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[ { "role": "user", "content": "Abstract: Background\nInfantile seborrhoeic dermatitis (ISD) is a chronic, inflammatory, scaling skin condition, which causes redness and a greasy scaling rash in infants and young children. It can last from weeks to months, but rarely years. When it occurs on the scalp, it is referred to as 'cradle cap'. While benign and self-limiting, irrelevant of its location on the body, it can distress parents. The effectiveness of commonly promoted treatments is unclear.\nObjectives\nTo assess the effects of interventions for infantile seborrhoeic dermatitis in children from birth to 24 months of age.\nSearch methods\nWe searched the following databases up to 22 May 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched trials registers and checked reference lists of included studies for further references to randomised controlled trials (RCTs). We searched for unpublished RCTs and grey literature via web search engines, and wrote to authors and pharmaceutical companies.\nSelection criteria\nWe included RCTs of interventions for ISD in children from birth up to 24 months who were clinically diagnosed by a healthcare practitioner with ISD or cradle cap. We allowed comparison of any treatment to no treatment or placebo, and the comparison of two or more treatments or a combination of treatments.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Change in severity score from baseline to end of study' and 'Percentage of infants treated who develop adverse effects or intolerance to treatment'. The secondary outcome was 'Improvement in quality of life (QoL) as reported by parents'.\nMain results\nWe included six RCTs (one with a cross-over design) randomising 310 children and reporting outcomes for 297 children. Most participants were aged under seven months with only two participants aged over one year (seven and 12 years old); where specified, 60% were boys. In two studies, condition severity was mild to moderate; one study included two participants with severe ISD; the other studies did not describe baseline severity or described it as body surface area affected.\nThe study setting was not always clear but likely a paediatric outpatient clinic in the following countries: Thailand, Israel, USA, France, and Australia.\nTwo studies compared oral biotin (a B group vitamin) against placebo, two studies compared proprietary products against placebo cream or a control shampoo, and two studies compared topical corticosteroids against other products. The studies were generally short-term, between 10 and 42 days' duration; only one study followed the participants until resolution of the rash or eight months of age.\nWe assessed the risk of bias as unclear for most aspects due to lack of reporting, but two of the studies were at high risk of performance and detection bias due to the appearance of the intervention, the trial design (open-label), or use of overlabelled tubes. Two trials had a high risk of attrition bias.\nAll the results given below were based on very low-quality evidence. Treatment duration ranged from one week to three weeks.\nFor the two trials comparing biotin versus placebo (n = 35), one did not report a measure of change in severity (only change in duration of rash) while the other did not report raw data (only 'no statistically significant difference'), measured at three weeks. Neither trial reported on adverse events.\nTwo trials compared proprietary products against placebo (n = 160). One trial assessed change in severity via percentage success (96% of participants in non-steroidal cream Promiseb versus 92% in placebo), and reported no adverse events (both assessed at day 14). The other trial assessed change in severity via reduction in lesional score (surface area covered), finding better results for lactamide MEA gel (a moisturising agent) plus shampoo (81.4%) compared with shampoo only (70.2%; P = 0.0092). No adverse events were described, but signs of discomfort were similar in both groups (both assessed at day 21).\nIn the comparison of topical steroids versus another product, change in severity was measured through evaluation of cure and body surface (n = 102).\nIn one trial comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion, there was no significant difference in participants cured (95.8% with hydrocortisone compared to 97.1% with licochalcone). One person in the licochalcone group developed more erythema, but there were no other adverse events (both outcomes assessed at day 14). In the trial comparing flumethasone pivalate 0.02% ointment versus eosin 2% aqueous solution, a reduction in body surface area affected was seen in both groups at day 10 (9% with corticosteroid versus 7% with aqueous solution), with all infants showing less than 10% involvement. There were no adverse events (both outcomes assessed at day 10).\nNo studies measured QoL.\nWe found no trials testing commonly used treatments such as mineral oils, salicylic acid, or antifungals.\nAuthors' conclusions\nOur review identified only a limited number of studies investigating the effects of interventions for ISD in infants and young children. Unlike the reviews investigating the effects of treatments in adults, our results showed that there is uncertainty regarding the effectiveness and safety of studied treatments due to the very low-certainty evidence for all comparisons and outcomes.\nWe assessed most bias domains as at unclear risk, but there was a high risk of bias for (mainly) performance, attrition, and detection bias. Evidence was limited further by imprecision (small studies, low number of events), indirectness (mainly with the outcomes assessed), and poor trial reporting. In most studies, the prognosis for the condition was favourable regardless of intervention but interpretation is limited by the very low-certainty evidence.\nFurther research is needed with large, well-conducted, and well-reported intervention trials, particularly of interventions commonly recommended or used, such as emollients or shampoos and brushing, antifungals, or steroids. All studies should report standardised and validated relevant outcome measures, including adverse events, severity, and QoL, and they should be conducted in primary care settings where the majority of ISD is managed. Future trials should compare against placebo, no treatment, or standard care.\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": "How effective (in terms of cure and improving quality of life) and safe are treatments for infantile seborrhoeic dermatitis (ISD) in children from birth up to 24 months of age, when compared with each other, no treatment, or placebo (an identical in appearance but inactive treatment)?" } ]

[ { "role": "user", "content": "Abstract: Background\nAlthough lifestyle interventions are commonly recommended in the management of patients with chronic gout, the evidence from trial data for their benefits and safety has not been previously examined in a systematic review.\nObjectives\nThe objective of this systematic review was to evaluate the benefits and safety of lifestyle interventions for the treatment of people with chronic gout.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for studies on 5 April 2013. We also searched the 2010 to 2011 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of included articles.\nSelection criteria\nStudies were included if they were randomised or quasi-randomised controlled trials (RCTs or CCTs) which compared lifestyle interventions to another therapy (active or placebo) in patients with chronic gout. Outcomes of interest were changes in gout attack frequency, joint pain, serum urate levels, tophus size, function, quality of life and adverse effects.\nData collection and analysis\nTwo review authors independently applied methods recommended by The Cochrane Collaboration for the selection, appraisal, data collection and synthesis of studies. We assessed the quality of the body of evidence for each outcome using the GRADE approach.\nMain results\nOnly one study (120 participants), at moderate risk of bias, was included in the review. Patients were randomised to one of three interventions: either skim milk powder (SMP) enriched with glycomacropeptide (GMP) and G600, non-enriched SMP or lactose powder, over a three-month period. