 0.1, or 0.2 mg/kg/d of oral isotretinoin for severe acne (low-quality evidence). Another trial (150 participants, severe acne) compared 0.1, 0.5, and 1 mg/kg/d oral isotretinoin for 20 weeks and, respectively, 58%, 80% and 90% of participants achieved 95% decrease in total inflammatory lesion count. One 24-week RCT of participants with moderate acne compared isotretinoin at (a) continuous low dose (0.25 to 0.4 mg/kg/day), (b) continuous conventional dose (0.5 to 0.7 mg/kg/day), and (c) intermittent regimen (0.5 to 0.7 mg/kg/day, for one week in a month). Continuous low dose (MD 3.72 lesions; 95% CI 2.13 to 5.31; 40 participants; one study) and conventional dose (MD 3.87 lesions; 95% CI 2.31 to 5.43; 40 participants; one study) had a greater decrease in inflammatory lesion counts compared to intermittent treatment (all outcomes, low-quality evidence).\nFourteen RCTs (906 participants, severe and moderate acne) reported that no serious adverse events were observed when comparing different doses/therapeutic regimens of oral isotretinoin during treatment (from 12 to 32 weeks) or follow-up after end of treatment (up to 48 weeks). Thirteen RCTs (858 participants) analysed frequency of less serious adverse effects, which included skin dryness, hair loss, and itching, but heterogeneity regarding the assessment of the outcome precluded data pooling; hence, there is uncertainty about the results (low- to very low-quality evidence, where assessed).\nImprovement in acne severity, assessed by physician's global evaluation, was not measured for this comparison.\nNone of the included RCTs reported birth defects, but oral isotretinoin is contraindicated during pregnancy due to known teratogenic effects.\nAuthors' conclusions\nEvidence was low-quality for most assessed outcomes.\nWe did not find any clear evidence from RCTs that isotretinoin improves acne severity compared with standard oral antibiotic and topical treatment when assessed by a decrease in total inflammatory lesion count, but it may slightly improve physician-assessed acne severity. Only one serious adverse event was reported in the isotretinoin group, which means we are uncertain of the risk of serious adverse effects; however, isotretinoin may result in increased minor adverse effects.\nHeterogeneity in the studies comparing different regimens, doses, or formulations of oral isotretinoin meant we were unable to undertake meta-analysis. Daily treatment may be more effective than treatment for one week each month. None of the randomised studies in this comparison reported serious adverse effects, or measured improvement in acne severity assessed by physician's global evaluation. We are uncertain if there is a difference in number of minor adverse effects, such as skin dryness, between doses/regimens.\nEvidence quality was lessened due to imprecision and attrition bias. Further studies should ensure clearly reported long- and short-term standardised assessment of improvement in total inflammatory lesion counts, participant-reported outcomes, and safety. Oral isotretinoin is a well-established treatment for severe acne, and for acne that has not responded to oral antibiotics plus topical agents. The clinical trial evidence for oral isotretinoin conducted around 30 years ago was low quality. Further trials are needed to evaluate different dose/regimens of oral isotretinoin in acne of all severities.\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": "Acne is a persistent inflammatory disease that can affect more than 80% of teenagers. Acne (including blackheads, whiteheads, and pimples) mostly appears on the face, but can also appear on the back and chest. Mental health problems, depression, and suicidal thoughts have been associated with acne. Isotretinoin, a currently widely used therapy derived from vitamin A, transformed acne treatment. However, it may cause adverse effects and has been associated with still uncertain psychiatric events and inflammatory bowel disease." } ]

[ { "role": "user", "content": "Abstract: Background\nPersistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide.\nObjectives\nTo evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women.\nSearch methods\nWe searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events.\nSelection criteria\nRandomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine).\nData collection and analysis\nWe used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets.\nMain results\nWe included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation.\nEfficacy endpoints by initial HPV DNA status\nhrHPV negative\nHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).\nHPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.\nHPV16/18 negative\nIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes.\nVaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions.\nRegardless of HPV DNA status\nIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).\nHPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).\nIn women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.\nAdverse effects\nThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.\nPregnancy outcomes\nAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively).\nAuthors' conclusions\nThere is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.\nWe did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.\n\nGiven the provided abstract, please respond to the following query: \"Protection against cervical precancer\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "1) Women free of hrHPV\nOutcomes were only measured in the younger age group for this comparison (15 to 25 years). HPV vaccines reduce the risk of cervical precancer associated with HPV16/18 from 164 to 2/10,000 women (high certainty). They reduce also any precancer from 287 to 106/10,000 (high certainty).\n2) Women free of HPV16/18\nThe effect of HPV vaccines on risk of precancer differ by age group. In younger women, HPV vaccines reduce the risk of precancer associated with HPV16/18 from 113 to 6/10,000 women (high certainty). HPV vaccines lower the number of women with any precancer from 231 to 95/10,000 (high certainty). In women older than 25, the vaccines reduce the number with precancer associated with HPV16/18 from 45 to 14/10,000 (moderate certainty).\n3) All women with or without HPV infection\nIn those vaccinated between 15 to 26 years of age, HPV vaccination reduces the risk of precancer associated with HPV16/18 from 341 to 157/10,000 (high certainty) and any precancer from 559 to 391/10,000 (high certainty).\nIn older women, vaccinated between 25 to 45 years of age, the effects of HPV vaccine on precancer are smaller, which may be due to previous exposure to HPV. The risk of precancer associated with HPV16/18 is probably reduced from 145/10,000 in unvaccinated women to 107/10,000 women following HPV vaccination (moderate certainty). The risk of any precancer is probably similar between unvaccinated and vaccinated women (343 versus 356/10,000, moderate certainty)." } ]

[ { "role": "user", "content": "Abstract: Background\nFibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects.\nObjectives\nTo assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults.\nSearch methods\nWe searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries.\nSelection criteria\nDouble-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain.\nData collection and analysis\nFrom all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of efficacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table.\nMain results\nWe identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a different agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200 participants); and one combined pregabalin with duloxetine (41 participants). Six studies compared the combination of multiple agents with each component alone and with inactive placebo; three studies compared combination pharmacotherapy with each individual component but did not include an inactive placebo group; two studies compared the combination of two agents with only one of the agents alone; and three studies compared the combination of two or more agents only with inactive placebo.\nHeterogeneity among studies in terms of class of agents evaluated, specific combinations used, outcomes reported, and doses given prevented any meta-analysis. None of the combinations of drugs found provided sufficient data for analysis compared with placebo or other comparators for our preferred outcomes. We therefore provide a narrative description of results. There was no or inadequate evidence in any comparison for primary and secondary outcomes. Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater). For each 'Risk of bias' item, only half or fewer of studies had unequivocal low risk of bias. Small size and selective reporting were common as high risk of bias.\nOur GRADE assessment was therefore very low for primary outcomes of pain relief of 30% or 50% or greater, PGIC much or very much improved or very much improved, any pain-related outcome, participants experiencing any adverse event, any serious adverse event, or withdrawing because of an adverse event.\nThree studies found some evidence that combination pharmacotherapy reduced pain compared to monotherapy; these trials tested three different combinations: melatonin and amitriptyline, fluoxetine and amitriptyline, and pregabalin and duloxetine. Adverse events experienced by participants were not serious, and where they were reported (in 12 out of 16 studies), all participants experienced them, regardless of treatment. Common adverse events were nausea, dizziness, somnolence, and headache.\nAuthors' conclusions\nThere are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.\n\nGiven the provided abstract, please respond to the following query: \"Bottom line\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "There is no good evidence to prove or disprove that combining drugs is better than using single drugs for fibromyalgia." } ]

[ { "role": "user", "content": "Abstract: Background\nVedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease.\nObjectives\nTo evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 30 November 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease.\nData collection and analysis\nWe used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence.\nMain results\nWe analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years.\nVedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence).\nVedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence).\nAuthors' conclusions\nHigh-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.\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 for studies that compared vedolizumab to placebo in people with Crohn's disease. We compared and summarised their results, and rated our confidence in the evidence, based on factors such as study methods and sizes." } ]

[ { "role": "user", "content": "Abstract: Background\nSpecialist nursing roles to manage stable disease populations are being used to meet the needs of both patients and health services. With increasing cost pressures on health departments, alternative models such as nurse-led care are gaining momentum as a substitute for traditional doctor-led care. This review evaluates the safety, effectiveness, and health outcomes of nurses practising in autonomous roles while using advanced practice skills, within the context of bronchiectasis management in subacute, ambulatory, and/or community care.\nObjectives\nTo compare the effectiveness of nurse-led care versus doctor-led care in the management of stable bronchiectasis.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register and bibliographies of selected papers in addition to grey literature such as electronic clinical trials registries. Searches were current as of March 2018.\nSelection criteria\nRandomised controlled trials were eligible for inclusion in the review.\nData collection and analysis\nTwo reviewers extracted and entered data from included studies. Primary outcomes were numbers of exacerbations requiring treatment with antibiotics, hospital admissions, and emergency department attendances.\nMain results\nWe included one United Kingdom (UK) study in the review. In this randomised controlled trial, a total of 80 participants, with a mean age of 58 years, were treated for 12 months by a specialist nurse or doctor, then were crossed over to the other clinician for the next 12 months. Two participants died during the study period. Six participants failed to cross over to nurse-led care because of unstable bronchiectasis. Overall, the level of study completion was high.\nData show no difference in the numbers of exacerbations requiring treatment with antibiotics (rate ratio 1.09, 95% confidence interval (CI) 0.91 to 1.30, 80 participants, moderate-certainty evidence). Investigators reported more hospital admissions in the nurse-led care group (rate ratio 1.52, 95% CI 1.04 to 2.23, 80 participants, moderate-certainty evidence) and did not report emergency department attendance.\nFor secondary outcomes, participants in the nurse-led care group used more healthcare resources during the first year of the trial. Increased admissions and greater use of resources made treatment costs for nurse-led groups' higher. Total costs for both years of the study were £8,464 and £5,228 for nurse-led care compared with doctor-led care. However, by the second year, treatment costs were almost equitable between the two groups, which may reflect the nurses' learning of how to better treat people with bronchiectasis. No statistically significant changes were observed in quality of life, exercise capacity, mortality, or lung function. Wide confidence intervals led to uncertainty regarding these results. Adverse events were not an outcome for this review.\nAuthors' conclusions\nThis update of the review shows that only one trial met review criteria. Review authors were unable to demonstrate effectiveness of nurse-led care compared with doctor-led care on the basis of findings of a single study. The included study reported no significant differences, but limited evidence means that differences in clinical outcomes between nurse-led care and usual care within the setting of a specialist clinic remain unclear. Further research is required to determine whether nurse-led care is cost-effective, if guidelines and protocols for bronchiectasis management are followed does this increases costs and how effective nurse-led management of bronchiectasis is in other clinical settings such as inpatient and outreach.\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 no significant differences between nurse-led and doctor-led care in terms of lung function, infective flareups (exacerbations), or quality of life. In the first year of the study we noted increased costs for nurse-led care with more hospital admissions and greater use of antibiotic injections." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute upper respiratory tract infections (URTIs), including the common cold and rhinosinusitis, are common afflictions that cause discomfort and debilitation and contribute significantly to workplace absenteeism. Treatment is generally by antipyretic and decongestant drugs and sometimes antibiotics, even though most infections are viral. Nasal irrigation with saline is often employed as an adjunct treatment for URTI symptoms despite a relative lack of evidence for benefit in this clinical setting. This review is an update of the Cochrane review by Kassel et al, which found that saline was probably effective in reducing the severity of some symptoms associated with acute URTIs.\nObjectives\nTo assess the effects of saline nasal irrigation for treating the symptoms of acute URTIs.\nSearch methods\nWe searched CENTRAL (2014, Issue 7), MEDLINE (1966 to July week 5, 2014), EMBASE (1974 to August 2014), CINAHL (1982 to August 2014), AMED (1985 to August 2014) and LILACS (1982 to August 2014).\nSelection criteria\nRandomised controlled trials (RCTs) comparing topical nasal saline treatment to other interventions in adults and children with clinically diagnosed acute URTIs.\nData collection and analysis\nTwo review authors (DK, BM) independently assessed trial quality with the Cochrane 'Risk of bias' tool and extracted data. We analysed all data using the Cochrane Review Manager software. Due to the large variability of outcome measures only a small number of outcomes could be pooled for statistical analysis.\nMain results\nWe identified five RCTs that randomised 544 children (three studies) and 205 adults (exclusively from two studies). They all compared saline irrigation to routine care or other nose sprays, rather than placebo. We included two new trials in this update, which did not contribute data of sufficient size or quality to materially change the original findings. Most trials were small and we judged them to be of low quality, contributing to an unclear risk of bias. Most outcome measures differed greatly between included studies and therefore could not be pooled. Most results showed no difference between nasal saline treatment and control. However, one larger trial, conducted with children, did show a significant reduction in nasal secretion score (mean difference (MD) -0.31, 95% confidence interval (CI) -0.48 to -0.14) and nasal breathing (obstruction) score (MD -0.33, 95% CI -0.47 to -0.19) in the saline group. However, a MD of -0.33 on a four-point symptom scale may have minimal clinical significance. The trial also showed a significant reduction in the use of decongestant medication by the saline group. Minor nasal discomfort and/or irritation was the only side effect reported by a minority of participants.\nAuthors' conclusions\nNasal saline irrigation possibly has benefits for relieving the symptoms of acute URTIs. However, the included trials were generally too small and had a high risk of bias, reducing confidence in the evidence supporting this. Future trials should involve larger numbers of participants and report standardised and clinically meaningful outcome measures.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We identified five studies, with a total of 749 participants enrolled and 565 participants providing data, which addressed the research question and met the inclusion criteria. They all compared saline irrigation with routine care or other nose sprays. These studies covered a wide range of ages, countries, sample sizes, dosing methods and frequency, and time since onset of URTI symptoms. They were also highly variable in their design and the symptoms that were measured. This is not surprising due to the lack of consistent measures of URTI symptoms and signs. This resulted in very few common outcome measures that could be combined across these five studies. The evidence is current to August 2014." } ]

[ { "role": "user", "content": "Abstract: Background\nIn late 2019, the first cases of coronavirus disease 2019 (COVID-19) were reported in Wuhan, China, followed by a worldwide spread. Numerous countries have implemented control measures related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers.\nObjectives\nTo assess the effectiveness of international travel-related control measures during the COVID-19 pandemic on infectious disease transmission and screening-related outcomes.\nSearch methods\nWe searched MEDLINE, Embase and COVID-19-specific databases, including the Cochrane COVID-19 Study Register and the WHO Global Database on COVID-19 Research to 13 November 2020.\nSelection criteria\nWe considered experimental, quasi-experimental, observational and modelling studies assessing the effects of travel-related control measures affecting human travel across international borders during the COVID-19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In this version we decided to focus on COVID-19 evidence only. Primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome.\nData collection and analysis\nTwo review authors independently screened titles and abstracts and subsequently full texts. For studies included in the analysis, one review author extracted data and appraised the study. At least one additional review author checked for correctness of data. To assess the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for observational studies concerned with screening, and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed the certainty of evidence with GRADE, and several review authors discussed these GRADE judgements.\nMain results\nOverall, we included 62 unique studies in the analysis; 49 were modelling studies and 13 were observational studies. Studies covered a variety of settings and levels of community transmission.\nMost studies compared travel-related control measures against a counterfactual scenario in which the measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of stringency of the measures (including relaxation of restrictions), or a combination of measures.\nConcerns with the quality of modelling studies related to potentially inappropriate assumptions about the structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to the selection of travellers and the reference test, and unclear reporting of certain methodological aspects.\nBelow we outline the results for each intervention category by illustrating the findings from selected outcomes.\nTravel restrictions reducing or stopping cross-border travel (31 modelling studies)\nThe studies assessed cases avoided and shift in epidemic development. We found very low-certainty evidence for a reduction in COVID-19 cases in the community (13 studies) and cases exported or imported (9 studies). Most studies reported positive effects, with effect sizes varying widely; only a few studies showed no effect.\nThere was very low-certainty evidence that cross-border travel controls can slow the spread of COVID-19. Most studies predicted positive effects, however, results from individual studies varied from a delay of less than one day to a delay of 85 days; very few studies predicted no effect of the measure.\nScreening at borders (13 modelling studies; 13 observational studies)\nScreening measures covered symptom/exposure-based screening or test-based screening (commonly specifying polymerase chain reaction (PCR) testing), or both, before departure or upon or within a few days of arrival. Studies assessed cases avoided, shift in epidemic development and cases detected. Studies generally predicted or observed some benefit from screening at borders, however these varied widely.\nFor symptom/exposure-based screening, one modelling study reported that global implementation of screening measures would reduce the number of cases exported per day from another country by 82% (95% confidence interval (CI) 72% to 95%) (moderate-certainty evidence). Four modelling studies predicted delays in epidemic development, although there was wide variation in the results between the studies (very low-certainty evidence). Four modelling studies predicted that the proportion of cases detected would range from 1% to 53% (very low-certainty evidence). Nine observational studies observed the detected proportion to range from 0% to 100% (very low-certainty evidence), although all but one study observed this proportion to be less than 54%.\nFor test-based screening, one modelling study provided very low-certainty evidence for the number of cases avoided. It reported that testing travellers reduced imported or exported cases as well as secondary cases. Five observational studies observed that the proportion of cases detected varied from 58% to 90% (very low-certainty evidence).\nQuarantine (12 modelling studies)\nThe studies assessed cases avoided, shift in epidemic development and cases detected. All studies suggested some benefit of quarantine, however the magnitude of the effect ranged from small to large across the different outcomes (very low- to low-certainty evidence). Three modelling studies predicted that the reduction in the number of cases in the community ranged from 450 to over 64,000 fewer cases (very low-certainty evidence). The variation in effect was possibly related to the duration of quarantine and compliance.\nQuarantine and screening at borders (7 modelling studies; 4 observational studies)\nThe studies assessed shift in epidemic development and cases detected. Most studies predicted positive effects for the combined measures with varying magnitudes (very low- to low-certainty evidence). Four observational studies observed that the proportion of cases detected for quarantine and screening at borders ranged from 68% to 92% (low-certainty evidence). The variation may depend on how the measures were combined, including the length of the quarantine period and days when the test was conducted in quarantine.\nAuthors' conclusions\nWith much of the evidence derived from modelling studies, notably for travel restrictions reducing or stopping cross-border travel and quarantine of travellers, there is a lack of 'real-world' evidence. The certainty of the evidence for most travel-related control measures and outcomes is very low and the true effects are likely to be substantially different from those reported here. Broadly, travel restrictions may limit the spread of disease across national borders. Symptom/exposure-based screening measures at borders on their own are likely not effective; PCR testing at borders as a screening measure likely detects more cases than symptom/exposure-based screening at borders, although if performed only upon arrival this will likely also miss a meaningful proportion of cases. Quarantine, based on a sufficiently long quarantine period and high compliance is likely to largely avoid further transmission from travellers. Combining quarantine with PCR testing at borders will likely improve effectiveness. Many studies suggest that effects depend on factors, such as levels of community transmission, travel volumes and duration, other public health measures in place, and the exact specification and timing of the measure. Future research should be better reported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel-related control measures from a societal perspective.\n\nGiven the provided abstract, please respond to the following query: \"Travel restrictions reducing or stopping cross-border travel\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "(31 modelling studies)\nMost studies showed that travel restrictions reducing or stopping cross-border travel were beneficial, but this beneficial effect ranged from small to large. Additionally, some studies found no effect. Studies also predicted that these restrictions would delay the outbreak, but the delay ranged from one day to 85 days in different studies." } ]