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the three-month study period. Low quality evidence indicated that there was no difference between the SMP/GMP/G600 group and combined control groups (SMP and lactose powder) at three months (mean difference (MD) -0.21, 95% confidence interval (CI) -0.76 to 0.34). There were no significant between-group differences in terms of withdrawals due to adverse effects (risk ratio (RR) 1.27, 95% CI 0.53 to 3.03), and serious adverse events resulting in hospitalisation (2/40 SMP/GMP/G600 group versus 3/80 controls; RR 1.33, 95% CI 0.23 to 7.66). Gastrointestinal adverse effects were the most commonly reported. Pain from self reported gout flares, measured on a 10-point Likert scale, improved more in the SMP/GMP/G600 group compared to controls (MD -1.03, 95% CI -1.96 to -0.10), an absolute difference of 10% (absolute risk difference -0.10, 95% CI -0.20 to -0.01). This is unlikely to be of clinical significance. There was no significant difference in physical function between SMP/GMP/G600 and the control groups at three-month followup (MD -0.03, 95% CI -0.14 to 0.08). Tophus regression and serum urate normalisation were not reported in this study.\nAuthors' conclusions\nWhile there is good evidence from observational studies of an association between various lifestyle risk factors and gout development, there is a paucity of high-quality evidence from randomised controlled trials to either support or refute the use of lifestyle modifications for improving outcomes in people with chronic gout.\n\nGiven the provided abstract, please respond to the following query: \"Best estimate of what happens to people with gout who consume enriched skim milk powder\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Gout attacks\nPeople who consumed enriched skim milk powder had 0.21 fewer gout attacks per month at 3 months (or 2.5 fewer gout attacks per year) .\n- People who consumed enriched skim milk powder had 0.49 gout attacks per month (or 6 gout attacks per year).\n- People who consumed standard skim milk powder or lactose had 0.70 gout attacks per month (or 8 gout attacks per year).\nWithdrawals due to adverse events\n4 more people out of 100 who consumed enriched skim milk powder discontinued the supplement at 3 months (4% more withdrawals absolute change, from 10% fewer to 18% more).\n- 18 out of 100 stopped consuming enriched skim milk powder.\n- 14 out of 100 stopped consuming standard skim milk powder or lactose.\nPain (lower score means less pain)\nPeople who consumed enriched skim milk powder rated their pain 1 point lower on a 0 to 10 point pain scale (10% absolute improvement; 20% to 1% improvement) at 3 months.\n- People who consumed enriched skim milk powder rated their pain to be 0.67 points on a scale of 0 to 10.\n- People who consumed standard skim milk powder or lactose rated their pain to be 1.7 points on a scale of 0 to 10.\nPhysical function (lower score means better function)\nPeople who consumed enriched skim milk powder rated their function 0.03 better (0.14 better to 0.08 worse) on a 0 to 3 point scale (1% absolute improvement; 5% improvement to 3% worse) at 3 months.\n- People who consumed enriched skim milk powder rated their function to be 0.08 points on a scale of 0 to 3.\n- People who consumed standard skim milk powder or lactose rated their function to be 0.11 points on a scale of 0 to 3.\nSerious adverse events\n1 more person out of 100 who consumed enriched skim milk powder reported a serious adverse event.\n- 5 out of 100 who consumed enriched skim milk powder had a serious adverse event.\n- 4 out of 100 who consumed standard skim milk powder or lactose had a serious adverse event." } ]

[ { "role": "user", "content": "Abstract: Background\nProgressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. This is an update of a previously published review.\nObjectives\nTo assess the effectiveness of treatment with oral non-steroidal anti-inflammatory drugs in cystic fibrosis.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs and searched online trials registries.\nLatest search of the Group's Trials Register: 21 November 2018.\nSelection criteria\nRandomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis.\nData collection and analysis\nTwo authors independently assessed trials for inclusion the review and their potential risk of bias. Two authors independently rated the quality of the evidence for each outcome using the GRADE guidelines.\nMain results\nThe searches identified 17 trials; four are included (287 participants aged five to 39 years; maximum follow-up of four years) and one is currently awaiting classification pending publication of the full trial report and two are ongoing. Three trials compared ibuprofen to placebo (two from the same center with some of the same participants); one trial assessed piroxicam versus placebo.\nThe three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1), mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42) (moderate-quality evidence); forced vital capacity (FVC), MD 1.27 (95% CI 0.26 to 2.28) (moderate-quality evidence); forced expiratory flow (FEF25%-75%), MD 1.80 (95% CI 0.15 to 3.45). The post hoc analysis of data from two trials split by age showed a slower rate of annual decline of FEV1 % predicted and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) (moderate-quality evidence) and MD 1.32% (95% CI 0.04 to 2.60) (moderate-quality evidence) respectively. Data from four trials demonstrated the proportion of participants with at least one hospitalization may be slightly lower in the ibuprofen group compared to placebo, Peto odds ratio 0.61 (95% CI 0.37 to 1.01) (moderate-quality evidence). In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.\nWe did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyze in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analyzable data were available for any other review outcome.\nAuthors' conclusions\nHigh-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.\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": "Inflammation in the lungs increases the damage done to them and is the most common reason for early death in people with cystic fibrosis. In high doses, non-steroidal anti-inflammatory drugs, particularly ibuprofen, may work against inflammation, but in low doses there is some evidence that they may cause the inflammation. The use of high doses has also raised concerns about the potential for unwanted effects, which has limited the use of these drugs in cystic fibrosis." } ]

[ { "role": "user", "content": "Abstract: Background\nStroke is one of the leading causes of disability worldwide. Functional impairment, resulting in poor performance in activities of daily living (ADL) among stroke survivors is common. Current rehabilitation approaches have limited effectiveness in improving ADL performance, function, muscle strength, and cognitive abilities (including spatial neglect) after stroke, with improving cognition being the number one research priority in this field. A possible adjunct to stroke rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve these outcomes in people after stroke.\nObjectives\nTo assess the effects of tDCS on ADL, arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase and seven other databases in January 2019. In an effort to identify further published, unpublished, and ongoing trials, we also searched trials registers and reference lists, handsearched conference proceedings, and contacted authors and equipment manufacturers.\nSelection criteria\nThis is the update of an existing review. In the previous version of this review, we focused on the effects of tDCS on ADL and function. In this update, we broadened our inclusion criteria to compare any kind of active tDCS for improving ADL, function, muscle strength and cognitive abilities (including spatial neglect) versus any kind of placebo or control intervention.\nData collection and analysis\nTwo review authors independently assessed trial quality and risk of bias, extracted data, and applied GRADE criteria. If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports.\nMain results\nWe included 67 studies involving a total of 1729 patients after stroke. We also identified 116 ongoing studies. The risk of bias did not differ substantially for different comparisons and outcomes. The majority of participants had ischaemic stroke, with mean age between 43 and 75 years, in the acute, postacute, and chronic phase after stroke, and level of impairment ranged from severe to less severe. Included studies differed in terms of type, location and duration of stimulation, amount of current delivered, electrode size and positioning, as well as type and location of stroke.\nWe found 23 studies with 781 participants examining the effects of tDCS versus sham tDCS (or any other passive intervention) on our primary outcome measure, ADL after stroke. Nineteen studies with 686 participants reported absolute values and showed evidence of effect regarding ADL performance at the end of the intervention period (standardised mean difference (SMD) 0.28, 95% confidence interval (CI) 0.13 to 0.44; random-effects model; moderate-quality evidence). Four studies with 95 participants reported change scores, and showed an effect (SMD 0.48, 95% CI 0.02 to 0.95; moderate-quality evidence). Six studies with 269 participants assessed the effects of tDCS on ADL at the end of follow-up and provided absolute values, and found improved ADL (SMD 0.31, 95% CI 0.01 to 0.62; moderate-quality evidence). One study with 16 participants provided change scores and found no effect (SMD -0.64, 95% CI -1.66 to 0.37; low-quality evidence). However, the results did not persist in a sensitivity analysis that included only trials with proper allocation concealment.\nThirty-four trials with a total of 985 participants measured upper extremity function at the end of the intervention period. Twenty-four studies with 792 participants that presented absolute values found no effect in favour of tDCS (SMD 0.17, 95% CI -0.05 to 0.38; moderate-quality evidence). Ten studies with 193 participants that presented change values also found no effect (SMD 0.33, 95% CI -0.12 to 0.79; low-quality evidence). Regarding the effects of tDCS on upper extremity function at the end of follow-up, we identified five studies with a total of 211 participants (absolute values) without an effect (SMD -0.00, 95% CI -0.39 to 0.39; moderate-quality evidence). Three studies with 72 participants presenting change scores found an effect (SMD 1.07; 95% CI 0.04 to 2.11; low-quality evidence). Twelve studies with 258 participants reported outcome data for lower extremity function and 18 studies with 553 participants reported outcome data on muscle strength at the end of the intervention period, but there was no effect (high-quality evidence). Three studies with 156 participants reported outcome data on muscle strength at follow-up, but there was no evidence of an effect (moderate-quality evidence). Two studies with 56 participants found no evidence of effect of tDCS on cognitive abilities (low-quality evidence), but one study with 30 participants found evidence of effect of tDCS for improving spatial neglect (very low-quality evidence). In 47 studies with 1330 participants, the proportions of dropouts and adverse events were comparable between groups (risk ratio (RR) 1.25, 95% CI 0.74 to 2.13; random-effects model; moderate-quality evidence).\nAuthors' conclusions\nThere is evidence of very low to moderate quality on the effectiveness of tDCS versus control (sham intervention or any other intervention) for improving ADL outcomes after stroke. However, the results did not persist in a sensitivity analyses including only trials with proper allocation concealment. Evidence of low to high quality suggests that there is no effect of tDCS on arm function and leg function, muscle strength, and cognitive abilities in people after stroke. Evidence of very low quality suggests that there is an effect on hemispatial neglect. There was moderate-quality evidence that adverse events and numbers of people discontinuing the treatment are not increased. Future studies should particularly engage with patients who may benefit the most from tDCS after stroke, but also should investigate the effects in routine application. Therefore, further large-scale randomised controlled trials with a parallel-group design and sample size estimation for tDCS are needed.\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 tDCS for improving ADL ranged from very low to high. It was low to moderate for upper extremity function, and moderate for adverse events and people discontinuing the treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nChildren who undergo surgical procedures in ambulatory and inpatient settings are at risk of experiencing acute pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce moderate to severe pain without many of the side effects associated with opioids. However, NSAIDs may cause bleeding, renal and gastrointestinal toxicity, and potentially delay wound and bone healing. Intravenous administration of ketorolac for postoperative pain in children has not been approved in many countries, but is routinely administered in clinical practise.\nObjectives\nTo assess the efficacy and safety of ketorolac for postoperative pain in children.\nSearch methods\nWe searched the following databases, without language restrictions, to November 2017: CENTRAL (The Cochrane Library 2017, Issue 10); MEDLINE, Embase, and LILACS. We also checked clinical trials registers and reference lists of reviews, and retrieved articles for additional studies.\nSelection criteria\nWe included randomised controlled trials that compared the analgesic efficacy of ketorolac (in any dose, administered via any route) with placebo or another active treatment, in treating postoperative pain in participants zero to 18 years of age following any type of surgery.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We analyzed trials in two groups; ketorolac versus placebo, and ketorolac versus opioid. However, we performed limited pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE, and created a 'Summary of findings' table.\nMain results\nWe included 13 studies, involving 920 randomised participants. There was considerable heterogeneity among study designs, including the comparator arms (placebo, opioid, another NSAID, or a different regimen of ketorolac), dosing regimens (routes and timing of administration, single versus multiple dose), outcome assessment methods, and types of surgery. Mean study population ages ranged from 356 days to 13.9 years. The majority of studies chose a dose of either 0.5 mg/kg (as a single or multiple dose regimen) or 1 mg/kg (single dose with 0.5 mg/kg for any subsequent doses). One study administered interventions intraoperatively; the remainder administered interventions postoperatively, often after the participant reported moderate to severe pain.\nThere were insufficient data to perform meta-analysis for either of our primary outcomes: participants with at least 50% pain relief; or mean postoperative pain intensity. Four studies individually reported statistically significant reductions in pain intensity when comparing ketorolac with placebo, but the studies were small and had various risks of bias, primarily due to incomplete outcome data and small sample sizes.\nWe found limited data available for the secondary outcomes of participants requiring rescue medication and opioid consumption. For the former, we saw no clear difference between ketorolac and placebo; 74 of 135 (55%) participants receiving ketorolac required rescue analgesia in the post-anaesthesia care unit (PACU) versus 81 of 127 (64%) receiving placebo (relative risk (RR) 0.85, 95% confidence interval (CI) 0.71 to 1.00, P = 0.05; 4 studies, 262 participants). For opioid consumption in the PACU, we saw no clear difference between ketorolac and placebo (P = 0.61). For the time period zero to four hours after administration of the interventions, participants receiving ketorolac received 1.58 mg less intravenous morphine equivalents than those receiving placebo (95% CI -2.58 mg to -0.57 mg, P = 0.002; 2 studies, 129 participants). However, we are uncertain whether ketorolac has an important effect on opioid consumption, as the data were sparse and the results were inconsistent. Only one study reported data for opioid consumption when comparing ketorolac with an opioid. There were no clear differences between the ketorolac and opioid group at any time point. There were no data assessing this outcome for the comparison of ketorolac with another NSAID.\nThere were insufficient data to allow us to analyze overall adverse event or serious adverse event rates. Although the majority of serious adverse events reported in those receiving ketorolac involved bleeding, the number of events was too low to conclude that bleeding risk was increased in those receiving ketorolac perioperatively. There was not a statistically significant increase in event rates for any specific adverse event, either in pooled analysis or in single studies, when comparing ketorolac and placebo. When comparing ketorolac with opioids or other NSAIDs, there were too few data to make any conclusions regarding event rates. Lastly, withdrawals due to adverse events were vary rare in all groups, reflecting the acute nature of such studies.\nWe assessed the quality of evidence for all outcomes for each comparison (placebo or active) as very low, due to issues with risk of bias in individual studies, imprecision, heterogeneity between studies, and low overall numbers of participants and events.\nAuthors' conclusions\nDue to the lack of data for our primary outcomes, and the very low-quality evidence for secondary outcomes, the efficacy and safety of ketorolac in treating postoperative pain in children were both uncertain. The evidence was insufficient to support or reject its use.\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": "We rated the quality of the evidence as very low, due to methodological issues with many of the studies, differences in study designs, and low overall numbers of children enrolled. Very low-quality evidence means that we are very uncertain about the results." } ]