[ { "role": "user", "content": "Abstract: Background\nExercise training is commonly recommended for adults with fibromyalgia. We defined flexibility exercise training programs as those involving movements of a joint or a series of joints, through complete range of motion, thus targeting major muscle-tendon units. This review is one of a series of reviews updating the first review published in 2002.\nObjectives\nTo evaluate the benefits and harms of flexibility exercise training in adults with fibromyalgia.\nSearch methods\nWe searched the Cochrane Library, MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PEDro (Physiotherapy Evidence Database), Thesis and Dissertation Abstracts, AMED (Allied and Complementary Medicine Database), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov up to December 2017, unrestricted by language, and we reviewed the reference lists of retrieved trials to identify potentially relevant trials.\nSelection criteria\nWe included randomized trials (RCTs) including adults diagnosed with fibromyalgia based on published criteria. Major outcomes were health-related quality of life (HRQoL), pain intensity, stiffness, fatigue, physical function, trial withdrawals, and adverse events.\nData collection and analysis\nTwo review authors independently selected articles for inclusion, extracted data, performed 'Risk of bias' assessments, and assessed the certainty of the body of evidence for major outcomes using the GRADE approach. All discrepancies were rechecked, and consensus was achieved by discussion.\nMain results\nWe included 12 RCTs (743 people). Among these RCTs, flexibility exercise training was compared to an untreated control group, land-based aerobic training, resistance training, or other interventions (i.e. Tai Chi, Pilates, aquatic biodanza, friction massage, medications). Studies were at risk of selection, performance, and detection bias (due to lack of adequate randomization and allocation concealment, lack of participant or personnel blinding, and lack of blinding for self-reported outcomes). With the exception of withdrawals and adverse events, major outcomes were self-reported and were expressed on a 0-to-100 scale (lower values are best, negative mean differences (MDs) indicate improvement). We prioritized the findings of flexibility exercise training compared to land-based aerobic training and present them fully here.\nVery low-certainty evidence showed that compared with land-based aerobic training, flexibility exercise training (five trials with 266 participants) provides no clinically important benefits with regard to HRQoL, pain intensity, fatigue, stiffness, and physical function. Low-certainty evidence showed no difference between these groups for withdrawals at completion of the intervention (8 to 20 weeks).\nMean HRQoL assessed on the Fibromyalgia Impact Questionnaire (FIQ) Total scale (0 to 100, higher scores indicating worse HRQoL) was 46 mm and 42 mm in the flexibility and aerobic groups, respectively (2 studies, 193 participants); absolute change was 4% worse (6% better to 14% worse), and relative change was 7.5% worse (10.5% better to 25.5% worse) in the flexibility group. Mean pain was 57 mm and 52 mm in the flexibility and aerobic groups, respectively (5 studies, 266 participants); absolute change was 5% worse (1% better to 11% worse), and relative change was 6.7% worse (2% better to 15.4% worse). Mean fatigue was 67 mm and 71 mm in the aerobic and flexibility groups, respectively (2 studies, 75 participants); absolute change was 4% better (13% better to 5% worse), and relative change was 6% better (19.4% better to 7.4% worse). Mean physical function was 23 points and 17 points in the flexibility and aerobic groups, respectively (1 study, 60 participants); absolute change was 6% worse (4% better to 16% worse), and relative change was 14% worse (9.1% better to 37.1% worse). We found very low-certainty evidence of an effect for stiffness. Mean stiffness was 49 mm to 79 mm in the flexibility and aerobic groups, respectively (1 study, 15 participants); absolute change was 30% better (8% better to 51% better), and relative change was 39% better (10% better to 68% better). We found no evidence of an effect in all-cause withdrawal between the flexibility and aerobic groups (5 studies, 301 participants). Absolute change was 1% fewer withdrawals in the flexibility group (8% fewer to 21% more), and relative change in the flexibility group compared to the aerobic training intervention group was 3% fewer (39% fewer to 55% more). It is uncertain whether flexibility leads to long-term effects (36 weeks after a 12-week intervention), as the evidence was of low certainty and was derived from a single trial.\nVery low-certainty evidence indicates uncertainty in the risk of adverse events for flexibility exercise training. One adverse effect was described among the 132 participants allocated to flexibility training. One participant had tendinitis of the Achilles tendon (McCain 1988), but it is unclear if the tendinitis was a pre-existing condition.\nAuthors' conclusions\nWhen compared with aerobic training, it is uncertain whether flexibility improves outcomes such as HRQoL, pain intensity, fatigue, stiffness, and physical function, as the certainty of the evidence is very low. Flexibility exercise training may lead to little or no difference for all-cause withdrawals. It is also uncertain whether flexibility exercise training has long-term effects due to the very low certainty of the evidence. We downgraded the evidence owing to the small number of trials and participants across trials, as well as due to issues related to unclear and high risk of bias (selection, performance, and detection biases). While flexibility exercise training appears to be well tolerated (similar withdrawal rates across groups), evidence on adverse events was scarce, therefore its safety is uncertain.\n\nGiven the provided abstract, please respond to the following query: \"Physical function\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "People who received flexibility exercise training were 6% worse (ranging from 4% better to 16% worse).\n• People who had flexibility training rated their physical function as 23 points.\n• People who had aerobic training rated their physical function as 17 points." } ]

[ { "role": "user", "content": "Abstract: Background\nOtitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Antibiotics are sometimes used to treat any bacteria present in the effusion, or associated biofilms.\nObjectives\nTo assess the effects (benefits and harms) of oral antibiotics for otitis media with effusion (OME) in children.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished studies to 20 January 2023.\nSelection criteria\nWe included randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared oral antibiotics with either placebo or no treatment.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing, 2) otitis media-specific quality of life and 3) anaphylaxis. Secondary outcomes were: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function and 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome.\nAlthough we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds.\nMain results\nWe identified 19 completed studies that met our inclusion criteria (2581 participants). They assessed a variety of oral antibiotics (including penicillins, cephalosporins, macrolides and trimethoprim), with most studies using a 10- to 14-day treatment course. We had some concerns about the risk of bias in all studies included in this review. Here we report our primary outcomes and main secondary outcome, at the longest reported follow-up time.\nAntibiotics versus placebo\nWe included 11 studies for this comparison, but none reported all of our outcomes of interest and limited meta-analysis was possible.\nHearing\nOne study found that more children may return to normal hearing by two months (resolution of the air-bone gap) after receiving antibiotics as compared with placebo, but the evidence is very uncertain (Peto odds ratio (OR) 9.59, 95% confidence interval (CI) 3.51 to 26.18; 20/49 children who received antibiotics returned to normal hearing versus 0/37 who received placebo; 1 study, 86 participants; very low-certainty evidence).\nDisease-specific quality of life\nNo studies assessed this outcome.\nPresence/persistence of OME\nAt 6 to 12 months of follow-up, the use of antibiotics compared with placebo may slightly reduce the number of children with persistent OME, but the confidence intervals were wide, and the evidence is very uncertain (risk ratio (RR) 0.89, 95% CI 0.68 to 1.17; 48% versus 54%; number needed to treat (NNT) 17; 2 studies, 324 participants; very low-certainty evidence).\nAdverse event: anaphylaxis\nNo studies provided specific data on anaphylaxis. Three of the included studies (448 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence).\nAntibiotics versus no treatment\nWe included eight studies for this comparison, but very limited meta-analysis was possible.\nHearing\nOne study found that the use of antibiotics compared to no treatment may result in little to no difference in final hearing threshold at three months (mean difference (MD) -5.38 dB HL, 95% CI -9.12 to -1.64; 1 study, 73 participants; low-certainty evidence). The only data identified on the return to normal hearing were reported at 10 days of follow-up, which we considered to be too short to accurately reflect the efficacy of antibiotics.\nDisease-specific quality of life\nNo studies assessed this outcome.\nPresence/persistence of OME\nAntibiotics may reduce the proportion of children who have persistent OME at up to three months of follow-up, when compared with no treatment (RR 0.64, 95% CI 0.50 to 0.80; 6 studies, 542 participants; low-certainty evidence).\nAdverse event: anaphylaxis\nNo studies provided specific data on anaphylaxis. Two of the included studies (180 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence).\nAuthors' conclusions\nThe evidence for the use of antibiotics for OME is of low to very low certainty. Although the use of antibiotics compared to no treatment may have a slight beneficial effect on the resolution of OME at up to three months, the overall impact on hearing is very uncertain. The long-term effects of antibiotics are unclear and few of the studies included in this review reported on potential harms. These important endpoints should be considered when weighing up the potential short- and long-term benefits and harms of antibiotic treatment in a condition with a high spontaneous resolution rate.\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 identify whether antibiotics are better than placebo (sham or dummy treatment), or no treatment, for children with OME.\nWe also wanted to see whether there are any unwanted effects associated with taking antibiotics for this condition." } ]

[ { "role": "user", "content": "Abstract: Background\nBiologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since important risks such as lymphomas, serious infections and tuberculosis (TB) reactivation may be more common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain  much needed risk estimates.\nObjectives\nTo compare the potential adverse effects of tumor necrosis factor inhibitor (adalimumab, certolizumab, etanercept, golimumab, infliximab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS).\nMethods\nRandomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes (serious adverse events (SAEs), withdrawals due to adverse events (AEs), total AEs, serious infections; specific AEs, namely, tuberculosis (TB) reactivation, lymphoma and congestive heart failure) were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed both Bayesian mixed-treatment comparison models and arm-based generalized linear mixed models.\nMain results\nWe included 160 RCTs with 48,676 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for TB reactivation, lymphoma, and congestive heart failure. Using standard dose, compared with control, biologics as a group were associated with a statistically significant higher rate of total AEs (odds ratio (OR) 1.28, 95% credible interval (CI) 1.09 to 1.50; number needed to treat to harm (NNTH) = 22, 95% confidence interval (CI) 14 to 60), withdrawals due to AEs (OR 1.47, 95% CI 1.20 to 1.86; NNTH = 26, 95% CI 15 to 58), serious infections (OR, 1.37, 95% CI 1.04 to 1.82, NNTH = 108 95% CI, 50 to 989) and TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706).\nThe rate of SAEs, lymphoma and congestive heart failure were not statistically significantly different between biologics and control treatment.\nCertolizumab pegol (OR 4.75, 95% CI 1.52 to 18.65; NNTH = 12, 95% CI 4 to 79) and anakinra (OR 4.05, 95% CI 1.22 to 16.84; NNTH = 14, 95% CI 4 to 181) were associated with a statistically significantly higher risk of serious infections compared with control treatment. Compared with control, certolizumab was associated with a statistically significantly higher risk of SAEs (as defined in included studies: OR 1.57, 95% CI 1.06 to 2.32; NNTH = 18, 95% CI 9 to 162). Infliximab was associated with a statistically significantly higher risk of total AEs OR 1.55, 95% CI 1.01 to 2.35; NNTH = 13, 95% CI 8 to 505) and withdrawals due to AEs compared with control (OR 2.34, 95% CI 1.40 to 4.14; NNTH = 10, 95% CI 5 to 30).\nThe overall numbers were relatively small for indirect comparisons. Indirect comparisons revealed that certolizumab pegol was associated with a statistically significantly higher odds of serious infections compared with abatacept, adalimumab, etanercept, golimumab and rituximab; and anakinra was statistically significantly more likely than rituximab to be associated with serious infections. Certolizumab pegol was associated with a statistically significant higher odds of SAEs compared with adalimumab and abatacept. No statistically significant differences were noted between biologics in total AEs or withdrawals due to AEs in indirect comparisons.\nAuthors' conclusions\nOverall, in the short term biologics were associated with statistically significantly higher rates of serious infections, TB reactivation, total AEs and withdrawals due to AEs. Serious infections included opportunistic infections as well as bacterial infections in most studies. Some biologics had a statistically higher association with certain adverse outcomes compared with control, but there was no consistency across the outcomes so caution is needed in interpreting these results.\nThere is a need for more research regarding the long-term safety of biologics and an urgent need for comparative safety reports of different biologics; preferably without industry involvement. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.\n\nGiven the provided abstract, please respond to the following query: \"Serious infections\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Among people who took any biologic, 35 people out of 1000 experienced serious infections compared with 26 people out of 1000 who took placebo (1% absolute harm)." } ]

[ { "role": "user", "content": "Abstract: Background\nPosterior capsule opacification (PCO) is a clouding of the posterior part of the lens capsule, a skin-like transparent structure, which surrounds the crystalline lens in the human eye. PCO is the most common postoperative complication following modern cataract surgery with implantation of a posterior chamber intraocular lens (IOL). The main symptoms of PCO are a decrease in visual acuity, 'cloudy', blurred vision and reduced contrast sensitivity. PCO is treated with a neodymium:YAG (Nd:YAG) laser to create a small opening in the opaque capsule and regain a clear central visual axis. This capsulotomy might cause further ocular complications, such as raised intraocular pressure or swelling of the central retina (macular oedema). This procedure is also a significant financial burden for health care systems worldwide. In recent decades, there have been advances in the selection of IOL materials and optimisation of IOL designs to help prevent PCO formation after cataract surgery. These include changes to the side structures holding the lens in the centre of the lens capsule bag, called IOL haptics, and IOL optic edge designs.\nObjectives\nTo compare the effects of different IOL optic edge designs on PCO after cataract surgery.\nSearch methods\nWe searched CENTRAL, Ovid MEDLINE, Ovid Embase, Latin American and Caribbean Health Sciences Literature Database (LILACS), the ISRCTN registry, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 17 November 2020.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared different types of IOL optic edge design. Our prespecified primary outcome was the proportion of eyes with Nd:YAG capsulotomy one year after surgery. Secondary outcomes included PCO score, best-corrected distance visual acuity (BCDVA) and quality of life score at one year. Due to availability of important long-term data, we also presented data at longer-term follow-up which is a post hoc change to our protocol.\nData collection and analysis\nWe used standard methods expected by Cochrane and the GRADE approach to assess the certainty of the evidence.\nMain results\nWe included 10 studies (1065 people, 1834 eyes) that compared sharp- and round-edged IOLs. Eight of these studies were within-person studies whereby one eye received a sharp-edged IOL and the fellow eye a round-edged IOL. The IOL materials were acrylic (2 studies), silicone (4 studies), polymethyl methacrylate (PMMA, 3 studies) and different materials (1 study). The studies were conducted in Austria, Germany, India, Japan, Sweden and the UK. Five studies were at high risk of bias in at least one domain. We judged two studies to be at low risk of bias in all domains.\nThere were few cases of Nd:YAG capsulotomy at one year (primary outcome): 1/371 in sharp-edged and 4/371 in round-edged groups. The effect estimate was in favour of sharp-edged IOLs but the confidence intervals were very wide and compatible with higher or lower chance of Nd:YAG capsulotomy in sharp-edged compared with round-edged lenses (Peto odds ratio (OR) 0.30, 95% CI 0.05 to 1.74; I2 = 0%; 6 studies, 742 eyes). This corresponds to seven fewer cases of Nd:YAG capsulotomy per 1000 sharp-edged IOLs inserted compared with round-edged IOLs (95% CI 9 fewer to 7 more). We judged this as low-certainty evidence, downgrading for imprecision and risk of bias.\nA similar reduced risk of Nd:YAG capsulotomy in sharp-edge compared with round-edge IOLs was seen at two, three and five years but as the number of Nd:YAG capsulotomy events increased with longer follow-up this effect was more precisely measured at longer follow-up: two years, risk ratio (RR) 0.35 (0.16 to 0.80); 703 eyes (6 studies); 89 fewer cases per 1000; three years, RR 0.21 (0.11 to 0.41); 538 eyes (6 studies); 170 fewer cases per 1000; five years, RR 0.21 (0.10 to 0.45); 306 eyes (4 studies); 331 fewer cases per 1000. Data at 9 years and 12 years were only available from one study.\nAll studies reported a PCO score. Four studies reported the AQUA (Automated Quantification of After-Cataract) score, four studies reported the EPCO (Evaluation of PCO) score and two studies reported another method of quantifying PCO. It was not possible to pool these data due to the way they were reported, but all studies consistently reported a statistically significant lower average PCO score (of the order of 0.5 to 3 units) with sharp-edged IOLs compared with round-edged IOLs. We judged this to be moderate-certainty evidence downgrading for risk of bias.\nThe logMAR visual acuity score was lower (better) in eyes that received a sharp-edged IOL but the difference was small and likely to be clinically unimportant at one year (mean difference (MD) -0.06 logMAR, 95% CI -0.12 to 0; 2 studies, 153 eyes; low-certainty evidence). Similar effects were seen at longer follow-up periods but non-statistically significant data were less fully reported: two years MD -0.01 logMAR (-0.05 to 0.02); 2 studies, 311 eyes; three years MD -0.09 logMAR (-0.22 to 0.03); 2 studies, 117 eyes; data at five years only available from one study.\nNone of the studies reported quality of life. Very low-certainty evidence on adverse events did not suggest any important differences between the groups.\nAuthors' conclusions\nThis review provides evidence that sharp-edged IOLs are likely to be associated with less PCO formation than round-edged IOLs, with less Nd:YAG capsulotomy. The effects on visual acuity were less certain. The impact of these lenses on quality of life has not been assessed and there are only very low-certainty comparative data on adverse events.\n\nGiven the provided abstract, please respond to the following query: \"Why we did this Cochrane Review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Different styles of plastic lenses have been designed to try to stop or reduce clouding once they are in the eye. Changes include making the edges of the lens round or sharp. We wanted to find out if differently shaped edges on the lens would make it less likely to cloud." } ]