[ { "role": "user", "content": "Abstract: Background\nEstablishing the subgroup analysis of the fallopian tubes (tubes) is a commonly undertaken diagnostic investigation for women with subfertility. This is usually achieved by flushing contrast medium through the tubes and visualising patency on radiographs, ultrasonography or laparoscopy. Many women were noted to conceive in the first three to six months after tubal flushing, raising the possibility that tubal flushing could also be a treatment for infertility. There has been debate about which contrast medium should be used (water-soluble or oil-soluble media) as this may influence pregnancy rates. An important adverse event during tubal flushing is intravasation (backflow of contrast medium into the blood or lymphatic vessels),which could lead to embolism although it is asymptomatic in most cases.\nObjectives\nTo evaluate the effectiveness and safety of tubal flushing with oil-soluble contrast media (OSCM) and water-soluble contrast media (WSCM) on subsequent fertility outcomes in women with subfertility.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, MEDLINE, Embase, CENTRAL, PsycINFO, reference lists of identified articles and trial registries. The most recent search was conducted in April 2020.\nSelection criteria\nRandomised controlled trials (RCTs) comparing tubal flushing with OSCM, WSCM with each other or with no treatment, in women with subfertility.\nData collection and analysis\nTwo review authors independently selected the trials, assessed risk of bias and extracted data. We contacted study authors for additional information. The overall quality of the evidence was assessed using GRADE methods.\nMain results\nFifteen trials involving 3864 women were included in this systematic review. Overall, the quality of evidence varied from very low to moderate: the main limitations were risk of bias, heterogeneity and imprecision.\nOSCM versus no treatment\nFour studies (506 women) were included in this comparison.\nTubal flushing with OSCM may increase the odds of live birth (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.57 to 6.85, 3 RCTs, 204 women, I2 = 0, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 11%, the chance following tubal flushing with OSCM would be between 16% and 46%.\nTubal flushing with OSCM may increase in the odds of clinical pregnancy (OR 3.54, 95% CI 2.08 to 6.02, 4 RCTs, 506 women, I2 = 18%, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 9%, the chance following tubal flushing with OSCM would be between 17% and 37%.\nNo study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities.\nWSCM versus no treatment\nOnly one study (334 women) was included in this comparison.\nWe are uncertain whether tubal flushing with WSCM increase live birth compared to no treatment (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 21%, the chance following tubal flushing with WSCM would be between 15% and 33%.\nWe are uncertain whether tubal flushing with WSCM increases clinical pregnancy compared to no treatment (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 27%, the chance following tubal flushing with WSCM would be between 29% and 40%.\nOne case with pelvic infection was reported in the WSCM group and no case with infection in the no treatment group in a one study (334 women). Meta-analysis was not performed due to the rare events.\nNo study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities.\nOSCM versus WSCM\nSix studies (2598 women) were included in this comparison.\nThree studies reported live birth, including two with higher live birth in the OSCM group (OR 1.64, 95% CI 1.27 to 2.11, 1119 women; OR 3.45, 95% CI 1.97 to 6.03, 398 women); and one with insufficient evidence of a difference between groups (OR 0.92, 95% CI 0.60 to 1.40, 533 women). Given the substantial heterogeneity observed (I2 = 86%), meta-analysis was not performed.\nTubal flushing with OSCM probably increased in the odds of intravasation (asymptomatic) compared to tubal flushing with WSCM (OR 5.00, 95% CI 2.25 to 11.12, 4 RCTs, 1912 women, I2 = 0, moderate-quality evidence). This suggests that if the chance of intravasation following tubal flushing with WSCM is assumed to be 1%, the chance following tubal flushing with OSCM would be between 2% and 9%.\nTubal flushing with OSCM may increase the odds of clinical pregnancy (OR 1.42, 95% CI 1.10 to 1.85, 6 RCTs, 2598 women, I2 = 41%, low-quality evidence). This suggests that if the chance of clinical pregnancy following tubal flushing with WSCM is assumed to be 26%, the chance following tubal flushing with OSCM would be between 28% and 39%.\nWe are uncertain whether tubal flushing with OSCM decreases the odds of infection (OR 0.22, 95% CI 0.04 to 1.22, 2 RCTs, 662 women, I2 = 0, very low-quality evidence) or haemorrhage (OR 0.65, 95% CI 0.40 to 1.06, 2 RCTs, 662 women, I2 = 0, very low-quality evidence).\nThree neonates with congenital abnormalities were reported in the OSCM group while no congenital abnormality was reported in the WSCM group in one study (1119 women). No meta-analysis was performed due to the rare events.\nAuthors' conclusions\nThe evidence suggests that compared to no treatment, tubal flushing with OSCM may increase the chance of live birth and clinical pregnancy, while it is uncertain whether tubal flushing with WSCM improves those outcomes. Compared to tubal flushing with WSCM, OSCM may improve clinical pregnancy while meta-analysis was impossible for live birth due to heterogeneity. Evidence also suggests that OSCM is associated with an increased risk of asymptomatic intravasation. Overall, adverse events, especially long-term adverse events, are poorly reported across studies.\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 overall quality of the evidence was very low to moderate for all comparisons. The main limitations were imprecision, risk of bias and inconsistency. There were too few studies to evaluate the risk of publication bias." } ]

[ { "role": "user", "content": "Abstract: Background\nDespite multi-modal analgesic techniques, acute postoperative pain remains an unmet health need, with up to three quarters of people undergoing surgery reporting significant pain. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained-release analgesia.\nObjectives\nTo assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain.\nSearch methods\nOn 13 January 2016 we searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, ISI Web of Science and reference lists of retrieved articles. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials.\nSelection criteria\nRandomised, double-blind, placebo- or active-controlled clinical trials in people aged 18 years or over undergoing elective surgery, at any surgical site, were included if they compared liposomal bupivacaine infiltration at the surgical site with placebo or other type of analgesia.\nData collection and analysis\nTwo review authors independently considered trials for inclusion, assessed risk of bias, and extracted data. We performed data analysis using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5.3. We planned to perform a meta-analysis and produce a 'Summary of findings' table for each comparison however there were insufficient data to ensure a clinically meaningful answer. As such we have produced two 'Summary of findings' tables in a narrative format. Where possible we assessed the quality of evidence using GRADE.\nMain results\nWe identified nine studies (10 reports, 1377 participants) that met inclusion criteria. Four Phase II dose-escalating/de-escalating trials, designed to evaluate and demonstrate efficacy and safety, presented pooled data that we could not use. Of the remaining five parallel-arm studies (965 participants), two were placebo controlled and three used bupivacaine hydrochloride local anaesthetic infiltration as a control. Using the Cochrane tool, we judged most studies to be at unclear risk of bias overall; however, two studies were at high risk of selective reporting bias and four studies were at high risk of bias due to size (fewer than 50 participants per treatment arm).\nThree studies (551 participants) reported the primary outcome cumulative pain intensity over 72 hours following surgery. Compared to placebo, liposomal bupivacaine was associated with a lower cumulative pain score between the end of the operation (0 hours) and 72 hours (one study, very low quality). Compared to bupivacaine hydrochloride, two studies showed no difference for this outcome (very low quality evidence), however due to differences in the surgical population and surgical procedure (breast augmentation versus knee arthroplasty) we did not perform a meta-analysis.\nNo serious adverse events were reported to be associated with the use of liposomal bupivacaine and none of the five studies reported withdrawals due to drug-related adverse events (moderate quality evidence).\nOne study reported a lower mean pain score at 12 hours associated with liposomal bupivacaine compared to bupivacaine hydrochloride, but not at 24, 48 or 72 hours postoperatively (very low quality evidence).\nTwo studies (382 participants) reported a longer time to first postoperative opioid dose compared to placebo (low quality evidence).\nTwo studies (325 participants) reported the total postoperative opioid consumption over the first 72 hours: one study reported a lower cumulative opioid consumption for liposomal bupivacaine compared to placebo (very low quality evidence); one study reported no difference compared to bupivacaine hydrochloride (very low quality evidence).\nThree studies (492 participants) reported the percentage of participants not requiring postoperative opioids over initial 72 hours following surgery. One of the two studies comparing liposomal bupivacaine to placebo demonstrated a higher number of participants receiving liposomal bupivacaine did not require postoperative opioids (very low quality evidence). The other two studies, one versus placebo and one versus bupivacaine hydrochloride, found no difference in opioid requirement (very low quality evidence). Due to significant heterogeneity between the studies (I2 = 92%) we did not pool the results.\nAll the included studies reported adverse events within 30 days of surgery, with nausea, constipation and vomiting being the most common. Of the five parallel-arm studies, none performed or reported health economic assessments or patient-reported outcomes other than pain.\nUsing GRADE, the quality of evidence ranged from moderate to very low. The major limitation was the sparseness of data for outcomes of interest. In addition, a number of studies had a high risk of bias resulting in further downgrading.\nAuthors' conclusions\nLiposomal bupivacaine at the surgical site does appear to reduce postoperative pain compared to placebo, however, at present the limited evidence does not demonstrate superiority to bupivacaine hydrochloride. There were no reported drug-related serious adverse events and no study withdrawals due to drug-related adverse events. Overall due to the low quality and volume of evidence our confidence in the effect estimate is limited and the true effect may be substantially different from our estimate.\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": "Despite painkillers, three in four people report pain following surgery. One method to treat pain is for the surgeon to inject a painkiller at the site of surgery to block the nerves that send pain signals to the brain. A new drug called liposomal bupivacaine has been developed which has been designed to release the painkiller over a much longer time and provide prolonged pain relief. This review has been designed to look at how good liposomal bupivacaine injected at the site of surgery is at treating pain and also to look at whether there are any risks associated with its use." } ]

[ { "role": "user", "content": "Abstract: Background\nWomen between the ages of 15 and 24 years have high rates of unintended pregnancy; over half of women in this age group want to avoid pregnancy. However, women under age 25 years have higher typical contraceptive failure rates within the first 12 months of use than older women. High discontinuation rates may also be a problem in this population. Concern that adolescents and young women will not find hormonal or intrauterine contraceptives acceptable or effective might deter healthcare providers from recommending these contraceptive methods.\nObjectives\nTo compare the contraceptive failure (pregnancy) rates and to examine the continuation rates for hormonal and intrauterine contraception among young women aged 25 years and younger.\nSearch methods\nWe searched until 4 August 2015 for randomized controlled trials (RCTs) that compared hormonal or intrauterine methods of contraception in women aged 25 years and younger. Computerized databases included the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, CINAHL, and LILACS. We also searched for current trials via ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP).\nSelection criteria\nWe considered RCTs in any language that reported the contraceptive failure rates for hormonal or intrauterine contraceptive methods, when compared with another contraceptive method, for women aged 25 years and younger. The other contraceptive method could have been another intrauterine contraceptive, another hormonal contraceptive or different dose of the same method, or a non-hormonal contraceptive. Treatment duration must have been at least three months. Eligible trials had to include the primary outcome of contraceptive failure rate (pregnancy). The secondary outcome was contraceptive continuation rate.\nData collection and analysis\nOne author conducted the primary data extraction and entered the information into Review Manager. Another author performed an independent data extraction and verified the initial entry. For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). Because of disparate interventions and outcome measures, we did not conduct meta-analysis.\nMain results\nFive trials met the inclusion criteria. The studies included a total of 1503 women, with a mean of 301 participants. The trials compared the following contraceptives: combined oral contraceptive (COC) versus transdermal contraceptive patch, vaginal contraceptive ring, or levonorgestrel intrauterine system 20 µg/day (LNG-IUS 20); LNG-IUS 12 µg/day (LNG-IUS 12) versus LNG-IUS 16 µg/day (LNG-IUS 16); and LNG-IUS 20 versus the copper T380A intrauterine device (IUD). In the trials comparing two different types of methods, the study arms did not differ significantly for contraceptive efficacy or continuation. The sample sizes were small for two of those studies. The only significant outcome was that a COC group had a higher proportion of women who discontinued for 'other personal reasons' compared with the group assigned to the LNG-IUS 20 (OR 0.27, 95% CI 0.09 to 0.85), which may have little clinic relevance. The trial comparing LNG-IUS 12 versus LNG-IUS 16 showed similar efficacy over one and three years. In three trials that examined different LNG-IUS, continuation was at least 75% at 6 to 36 months.\nAuthors' conclusions\nWe considered the overall quality of evidence to be moderate to low. Limitations were due to trial design or limited reporting. Different doses in the LNG-IUS did not appear to influence efficacy over three years. In another study, continuation of the LNG-IUS appeared at least as high as that for the COC. The current evidence was insufficient to compare efficacy and continuation rates for hormonal and intrauterine contraceptive methods in women aged 25 years and younger.\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": "Women aged 25 years and younger are more likely to stop using birth control than women over 25 years of age. They are also more likely to get pregnant while using birth control compared with older women. We do not know which birth control methods have the lowest pregnancy rates and the highest continued use in young women." } ]