[ { "role": "user", "content": "Abstract: Background\nThere has been extensive debate in the surgical literature regarding the optimum surgical access approach to the infrarenal abdominal aorta during an operation to repair an abdominal aortic aneurysm. The published trials comparing retroperitoneal (RP) and transperitoneal (TP) aortic surgery show conflicting results. This is an update of the review first published in 2016.\nObjectives\nTo assess the effectiveness and safety of the retroperitoneal versus transperitoneal approach for elective open abdominal aortic aneurysm repair on mortality, complications, hospital stay and blood loss.\nSearch methods\nThe Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials registers to 30 November 2020. The review authors searched the Chinese Biomedical Literature Database and handsearched reference lists of relevant articles to identify additional trials.\nSelection criteria\nWe included randomized controlled trials (RCTs) that assessed the RP approach versus the TP approach for elective open abdominal aortic aneurysm (AAA) repair. There were no restrictions on language or publication status.\nData collection and analysis\nTwo review authors independently extracted data from the included trials. We resolved any disagreements through discussion with a third review author. Two review authors independently assessed the risk of bias in included trials with the Cochrane risk of bias tool. For dichotomous outcomes, we calculated the odds ratio (OR) with the corresponding 95% confidence interval (CI). For continuous data, we calculated a pooled estimate of treatment effect by calculating the mean difference (MD) and standard deviation (SD) with corresponding 95% CIs. We pooled data using a fixed-effect model, unless we identified heterogeneity, in which case we used a random-effects model. We used GRADE to assess the overall certainty of the evidence. We evaluated the outcomes of mortality, complications, intensive care unit (ICU) stay, hospital stay, blood loss, aortic cross-clamp time and operating time.\nMain results\nWe identified no new studies from the updated searches. After reassessment, we included one study which had previously been excluded. Five RCTs with a combined total of 152 participants are included. The overall certainty of the evidence ranged from low to very low because of the low methodological quality of the included trials (unclear random sequence generation method and allocation concealment, and no blinding of outcome assessors), small sample sizes, small number of events, high heterogeneity and inconsistency between the included trials, no power calculations and relatively short follow-up.\nThere was no evidence of a difference between the RP approach and the TP approach regarding mortality (odds ratio (OR) 0.32, 95% CI 0.01 to 8.25; 3 studies, 110 participants; very low-certainty evidence). Similarly, there was no evidence of a difference in complications such as hematoma (OR 0.90, 95% CI 0.13 to 6.48; 2 studies, 75 participants; very low-certainty evidence), abdominal wall hernia (OR 10.76, 95% CI 0.55 to 211.78; 1 study, 48 participants; very low-certainty evidence), or chronic wound pain (OR 2.20, 95% CI 0.36 to 13.34; 1 study, 48 participants; very low-certainty evidence) between the RP and TP approaches in participants undergoing elective open AAA repair. The RP approach may reduce ICU stay (mean difference (MD) -19.02 hours, 95% CI -30.83 to -7.21; 3 studies, 106 participants; low-certainty evidence); hospital stay (MD -3.30 days, 95% CI -4.85 to-1.75; 5 studies, 152 participants; low-certainty evidence); and blood loss (MD -504.87 mL, 95% CI -779.19 to -230.56; 4 studies, 129 participants; very low-certainty evidence). There was no evidence of a difference between the RP approach and the TP approach regarding aortic cross-clamp time (MD 0.69 min, 95% CI -7.23 to 8.60; 4 studies, 129 participants; very low-certainty evidence) or operating time (MD -15.94 min, 95% CI -34.76 to 2.88; 4 studies, 129 participants; very low-certainty evidence).\nAuthors' conclusions\nVery low-certainty evidence from five small RCTs showed no clear evidence of a difference between the RP approach and the TP approach for elective open AAA repair in terms of mortality, or for rates of complications including hematoma (very low-certainty evidence), abdominal wall hernia (very low-certainty evidence), or chronic wound pain (very low-certainty evidence). However, a shorter intensive care unit (ICU) stay and shorter hospital stay was probably indicated following the RP approach compared to the TP approach (both low-certainty evidence). A possible reduction in blood loss was also shown after the RP approach (very low-certainty evidence). There is no clear difference between the RP approach and TP approach in aortic cross-clamp time or operating time. Further well-designed, large-scale RCTs assessing the RP approach versus TP approach for elective open AAA repair are required.\n\nGiven the provided abstract, please respond to the following query: \"Reliability of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Four of the five included trials had methodological weaknesses - such as unclear randomization methods, and no reporting of blinding of the people assessing the outcome - which compromised the value of their results. In addition, the included trials only included a small number of people, few outcomes were reported, participants were followed up for a relatively short time, and there were inconsistencies between the included trials, resulting in evidence of very low to low certainty. More large-scale RCTs of the RP approach versus the TP approach for planned surgical open AAA repair are needed." } ]

[ { "role": "user", "content": "Abstract: Background\nVitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth and this has been associated with an increased risk of developing chronic lung disease.\nObjectives\nTo evaluate supplementation with vitamin A on the incidence of death or neonatal chronic lung disease and long-term neurodevelopmental disability in very low birth weight (VLBW) infants compared with a control (placebo or no supplementation), and to consider the effect of the supplementation route, dose, and timing.\nSearch methods\nFor the original review and subsequent updates, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, Science Citation Index, and the Oxford Database of Perinatal Trials. The reference lists of relevant trials, paediatric and nutrition journals, and conference abstracts and proceedings were handsearched up to 2010.\nFor the 2016 update, we used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1 May 2016), EMBASE (1 May 2016), and CINAHL (1 May 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nRandomised controlled trials comparing vitamin A supplementation with a control (placebo or no supplementation) or other dosage regimens in VLBW infants (birth weight ≤ 1500 grams or less than 32 weeks' gestation).\nData collection and analysis\nTwo review authors screened the search results, extracted data, and assessed the trials for risk of bias. Results were reported as risk ratios (RR), risk differences (RD), and number needed to treat to benefit (NNTB), all with 95% confidence intervals (CI). Trialists were contacted for additional data.\nMain results\nEleven trials met the inclusion criteria. Ten trials (1460 infants) compared vitamin A supplementation with a control and one (120 infants) compared different regimens of vitamin A supplementation. Compared to the control group, vitamin A appeared to have a small benefit in reducing the risk of death or oxygen requirement at one month of age (typical RR 0.93, 95% CI 0.88 to 0.99; typical RD −0.05, 95% CI −0.10 to −0.01; NNTB 20, 95% CI 10 to 100; 6 studies, 1165 infants) and the risk of chronic lung disease (oxygen requirement) at 36 weeks' postmenstrual age (typical RR 0.87, 95% CI 0.77 to 0.99; typical RD −0.07, 95% CI −0.13 to −0.01; NNTB 11, 95% CI 6 to 100; 5 studies, 986 infants) (moderate-quality evidence). There was a marginal reduction of the combined outcome of death or chronic lung disease (typical RR 0.92, 95% CI 0.84 to 1.01; typical RD −0.05, 95% CI −0.11 to 0.01; 4 studies, 1089 infants). Neurodevelopmental assessment of 88% of the surviving infants in the largest trial showed no difference between the groups at 18 to 22 months of age, corrected for prematurity (low-quality evidence). There is no evidence to support different vitamin A dosing regimens. No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful.\nAuthors' conclusions\nWhether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.\n\nGiven the provided abstract, please respond to the following query: \"Conclusions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention." } ]

[ { "role": "user", "content": "Abstract: Background\nThe development of supraglottic airway devices has revolutionized airway management during general anaesthesia. Two devices are widely used in clinical practice to facilitate positive pressure ventilation: the ProSeal laryngeal mask airway (pLMA) and the Classic laryngeal mask airway (cLMA). It is not clear whether these devices have important clinical differences in terms of efficacy or complications.\nObjectives\nTo compare the effectiveness of the ProSeal laryngeal mask airway (pLMA) and the Classic LMA (cLMA) for positive pressure ventilation in adults undergoing elective surgery.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 3) in the Cochrane Library; MEDLINE (Ovid SP, 1997 to April 2017); Embase (Ovid SP, 1997 to April 2017); the Institute for Scientific Information (ISI) Web of Science (1946 to April 2017); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host, 1982 to April 2017).\nWe searched trial registries for ongoing studies to April 2017.\nWe did not impose language restrictions. We restricted our search to the time from 1997 to April 2017 because pLMA was introduced into clinical practice in the year 2000.\nSelection criteria\nWe included randomized controlled trials (RCTs) that compared the effectiveness of pLMA and cLMA for positive pressure ventilation in adults undergoing elective surgery. We planned to include only data related to the first phase of cross-over RCTs.\nData collection and analysis\nWe used standard methodological procedures expected by the Cochrane Collaboration.\nMain results\nWe included eight RCTs that involved a total of 829 participants (416 and 413 participants in the pLMA and cLMA groups, respectively). We identified six cross-over studies that are awaiting classification; one is completed but has not been published, and data related to the first treatment period for the other five studies were not yet available. Seven included studies provided data related to the primary outcome, and eight studies provided data related to more than one secondary outcome.\nOur analysis was hampered by the fact that a large proportion of the included studies reported no events in either study arm. No studies reported significant differences between devices in relation to the primary review outcome: failure to adequately mechanically ventilate. We evaluated this outcome by assessing two variables: inadequate oxygenation (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.17 to 3.31; four studies, N = 617) and inadequate ventilation (not estimable; one study, N = 80).\nMore time was required to establish an effective airway using pLMA (mean difference (MD) 10.12 seconds, 95% CI 5.04 to 15.21; P < 0.0001; I² = 73%; two studies, N = 434). Peak airway pressure during positive pressure ventilation was lower in cLMA participants (MD 0.84, 95% CI 0.02 to 1.67; P = 0.04; I² = 0%; four studies, N = 259). Mean oropharyngeal leak (OPL) pressure was higher in pLMA participants (MD 6.93, 95% CI 4.23 to 9.62; P < 0.00001; I² = 87%; six studies, N = 709).\nThe quality of evidence for all outcomes, as assessed by GRADE score, is low mainly owing to issues related to blinding and imprecision.\nData show no important differences between devices with regard to failure to insert the device, use of an alternate device, mucosal injury, sore throat, bronchospasm, gastric insufflation, regurgitation, coughing, and excessive leak. Data were insufficient to allow estimation of differences for obstruction related to the device. None of the studies reported postoperative nausea and vomiting as an outcome.\nAuthors' conclusions\nWe are uncertain about the effects of either of the airway devices in terms of failure of oxygenation or ventilation because there were very few events. Results were uncertain in terms of differences for several complications. Low-quality evidence suggests that the ProSeal laryngeal mask airway makes a better seal and therefore may be more suitable than the Classic laryngeal mask airway for positive pressure ventilation. The Classic laryngeal mask airway may be quicker to insert, but this is unlikely to be clinically meaningful.\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 are unsure whether these devices exhibit important differences in providing adequate oxygenation and ventilation because there was not enough data to enable us to draw any firm conclusions. ProSeal laryngeal mask airway may provides a better seal because it leaks at higher pressure, but Classic laryngeal mask airway may be quicker to insert. However, these findings are not important clinically." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of the original Cochrane Review published in Issue 10, 2013.\nExtramammary Paget's disease is a rare form of superficial skin cancer. The most common site of involvement is the vulva. It is seen mainly in postmenopausal white women. Paget's disease of the vulva often spreads in an occult fashion, with margins extending beyond the apparent edges of the lesion. There is a range of interventions from surgical to non-invasive techniques or treatments. The challenges of interventions are to remove or treat disease that may not be visible, without overtreatment and with minimisation of morbidity from radical surgery. There is little consensus regarding treatment. Surgery, by default, is the most common treatment, but it is challenging to excise the disease adequately, and recurrence is common, leading to repeated operations, and destruction of anatomy. Alternative treatments of photodynamic therapy, laser therapy, radiotherapy, topical treatments or even chemotherapy have been mooted, and it is important to evaluate the available evidence. It is essential to assess whether newer cell-specific treatments, such as photodynamic therapy and imiquimod, can reduce the need for radical surgery.\nObjectives\nTo evaluate the benefits and harms of different treatment modalities for the management of Paget's disease of the vulva.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid) up to 8 May 2018. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles.\nSelection criteria\nWe searched for randomised controlled trials (RCTs) and well-designed non-randomised studies that compared different interventions in women with Paget's disease of the vulva,\nData collection and analysis\nTwo review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and, therefore, analysed no data.\nMain results\nThe search for the original version of the review identified 635 unique references. We found 31 references (which reported on 30 studies) in full text after inspection of titles and abstracts, but we excluded them all as they did not meet the inclusion criteria. However, we have included a comprehensive narrative account of studies where we identified an analysis of more than 10 women, as this forms the only evidence base in this rare disease. Surgery continues to be the mainstay of treatment in the current literature, with other treatments limited to case reports or treatment of inoperable or recurrent disease.\nThis update between September 2013 and May 2018 identified 35 new studies. None of these met the inclusion criteria. There was only one prospective study of 5% imiquimod in recurrent Paget's disease of the vulva, which although of good quality only included eight women.\nAuthors' conclusions\nSince the last version of the review was published there are many more cases in the literature reporting a clinical response to 5% imiquimod cream. There is one prospective study of eight women treated with 5% imiquimod for recurrent Paget's disease of the vulva, and one prospective trial of 20 women was due to be reported. This increasing evidence for the safety and efficacy of 5% imiquimod will be helpful for women and clinicians alike. Ideally, a multicentre RCT of reasonable size is needed, but ongoing publications of high-quality non-randomised prospective studies will enhance the current available literature.\n\nGiven the provided abstract, please respond to the following query: \"Key results and quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched scientific databases and contacted experts and identified and checked the titles and abstracts of 635 possibly relevant articles and retrieved 31 of these references in full text. However, we found no studies that met our inclusion criteria. We identified several non-randomised studies and drafted a detailed narrative of their results, but these studies were of poor quality and were at high risk of bias. Therefore, there is currently no evidence to determine whether any form of treatment is better or worse in terms of prolonging survival, delaying progression or recurrence, improving QoL or minimising toxicity. The review highlights the need for good-quality studies comparing different interventions for the management of Paget's disease of the vulva. Women and clinicians would value more evidence for guiding surgical and non-surgical management of this disease. In particular, non-invasive medical management would spare women from the side effects and consequences of surgery." } ]

[ { "role": "user", "content": "Abstract: Background\nInfants in the neonatal intensive care unit (NICU) are subjected to stress, including sound of high intensity. The sound environment in the NICU is louder than most home or office environments and contains disturbing noises of short duration and at irregular intervals. There are competing auditory signals that frequently challenge preterm infants, staff and parents. The sound levels in NICUs often exceed the maximum acceptable level of 45 decibels (dB), recommended by the American Academy of Pediatrics. Hearing impairment is diagnosed in 2% to 10% of preterm infants versus 0.1% of the general paediatric population. Noise may cause apnoea, hypoxaemia, alternation in oxygen saturation, and increased oxygen consumption secondary to elevated heart and respiratory rates and may, therefore, decrease the amount of calories available for growth. Elevated levels of speech are needed to overcome the noisy environment in the NICU, thereby increasing the negative impacts on staff, newborns, and their families. High noise levels are associated with an increased rate of errors and accidents, leading to decreased performance among staff. The aim of interventions included in this review is to reduce sound levels to 45 dB or less. This can be achieved by lowering the sound levels in an entire unit, treating the infant in a section of a NICU, in a 'private' room, or in incubators in which the sound levels are controlled, or reducing the sound levels that reaches the individual infant by using earmuffs or earplugs. By lowering the sound levels that reach the neonate, the resulting stress on the cardiovascular, respiratory, neurological, and endocrine systems can be diminished, thereby promoting growth and reducing adverse neonatal outcomes.\nObjectives\nPrimary objective\nTo determine the effects of sound reduction on growth and long-term neurodevelopmental outcomes of neonates.\nSecondary objectives\n1. To evaluate the effects of sound reduction on short-term medical outcomes (bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity).\n2. To evaluate the effects of sound reduction on sleep patterns at three months of age.\n3. To evaluate the effects of sound reduction on staff performance.\n4. To evaluate the effects of sound reduction in the neonatal intensive care unit (NICU) on parents' satisfaction with the care.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings, clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp), Pediatric Academic Societies Annual meetings 2000 to 2014 (Abstracts2ViewTM), reference lists of identified trials, and reviews to November 2014.\nSelection criteria\nPreterm infants (< 32 weeks' postmenstrual age (PMA) or < 1500 g birth weight) cared for in the resuscitation area, during transport, or once admitted to a NICU or a stepdown unit.\nData collection and analysis\nWe performed data collection and analyses according to the Cochrane Neonatal Review Group.\nMain results\nOne small, high quality study assessing the effects of silicone earplugs versus no earplugs qualified for inclusion. The original inclusion criteria in our protocol stipulated an age of < 48 hours at the time of initiating sound reduction. We made a deviation from our protocol and included this study in which some infants would have been > 48 hours old. There was no significant difference in weight at 34 weeks postmenstrual age (PMA): mean difference (MD) 111 g (95% confidence interval (CI) -151 to 374 g) (n = 23). There was no significant difference in weight at 18 to 22 months corrected age between the groups: MD 0.31 kg, 95% CI -1.53 to 2.16 kg (n = 14). There was a significant difference in Mental Developmental Index (Bayley II) favouring the silicone earplugs group at 18 to 22 months corrected age: MD 14.00, 95% CI 3.13 to 24.87 (n = 12), but not for Psychomotor Development Index (Bayley II) at 18 to 22 months corrected age: MD -2.16, 95% CI -18.44 to 14.12 (n =12).\nAuthors' conclusions\nTo date, only 34 infants have been enrolled in a randomised controlled trial (RCT) testing the effectiveness of reducing sound levels that reach the infants' ears in the NICU. Based on the small sample size of this single trial, we cannot make any recommendations for clinical practice. Larger, well designed, conducted and reported trials 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": "Infants in the neonatal intensive care unit (NICU) are subjected to stress, including high intensity sound. The sound environment in the NICU is louder than most home or office environments and contains disturbing noises of short duration and at irregular intervals. There are competing sound signals that frequently challenge preterm infants, staff, and parents. The sound levels in NICUs range from 7 dB to 120 dB, often exceeding the maximum acceptable level of 45 dB, recommended by the American Academy of Pediatrics. Hearing impairment is diagnosed in 2% to 10% of preterm infants versus 0.1% of the general paediatric population. Noise may cause apnoea, hypoxaemia, alternation in oxygen saturation, and increased oxygen consumption secondary to elevated heart and respiratory rates and may, therefore, decrease the amount of calories available for growth. Elevated levels of speech are needed to overcome the noisy environment in the NICU, thereby increasing the negative impacts on staff, newborns, and their families. High noise levels are associated with an increased rate of errors and accidents, leading to decreased performance among staff. The aim of all interventions considered for inclusion in this review is to reduce the sound levels that reach the individual neonate to 45 dB or less. This can be achieved by lowering the sound levels in an entire unit, treating the infant in a section of a NICU or in a 'private' room, or in incubators in which the sound levels are controlled, or reducing the sound levels that reaches the individual infant by using earmuffs or earplugs. By lowering the sound levels that reach the neonate, the resulting stress can be diminished, thereby promoting growth and reducing adverse neonatal outcomes." } ]

[ { "role": "user", "content": "Abstract: Background\nLactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.\nObjectives\nTo assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates. Secondarily, we assessed the effects of lactoferrin supplementation to enteral feeds on the duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to update our search. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 9), MEDLINE via PubMed (1966 to 20 January 2020), PREMEDLINE (1996 to 20 January 2020), Embase (1980 to 20 January 2020), and CINAHL (1982 to 20 January 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.\nSelection criteria\nIn our search, we included randomized controlled trials (RCTs) evaluating enteral lactoferrin supplementation at any dose or duration to prevent sepsis or NEC in preterm neonates.\nData collection and analysis\nWe used the standard methods of Cochrane Neonatal and the GRADE approach to assess the certainty of evidence.\nMain results\nMeta-analysis of data from twelve randomized controlled trials showed that lactoferrin supplementation to enteral feeds decreased suspected or confirmed late-onset sepsis (typical RR 0.80, 95% CI 0.72 to 0.89; typical RD -0.05, 95% CI, -0.07 to -0.02; NNTB 20, 95% CI 14 to 50; 12 studies, 5425 participants, low-certainty evidence) and decreased length of hospital stay (MD -2.38 to 95% CI, -4.67 to -0.09; 3 studies, 1079 participants, low-certainty evidence). A subgroup analysis including data of infants with confirmed sepsis demonstrates a decrease in confirmed late-onset sepsis (typical RR 0.83, 95% CI 0.73 to 0.94; typical RD -0.03, 95% CI, -0.04 to -0.01; NNTB 33, 95% CI 25 to 100; 12 studies, 5425 participants, low-certainty evidence).\nSensitivity analysis including only good methodological certainty studies suggested a decrease in late-onset sepsis (both suspected and confirmed) with enteral lactoferrin supplementation (typical RR 0.82, 95% CI, 0.74 to 0.91; typical RD -0.04, 95% CI, -0.06 to -0.02; NNTB 20, 95% CI 14 to 50; 9 studies, 4702 participants, low-certainty evidence).\nThere were no differences in NEC stage II or III (typical RR 1.10, 95% CI, 0.86 to 1.41; typical RD -0.00, 95% CI, -0.02 to 0.01; 7 studies, 4874 participants; low-certainty evidence) or 'all-cause mortality' (typical RR 0.90, 95% CI 0.69 to 1.17; typical RD -0.00, 95% CI, -0.01 to 0.01; 11 studies, 5510 participants; moderate-certainty evidence). One study reported no differences in neurodevelopmental testing by Mullen's or Bayley III at 24 months of age after enteral lactoferrin supplementation (one study, 292 participants, low-certainty evidence).\nLactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.25, 95% CI 0.14 to 0.46; RD -0.13, 95% CI -0.18 to -0.08; NNTB 8, 95% CI 6 to 13; 3 studies, 564 participants; low-certainty evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; 1 study, 496 participants; very low-certainty evidence), but not 'all-cause mortality' (very low-certainty evidence).\nLactoferrin supplementation to enteral feeds with or without probiotics had no effect on CLD, duration of mechanical ventilation or threshold retinopathy of prematurity (low-certainty evidence). Investigators reported no adverse effects in the included studies.\nAuthors' conclusions\nWe found low-certainty evidence from studies of good methodological quality that lactoferrin supplementation of enteral feeds decreases late-onset sepsis (both suspected and confirmed, and confirmed only) but not NEC ≥ stage II or 'all cause mortality' or neurodevelopmental outcomes at 24 months of age in preterm infants without adverse effects. Low- to very low-certainty evidence suggests that lactoferrin supplementation of enteral feeds in combination with probiotics decreases late-onset sepsis (data from confirmed sepsis only) and NEC ≥ stage II in preterm infants without adverse effects, however, there were few included studies of poor methodological quality. The presence of publication bias and small studies of poor methodology that may inflate the effect size make recommendations for clinical practice difficult.\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": "Lactoferrin given with feeds with or without a probiotic decreases blood infection including fungal infection in preterm infants with no adverse effects. Lactoferrin with probiotics, but not lactoferrin alone, decreases gastrointestinal injury. Clarification regarding dosing, duration, type of lactoferrin (human or bovine), and development of preterm babies is still needed." } ]