[ { "role": "user", "content": "Abstract: Background\nDevelopmental co-ordination disorder (DCD) is a common childhood disorder, which can persist into adolescence and adulthood. Children with DCD have difficulties in performing the essential motor tasks required for self-care, academic, social and recreational activities.\nObjectives\nTo assess the effectiveness of task-oriented interventions on movement performance, psychosocial functions, activity, and participation for children with DCD and to examine differential intervention effects as a factor of age, sex, severity of DCD, intervention intensity, and type of intervention.\nSearch methods\nIn March 2017, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, 13 other databases, and five trials registers. We also searched reference lists, and contacted members of the mailing list of the International Conference on DCD to identify additional studies.\nSelection criteria\nWe included all randomised controlled trials (RCTs) and quasi-RCTs that compared the task-oriented intervention with either an inactive control intervention or an active control intervention in children and adolescents aged four to 18 years with a diagnosis of DCD.\nTypes of outcome measures included changes in motor function, as assessed by standardised performance outcome tests and questionnaires; adverse events; and measures of participation.\nData collection and analysis\nAll review authors participated in study selection, data extraction, and assessments of risk of bias and quality, and two review authors independently performed all tasks. Specifically, two review authors independently screened titles and abstracts to eliminate irrelevant studies, extracted data from the included studies, assessed risk of bias, and rated the quality of the evidence using the GRADE approach. In cases of ambiguity or information missing from the paper, one review author contacted trial authors.\nMain results\nThis review included 15 studies (eight RCTs and seven quasi-RCTs).\nStudy characteristics\nThe trials included 649 participants of both sexes, ranging in age from five to 12 years.\nThe participants were from Australia, Canada, China, Sweden, Taiwan, and the UK.\nTrials were conducted in hospital settings; at a university-based clinic, laboratory, or centre; in community centres; at home or school, or both at home and school.\nThe durations of task-oriented interventions were mostly short term (less than six months), with the total number of sessions ranging from five to 50. The length of each session ranged from 30 to 90 minutes, and the frequencies ranged from once to seven times per week.\nWe judged the risk of bias as moderate to high across the studies. Some elements were impossible to achieve (such as blinding of administering personnel or participants).\nKey results: primary outcomes\nA meta-analysis of two RCTs and four quasi-RCTs found in favour of task-oriented interventions for improved motor performance compared to no intervention (mean difference (MD) -3.63, 95% confidence interval (CI) -5.88 to -1.39; P = 0.002; I2 = 43%; 6 trials, 169 children; very low-quality evidence).\nA meta-analysis of two RCTs found no effect of task-oriented interventions for improved motor performance compared to no intervention (MD -2.34, 95% CI -7.50 to 2.83; P = 0.38; I2 = 42%; 2 trials, 51 children; low-quality evidence).\nTwo studies reported no adverse effects or events. Through personal correspondence, the authors of nine studies indicated that no injuries had occurred.\nKey results: secondary outcomes\nDue to the limited number of studies with complete and consistent data, we were unable to perform any meta-analyses on our secondary measures or any subgroup analysis on age, sex, severity of DCD, and intervention intensity.\nAuthors' conclusions\nWe have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. The conclusions drawn from previous reviews, which unanimously reported beneficial effects of intervention, are inconsistent with our conclusions. This review highlights the need for carefully designed and executed RCTs to investigate the effect of interventions for children with DCD.\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": "DCD is a common childhood disorder characterised by difficulties in performing essential movement-based activities. DCD can make it difficult for children to take care of themselves at home, do well at school, or participate in sport and leisure activities because they find it difficult to move their hands and body effectively. Their movement problems can affect their confidence and social life. Task-oriented interventions use specific activities that are meaningful to the children and provide them with an opportunity to practise these activities to improve corresponding motor skills. This review investigated how effective task-oriented interventions are for the movement performance, psychosocial functions, activity, and participation for children with DCD." } ]

[ { "role": "user", "content": "Abstract: Background\nOmega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this.\nObjectives\nTo assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids.\nSearch methods\nWe searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors.\nSelection criteria\nWe included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression.\nMain results\nWe included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily).\nMeta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression. There is little evidence of effects of eating fish.\nIncreasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear.\nIncreasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by ˜15% in a dose-dependent way (high-certainty evidence).\nAuthors' conclusions\nThis is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia.\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 randomised trials (where participants have an equal chance of being assigned to either treatment) examining effects of increasing fish- and plant-based omega-3 fats on heart and circulatory disease (called cardiovascular diseases, which include heart attacks and stroke), fatness and blood fats (lipids, including cholesterol, triglycerides, high-density lipoprotein (HDL – 'good' cholesterol) and low-density lipoprotein (LDL – 'bad' cholesterol))." } ]

[ { "role": "user", "content": "Abstract: Background\nMalaria is transmitted through the bite of Plasmodium-infected adult female Anopheles mosquitoes. Ivermectin, an anti-parasitic drug, acts by killing mosquitoes that are exposed to the drug while feeding on the blood of people (known as blood feeds) who have ingested the drug. This effect on mosquitoes has been demonstrated by individual randomized trials. This effect has generated interest in using ivermectin as a tool for malaria control.\nObjectives\nTo assess the effect of community administration of ivermectin on malaria transmission.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation index - expanded, the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, and the National Institutes of Health (NIH) RePORTER database to 14 January 2021.\nWe checked the reference lists of included studies for other potentially relevant studies, and contacted researchers working in the field for unpublished and ongoing trials.\nSelection criteria\nWe included cluster-randomized controlled trials (cRCTs) that compared ivermectin, as single or multiple doses, with a control treatment or placebo given to populations living in malaria-endemic areas, in the context of mass drug administration. Primary outcomes were prevalence of malaria parasite infection and incidence of clinical malaria in the community.\nData collection and analysis\nTwo review authors independently extracted data on the number of events and the number of participants in each trial arm at the time of assessment. For rate data, we noted the total time at risk in each trial arm. To assess risk of bias, we used Cochrane's RoB 2 tool for cRCTs. We documented the method of data analysis, any adjustments for clustering or other covariates, and recorded the estimate of the intra-cluster correlation (ICC) coefficient.\nWe re-analysed the trial data provided by the trial authors to adjust for cluster effects. We used a Poisson mixed-effect model with small sample size correction, and a cluster-level analysis using the linear weighted model to adequately adjust for clustering.\nMain results\nWe included one cRCT and identified six ongoing trials.\nThe included cRCT examined the incidence of malaria in eight villages in Burkina Faso, randomized to two arms. Both trial arms received a single dose of ivermectin 150 µg/kg to 200 µg/kg, together with a dose of albendazole. The villages in the intervention arm received an additional five doses of ivermectin, once every three weeks. Children were enrolled into an active cohort, in which they were repeatedly screened for malaria infection.\nThe primary outcome was the cumulative incidence of uncomplicated malaria in a cohort of children aged five years and younger, over the 18-week study. We judged the study to be at high risk of bias, as the analysis did not account for clustering or correlation between participants in the same village.\nThe study did not demonstrate an effect of Ivermectin on the cumulative incidence of uncomplicated malaria in the cohort of children over the 18-week study (risk ratio 0.86, 95% confidence interval (CI) 0.62 to 1.17; P = 0.2607; very low-certainty evidence).\nAuthors' conclusions\nWe are uncertain whether community administration of ivermectin has an effect on malaria transmission, based on one trial published to date.\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": "We searched for studies published up to 14 January 2021." } ]