[ { "role": "user", "content": "Abstract: Background\nInadvertent perioperative hypothermia is a phenomenon that can occur as a result of the suppression of the central mechanisms of temperature regulation due to anaesthesia, and of prolonged exposure of large surfaces of skin to cold temperatures in operating rooms. Inadvertent perioperative hypothermia has been associated with clinical complications such as surgical site infection and wound-healing delay, increased bleeding or cardiovascular events. One of the most frequently used techniques to prevent inadvertent perioperative hypothermia is active body surface warming systems (ABSW), which generate heat mechanically (heating of air, water or gels) that is transferred to the patient via skin contact.\nObjectives\nTo assess the effectiveness of pre- or intraoperative active body surface warming systems (ABSW), or both, to prevent perioperative complications from unintended hypothermia during surgery in adults.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2015); MEDLINE (PubMed) (1964 to October 2015), EMBASE (Ovid) (1980 to October 2015), and CINAHL (Ovid) (1982 to October 2015).\nSelection criteria\nWe included randomized controlled trials (RCTs) that compared an ABSW system aimed at maintaining normothermia perioperatively against a control or against any other ABSW system. Eligible studies also had to include relevant clinical outcomes other than measuring temperature alone.\nData collection and analysis\nSeveral authors, by pairs, screened references and determined eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, with the collaboration of a third author.\nMain results\nWe included 67 trials with 5438 participants that comprised 79 comparisons. Forty-five RCTs compared ABSW versus control, whereas 18 compared two different types of ABSW, and 10 compared two different techniques to administer the same type of ABSW. Forced-air warming (FAW) was by far the most studied intervention.\nTrials varied widely regarding whether the interventions were applied alone or in combination with other active (based on a different mechanism of heat transfer) and/or passive methods of maintaining normothermia. The type of participants and surgical interventions, as well as anaesthesia management, co-interventions and the timing of outcome measurement, also varied widely. The risk of bias of included studies was largely unclear due to limitations in the reports. Most studies were open-label, due to the nature of the intervention and the fact that temperature was usually the principal outcome. Nevertheless, given that outcome measurement could have been conducted in a blinded manner, we rated the risk of detection and performance bias as high.\nThe comparison of ABSW versus control showed a reduction in the rate of surgical site infection (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.20 to 0.66; 3 RCTs, 589 participants, low-quality evidence). Only one study at low risk of bias observed a beneficial effect with forced-air warming on major cardiovascular complications (RR 0.22, 95% CI 0.05 to 1.00; 1 RCT with 12 events, 300 participants, low-quality evidence) in people at high cardiovascular risk. We found no beneficial effect for mortality. ABSW also reduced blood loss during surgery but the magnitude of this effect seems to be irrelevant (MD -46.17 mL, 95% CI -82.74 to -9.59; I² = 78%; 20 studies, 1372 participants). The same conclusion applies to total fluids infused during surgery (MD -144.49 mL, 95% CI -221.57 to -67.40; I² = 73%; 24 studies, 1491 participants). These effects did not translate into a significant reduction in the number of participants being transfused or the average amount of blood transfused. ABSW was associated with a reduction in shivering (RR 0.39, 95% CI 0.28 to 0.54; 29 studies, 1922 participants) and in thermal comfort (standardized mean difference (SMD) 0.76, 95% CI 0.29 to 1.24; I² = 77%, 4 trials, 364 participants).\nFor the comparison between different types of ABSW system or modes of administration of a particular type of ABSW, we found no evidence for the superiority of any system in terms of clinical outcomes, except for extending systemic warming to the preoperative period in participants undergoing major abdominal surgery (one study at low risk of bias).\nThere were limited data on adverse effects (the most relevant being thermal burns). While some trials included a narrative report mentioning that no adverse effects were observed, the majority made no reference to it. Nothing so far suggests that ABSW involves a significant risk to patients.\nAuthors' conclusions\nForced-air warming seems to have a beneficial effect in terms of a lower rate of surgical site infection and complications, at least in those undergoing abdominal surgery, compared to not applying any active warming system. It also has a beneficial effect on major cardiovascular complications in people with substantial cardiovascular disease, although the evidence is limited to one study. It also improves patient's comfort, although we found high heterogeneity among trials. While the effect on blood loss is statistically significant, this difference does not translate to a significant reduction in transfusions. Again, we noted high heterogeneity among trials for this outcome. The clinical relevance of blood loss reduction is therefore questionable. The evidence for other types of ABSW is scant, although there is some evidence of a beneficial effect in the same direction on chills/shivering with electric or resistive-based heating systems. Some evidence suggests that extending systemic warming to the preoperative period could be more beneficial than limiting it only to during surgery. Nothing suggests that ABSW systems pose a significant risk to patients.\nThe difficulty in observing a clinically-relevant beneficial effect with ABSW in outcomes other than temperature may be explained by the fact that many studies applied concomitant procedures that are routinely in place as co-interventions to prevent hypothermia, whether passive or active warming systems based in other physiological mechanisms (e.g. irrigation fluid or gas warming), as well as a stricter control of temperature in the context of the study compared with usual practice. These may have had a beneficial effect on the participants in the control group, leading to an underestimation of the net benefit of ABSW.\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 reviewed the effects of warming the body by transferring heat through the skin surface to prevent complications caused by unintended low body temperature (hypothermia) in adults undergoing surgery." } ]

[ { "role": "user", "content": "Abstract: Background\nPosterior vaginal wall prolapse (also known as 'posterior compartment prolapse') can cause a sensation of bulge in the vagina along with symptoms of obstructed defecation and sexual dysfunction. Interventions for prevention and conservative management include lifestyle measures, pelvic floor muscle training, and pessary use. We conducted this review to assess the surgical management of posterior vaginal wall prolapse.\nObjectives\nTo evaluate the safety and effectiveness of any surgical intervention compared with another surgical intervention for management of posterior vaginal wall prolapse.\nSearch methods\nWe searched the Cochrane Incontinence Group Specialised Register of controlled trials, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (searched April 2017). We also searched the reference lists of relevant articles, and we contacted researchers in the field.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing different types of surgery for posterior vaginal wall prolapse.\nData collection and analysis\nWe used Cochrane methods. Our primary outcomes were subjective awareness of prolapse, repeat surgery for any prolapse, and objectively determined recurrent posterior wall prolapse.\nMain results\nWe identified 10 RCTs evaluating 1099 women. Evidence quality ranged from very low to moderate. The main limitations of evidence quality were risk of bias (associated mainly with performance, detection, and attrition biases) and imprecision (associated with small overall sample sizes and low event rates).\nTransanal repair versus transvaginal repair (four RCTs; n = 191; six months' to four years' follow-up)\nAwareness of prolapse is probably more common after the transanal approach (risk ratio (RR) 2.78, 95% confidence interval (CI) 1.00 to 7.70; 2 RCTs; n = 87; I2 = 0%; low-quality evidence). If 10% of women are aware of prolapse after transvaginal repair, between 10% and 79% are likely to be aware after transanal repair.\nRepeat surgery for any prolapse: Evidence is insufficient to show whether there were any differences between groups (RR 2.42, 95% CI 0.75 to 7.88; 1 RCT; n = 57; low-quality evidence).\nRecurrent posterior vaginal wall prolapse is probably more likely after transanal repair (RR 4.12, 95% CI 1.56 to 10.88; 2 RCTs; n = 87; I2 = 35%; moderate-quality evidence). If 10% of women have recurrent prolapse on examination after transvaginal repair, between 16% and 100% are likely to have recurrent prolapse after transanal repair.\nPostoperative obstructed defecation is probably more likely with transanal repair (RR 1.67, 95% CI 1.00 to 2.79; 3 RCTs; n = 113; I2 = 10%; low-quality evidence).\nPostoperative dyspareunia: Evidence is insufficient to show whether there were any differences between groups (RR 0.32, 95% CI 0.09 to 1.15; 2 RCTs; n = 80; I2 = 5%; moderate-quality evidence).\nPostoperative complications: Trials have provided no conclusive evidence of any differences between groups (RR 3.57, 95% CI 0.94 to 13.54; 3 RCTs; n = 135; I2 = 37%; low-quality evidence). If 2% of women have complications after transvaginal repair, then between 2% and 21% are likely to have complications after transanal repair.\nEvidence shows no clear differences between groups in operating time (in minutes) (mean difference (MD) 1.49, 95% CI -11.83 to 8.84; 3 RCTs; n = 137; I2 = 90%; very low-quality evidence).\nBiological graft versus native tissue repair\nEvidence is insufficient to show whether there were any differences between groups in rates of awareness of prolapse (RR 1.09, 95% CI 0.45 to 2.62; 2 RCTs; n = 181; I2 = 13%; moderate-quality evidence) or repeat surgery for any prolapse (RR 0.60, 95% CI 0.18 to 1.97; 2 RCTs; n = 271; I2 = 0%; moderate-quality evidence). Trials have provided no conclusive evidence of a difference in rates of recurrent posterior vaginal wall prolapse (RR 0.55, 95% CI 0.30 to 1.01; 3 RCTs; n = 377; I2 = 6%; moderate-quality evidence); if 13% of women have recurrent prolapse on examination after native tissue repair, between 4% and 13% are likely to have recurrent prolapse after biological graft. Evidence is insufficient to show whether there were any differences between groups in rates of postoperative obstructed defecation (RR 0.96, 95% CI 0.50 to 1.86; 2 RCTs; n = 172; I2 = 42%; moderate-quality evidence) or postoperative dyspareunia (RR 1.27, 95% CI 0.26 to 6.25; 2 RCTs; n = 152; I2 = 74%; low-quality evidence). Postoperative complications were more common with biological repair (RR 1.82, 95% CI 1.22 to 2.72; 3 RCTs; n = 448; I2 = 0%; low-quality evidence).\nOther comparisons\nSingle RCTs compared site-specific vaginal repair versus midline fascial plication (n = 74), absorbable graft versus native tissue repair (n = 132), synthetic graft versus native tissue repair (n = 191), and levator ani plication versus midline fascial plication (n = 52). Data were scanty, and evidence was insufficient to show any conclusions about the relative effectiveness or safety of any of these interventions. The mesh exposure rate in the synthetic group compared with the native tissue group was 7%.\nAuthors' conclusions\nTransvaginal repair may be more effective than transanal repair for posterior wall prolapse in preventing recurrence of prolapse, in the light of both objective and subjective measures. However, data on adverse effects were scanty. Evidence was insufficient to permit any conclusions about the relative effectiveness or safety of other types of surgery. Evidence does not support the utilisation of any mesh or graft materials at the time of posterior vaginal repair. Withdrawal of some commercial transvaginal mesh kits from the market may limit the generalisability of our findings.\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": "Which surgical interventions for posterior vaginal wall prolapse have the best outcomes, and what are the complications of each intervention?" } ]

[ { "role": "user", "content": "Abstract: Background\nMobile phone-based smoking cessation support (mCessation) offers the opportunity to provide behavioural support to those who cannot or do not want face-to-face support. In addition, mCessation can be automated and therefore provided affordably even in resource-poor settings. This is an update of a Cochrane Review first published in 2006, and previously updated in 2009 and 2012.\nObjectives\nTo determine whether mobile phone-based smoking cessation interventions increase smoking cessation rates in people who smoke.\nSearch methods\nFor this update, we searched the Cochrane Tobacco Addiction Group's Specialised Register, along with clinicaltrials.gov and the ICTRP. The date of the most recent searches was 29 October 2018.\nSelection criteria\nParticipants were smokers of any age. Eligible interventions were those testing any type of predominantly mobile phone-based programme (such as text messages (or smartphone app) for smoking cessation. We included randomised controlled trials with smoking cessation outcomes reported at at least six-month follow-up.\nData collection and analysis\nWe used standard methodological procedures described in the Cochrane Handbook for Systematic Reviews of Interventions. We performed both study eligibility checks and data extraction in duplicate. We performed meta-analyses of the most stringent measures of abstinence at six months' follow-up or longer, using a Mantel-Haenszel random-effects method, pooling studies with similar interventions and similar comparators to calculate risk ratios (RR) and their corresponding 95% confidence intervals (CI). We conducted analyses including all randomised (with dropouts counted as still smoking) and complete cases only.\nMain results\nThis review includes 26 studies (33,849 participants). Overall, we judged 13 studies to be at low risk of bias, three at high risk, and the remainder at unclear risk. Settings and recruitment procedures varied across studies, but most studies were conducted in high-income countries. There was moderate-certainty evidence, limited by inconsistency, that automated text messaging interventions were more effective than minimal smoking cessation support (RR 1.54, 95% CI 1.19 to 2.00; I2 = 71%; 13 studies, 14,133 participants). There was also moderate-certainty evidence, limited by imprecision, that text messaging added to other smoking cessation interventions was more effective than the other smoking cessation interventions alone (RR 1.59, 95% CI 1.09 to 2.33; I2 = 0%, 4 studies, 997 participants). Two studies comparing text messaging with other smoking cessation interventions, and three studies comparing high- and low-intensity messaging, did not show significant differences between groups (RR 0.92 95% CI 0.61 to 1.40; I2 = 27%; 2 studies, 2238 participants; and RR 1.00, 95% CI 0.95 to 1.06; I2 = 0%, 3 studies, 12,985 participants, respectively) but confidence intervals were wide in the former comparison. Five studies compared a smoking cessation smartphone app with lower-intensity smoking cessation support (either a lower-intensity app or non-app minimal support). We pooled the evidence and deemed it to be of very low certainty due to inconsistency and serious imprecision. It provided no evidence that smartphone apps improved the likelihood of smoking cessation (RR 1.00, 95% CI 0.66 to 1.52; I2 = 59%; 5 studies, 3079 participants). Other smartphone apps tested differed from the apps included in the analysis, as two used contingency management and one combined text messaging with an app, and so we did not pool them. Using complete case data as opposed to using data from all participants randomised did not substantially alter the findings.\nAuthors' conclusions\nThere is moderate-certainty evidence that automated text message-based smoking cessation interventions result in greater quit rates than minimal smoking cessation support. There is moderate-certainty evidence of the benefit of text messaging interventions in addition to other smoking cessation support in comparison with that smoking cessation support alone. The evidence comparing smartphone apps with less intensive support was of very low certainty, and more randomised controlled trials are needed to test these interventions.\n\nGiven the provided abstract, please respond to the following query: \"Search date\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for published and unpublished studies in October 2018." } ]

[ { "role": "user", "content": "Abstract: Background\nChildren and adolescents diagnosed with cancer are at high risk of experiencing severe side effects from cancer treatment, many of which are amenable to physical therapy. These side effects can negatively impact a child's quality of life and ability to participate in daily activities (e.g. play and attendance at school). Researchers have evaluated physical therapy interventions in children with cancer and childhood cancer survivors. However, factors such as small sample sizes, varying intervention protocols and differences in cancer types among trials make it difficult to draw conclusions about efficacy.\nObjectives\nThe primary aim of this review was to evaluate the efficacy of physical therapy interventions - with a specific focus on symptom relief and compensation of therapy-related side effects - on the quality of life of children and adolescents diagnosed with cancer. Participants must be between the ages of 0 and 19 years at the time of the physical therapy intervention study. The intervention may occur prior to, during or following cancer treatment. The intervention must be compared to a control group of children receiving standard care, no physical therapy intervention or a comparison intervention. We have excluded general physical exercise studies where the primary aim was to improve physical fitness through aerobic, anaerobic, resistance exercise or combined physical exercise training regimens (i.e. combined aerobic and resistance exercise regimens). We have also intended to record the occurrence of any adverse effects resulting from physical therapy interventions.\nThe secondary aims were to evaluate the efficacy of physical therapy on impairments of pain, peripheral neuropathy, balance, gait, functional abilities and mobility, motor function and performance, range of motion, strength and fatigue.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, CINAHL, PEDro, ongoing trial registries, conference proceedings and the reference lists of relevant studies and reviews in March 2020. We also contacted oncology rehabilitation researchers working in paediatrics in March 2020 to identify additional studies.\nSelection criteria\nThe review included randomised controlled trials (RCTs), cross-over trials, and controlled clinical trials (CCTs) that compared the effects of physical therapy interventions to a control group, and involved children and adolescents diagnosed with cancer between the ages of 0 and 19 years at the time of the intervention. We excluded studies examining general physical exercise interventions where the primary aim was to improve physical fitness through aerobic exercise, resistance exercise or combined physical exercise training regimens (i.e. combined aerobic and resistance exercise regimens).\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe found no RCTs, cross-over trials or CCTs comparing the effects of physical therapy interventions with a focus on symptom relief and compensation of therapy-related side effects for children and adolescents between the ages of 0 and 19 years.\nAuthors' conclusions\nResults demonstrate that the evidence to date is inadequate to inform clinical practice. Recommendations for future research include the need for large-scale, high-quality designs that examine: (1) paediatric populations with same cancer types; (2) similar intervention protocols; (3) long-term outcomes; (4) physical therapy interventions (e.g. electrophysical modalities and sensory interventions); and (5) outcomes commonly impaired in children with cancer (e.g. peripheral neuropathy and gait deficits).\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 reviewed the evidence on the effects of physical therapy interventions, other than general physical exercise interventions, on the quality of life of children and adolescents diagnosed with cancer compared to a control group of children receiving standard care, no physical therapy intervention or a comparison intervention. We also reviewed the occurrence of any harms (adverse effects) resulting from the physical therapy interventions. For the purpose of this review, physical therapy interventions of interest had to have a focus on symptom relief or address therapy-related side effects (symptoms and impairments). We excluded studies examining general physical exercise interventions where the primary aim was to improve physical fitness through aerobic exercise, resistance exercise or combined physical exercise training regimens (i.e. combined aerobic and resistance exercise regimens)." } ]

[ { "role": "user", "content": "Abstract: Background\nPanic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition.\nObjectives\nTo assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults.\nSearch methods\nWe conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status.\nSelection criteria\nWe included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response).\nData collection and analysis\nAs a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome.\nMain results\nWe identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).\nThe quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.\nOverall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise.\nAuthors' conclusions\nThere is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.\n\nGiven the provided abstract, please respond to the following query: \"Why is this review important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Many people suffer from panic disorder. Panic disorder can occur on its own or with agoraphobia. People with panic disorder experience recurring panic attacks. During a panic attack people feel the sudden onset of intense fear alongside a series of bodily symptoms such as a racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. People with agoraphobia feel an intense fear of developing a panic attack in situations where escape might be difficult or embarrassing. This fear often leads to the avoidance of such situations.\nThere are many different types of talking therapies that are used to treat panic disorder with or without agoraphobia. However it is not clear whether certain talking therapies are more effective than others at treating panic disorder with or without agoraphobia. In this review we compared the effectiveness of different types of talking therapy." } ]

[ { "role": "user", "content": "Abstract: Background\nTardive dyskinesia is a chronic and disabling abnormal movement disorder affecting the muscles of the face, neck, tongue and the limbs. It is a common side effect of long-term antipsychotic medication use in individuals with schizophrenia and other related psychotic disorders. While there are no known effective treatments for tardive dyskinesia to date, some reports suggest that pyridoxal 5 phosphate may be effective in reducing the severity of tardive dyskinesia symptoms.\nObjectives\nTo determine the effectiveness of pyridoxal 5 phosphate (vitamin B6 or Pyridoxine or Pyridoxal phosphate) in the treatment of neuroleptic-induced tardive dyskinesia among people with schizophrenia and other related psychotic disorders.\nSearch methods\nThe Cochrane schizophrenia group's register of clinical trials was searched (January 2013) using the phrase: [*Pyridoxal* OR *Pyridoxine* OR *P5P* OR *PLP* OR *tardoxal* OR *Vitamin B6* O *Vitamin B 6* R in title, abstract or index terms of REFERENCE, or interventions of STUDY. References of relevant identified studies were handsearched and where necessary, the first authors of relevant studies were contacted.\nSelection criteria\nStudies described as randomised controlled trials comparing the effectiveness pyridoxal 5 phosphate with placebo in the treatment of neuroleptic-induced tardive dyskinesia among patients with schizophrenia.\nData collection and analysis\nThe review authors independently extracted data from each selected study. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a fixed-effect model. For continuous data, we calculated mean differences (MD) with 95% CIs, again based on a fixed-effect model. We assessed risk of bias for each included study and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to rate quality of evidence.\nMain results\nOf the 12 records retrieved by the search, three trials published in 2001, 2003 and 2007, involving 80 inpatients with schizophrenia, aged 18 to 71 years, admitted in a psychiatric facility and followed up for a period nine weeks to 26 weeks, were included. Overall, pyridoxal 5 phosphate produced a significant improvement in tardive dyskinesia symptoms when compared with placebo, assessed by a change in Extrapyramidal Symptoms Rating Scale (ESRS) scores from baseline to the end of the first phase of the included studies (2 RCTs n = 65, RR 19.97, CI 2.87 to 139.19, low quality evidence). The endpoint tardive dyskinesia score (a measure of its severity) assessed with the ESRS, was significantly lower among participants on pyridoxal 5 phosphate compared to those on placebo (2 RCTs n = 60, MD -4.07, CI -6.36 to -1.79, low quality evidence).\nIt was unclear whether pyridoxal 5 phosphate led to more side effects (n = 65, 2 RCTs, RR 3.97, CI 0.20 to 78.59, low quality evidence) or caused deterioration in tardive dyskinesia symptoms when compared to placebo (n = 65, 2 RCTs, RR 0.16, CI 0.01 to 3.14, low quality evidence). Five participants taking pyridoxal 5 phosphate withdrew from the study because they were not willing to take more medications while none of the participants taking placebo discontinued their medications (n = 65, 2 RCTs, RR 8.72, CI 0.51 to 149.75, low quality evidence).\nThere was no significant difference in the endpoint positive and negative psychiatric symptoms scores, measured using the Positive and Negative symptoms Scale (PANSS) between participants taking pyridoxal 5 phosphate and those taking placebo. For the positive symptoms: (n = 15, 1 RCT, MD -1.50, CI -4.80 to 1.80, low quality evidence). For negative the symptoms: (n = 15, 1 RCT, MD -1.10, CI -5.92 to 3.72, low quality evidence).\nAuthors' conclusions\nPyridoxal 5 phosphate may have some benefits in reducing the severity of tardive dyskinesia symptoms among individuals with schizophrenia. However, the quality of evidence supporting the effectiveness of pyridoxal 5 phosphate in treating tardive dyskinesia is low, based on few studies, short follow-up periods, small sample sizes and inadequate adherence to standardised reporting guidelines for randomised controlled trials among the included studies.\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": ".\nTo look at the effects of pyridoxal 5 phosphate in the treatment of the movement disorder tardive dyskinesia, which is caused by long term use of antipsychotic drugs in people with schizophrenia." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is the fourth update of a Cochrane Review first published in 2002 and last updated in 2016.\nIt is common clinical practice to follow patients with colorectal cancer for several years following their curative surgery or adjuvant therapy, or both. Despite this widespread practice, there is considerable controversy about how often patients should be seen, what tests should be performed, and whether these varying strategies have any significant impact on patient outcomes.\nObjectives\nTo assess the effect of follow-up programmes (follow-up versus no follow-up, follow-up strategies of varying intensity, and follow-up in different healthcare settings) on overall survival for patients with colorectal cancer treated with curative intent. Secondary objectives are to assess relapse-free survival, salvage surgery, interval recurrences, quality of life, and the harms and costs of surveillance and investigations.\nSearch methods\nFor this update, on 5 April 2109 we searched CENTRAL, MEDLINE, Embase, CINAHL, and Science Citation Index. We also searched reference lists of articles, and handsearched the Proceedings of the American Society for Radiation Oncology. In addition, we searched the following trials registries: ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We contacted study authors. We applied no language or publication restrictions to the search strategies.\nSelection criteria\nWe included only randomised controlled trials comparing different follow-up strategies for participants with non-metastatic colorectal cancer treated with curative intent.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Two review authors independently determined study eligibility, performed data extraction, and assessed risk of bias and methodological quality. We used GRADE to assess evidence quality.\nMain results\nWe identified 19 studies, which enrolled 13,216 participants (we included four new studies in this second update). Sixteen out of the 19 studies were eligible for quantitative synthesis. Although the studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon-led) and 'intensity' of follow-up, there was very little inconsistency in the results.\nOverall survival: we found intensive follow-up made little or no difference (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.80 to 1.04: I² = 18%; high-quality evidence). There were 1453 deaths among 12,528 participants in 15 studies. In absolute terms, the average effect of intensive follow-up on overall survival was 24 fewer deaths per 1000 patients, but the true effect could lie between 60 fewer to 9 more per 1000 patients.\nColorectal cancer-specific survival: we found intensive follow-up probably made little or no difference (HR 0.93, 95% CI 0.81 to 1.07: I² = 0%; moderate-quality evidence). There were 925 colorectal cancer deaths among 11,771 participants enrolled in 11 studies. In absolute terms, the average effect of intensive follow-up on colorectal cancer-specific survival was 15 fewer colorectal cancer-specific survival deaths per 1000 patients, but the true effect could lie between 47 fewer to 12 more per 1000 patients.\nRelapse-free survival: we found intensive follow-up made little or no difference (HR 1.05, 95% CI 0.92 to 1.21; I² = 41%; high-quality evidence). There were 2254 relapses among 8047 participants enrolled in 16 studies. The average effect of intensive follow-up on relapse-free survival was 17 more relapses per 1000 patients, but the true effect could lie between 30 fewer and 66 more per 1000 patients.\nSalvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I² = 31%; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies. In absolute terms, the effect of intensive follow-up on salvage surgery was 60 more episodes of salvage surgery per 1000 patients, but the true effect could lie between 33 to 96 more episodes per 1000 patients.\nInterval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I² = 66%; moderate-quality evidence). There were 376 interval recurrences reported in 3933 participants enrolled in seven studies. Intensive follow-up was associated with fewer interval recurrences (52 fewer per 1000 patients); the true effect is between 18 and 75 fewer per 1000 patients.\nIntensive follow-up probably makes little or no difference to quality of life, anxiety, or depression (reported in 7 studies; moderate-quality evidence). The data were not available in a form that allowed analysis.\nIntensive follow-up may increase the complications (perforation or haemorrhage) from colonoscopies (OR 7.30, 95% CI 0.75 to 70.69; 1 study, 326 participants; very low-quality evidence). Two studies reported seven colonoscopic complications in 2292 colonoscopies, three perforations and four gastrointestinal haemorrhages requiring transfusion. We could not combine the data, as they were not reported by study arm in one study.\nThe limited data on costs suggests that the cost of more intensive follow-up may be increased in comparison with less intense follow-up (low-quality evidence). The data were not available in a form that allowed analysis.\nAuthors' conclusions\nThe results of our review suggest that there is no overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Although more participants were treated with salvage surgery with curative intent in the intensive follow-up groups, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported.\n\nGiven the provided abstract, please respond to the following query: \"We asked...\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We asked if follow-up (i.e. tests and doctor visits) after colorectal cancer has been treated curatively is helpful. We looked at all different kinds of follow-up: some versus none; more tests versus fewer tests; and follow-up done by surgeons, general practitioners (GPs), or nurses." } ]

[ { "role": "user", "content": "Abstract: Background\nMultiparametric magnetic resonance imaging (MRI), with or without MRI-targeted biopsy, is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision-making.\nObjectives\nTo determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, the MRI pathway (MRI with or without MRI-targeted biopsy) and systematic biopsy as compared to template-guided biopsy as the reference standard in detecting clinically significant prostate cancer as the target condition, defined as International Society of Urological Pathology (ISUP) grade 2 or higher. Secondary target conditions were the detection of grade 1 and grade 3 or higher-grade prostate cancer, and a potential change in the number of biopsy procedures.\nSearch methods\nWe performed a comprehensive systematic literature search up to 31 July 2018. We searched CENTRAL, MEDLINE, Embase, eight other databases and one trials register.\nSelection criteria\nWe considered for inclusion any cross-sectional study if it investigated one or more index tests verified by the reference standard, or if it investigated the agreement between the MRI pathway and systematic biopsy, both performed in the same men. We included only studies on men who were biopsy naïve or who previously had a negative biopsy (or a mix of both). Studies involving MRI had to report on both MRI-positive and MRI-negative men. All studies had to report on the primary target condition.\nData collection and analysis\nTwo reviewers independently extracted data and assessed the risk of bias using the QUADAS-2 tool. To estimate test accuracy, we calculated sensitivity and specificity using the bivariate model. To estimate agreement between the MRI pathway and systematic biopsy, we synthesised detection ratios by performing random-effects meta-analyses. To estimate the proportions of participants with prostate cancer detected by only one of the index tests, we used random-effects multinomial or binary logistic regression models. For the main comparisions, we assessed the certainty of evidence using GRADE.\nMain results\nThe test accuracy analyses included 18 studies overall.\nMRI compared to template-guided biopsy: Based on a pooled sensitivity of 0.91 (95% confidence interval (CI): 0.83 to 0.95; 12 studies; low certainty of evidence) and a pooled specificity of 0.37 (95% CI: 0.29 to 0.46; 12 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI may result in 273 (95% CI: 249 to 285) true positives, 441 false positives (95% CI: 378 to 497), 259 true negatives (95% CI: 203 to 322) and 27 (95% CI: 15 to 51) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.\nMRI-targeted biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.80 (95% CI: 0.69 to 0.87; 8 studies; low certainty of evidence) and a pooled specificity of 0.94 (95% CI: 0.90 to 0.97; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI-targeted biopsy may result in 240 (95% CI: 207 to 261) true positives, 42 (95% CI: 21 to 70) false positives, 658 (95% CI: 630 to 679) true negatives and 60 (95% CI: 39 to 93) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.\nThe MRI pathway compared to template-guided biopsy: Based on a pooled sensitivity of 0.72 (95% CI: 0.60 to 0.82; 8 studies; low certainty of evidence) and a pooled specificity of 0.96 (95% CI: 0.94 to 0.98; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, the MRI pathway may result in 216 (95% CI: 180 to 246) true positives, 28 (95% CI: 14 to 42) false positives, 672 (95% CI: 658 to 686) true negatives and 84 (95% CI: 54 to 120) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations, inconsistency and imprecision.\nSystemic biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.63 (95% CI: 0.19 to 0.93; 4 studies; low certainty of evidence) and a pooled specificity of 1.00 (95% CI: 0.91 to 1.00; 4 studies; low certainty of evidence) using a baseline prevalence of 30%, systematic biopsy may result in 189 (95% CI: 57 to 279) true positives, 0 (95% CI: 0 to 63) false positives, 700 (95% CI: 637 to 700) true negatives and 111 (95% CI: 21 to 243) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.\nAgreement analyses: In a mixed population of both biopsy-naïve and prior-negative biopsy men comparing the MRI pathway to systematic biopsy, we found a pooled detection ratio of 1.12 (95% CI: 1.02 to 1.23; 25 studies). We found pooled detection ratios of 1.44 (95% CI 1.19 to 1.75; 10 studies) in prior-negative biopsy men and 1.05 (95% CI: 0.95 to 1.16; 20 studies) in biopsy-naïve men.\nAuthors' conclusions\nAmong the diagnostic strategies considered, the MRI pathway has the most favourable diagnostic accuracy in clinically significant prostate cancer detection. Compared to systematic biopsy, it increases the number of significant cancer detected while reducing the number of insignificant cancer diagnosed. The certainty in our findings was reduced by study limitations, specifically issues surrounding selection bias, as well as inconsistency. Based on these findings, further improvement of prostate cancer diagnostic pathways should be pursued.\n\nGiven the provided abstract, please respond to the following query: \"What is the aim 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 compare MRI alone, MRI together with a biopsy, and a pathway that uses MRI to help decide whether to do a biopsy or not (hereinafter named ‘the MRI pathway’) with the standard ultrasound guided biopsy (hereinafter called ‘systematic biopsy’) in reference to template-guided biopsy." } ]

[ { "role": "user", "content": "Abstract: Background\nBreast cancer-related lymphoedema can be a debilitating long-term sequela of breast cancer treatment. Several studies have investigated the effectiveness of different treatment strategies to reduce the risk of breast cancer-related lymphoedema.\nObjectives\nTo assess the effects of conservative (non-surgical and non-pharmacological) interventions for preventing clinically-detectable upper-limb lymphoedema after breast cancer treatment.\nSearch methods\nWe searched the Cochrane Breast Cancer Group's (CBCG) Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, PsycINFO, and the World Health Organization (WHO) International Clinical Trials Registry Platform in May 2013. Reference lists of included trials and other systematic reviews were searched.\nSelection criteria\nRandomised controlled trials that reported lymphoedema as the primary outcome and compared any conservative intervention to either no intervention or to another conservative intervention.\nData collection and analysis\nThree authors independently assessed the risk of bias and extracted data. Outcome measures included lymphoedema, infection, range of motion of the shoulder, pain, psychosocial morbidity, level of functioning in activities of daily life (ADL), and health-related quality of life (HRQoL). Where possible, meta-analyses were performed. Risk ratio (RRs) or hazard ratio (HRs) were reported for dichotomous outcomes or lymphoedema incidence, and mean differences (MDs) for range of motion and patient-reported outcomes.\nMain results\nTen trials involving 1205 participants were included. The duration of patient follow-up ranged from 2 days to 2 years after the intervention. Overall, the quality of the evidence generated by these trials was low, due to risk of bias in the included trials and inconsistency in the results.\nManual lymph drainage\nIn total, four studies used manual lymph drainage (MLD) in combination with usual care or other interventions. In one study, lymphoedema incidence was lower in patients receiving MLD and usual care (consisting of standard education or exercise, or both) compared to usual care alone. A second study reported no difference in lymphoedema incidence when MLD was combined with physiotherapy and education compared to physiotherapy alone. Two other studies combining MLD with compression and scar massage or exercise observed a reduction in lymphoedema incidence compared to education only, although this was not significant in one of the studies. Two out of the four studies reported on shoulder mobility where MLD combined with exercise gave better shoulder mobility for lateral arm movement (shoulder abduction) and forward flexion in the first weeks after breast cancer surgery, compared to education only (mean difference for abduction 22°; 95% confidence interval (CI) 14 to 30; mean difference for forward flexion 14°; 95% CI 7 to 22). Two of the studies on MLD reported on pain, with inconsistent results. Results on HRQoL in two studies on MLD were also contradictory.\nExercise: early versus delayed start of shoulder mobilising exercises\nThree studies examined early versus late start of postoperative shoulder exercises. The pooled relative risk of lymphoedema after an early start of exercises was 1.69 (95% CI 0.94 to 3.01, 3 studies, 378 participants). Shoulder forward flexion was better at one and six months follow-up for participants who started early with mobilisation exercises compared to a delayed start (two studies), but no meta-analysis could be performed due to statistical heterogeneity. There was no difference in shoulder mobility or self-reported shoulder disability at 12 months follow-up (one study). One study evaluated HRQoL and reported difference at one year follow-up (mean difference 1.6 points, 95% CI -2.14 to 5.34, on the Trial Outcome Index of the FACT-B). Two studies collected data on wound drainage volumes and only one study reported higher wound drainage volumes in the early exercise group.\nExercise: resistance training\nTwo studies compared progressive resistance training to restricted activity. Resistance training after breast cancer treatment did not increase the risk of developing lymphoedema (RR 0.58; 95% CI 0.30 to 1.13, two studies, 358 participants) provided that symptoms are monitored and treated immediately if they occur. One out of the two studies measured pain where participants in the resistance training group reported pain more often at three months and six months compared to the control group. One study reported HRQoL and found no significant difference between the groups.\nPatient education, monitoring and early intervention\nOne study investigated the effects of a comprehensive outpatient follow-up programme, consisting of patient education, exercise, monitoring of lymphoedema symptoms and early intervention for lymphoedema, compared to education alone. Lymphoedema incidence was lower in the comprehensive outpatient follow-up programme (at any time point) compared to education alone (65 people). Participants in the outpatient follow-up programme had a significantly faster recovery of shoulder abduction compared to the education alone group.\nAuthors' conclusions\nBased on the current available evidence, we cannot draw firm conclusions about the effectiveness of interventions containing MLD. The evidence does not indicate a higher risk of lymphoedema when starting shoulder-mobilising exercises early after surgery compared to a delayed start (i.e. seven days after surgery). Shoulder mobility (that is, lateral arm movements and forward flexion) is better in the short term when starting shoulder exercises earlier compared to later. The evidence suggests that progressive resistance exercise therapy does not increase the risk of developing lymphoedema, provided that symptoms are closely monitored and adequately treated if they occur.\nGiven the degree of heterogeneity encountered, limited precision, and the risk of bias across the included studies, the results of this review should be interpreted with caution.\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": "About one in five people treated for breast cancer develop lymphoedema later on. We reviewed the available evidence to determine whether some methods, such as manual lymph drainage (a massage therapy), compression, exercise or only education could help prevent lymphoedema." } ]