[ { "role": "user", "content": "Abstract: Background\nContinuous fetal heart rate monitoring by cardiotocography (CTG) is used in labour for women with complicated pregnancies. Fetal heart rate abnormalities are common and may result in the decision to expedite delivery by caesarean section. Fetal scalp stimulation (FSS) is a second-line test of fetal well-being that may provide reassurance that the labour can continue.\nObjectives\nTo evaluate methods of FSS as second-line tests of intrapartum fetal well-being in cases of non-reassuring CTG. FSS and CTG were compared to CTG alone, and to CTG with fetal blood sampling (FBS).\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth’s Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, the WHO ICTRP and conference proceedings), ClinicalTrials.gov (18 October 2022), and reference lists of retrieved studies.\nSelection criteria\nEligible studies were randomised controlled trials (RCTs) that compared any form of FSS to assess fetal well-being in labour. Quasi-RCTs, cluster-RCTs and studies published in abstract form were also eligible for inclusion, but none were identified.\nData collection and analysis\nTwo review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the certainty of the evidence using the GRADE approach.\nMain results\nTwo trials, involving 377 women, met the inclusion criteria for this review. Both trials were conducted in hospital settings and included women with singleton, term (37+0 weeks or more) pregnancies, a cephalic presentation, and abnormal CTG. Follow-up was until hospital discharge after the birth. A pilot trial of 50 women in a high-income country (Ireland) compared CTG and digital fetal scalp stimulation (dFSS) with CTG and fetal blood sampling (FBS). A single-centre trial of 327 women in a lower middle-income country (India) compared CTG and manual fetal stimulation (abdominal or vaginal scalp stimulation) with CTG alone. The two included studies were at moderate or unclear risk of bias. Both trials provided clear information on allocation concealment but it was not possible to blind participants or health professionals in relation to the intervention. Although objective outcome measures were reported, outcome assessment was not blinded or blinding was unclear.\ndFSS and CTG versus FBS and CTG\nThere were no perinatal deaths and data were not reported for neurodevelopmental disability at >/= 12 months. The risk of caesarean section (CS) may be lower with dFSS compared to FBS (risk ratio (RR) 0.38, 95% confidence interval (CI) 0.16 to 0.92; 1 pilot trial, 50 women; very low-certainty evidence) but the evidence is very uncertain. There were no cases of neonatal encephalopathy reported. The evidence was also very uncertain between dFSS and FBS for assisted vaginal birth (RR 1.44, 95% CI 0.76 to 2.75; very low-certainty evidence) and for the spontaneous vaginal birth rate (RR 2.33, 95% CI 0.68 to 8.01, very low-certainty evidence). Maternal acceptability of the procedures was not reported.\nFSS and CTG versus CTG alone\nManual stimulation of the fetus was performed either abdominally (92/164) or vaginally (72/164). There were no perinatal deaths and data were not reported for neurodevelopmental disability at >/= 12 months. There may be little differences in the risk of CS on comparing manual fetal stimulation and CTG with CTG alone (RR 0.83, 95% CI 0.59 to 1.18; 1 trial, 327 women; very low-certainty evidence), but again the evidence was very uncertain. There were no cases of neonatal encephalopathy reported. There may be no differences in the risk of assisted vaginal birth (RR 1.43, 95% CI 0.78 to 2.60; very low-certainty evidence) or in the rates of spontaneous vaginal birth (RR 1.01, 95% CI 0.85 to 1.21, very low-certainty evidence), but again the evidence is very uncertain. Maternal acceptability of abdominal stimulation/FSS was not reported although 13 women withdrew consent after randomisation due to concerns about fetal well-being.\nAuthors' conclusions\nThere is very low-certainty evidence available which makes it unclear whether stimulating the fetal scalp is a safe and effective way to confirm fetal well-being in labour. Evidence was downgraded based on limitations in study design and imprecision. Further high-quality studies of adequate sample size are required to evaluate this research question. In order to be generalisable, these trials should be conducted in different settings, including broad clinical criteria at both preterm and term gestational ages, and standardising the method of stimulation. There is an ongoing study (FIRSST) that will be incorporated into this review in a subsequent update.\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 searched for evidence on 18 October 2022 and identified two eligible studies (involving 377 women). A pilot study of 50 women in Ireland compared digital fetal scalp stimulation (dFSS) and CTG with fetal blood sampling (FBS) and CTG. A study in India of 327 women compared manual fetal scalp stimulation (FSS) (abdominal side to side movement of the fetal head or vaginal pinching of the fetal scalp) and CTG with CTG alone. In both studies, women and hospital staff were aware that fetal scalp stimulation had been performed. This may have had an impact on the results. Both studies were conducted in hospitals and recruited women in labour at term with a single baby presenting head first. Overall, the included studies were at moderate or unclear risk of bias, and the certainty of the generated evidence was very low or unclear.\ndFSS and CTG versus FBS and CTG\nThere were no perinatal deaths and no data reported on disability in the babies at or after 12 months. We found very low-certainty evidence that stimulation of the baby's scalp in addition to CTG may lower the risk of caesarean section compared to scalp blood sampling and CTG (1 pilot trial; 50 women). There were no babies born with evidence of brain injury during labour. There was no difference in the risk of assisted vaginal birth by vacuum or forceps, or in the rate of spontaneous vaginal birth. The acceptability of the procedures to the mother was not reported.\nFSS and CTG versus CTG alone\nThere were no perinatal deaths and no data reported on disability in the babies at or after 12 months. We found that stimulation of the baby's scalp in addition to CTG had little or no difference in the risk of caesarean section compared to CTG alone (1 trial; 327 women). There were no babies born with evidence of brain injury during labour. There was no difference in the risk of assisted vaginal birth by vacuum or forceps, or in the rate of spontaneous vaginal birth. All of the evidence was found to be of very low certainty. The acceptability of the procedures to the mother was not reported." } ]

[ { "role": "user", "content": "Abstract: Background\nWith potential antiviral and anti-inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. They may modulate the exuberant immune response to SARS-CoV-2 infection. Furthermore, a direct antiviral effect has been described. An understanding of the current evidence regarding the efficacy and safety of JAK inhibitors as a treatment for coronavirus disease 2019 (COVID-19) is required.\nObjectives\nTo assess the effects of systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo) on clinical outcomes in individuals (outpatient or in-hospital) with any severity of COVID-19, and to maintain the currency of the evidence using a living systematic review approach.\nSearch methods\nWe searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, medRxiv, and Cochrane Central Register of Controlled Trials), Web of Science, WHO COVID-19 Global literature on coronavirus disease, and the US Department of Veterans Affairs Evidence Synthesis Program (VA ESP) Covid-19 Evidence Reviews to identify studies up to February 2022. We monitor newly published randomised controlled trials (RCTs) weekly using the Cochrane COVID-19 Study Register, and have incorporated all new trials from this source until the first week of April 2022.