[ { "role": "user", "content": "Abstract: Background\nInadvertent postoperative hypothermia (a drop in core body temperature to below 36°C) occurs as an effect of surgery when anaesthetic drugs and exposure of the skin for long periods of time during surgery result in interference with normal temperature regulation. Once hypothermia has occurred, it is important that patients are rewarmed promptly to minimise potential complications. Several different interventions are available for rewarming patients.\nObjectives\nTo estimate the effectiveness of treating inadvertent perioperative hypothermia through postoperative interventions to decrease heat loss and apply passive and active warming systems in adult patients who have undergone surgery.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE (Ovid SP) (1956 to 21 February 2014), EMBASE (Ovid SP) (1982 to 21 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 21 February 2014) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EBSCO host (1980 to 21 February 2014), as well as reference lists of articles. We also searched www.controlled-trials.com and www.clincialtrials.gov.\nSelection criteria\nRandomized controlled trials of postoperative warming interventions aiming to reverse hypothermia compared with control or with each other.\nData collection and analysis\nThree review authors identified studies for inclusion in this review. One review author extracted data and completed risk of bias assessments; two review authors checked the details. Meta-analysis was conducted when appropriate by using standard methodological procedures as expected by The Cochrane Collaboration.\nMain results\nWe included 11 trials with 699 participants. Ten trials provided data for analysis. Trials varied in the numbers and types of participants included and in the types of surgery performed. Most trials were at high or unclear risk of bias because of inappropriate or unclear randomization procedures, and because blinding of assessors and participants generally was not possible. This may have influenced results, but it is unclear how the results may have been influenced. Active warming was found to reduce the mean time taken to achieve normothermia by about 30 minutes in comparison with use of warmed cotton blankets (mean difference (MD) -32.13 minutes, 95% confidence interval (CI) -42.55 to -21.71; moderate-quality evidence), but no significant difference in shivering was noted. Active warming was found to reduce mean time taken to achieve normothermia by almost an hour and a half in comparison with use of unwarmed cotton blankets (MD -88.86 minutes, 95% CI -123.49 to -54.23; moderate-quality evidence), and people in the active warming group were less likely to shiver than those in the unwarmed cotton blanket group (Relative Risk=0.61 95% CI= 0.42 to 0.86; low quality evidence). There was no effect on mean temperature difference in degrees celsius at 60 minutes (MD=0.18°C, 95% CI=-0.10 to 0.46; moderate quality evidence), and no data were available in relation to major cardiovascular complications. Forced air warming was found to reduce time taken to achieve normothermia by about one hour in comparison to circulating hot water devices (MD=-54.21 minutes 95% CI= -94.95, -13.47). There was no statistically significant difference between thermal insulation and cotton blankets on mean time to achieve normothermia (MD =-0.29 minutes, 95% CI=-25.47 to 24.89; moderate quality evidence) or shivering (Relative Risk=1.36 95% CI= 0.69 to 2.67; moderate quality evidence), and no data were available for mean temperature difference or major cardiovascular complications. Insufficient evidence was available about other comparisons, adverse effects or any other secondary outcomes.\nAuthors' conclusions\nActive warming, particularly forced air warming, appears to offer a clinically important reduction in mean time taken to achieve normothermia (normal body temperature between 36°C and 37.5°C) in patients with postoperative hypothermia. However, high-quality evidence on other important clinical outcomes is lacking; therefore it is unclear whether active warming offers other benefits and harms. High-quality evidence on other warming methods is also lacking; therefore it is unclear whether other rewarming methods are effective in reversing postoperative hypothermia.\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 can be quite certain that temperature goes back to normal (between 36°C and 37.5°C) more than an hour faster when active warming methods are used to warm hypothermic patients than when hospital blankets are used, and that this result is important for people involved in the care of patients with hypothermia after surgery. Not enough evidence was found to show whether active warming methods provide other benefits or harms to patients. Some evidence suggests that forced air warming (one type of active warming) is better at rewarming patients than circulating hot water devices and radiant heaters (other types of active warming), but we do not know whether forced air warming is the best active warming method overall, as evidence on all methods of active warming was not available." } ]

[ { "role": "user", "content": "Abstract: Background\nAntipsychotic-induced weight gain is an extremely common problem in people with schizophrenia and is associated with increased morbidity and mortality. Adjunctive pharmacological interventions may be necessary to help manage antipsychotic-induced weight gain. This review splits and updates a previous Cochrane Review that focused on both pharmacological and behavioural approaches to this problem.\nObjectives\nTo determine the effectiveness of pharmacological interventions for preventing antipsychotic-induced weight gain in people with schizophrenia.\nSearch methods\nThe Cochrane Schizophrenia Information Specialist searched Cochrane Schizophrenia's Register of Trials on 10 February 2021. There are no language, date, document type, or publication status limitations for inclusion of records in the register.\nSelection criteria\nWe included all randomised controlled trials (RCTs) that examined any adjunctive pharmacological intervention for preventing weight gain in people with schizophrenia or schizophrenia-like illnesses who use antipsychotic medications.\nData collection and analysis\nAt least two review authors independently extracted data and assessed the quality of included studies. For continuous outcomes, we combined mean differences (MD) in endpoint and change data in the analysis. For dichotomous outcomes, we calculated risk ratios (RR). We assessed risk of bias for included studies and used GRADE to judge certainty of evidence and create summary of findings tables. The primary outcomes for this review were clinically important change in weight, clinically important change in body mass index (BMI), leaving the study early, compliance with treatment, and frequency of nausea. The included studies rarely reported these outcomes, so, post hoc, we added two new outcomes, average endpoint/change in weight and average endpoint/change in BMI.\nMain results\nSeventeen RCTs, with a total of 1388 participants, met the inclusion criteria for the review. Five studies investigated metformin, three topiramate, three H2 antagonists, three monoamine modulators, and one each investigated monoamine modulators plus betahistine, melatonin and samidorphan. The comparator in all studies was placebo or no treatment (i.e. standard care alone). We synthesised all studies in a quantitative meta-analysis. Most studies inadequately reported their methods of allocation concealment and blinding of participants and personnel. The resulting risk of bias and often small sample sizes limited the overall certainty of the evidence. Only one reboxetine study reported the primary outcome, number of participants with clinically important change in weight. Fewer people in the treatment condition experienced weight gains of more than 5% and more than 7% of their bodyweight than those in the placebo group (> 5% weight gain RR 0.27, 95% confidence interval (CI) 0.11 to 0.65; 1 study, 43 participants; > 7% weight gain RR 0.24, 95% CI 0.07 to 0.83; 1 study, 43 participants; very low-certainty evidence). No studies reported the primary outcomes, 'clinically important change in BMI', or 'compliance with treatment'. However, several studies reported 'average endpoint/change in body weight' or 'average endpoint/change in BMI'.\nMetformin may be effective in preventing weight gain (MD −4.03 kg, 95% CI −5.78 to −2.28; 4 studies, 131 participants; low-certainty evidence); and BMI increase (MD −1.63 kg/m2, 95% CI −2.96 to −0.29; 5 studies, 227 participants; low-certainty evidence). Other agents that may be slightly effective in preventing weight gain include H2 antagonists such as nizatidine, famotidine and ranitidine (MD −1.32 kg, 95% CI −2.09 to −0.56; 3 studies, 248 participants; low-certainty evidence) and monoamine modulators such as reboxetine and fluoxetine (weight: MD −1.89 kg, 95% CI −3.31 to −0.47; 3 studies, 103 participants; low-certainty evidence; BMI: MD −0.66 kg/m2, 95% CI −1.05 to −0.26; 3 studies, 103 participants; low-certainty evidence). Topiramate did not appear effective in preventing weight gain (MD −4.82 kg, 95% CI −9.99 to 0.35; 3 studies, 168 participants; very low-certainty evidence). For all agents, there was no difference between groups in terms of individuals leaving the study or reports of nausea. However, the results of these outcomes are uncertain given the very low-certainty evidence.\nAuthors' conclusions\nThere is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain.\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 find out whether add-on medications to prevent weight gain caused by antipsychotics were effective in people with schizophrenia." } ]

[ { "role": "user", "content": "Abstract: Background\nThe use of etomidate for emergency airway interventions in critically ill patients is very common. In one large registry trial, etomidate was the most commonly used agent for this indication. Etomidate is known to suppress adrenal gland function, but it remains unclear whether or not this adrenal gland dysfunction affects mortality.\nObjectives\nThe primary objective was to assess, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects mortality.\nThe secondary objectives were to address, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects adrenal gland function, organ dysfunction, or health services utilization (as measured by intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation, or vasopressor requirements).\nWe repeated analyses within subgroups defined by the aetiologies of critical illness, timing of adrenal gland function measurement, and the type of comparator drug used.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; CINAHL; EMBASE; LILACS; International Pharmaceutical Abstracts; Web of Science; the Database of Abstracts of Reviews of Effects (DARE); and ISI BIOSIS Citation indexSM on 8 February 2013. We reran the searches in August 2014. We will deal with any studies of interest when we update the review.\nWe also searched the Scopus database of dissertations and conference proceedings and the US Food and Drug Administration Database. We handsearched major emergency medicine, critical care, and anaesthesiology journals.\nWe handsearched the conference proceedings of major emergency medicine, anaesthesia, and critical care conferences from 1990 to current, and performed a grey literature search of the following: Current Controlled Trials; National Health Service – The National Research Register; ClinicalTrials.gov; NEAR website.\nSelection criteria\nWe included randomized controlled trials in patients undergoing emergency endotracheal intubation for critical illness, including but not limited to trauma, stroke, myocardial infarction, arrhythmia, septic shock, hypovolaemic or haemorrhagic shock, and undifferentiated shock states. We included single (bolus) dose etomidate for emergency airway intervention compared to any other rapid-acting intravenous bolus single-dose induction agent.\nData collection and analysis\nRefinement of our initial search results by title review, and then by abstract review was carried out by three review authors. Full-text review of potential studies was based on their adherence to our inclusion and exclusion criteria. This was decided by three independent review authors. We reported the decisions regarding inclusion and exclusion in accordance with the PRISMA statement.\nElectronic database searching yielded 1635 potential titles, and our grey literature search yielded an additional 31 potential titles. Duplicate titles were filtered leaving 1395 titles which underwent review of their titles and abstracts by three review authors. Sixty seven titles were judged to be relevant to our review, however only eight met our inclusion criteria and seven were included in our analysis.\nMain results\nWe included eight studies in the review and seven in the meta-analysis. Of those seven studies, only two were judged to be at low risk of bias. Overall, no strong evidence exists that etomidate increases mortality in critically ill patients when compared to other bolus dose induction agents (odds ratio (OR) 1.17; 95% confidence interval (CI) 0.86 to 1.60, 6 studies, 772 participants, moderate quality evidence). Due to a large number of participants lost to follow-up, we performed a post hoc sensitivity analysis. This gave a similar result (OR 1.15; 95% CI 0.86 to 1.53). There was evidence that the use of etomidate in critically ill patients was associated with a positive adrenocorticotropic hormone (ACTH) stimulation test, and this difference was more pronounced at between 4 to 6 hours (OR 19.98; 95% CI 3.95 to 101.11) than after 12 hours (OR 2.37; 95% CI 1.61 to 3.47) post-dosing. Etomidate's use in critically ill patients was associated with a small increase in SOFA score, indicating a higher risk of multisystem organ failure (mean difference (MD) 0.70; 95% CI 0.01 to 1.39, 2 studies, 591 participants, high quality evidence), but this difference was not clinically meaningful. Etomidate use did not have an effect on ICU LOS (MD 1.70 days; 95% CI -2.00 to 5.40, 4 studies, 621 participants, moderate quality evidence), hospital LOS (MD 2.41 days; 95% CI -7.08 to 11.91, 3 studies, 152 participants, moderate quality evidence), duration of mechanical ventilation (MD 2.14 days; 95% CI -1.67 to 5.95, 3 studies, 621 participants, moderate quality evidence), or duration of vasopressor use (MD 1.00 day; 95% CI -0.53 to 2.53, 1 study, 469 participants).\nAuthors' conclusions\nAlthough we have not found conclusive evidence that etomidate increases mortality or healthcare resource utilization in critically ill patients, it does seem to increase the risk of adrenal gland dysfunction and multi-organ system dysfunction by a small amount. The clinical significance of this finding is unknown. This evidence is judged to be of moderate quality, owing mainly to significant attrition bias in some of the smaller studies, and new research may influence the outcomes of our review. The applicability of these data may be limited by the fact that 42% of the patients in our review were intubated for \"being comatose\", a population less likely to benefit from the haemodynamic stability inherent in etomidate use, and less at risk from its potential negative downstream effects of adrenal suppression.\n\nGiven the provided abstract, please respond to the following query: \"Results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "No strong evidence exists to suggest that etomidate, when compared to other bolus dose induction agents, increases mortality in critically ill patients. We must be careful in interpreting this finding because only large studies would be able to show a difference in mortality. So far, no such study has been completed.\nEtomidate does seem to impair adrenal gland functioning. Functioning is impaired most between four and six hours after etomidate is given.\nSequential Organ Failure Assessment (SOFA) scores are used to find out how badly someone’s organs are failing. Using etomidate results in worse SOFA scores but this difference is small and not clinically meaningful.\nThe effects of impaired adrenal gland functioning and higher SOFA scores on people’s health is unknown. Using etomidate does not seem to increase the length of time someone is in hospital (including an intensive care unit), the length of time a person is connected to a mechanical ventilator (a machine to assist with breathing), or the use of vasopressors (medicines to increase blood pressure)." } ]

[ { "role": "user", "content": "Abstract: Background\nA detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available.\nObjectives\nPrimary objective\nTo assess the pharmacology of pravastatin by characterizing the dose-related effect and variability of the effect of pravastatin on the surrogate marker: low-density lipoprotein (LDL cholesterol). The effect of pravastatin on morbidity and mortality is not the objective of this systematic review.\nSecondary objectives\n• To assess the dose-related effect and variability of effect of pravastatin on the following surrogate markers: total cholesterol; high-density lipoprotein (HDL cholesterol); and triglycerides. \n• To assess the effect of pravastatin on withdrawals due to adverse effects.\nSearch methods\nThe Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to September 2021: CENTRAL (2021, Issue 8), Ovid MEDLINE, Ovid Embase, Bireme LILACS, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.\nSelection criteria\nRandomized placebo-controlled trials evaluating the dose response of different fixed doses of pravastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.\nData collection and analysis\nTwo review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered lipid data from placebo-controlled trials into Review Manager 5 as continuous data and withdrawal due to adverse effects (WDAEs) data as dichotomous data. We searched for WDAEs information from all trials. We assessed all trials using Cochrane's risk of bias tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.\nMain results\nSixty-four RCTs evaluated the dose-related efficacy of pravastatin in 9771 participants. The participants were of any age, with and without evidence of cardiovascular disease, and pravastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over the doses of 5 mg to 160 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol, and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of pravastatin on blood HDL cholesterol. Pravastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 21.7% to 31.9%, total cholesterol by 16.1% to 23.3%,and triglycerides by 5.8% to 20.0%. The certainty of evidence for these effects was judged to be moderate to high. For every two-fold dose increase there was a 3.4% (95% confidence interval (CI) 2.2 to 4.6) decrease in blood LDL cholesterol. This represented a dose-response slope that was less than the other studied statins: atorvastatin, rosuvastatin, fluvastatin, pitavastatin and cerivastatin. From other systematic reviews we conducted on statins for its effect to reduce LDL cholesterol, pravastatin is similar to fluvastatin, but has a decreased effect compared to atorvastatin, rosuvastatin, pitavastatin and cerivastatin. The effect of pravastatin compared to placebo on WADES has a risk ratio (RR) of 0.81 (95% CI 0.63 to 1.03). The certainty of evidence was judged to be very low.\nAuthors' conclusions\nPravastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. This review did not provide a good estimate of the incidence of harms associated with pravastatin because of the lack of reporting of adverse effects in 48.4% of the randomized placebo-controlled trials.\n\nGiven the provided abstract, please respond to the following query: \"What are cholesterol and blood fats?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Cholesterol is required to build and maintain all animal cell membranes and is critical to human life. Main components of cholesterol are low-density lipoprotein, high-density lipoprotein, and triglycerides. Low-density lipoprotein transports fat molecules around the body in the blood and delivers fat molecules to cells. High-density lipoprotein removes fat molecules from cells and transports it to the liver. Cholesterol and its components low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol can be measured in the blood. Triglycerides are found in all lipoproteins and can also be measured in the blood. Blood fats are thought to be related to adverse events affecting the heart and blood vessels." } ]

[ { "role": "user", "content": "Abstract: Background\nAcetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources.\nObjectives\nThe main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults.\nSearch methods\nWe searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017.\nSelection criteria\nWe included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration.\nData collection and analysis\nTwo review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved disagreements by discussion between review authors and further disagreements through consultation with the last review author. We assessed risk of bias in 10 methodological domains using the Cochrane risk of bias tool and examined risk of random error through trial sequential analysis. We used the principles of the GRADE approach to prepare an overall assessment of the quality of evidence. For our primary outcomes (recovery times to train-of-four ratio (TOFR) > 0.9), we presented data as mean differences (MDs) with 95 % confidence intervals (CIs), and for our secondary outcomes (risk of adverse events and risk of serious adverse events), we calculated risk ratios (RRs) with CIs.\nMain results\nWe included 41 studies (4206 participants) in this updated review, 38 of which were new studies. Twelve trials were eligible for meta-analysis of primary outcomes (n = 949), 28 trials were eligible for meta-analysis of secondary outcomes (n = 2298), and 10 trials (n = 1647) were ineligible for meta-analysis.\nWe compared sugammadex 2 mg/kg and neostigmine 0.05 mg/kg for reversal of rocuronium-induced moderate neuromuscular blockade (NMB). Sugammadex 2 mg/kg was 10.22 minutes (6.6 times) faster then neostigmine 0.05 mg/kg (1.96 vs 12.87 minutes) in reversing NMB from the second twitch (T2) to TOFR > 0.9 (MD 10.22 minutes, 95% CI 8.48 to 11.96; I2 = 84%; 10 studies, n = 835; GRADE: moderate quality).\nWe compared sugammadex 4 mg/kg and neostigmine 0.07 mg/kg for reversal of rocuronium-induced deep NMB. Sugammadex 4 mg/kg was 45.78 minutes (16.8 times) faster then neostigmine 0.07 mg/kg (2.9 vs 48.8 minutes) in reversing NMB from post-tetanic count (PTC) 1 to 5 to TOFR > 0.9 (MD 45.78 minutes, 95% CI 39.41 to 52.15; I2 = 0%; two studies, n = 114; GRADE: low quality).\nFor our secondary outcomes, we compared sugammadex, any dose, and neostigmine, any dose, looking at risk of adverse and serious adverse events. We found significantly fewer composite adverse events in the sugammadex group compared with the neostigmine group (RR 0.60, 95% CI 0.49 to 0.74; I2 = 40%; 28 studies, n = 2298; GRADE: moderate quality). Risk of adverse events was 28% in the neostigmine group and 16% in the sugammadex group, resulting in a number needed to treat for an additional beneficial outcome (NNTB) of 8. When looking at specific adverse events, we noted significantly less risk of bradycardia (RR 0.16, 95% CI 0.07 to 0.34; I2= 0%; 11 studies, n = 1218; NNTB 14; GRADE: moderate quality), postoperative nausea and vomiting (PONV) (RR 0.52, 95% CI 0.28 to 0.97; I2 = 0%; six studies, n = 389; NNTB 16; GRADE: low quality) and overall signs of postoperative residual paralysis (RR 0.40, 95% CI 0.28 to 0.57; I2 = 0%; 15 studies, n = 1474; NNTB 13; GRADE: moderate quality) in the sugammadex group when compared with the neostigmine group. Finally, we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events (RR 0.54, 95% CI 0.13 to 2.25; I2= 0%; 10 studies, n = 959; GRADE: low quality).\nApplication of trial sequential analysis (TSA) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9, adverse events, and overall signs of postoperative residual paralysis.\nAuthors' conclusions\nReview results suggest that in comparison with neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block. Sugammadex 2 mg/kg is 10.22 minutes (˜ 6.6 times) faster in reversing moderate neuromuscular blockade (T2) than neostigmine 0.05 mg/kg (GRADE: moderate quality), and sugammadex 4 mg/kg is 45.78 minutes (˜ 16.8 times) faster in reversing deep neuromuscular blockade (PTC 1 to 5) than neostigmine 0.07 mg/kg (GRADE: low quality). With an NNTB of 8 to avoid an adverse event, sugammadex appears to have a better safety profile than neostigmine. Patients receiving sugammadex had 40% fewer adverse events compared with those given neostigmine. Specifically, risks of bradycardia (RR 0.16, NNTB 14; GRADE: moderate quality), PONV (RR 0.52, NNTB 16; GRADE: low quality), and overall signs of postoperative residual paralysis (RR 0.40, NNTB 13; GRADE: moderate quality) were reduced. Both sugammadex and neostigmine were associated with serious adverse events in less than 1% of patients, and data showed no differences in risk of serious adverse events between groups (RR 0.54; GRADE: low quality).\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We identified 41 randomized controlled trials comparing sugammadex with neostigmine that provided suitable data on efficacy and safety. All of these trials included adults undergoing surgery and involved a total of 4206 participants." } ]

[ { "role": "user", "content": "Abstract: Background\nTrachoma remains a major cause of avoidable blindness among underprivileged populations in many developing countries. It is estimated that about 146 million people have active trachoma and nearly six million people are blind due to complications associated with repeat infections.\nObjectives\nThe objective of this review was to assess the effects of face washing promotion for the prevention of active trachoma in endemic communities.\nSearch methods\nWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), PubMed (January 1948 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (accessed 10 January 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 January 2015.\nTo identify further relevant trials we checked the reference lists of the included trials. Also, we used the Science Citation Index to search for references to publications that cited the trials included in the review. We contacted investigators and experts in the field to identify additional trials.\nSelection criteria\nWe included randomized controlled trials (RCTs) or quasi-RCTs that compared face washing with no treatment or face washing combined with antibiotics against antibiotics alone. Trial participants were residents of endemic trachoma communities.\nData collection and analysis\nTwo review authors independently extracted data and assessed trial quality. We contacted trial authors for additional information when needed. Two trials met our inclusion criteria; but we did not conduct meta-analysis due to methodological heterogeneity.\nMain results\nWe included two cluster-RCTs, which provided data from 2447 participants. Both trials were conducted in areas endemic to trachoma: Northern Australia and Tanzania. The follow-up period was three months in one trial and 12 months in the other; both trials had about 90% participant follow-up at final visit. Overall the quality of the evidence is uncertain due to the trials not reporting many design methods and the differences in outcomes reported between trials.\nFace washing combined with topical tetracycline was compared with topical tetracycline alone in three pairs of villages in one trial. The trial found that face washing combined with topical tetracycline reduced 'severe' active trachoma compared with topical tetracycline alone at 12 months (adjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.97); however, the trial did not find any important difference between the intervention and control villages in reducing other types of active trachoma (adjusted OR 0.81, 95% CI 0.42 to 1.59). Intervention villages had a higher prevalence of clean faces than the control villages among children with severe trachoma (adjusted OR 0.35, 95% CI 0.21 to 0.59) and any trachoma (adjusted OR 0.58, 95% CI 0.47 to 0.72) at 12 months follow-up. The second trial compared eye washing to no treatment or to topical tetracycline alone or to a combination of eye washing and tetracycline drops in children with follicular trachoma. At three months, the trial found no evidence of benefit of eye washing alone or in combination with tetracycline eye drops in reducing follicular trachoma amongst children with follicular trachoma (risk ratio (RR) 1.03, 95% CI 0.96 to 1.11; one trial, 1143 participants).\nAuthors' conclusions\nThere is evidence from one trial that face washing combined with topical tetracycline may be effective in reducing severe active trachoma and in increasing the prevalence of clean faces at one year follow-up. Current evidence is inconclusive as to the effectiveness of face washing alone or in combination with topical tetracycline in reducing active or severe trachoma.\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": "Both trials reported the number of children with active trachoma as an outcome measure; one trial also reported the number of children with severe trachoma and the percentage of clean faces after one year. One trial reported that face washing was effective in increasing facial cleanliness and in reducing severe trachoma at one year; the second trial did not show that eye washing alone or in combination with tetracycline eye drops reduced follicular trachoma amongst children who had follicular trachoma at time of enrollment." } ]

[ { "role": "user", "content": "Abstract: Background\nIndividuals dying of coronavirus disease 2019 (COVID-19) may experience distressing symptoms such as breathlessness or delirium. Palliative symptom management can alleviate symptoms and improve the quality of life of patients. Various treatment options such as opioids or breathing techniques have been discussed for use in COVID-19 patients. However, guidance on symptom management of COVID-19 patients in palliative care has often been derived from clinical experiences and guidelines for the treatment of patients with other illnesses. An understanding of the effectiveness of pharmacological and non-pharmacological palliative interventions to manage specific symptoms of COVID-19 patients is required.\nObjectives\nTo assess the efficacy and safety of pharmacological and non-pharmacological interventions for palliative symptom control in individuals with COVID-19.\nSearch methods\nWe searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), Embase, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), medRxiv); Web of Science Core Collection (Science Citation Index Expanded, Emerging Sources); CINAHL; WHO COVID-19 Global literature on coronavirus disease; and COAP Living Evidence on COVID-19 to identify completed and ongoing studies without language restrictions until 23 March 2021.\nWe screened the reference lists of relevant review articles and current treatment guidelines for further literature.\nSelection criteria\nWe followed standard Cochrane methodology as outlined in the Cochrane Handbook for Systematic Reviews of Interventions.\nWe included studies evaluating palliative symptom management for individuals with a confirmed diagnosis of COVID-19 receiving interventions for palliative symptom control, with no restrictions regarding comorbidities, age, gender, or ethnicity. Interventions comprised pharmacological as well as non-pharmacological treatment (e.g. acupressure, physical therapy, relaxation, or breathing techniques). We searched for the following types of studies: randomized controlled trials (RCT), quasi-RCTs, controlled clinical trials, controlled before-after studies, interrupted time series (with comparison group), prospective cohort studies, retrospective cohort studies, (nested) case-control studies, and cross-sectional studies.\nWe searched for studies comparing pharmacological and non-pharmacological interventions for palliative symptom control with standard care.\nWe excluded studies evaluating palliative interventions for symptoms caused by other terminal illnesses. If studies enrolled populations with or exposed to multiple diseases, we would only include these if the authors provided subgroup data for individuals with COVID-19. We excluded studies investigating interventions for symptom control in a curative setting, for example patients receiving life-prolonging therapies such as invasive ventilation.\nData collection and analysis\nWe used a modified version of the Newcastle Ottawa Scale for non-randomized studies of interventions (NRSIs) to assess bias in the included studies. We included the following outcomes: symptom relief (primary outcome); quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; serious adverse events; and grade 3 to 4 adverse events.\nWe rated the certainty of evidence using the GRADE approach.\nAs meta-analysis was not possible, we used tabulation to synthesize the studies and histograms to display the outcomes.\nMain results\nOverall, we identified four uncontrolled retrospective cohort studies investigating pharmacological interventions for palliative symptom control in hospitalized patients and patients in nursing homes. None of the studies included a comparator. We rated the risk of bias high across all studies. We rated the certainty of the evidence as very low for the primary outcome symptom relief, downgrading mainly for high risk of bias due to confounding and unblinded outcome assessors.\nPharmacological interventions for palliative symptom control\nWe identified four uncontrolled retrospective cohort studies (five references) investigating pharmacological interventions for palliative symptom control. Two references used the same register to form their cohorts, and study investigators confirmed a partial overlap of participants. We therefore do not know the exact number of participants, but individual reports included 61 to 2105 participants. Participants received multimodal pharmacological interventions: opioids, neuroleptics, anticholinergics, and benzodiazepines for relieving dyspnea (breathlessness), delirium, anxiety, pain, audible upper airway secretions, respiratory secretions, nausea, cough, and unspecified symptoms.\nPrimary outcome: symptom relief\nAll identified studies reported this outcome. For all symptoms (dyspnea, delirium, anxiety, pain, audible upper airway secretions, respiratory secretions, nausea, cough, and unspecified symptoms), a majority of interventions were rated as completely or partially effective by outcome assessors (treating clinicians or nursing staff). Interventions used in the studies were opioids, neuroleptics, anticholinergics, and benzodiazepines.\nWe are very uncertain about the effect of pharmacological interventions on symptom relief (very low-certainty evidence). The initial rating of the certainty of evidence was low since we only identified uncontrolled NRSIs. Our main reason for downgrading the certainty of evidence was high risk of bias due to confounding and unblinded outcome assessors. We therefore did not find evidence to confidently support or refute whether pharmacological interventions may be effective for palliative symptom relief in COVID-19 patients.\nSecondary outcomes\nWe planned to include the following outcomes: quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; serious adverse events; and grade 3 to 4 adverse events.\nWe did not find any data for these outcomes, or any other information on the efficacy and safety of used interventions.\nNon-pharmacological interventions for palliative symptom control\nNone of the identified studies used non-pharmacological interventions for palliative symptom control.\nAuthors' conclusions\nWe found very low certainty evidence for the efficacy of pharmacological interventions for palliative symptom relief in COVID-19 patients. We found no evidence on the safety of pharmacological interventions or efficacy and safety of non-pharmacological interventions for palliative symptom control in COVID-19 patients. The evidence presented here has no specific implications for palliative symptom control in COVID-19 patients because we cannot draw any conclusions about the effectiveness or safety based on the identified evidence. More evidence is needed to guide clinicians, nursing staff, and caregivers when treating symptoms of COVID-19 patients at the end of life. Specifically, future studies ought to investigate palliative symptom control in prospectively registered studies, using an active-controlled setting, assess patient-reported outcomes, and clearly define interventions.\nThe publication of the results of ongoing studies will necessitate an update of this review. The conclusions of an updated review could differ from those of the present review and may allow for a better judgement regarding pharmacological and non-pharmacological interventions for palliative symptom control in COVID-19 patients.\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 studies that were published in five papers. Individual papers included between 61 and 2105 participants, and two papers partially reported on the same participants. All of the included studies investigated different drug treatments for palliative symptom management in people with COVID-19.\nDrugs for symptom control at the end of life\nAll of the included studies reported on the effectiveness of palliative care for symptom relief. In all studies, clinicians or nursing staff rated symptom relief rather than the patients themselves. Since the quality of the evidence was very low, we do not know the true effect of drug treatments on symptom relief and have very low confidence in the results of the studies. We did not find any data on quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; or safety of the drug treatments.\nNon-drug therapies for symptom control at the end of life\nWe did not find any data on the benefits and harms of non-drug therapies for symptom control of COVID-19 patients at the end of life." } ]

[ { "role": "user", "content": "Abstract: Background\nPharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview.\nObjectives\nTo summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP.\nMethods\nThe Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non-specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety.\nMain results\nSeven Cochrane Reviews that included 103 studies (22,238 participants) were included. There is high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub-acute LBP and five reviews included participants with chronic LBP.\nAcute LBP\nParacetamol\nThere was high-certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI -0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33).\nNSAIDs\nThere was moderate-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD -7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.98 to -3.61), high-certainty evidence for a small between-group difference for reducing disability (MD -2.02 on a 0-24 scale (higher scores indicate worse disability), 95% CI -2.89 to -1.15), and very low-certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18).\nMuscle relaxants and benzodiazepines\nThere was moderate-certainty evidence for a small between-group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98).\nOpioids\nNone of the included Cochrane Reviews aimed to identify evidence for acute LBP.\nAntidepressants\nNo evidence was identified by the included reviews for acute LBP.\nChronic LBP\nParacetamol\nNo evidence was identified by the included reviews for chronic LBP.\nNSAIDs\nThere was low-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD -6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.74 to -3.19), reducing disability (MD -0.85 on a 0-24 scale (higher scores indicate worse disability), 95% CI -1.30 to -0.40), and no evidence of an increased risk of adverse events (RR 1.04, 95% CI -0.92 to 1.17), all at intermediate-term follow-up (> 3 months and ≤ 12 months postintervention).\nMuscle relaxants and benzodiazepines\nThere was low-certainty evidence for a small between-group difference favouring benzodiazepines compared to placebo for a higher chance of pain relief (RR 0.71, 95% CI 0.54 to 0.93), and low-certainty evidence for no evidence of difference between muscle relaxants and placebo in the risk of adverse events (RR 1.02, 95% CI 0.67 to 1.57).\nOpioids\nThere was high-certainty evidence for a small between-group difference favouring tapentadol compared to placebo at reducing pain intensity (MD -8.00 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.22 to -0.38), moderate-certainty evidence for a small between-group difference favouring strong opioids for reducing pain intensity (SMD -0.43, 95% CI -0.52 to -0.33), low-certainty evidence for a medium between-group difference favouring tramadol for reducing pain intensity (SMD -0.55, 95% CI -0.66 to -0.44) and very low-certainty evidence for a small between-group difference favouring buprenorphine for reducing pain intensity (SMD -0.41, 95% CI -0.57 to -0.26).\nThere was moderate-certainty evidence for a small between-group difference favouring strong opioids compared to placebo for reducing disability (SMD -0.26, 95% CI -0.37 to -0.15), moderate-certainty evidence for a small between-group difference favouring tramadol for reducing disability (SMD -0.18, 95% CI -0.29 to -0.07), and low-certainty evidence for a small between-group difference favouring buprenorphine for reducing disability (SMD -0.14, 95% CI -0.53 to -0.25).\nThere was low-certainty evidence for a small between-group difference for an increased risk of adverse events for opioids (all types) compared to placebo; nausea (RD 0.10, 95% CI 0.07 to 0.14), headaches (RD 0.03, 95% CI 0.01 to 0.05), constipation (RD 0.07, 95% CI 0.04 to 0.11), and dizziness (RD 0.08, 95% CI 0.05 to 0.11).\nAntidepressants\nThere was low-certainty evidence for no evidence of difference for antidepressants (all types) compared to placebo for reducing pain intensity (SMD -0.04, 95% CI -0.25 to 0.17) and reducing disability (SMD -0.06, 95% CI -0.40 to 0.29).\nAuthors' conclusions\nWe found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.\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 for all Cochrane systematic reviews that assessed the benefits and harms of medicines for adults with non-specific LBP to produce an overview of Cochrane evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nIn the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens.\nObjectives\nTo evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment.\nSearch methods\nWe searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020.\nSelection criteria\nRandomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment.\nData collection and analysis\nTwo review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods.\nMain results\nThirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision.\nLNG-IUS versus non-intrauterine progestogens\nPrimary outcomes\nRegression of endometrial hyperplasia\nThe LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence),\nAdverse effects associated with LNG-IUS\nThere was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis.\nSecondary outcomes\nThe LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use.\nLNG-IUS versus no treatment\nRegression of endometrial hyperplasia\nOne study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome.\nAuthors' conclusions\nThere is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use.\n\nGiven the provided abstract, please respond to the following query: \"Study characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included 13 randomised controlled trials (RCTs) comparing the LNG-IUS in 1657 women with EH to non-intrauterine progestogens (1327 women) or no treatment (190 women). We found no trials comparing the LNG-IUS with surgery or placebo. The women were aged between 22 and 70 years. All studies evaluated women with EH without atypia, and one of the studies also included women with EH with atypia. Two studies did not have enough data to analyse. The evidence is current to May 2020." } ]

[ { "role": "user", "content": "Abstract: Background\nPlague is a severe disease associated with high mortality. Late diagnosis leads to advance stage of the disease with worse outcomes and higher risk of spread of the disease. A rapid diagnostic test (RDT) could help in establishing a prompt diagnosis of plague. This would improve patient care and help appropriate public health response.\nObjectives\nTo determine the diagnostic accuracy of the RDT based on the antigen F1 (F1RDT) for detecting plague in people with suspected disease.\nSearch methods\nWe searched the CENTRAL, Embase, Science Citation Index, Google Scholar, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov up to 15 May 2019, and PubMed (MEDLINE) up to 27 August 2019, regardless of language, publication status, or publication date. We handsearched the reference lists of relevant papers and contacted researchers working in the field.\nSelection criteria\nWe included cross-sectional studies that assessed the accuracy of the F1RDT for diagnosing plague, where participants were tested with both the F1RDT and at least one reference standard. The reference standards were bacterial isolation by culture, polymerase chain reaction (PCR), and paired serology (this is a four-fold difference in F1 antibody titres between two samples from acute and convalescent phases).\nData collection and analysis\nTwo review authors independently selected studies and extracted data. We appraised the methodological quality of each selected studies and applicability by using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When meta-analysis was appropriate, we used the bivariate model to obtain pooled estimates of sensitivity and specificity. We stratified all analyses by the reference standard used and presented disaggregated data for forms of plague. We assessed the certainty of the evidence using GRADE.\nMain results\nWe included eight manuscripts reporting seven studies. Studies were conducted in three countries in Africa among adults and children with any form of plague. All studies except one assessed the F1RDT produced at the Institut Pasteur of Madagascar (F1RDT-IPM) and one study assessed a F1RDT produced by New Horizons (F1RDT-NH), utilized by the US Centers for Disease Control and Prevention. We could not pool the findings from the F1RDT-NH in meta-analyses due to a lack of raw data and a threshold of the test for positivity different from the F1RDT-IPM.\nRisk of bias was high for participant selection (retrospective studies, recruitment of participants not consecutive or random, unclear exclusion criteria), low or unclear for index test (blinding of F1RDT interpretation unknown), low for reference standards, and high or unclear for flow and timing (time of sample transportation was longer than seven days, which can lead to decreased viability of the pathogen and overgrowth of contaminating bacteria, with subsequent false-negative results and misclassification of the target condition).\nF1RDT for diagnosing all forms of plague\nF1RDT-IPM pooled sensitivity against culture was 100% (95% confidence interval (CI) 82 to 100; 4 studies, 1692 participants; very low certainty evidence) and pooled specificity was 70.3% (95% CI 65 to 75; 4 studies, 2004 participants; very low-certainty evidence).\nThe performance of F1RDT-IPM against PCR was calculated from a single study in participants with bubonic plague (see below).\nThere were limited data on the performance of F1RDT against paired serology.\nF1RDT for diagnosing pneumonic plague\nPerformed in sputum, F1RDT-IPM pooled sensitivity against culture was 100% (95% CI 0 to 100; 2 studies, 56 participants; very low-certainty evidence) and pooled specificity was 71% (95% CI 59 to 80; 2 studies, 297 participants; very low-certainty evidence).\nThere were limited data on the performance of F1RDT against PCR or against paired serology for diagnosing pneumonic plague.\nF1RDT for diagnosing bubonic plague\nPerformed in bubo aspirate, F1RDT-IPM pooled sensitivity against culture was 100% (95% CI not calculable; 2 studies, 1454 participants; low-certainty evidence) and pooled specificity was 67% (95% CI 65 to 70; 2 studies, 1198 participants; very low-certainty evidence).\nPerformed in bubo aspirate, F1RDT-IPM pooled sensitivity against PCR for the caf1 gene was 95% (95% CI 89 to 99; 1 study, 88 participants; very low-certainty evidence) and pooled specificity was 93% (95% CI 84 to 98; 1 study, 61 participants; very low-certainty evidence).\nThere were no data providing data on both F1RDT and paired serology for diagnosing bubonic plague.\nAuthors' conclusions\nAgainst culture, the F1RDT appeared highly sensitive for diagnosing either pneumonic or bubonic plague, and can help detect plague in remote areas to assure management and enable a public health response. False positive results mean culture or PCR confirmation may be needed. F1RDT does not replace culture, which provides additional information on resistance to antibiotics and bacterial strains.\n\nGiven the provided abstract, please respond to the following query: \"How confident are we in the review\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "'s results?\nOverall, the reliability of the evidence was very low. Results should be interpreted with caution. There were concerns about the quality of the methodology of all included studies. Also, culture might not work well as a reference standard (comparator) when people received antibiotics before sample collection for testing." } ]

[ { "role": "user", "content": "Abstract: Background\nThe prevention of long-term psychological distress following traumatic events is a major concern. Systematic reviews have suggested that individual psychological debriefing is not an effective intervention at preventing post-traumatic stress disorder (PTSD). Over the past 20 years, other forms of intervention have been developed with the aim of preventing PTSD.\nObjectives\nTo examine the efficacy of psychological interventions aimed at preventing PTSD in individuals exposed to a traumatic event but not identified as experiencing any specific psychological difficulties, in comparison with control conditions (e.g. usual care, waiting list and no treatment) and other psychological interventions.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and ProQuest's Published International Literature On Traumatic Stress (PILOTS) database to 3 March 2018. An earlier search of CENTRAL and the Ovid databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to May 2016). We handsearched reference lists of relevant guidelines, systematic reviews and included study reports. Identified studies were shared with key experts in the field.\nWe conducted an update search (15 March 2019) and placed any new trials in the 'awaiting classification' section. These will be incorporated into the next version of this review, as appropriate.\nSelection criteria\nWe searched for randomised controlled trials of any multiple session (two or more sessions) early psychological intervention or treatment designed to prevent symptoms of PTSD. We excluded single session individual/group psychological interventions. Comparator interventions included waiting list/usual care and active control condition. We included studies of adults who experienced a traumatic event which met the criterion A1 according to the Diagnostic and Statistical Manual (DSM-IV) for PTSD.\nData collection and analysis\nWe entered data into Review Manager 5 software. We analysed categorical outcomes as risk ratios (RRs), and continuous outcomes as mean differences (MD) or standardised mean differences (SMDs), with 95% confidence intervals (CI). We pooled data with a fixed-effect meta-analysis, except where there was heterogeneity, in which case we used a random-effects model. Two review authors independently assessed the included studies for risk of bias and discussed any conflicts with a third review author.\nMain results\nThis is an update of a previous review.\nWe included 27 studies with 3963 participants. The meta-analysis included 21 studies of 2721 participants. Seventeen studies compared multiple session early psychological intervention versus treatment as usual and four studies compared a multiple session early psychological intervention with active control condition.\nLow-certainty evidence indicated that multiple session early psychological interventions may be more effective than usual care in reducing PTSD diagnosis at three to six months' follow-up (RR 0.62, 95% CI 0.41 to 0.93; I2 = 34%; studies = 5; participants = 758). However, there was no statistically significant difference post-treatment (RR 1.06, 95% CI 0.85 to 1.32; I2 = 0%; studies = 5; participants = 556; very low-certainty evidence) or at seven to 12 months (RR 0.94, 95% CI 0.20 to 4.49; studies = 1; participants = 132; very low-certainty evidence). Meta-analysis indicated that there was no statistical difference in dropouts compared with usual care (RR 1.34, 95% CI 0.91 to 1.95; I2 = 34%; studies = 11; participants = 1154; low-certainty evidence) .At the primary endpoint of three to six months, low-certainty evidence indicated no statistical difference between groups in reducing severity of PTSD (SMD –0.10, 95% CI –0.22 to 0.02; I2 = 34%; studies = 15; participants = 1921), depression (SMD –0.04, 95% CI –0.19 to 0.10; I2 = 6%; studies = 7; participants = 1009) or anxiety symptoms (SMD –0.05, 95% CI –0.19 to 0.10; I2 = 2%; studies = 6; participants = 945).\nNo studies comparing an intervention and active control reported outcomes for PTSD diagnosis. Low-certainty evidence showed that interventions may be associated with a higher dropout rate than active control condition (RR 1.61, 95% CI 1.11 to 2.34; studies = 2; participants = 425). At three to six months, low-certainty evidence indicated no statistical difference between interventions in terms of severity of PTSD symptoms (SMD –0.02, 95% CI –0.31 to 0.26; I2 = 43%; studies = 4; participants = 465), depression (SMD 0.04, 95% CI –0.16 to 0.23; I2 = 0%; studies = 2; participants = 409), anxiety (SMD 0.00, 95% CI –0.19 to 0.19; I2 = 0%; studies = 2; participants = 414) or quality of life (MD –0.03, 95% CI –0.06 to 0.00; studies = 1; participants = 239).\nNone of the included studies reported on adverse events or use of health-related resources.\nAuthors' conclusions\nWhile the review found some beneficial effects of multiple session early psychological interventions in the prevention of PTSD, the certainty of the evidence was low due to the high risk of bias in the included trials. The clear practice implication of this is that, at present, multiple session interventions aimed at everyone exposed to traumatic events cannot be recommended. There are a number of ongoing studies, demonstrating that this is a fast moving field of research. Future updates of this review will integrate the results of these new studies.\n\nGiven the provided abstract, please respond to the following query: \"What should happen next?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The current evidence base is small. However, new studies are being conducted and future updates of this review will incorporate the results of these." } ]

[ { "role": "user", "content": "Abstract: Background\nOral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. It was previously found that 5-ASA drugs in doses of at least 2 g/day were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis (UC). This review is an update of a previously published Cochrane Review.\nObjectives\nTo assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators (i.e. other formulations of 5-ASA) for induction of remission in active UC. A secondary objective was to compare the efficacy and safety of once-daily dosing of oral 5-ASA versus conventional dosing regimens (two or three times daily).\nSearch methods\nWe searched MEDLINE, Embase and the Cochrane Library on 11 June 2019. We also searched references, conference proceedings and study registers to identify additional studies.\nSelection criteria\nWe considered randomized controlled trials (RCTs) including adults (aged 18 years or more) with active UC for inclusion. We included studies that compared oral 5-ASA therapy with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily to conventional dosing as well as dose-ranging studies.\nData collection and analysis\nOutcomes include failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events (AEs), serious adverse events (SAEs), withdrawals due to AEs, and withdrawals or exclusions after entry. We analyzed five comparisons: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once-daily dosing versus conventional dosing, 5-ASA (e.g. MMX mesalamine, Ipocol, Balsalazide, Pentasa, Olsalazine and 5-ASA micropellets) versus comparator 5-ASA (e.g. Asacol, Claversal, Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (95% CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence.\nMain results\nWe include 54 studies (9612 participants). We rated most studies at low risk of bias.\nSeventy-one per cent (1107/1550) of 5-ASA participants failed to enter clinical remission compared to 83% (695/837) of placebo participants (RR 0.86, 95% CI 0.82 to 0.89; 2387 participants, 11 studies; high-certainty evidence). We also observed a dose-response trend for 5-ASA. There was no difference in clinical remission rates between 5-ASA and SASP. Fifty-four per cent (150/279) of 5-ASA participants failed to enter remission compared to 58% (144/247) of SASP participants (RR 0.90, 95% CI 0.77 to 1.04; 526 participants, 8 studies; moderate-certainty evidence).\nThere was no difference in remission rates between once-daily dosing and conventional dosing. Sixty per cent (533/881) of once-daily participants failed to enter clinical remission compared to 61% (538/880) of conventionally-dosed participants (RR 0.99, 95% CI 0.93 to 1.06; 1761 participants, 5 studies; high-certainty evidence). Eight per cent (15/179) of participants dosed once daily failed to adhere to their medication regimen compared to 6% (11/179) of conventionally-dosed participants (RR 1.36, 95% CI 0.64 to 2.86; 358 participants, 2 studies; low-certainty evidence).\nThere does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent (507/1022) of participants in the 5-ASA group failed to enter remission compared to 52% (491/946) of participants in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02; 1968 participants, 11 studies; moderate-certainty evidence).\nThere was no evidence of a difference in the incidence of adverse events and serious adverse events between 5-ASA and placebo, once-daily and conventionally-dosed 5-ASA, and 5-ASA and comparator 5-ASA formulation studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening UC. SASP was not as well tolerated as 5-ASA. Twenty-nine per cent (118/411) of SASP participants experienced an AE compared to 15% (72/498) of 5-ASA participants (RR 0.48, 95% CI 0.36 to 0.63; 909 participants, 12 studies; moderate-certainty evidence).\nAuthors' conclusions\nThere is high-certainty evidence that 5-ASA is superior to placebo, and moderate-certainty evidence that 5-ASA is not more effective than SASP. Considering relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. High-certainty evidence suggests 5-ASA dosed once daily appears to be as efficacious as conventionally-dosed 5-ASA. There may be little or no difference in efficacy or safety among the various 5-ASA formulations.\n\nGiven the provided abstract, please respond to the following query: \"What did the researchers investigate?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The researchers examined whether oral 5-ASA helps to cause remission in people with UC. The researchers investigated whether oral 5-ASA was better than placebo (a fake medication) or a different 5-ASA formulation." } ]

[ { "role": "user", "content": "Abstract: Background\nHigh intracranial pressure (ICP) is the most frequent cause of death and disability after severe traumatic brain injury (TBI). It is usually treated with general maneuvers (normothermia, sedation, etc.) and a set of first-line therapeutic measures (moderate hypocapnia, mannitol, etc.). When these measures fail, second-line therapies are initiated, which include: barbiturates, hyperventilation, moderate hypothermia, or removal of a variable amount of skull bone (secondary decompressive craniectomy).\nObjectives\nTo assess the effects of secondary decompressive craniectomy (DC) on outcomes of patients with severe TBI in whom conventional medical therapeutic measures have failed to control raised ICP.\nSearch methods\nThe most recent search was run on 8 December 2019. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP) and ISI Web of Science (SCI-EXPANDED & CPCI-S). We also searched trials registries and contacted experts.\nSelection criteria\nWe included randomized studies assessing patients over the age of 12 months with severe TBI who either underwent DC to control ICP refractory to conventional medical treatments or received standard care.\nData collection and analysis\nWe selected potentially relevant studies from the search results, and obtained study reports. Two review authors independently extracted data from included studies and assessed risk of bias. We used a random-effects model for meta-analysis. We rated the quality of the evidence according to the GRADE approach.\nMain results\nWe included three trials (590 participants). One single-site trial included 27 children; another multicenter trial (three countries) recruited 155 adults, the third trial was conducted in 24 countries, and recruited 408 adolescents and adults. Each study compared DC combined with standard care (this could include induced barbiturate coma or cooling of the brain, or both). All trials measured outcomes up to six months after injury; one also measured outcomes at 12 and 24 months (the latter data remain unpublished). All trials were at a high risk of bias for the criterion of performance bias, as neither participants nor personnel could be blinded to these interventions. The pediatric trial was at a high risk of selection bias and stopped early; another trial was at risk of bias because of atypical inclusion criteria and a change to the primary outcome after it had started.\nMortality: pooled results for three studies provided moderate quality evidence that risk of death at six months was slightly reduced with DC (RR 0.66, 95% CI 0.43 to 1.01; 3 studies, 571 participants; I2 = 38%; moderate-quality evidence), and one study also showed a clear reduction in risk of death at 12 months (RR 0.59, 95% CI 0.45 to 0.76; 1 study, 373 participants; high-quality evidence).\nNeurological outcome: conscious of controversy around the traditional dichotomization of the Glasgow Outcome Scale (GOS) scale, we chose to present results in three ways, in order to contextualize factors relevant to clinical/patient decision-making.\nFirst, we present results of death in combination with vegetative status, versus other outcomes. Two studies reported results at six months for 544 participants. One employed a lower ICP threshold than the other studies, and showed an increase in the risk of death/vegetative state for the DC group. The other study used a more conventional ICP threshold, and results favoured the DC group (15.7% absolute risk reduction (ARR) (95% CI 6% to 25%). The number needed to treat for one beneficial outcome (NNTB) (i.e. to avoid death or vegetative status) was seven. The pooled result for DC compared with standard care showed no clear benefit for either group (RR 0.99, 95% CI 0.46 to 2.13; 2 studies, 544 participants; I2 = 86%; low-quality evidence). One study reported data for this outcome at 12 months, when the risk for death or vegetative state was clearly reduced by DC compared with medical treatment (RR 0.68, 95% CI 0.54 to 0.86; 1 study, 373 participants; high-quality evidence).\nSecond, we assessed the risk of an 'unfavorable outcome' evaluated on a non-traditional dichotomized GOS-Extended scale (GOS-E), that is, grouping the category 'upper severe disability' into the 'good outcome' grouping. Data were available for two studies (n = 571). Pooling indicated little difference between DC and standard care regarding the risk of an unfavorable outcome at six months following injury (RR 1.06, 95% CI 0.69 to 1.63; 544 participants); heterogeneity was high, with an I2 value of 82%. One trial reported data at 12 months and indicated a clear benefit of DC (RR 0.81, 95% CI 0.69 to 0.95; 373 participants).\nThird, we assessed the risk of an 'unfavorable outcome' using the (traditional) dichotomized GOS/GOS-E cutoff into 'favorable' versus 'unfavorable' results. There was little difference between DC and standard care at six months (RR 1.00, 95% CI 0.71 to 1.40; 3 studies, 571 participants; low-quality evidence), and heterogeneity was high (I2 = 78%). At 12 months one trial suggested a similar finding (RR 0.95, 95% CI 0.83 to 1.09; 1 study, 373 participants; high-quality evidence).\nWith regard to ICP reduction, pooled results for two studies provided moderate quality evidence that DC was superior to standard care for reducing ICP within 48 hours (MD −4.66 mmHg, 95% CI −6.86 to −2.45; 2 studies, 182 participants; I2 = 0%). Data from the third study were consistent with these, but could not be pooled.\nData on adverse events are difficult to interpret, as mortality and complications are high, and it can be difficult to distinguish between treatment-related adverse events and the natural evolution of the condition. In general, there was low-quality evidence that surgical patients experienced a higher risk of adverse events.\nAuthors' conclusions\nDecompressive craniectomy holds promise of reduced mortality, but the effects of long-term neurological outcome remain controversial, and involve an examination of the priorities of participants and their families. Future research should focus on identifying clinical and neuroimaging characteristics to identify those patients who would survive with an acceptable quality of life; the best timing for DC; the most appropriate surgical techniques; and whether some synergistic treatments used with DC might improve patient outcomes.\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": "The skull is a rigid bone 'box' that protects the brain. Consequently, if an injury causes the brain to swell, this leads to an increase in pressure within the skull. This excess pressure is known as high intracranial pressure (ICP), and is a frequent cause of death and disability in brain-injured people. If ICP cannot be controlled using standard medical measures, then DC may be tried. DC is the surgical removal of a portion of the skull to relieve pressure on the brain. Clinicians are uncertain how effective it is, and do not agree on its role in treatment of TBI." } ]

[ { "role": "user", "content": "Abstract: Background\nIrritable bowel syndrome (IBS) is a prevalent condition that currently lacks highly effective therapies for its management. Biofeedback has been proposed as a therapy that may help individuals learn to exert conscious control over sympatho-vagal balance as an indirect method of symptom management.\nObjectives\nOur primary objective was to assess the efficacy and safety of biofeedback-based interventions for IBS in adults and children.\nSearch methods\nWe searched the Cochrane Inflammatory Bowel Disease (IBD) Group Specialized Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Allied and Complementary Medicine Database (AMED) from inception to 24 July 2019. We also searched reference lists from published trials, trial registries, device manufacturers, conference proceedings, theses, and dissertations.\nSelection criteria\nWe judged randomized controlled trials to be eligible for inclusion if they met the Association for Applied Psychophysiology and Biofeedback definition of biofeedback, and if they compared a biofeedback intervention to an active, sham, or no-treatment control for the management of IBS.\nData collection and analysis\nTwo authors independently screened trials for inclusion, extracted data, and assessed risk of bias. Primary outcomes were IBS global or clinical improvement scores and overall quality of life measures. Secondary outcome measures were adverse events, assessments of stool frequency and consistency, changes in abdominal pain, depression, and anxiety. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and 95% CI. We used GRADE criteria to assess the overall certainty of the evidence.\nMain results\nWe identified eight randomized trials with a total of 300 adult participants for our analysis. We did not identify any trials in children. Four trials assessed thermal biofeedback. One trial assessed rectosigmoidal biofeedback. Two trials assessed heart rate variability biofeedback. Two trials assessed electrocutaneous biofeedback. Comparators were: no treatment (symptom monitoring group; three studies), attention control (pseudomeditation; two studies), relaxation control (one study), counseling (two studies), hypnotherapy (one study), standard therapy (one study), and sham biofeedback (one study). We judged all trials to have a high or unclear risk of bias.\nGlobal/Clinical improvement\nThe clinical benefit of biofeedback plus standard therapy compared to standard therapy alone was uncertain (RR 4.20, 95% CI 1.40 to 12.58; 1 study, 20 participants; very low-certainty evidence). The same study also compared biofeedback plus standard therapy to sham biofeedback plus standard therapy. The clinical benefit in the biofeedback group was uncertain (RR 2.33, 95% CI 1.13 to 4.80; 1 study, 20 participants; very low-certainty evidence).\nThe clinical benefit of heart rate biofeedback compared to hypnotherapy was uncertain when measured with the IBS severity scoring system (IBS-SSS) (MD -58.80, 95% CI -109.11 to -8.49; 1 study, 61 participants; low-certainty evidence). Compared to counseling, the effect of heart rate biofeedback was unclear when measured with a composite symptom reduction score (MD 7.03, 95% CI -51.07 to 65.13; 1 study, 29 participants; low-certainty evidence) and when evaluated for clinical response (50% improvement) (RR 1.09, 95% CI 0.48 to 2.45; 1 study, 29 participants; low-certainty evidence).\nThe clinical benefit of thermal biofeedback used in a multi-component psychological intervention (MCPI) compared to no treatment was uncertain when measured with a composite clinical symptom reduction score (MD 30.34, 95% CI 8.47 to 52.21; 3 studies, 101 participants; very low-certainty evidence), and when evaluated as clinical response (50% improvement) (RR 2.12, 95% CI 1.24 to 3.62; 3 studies, 101 participants; very low-certainty evidence). Compared to attention control, the effects of thermal biofeedback within an MCPI were unclear when measured with a composite clinical symptom reduction score (MD 4.02, 95% CI -21.41 to 29.45; 2 studies, 80 participants; very low-certainty evidence) and when evaluated as clinical response (50% improvement) (RR 1.10, 95% CI 0.72 to 1.69, 2 studies, 80 participants; very low-certainty evidence).\nQuality of life\nA single trial used overall quality of life as an outcome measure, and reported that both the biofeedback and cognitive therapy groups improved after treatment. The trial did not note any between-group differences, and did not report any outcome data.\nAdverse events\nOnly one of the eight trials explicitly reported adverse events. This study reported no adverse events in either the biofeedback or cognitive therapy groups (RD 0.00, 95% CI -0.12 to 0.12; 29 participants; low-certainty evidence).\nAuthors' conclusions\nThere is currently not enough evidence to assess whether biofeedback interventions are effective for controlling symptoms of IBS. Given the positive results reported in small trials to date, biofeedback deserves further study in people with IBS. Future research should include active control groups that use high provider-participant interaction, in an attempt to balance non-specific effects of interventions between groups, and report both commonly used outcome measures (e.g. IBS-SSS) and historical outcome measures (e.g. the composite primary symptom reduction (CPSR) score) to allow for meta-analysis with previous studies. Future studies should be explicit in their reporting of adverse events.\n\nGiven the provided abstract, please respond to the following query: \"Study Characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for studies that compared biofeedback to either no treatment, sham treatment, or to other active treatments for IBS. We reviewed eight trials that included 300 total participants and assessed the effect of biofeedback on IBS. Each of these studies only included adults, and was carried out in an outpatient setting. The studies ranged from eight weeks to six months in length. The types of biofeedback devices varied, and included heart rate variability, measures of skin temperature or electrical resistance, and the tension of the muscles of the anus." } ]