\nSelection criteria\nWe included RCTs that compared systemic JAK inhibitors plus standard of care to standard of care alone (plus/minus placebo) for the treatment of individuals with COVID-19. We used the WHO definitions of illness severity for COVID-19.\nData collection and analysis\nWe assessed risk of bias of primary outcomes using Cochrane's Risk of Bias 2 (RoB 2) tool. We used GRADE to rate the certainty of evidence for the following primary outcomes: all-cause mortality (up to day 28), all-cause mortality (up to day 60), improvement in clinical status: alive and without need for in-hospital medical care (up to day 28), worsening of clinical status: new need for invasive mechanical ventilation or death (up to day 28), adverse events (any grade), serious adverse events, secondary infections.\nMain results\nWe included six RCTs with 11,145 participants investigating systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo). Standard of care followed local protocols and included the application of glucocorticoids (five studies reported their use in a range of 70% to 95% of their participants; one study restricted glucocorticoid use to non-COVID-19 specific indications), antibiotic agents, anticoagulants, and antiviral agents, as well as non-pharmaceutical procedures. At study entry, about 65% of participants required low-flow oxygen, about 23% required high-flow oxygen or non-invasive ventilation, about 8% did not need any respiratory support, and only about 4% were intubated. We also identified 13 ongoing studies, and 9 studies that are completed or terminated and where classification is pending.\nIndividuals with moderate to severe disease\nFour studies investigated the single agent baricitinib (10,815 participants), one tofacitinib (289 participants), and one ruxolitinib (41 participants).\nSystemic JAK inhibitors probably decrease all-cause mortality at up to day 28 (95 of 1000 participants in the intervention group versus 131 of 1000 participants in the control group; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91; 6 studies, 11,145 participants; moderate-certainty evidence), and decrease all-cause mortality at up to day 60 (125 of 1000 participants in the intervention group versus 181 of 1000 participants in the control group; RR 0.69, 95% CI 0.56 to 0.86; 2 studies, 1626 participants; high-certainty evidence).\nSystemic JAK inhibitors probably make little or no difference in improvement in clinical status (discharged alive or hospitalised, but no longer requiring ongoing medical care) (801 of 1000 participants in the intervention group versus 778 of 1000 participants in the control group; RR 1.03, 95% CI 1.00 to 1.06; 4 studies, 10,802 participants; moderate-certainty evidence). They probably decrease the risk of worsening of clinical status (new need for invasive mechanical ventilation or death at day 28) (154 of 1000 participants in the intervention group versus 172 of 1000 participants in the control group; RR 0.90, 95% CI 0.82 to 0.98; 2 studies, 9417 participants; moderate-certainty evidence).\nSystemic JAK inhibitors probably make little or no difference in the rate of adverse events (any grade) (427 of 1000 participants in the intervention group versus 441 of 1000 participants in the control group; RR 0.97, 95% CI 0.88 to 1.08; 3 studies, 1885 participants; moderate-certainty evidence), and probably decrease the occurrence of serious adverse events (160 of 1000 participants in the intervention group versus 202 of 1000 participants in the control group; RR 0.79, 95% CI 0.68 to 0.92; 4 studies, 2901 participants; moderate-certainty evidence). JAK inhibitors may make little or no difference to the rate of secondary infection (111 of 1000 participants in the intervention group versus 113 of 1000 participants in the control group; RR 0.98, 95% CI 0.89 to 1.09; 4 studies, 10,041 participants; low-certainty evidence). Subgroup analysis by severity of COVID-19 disease or type of JAK inhibitor did not identify specific subgroups which benefit more or less from systemic JAK inhibitors.\nIndividuals with asymptomatic or mild disease\nWe did not identify any trial for this population.\nAuthors' conclusions\nIn hospitalised individuals with moderate to severe COVID-19, moderate-certainty evidence shows that systemic JAK inhibitors probably decrease all-cause mortality. Baricitinib was the most often evaluated JAK inhibitor. Moderate-certainty evidence suggests that they probably make little or no difference in improvement in clinical status. Moderate-certainty evidence indicates that systemic JAK inhibitors probably decrease the risk of worsening of clinical status and make little or no difference in the rate of adverse events of any grade, whilst they probably decrease the occurrence of serious adverse events. Based on low-certainty evidence, JAK inhibitors may make little or no difference in the rate of secondary infection. Subgroup analysis by severity of COVID-19 or type of agent failed to identify specific subgroups which benefit more or less from systemic JAK inhibitors.\nCurrently, there is no evidence on the efficacy and safety of systemic JAK inhibitors for individuals with asymptomatic or mild disease (non-hospitalised individuals).\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 found moderate- to high-certainty evidence from 6 studies to conclude that systemic Janus kinase (JAK) inhibitors are an effective treatment for coronavirus disease 2019 (COVID-19) in hospitalised people, because they resulted in fewer deaths and a lower rate of clinical deterioration. Evaluation of systemic JAK inhibitors is ongoing in 13 studies whilst the results of 9 further studies are awaiting publication. We will update this review and may adapt our conclusions when their results become available." } ]

[ { "role": "user", "content": "Abstract: Background\nPelvic floor muscle training (PFMT) is the most commonly used physical therapy treatment for women with stress urinary incontinence (SUI). It is sometimes also recommended for mixed urinary incontinence (MUI) and, less commonly, urgency urinary incontinence (UUI).\nThis is an update of a Cochrane Review first published in 2001 and last updated in 2014.\nObjectives\nTo assess the effects of PFMT for women with urinary incontinence (UI) in comparison to no treatment, placebo or sham treatments, or other inactive control treatments; and summarise the findings of relevant economic evaluations.\nSearch methods\nWe searched the Cochrane Incontinence Specialised Register (searched 12 February 2018), which contains trials identified from CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, handsearching of journals and conference proceedings, and the reference lists of relevant articles.\nSelection criteria\nRandomised or quasi-randomised controlled trials in women with SUI, UUI or MUI (based on symptoms, signs or urodynamics). One arm of the trial included PFMT. Another arm was a no treatment, placebo, sham or other inactive control treatment arm.\nData collection and analysis\nAt least two review authors independently assessed trials for eligibility and risk of bias. We extracted and cross-checked data. A third review author resolved disagreements. We processed data as described in the Cochrane Handbook for Systematic Reviews of Interventions. We subgrouped trials by diagnosis of UI. We undertook formal meta-analysis when appropriate.\nMain results\nThe review included 31 trials (10 of which were new for this update) involving 1817 women from 14 countries. Overall, trials were of small-to-moderate size, with follow-ups generally less than 12 months and many were at moderate risk of bias. There was considerable variation in the intervention's content and duration, study populations and outcome measures. There was only one study of women with MUI and only one study with UUI alone, with no data on cure, cure or improvement, or number of episodes of UI for these subgroups.\nSymptomatic cure of UI at the end of treatment: compared with no treatment or inactive control treatments, women with SUI who were in the PFMT groups were eight times more likely to report cure (56% versus 6%; risk ratio (RR) 8.38, 95% confidence interval (CI) 3.68 to 19.07; 4 trials, 165 women; high-quality evidence). For women with any type of UI, PFMT groups were five times more likely to report cure (35% versus 6%; RR 5.34, 95% CI 2.78 to 10.26; 3 trials, 290 women; moderate-quality evidence).\nSymptomatic cure or improvement of UI at the end of treatment: compared with no treatment or inactive control treatments, women with SUI who were in the PFMT groups were six times more likely to report cure or improvement (74% versus 11%; RR 6.33, 95% CI 3.88 to 10.33; 3 trials, 242 women; moderate-quality evidence). For women with any type of UI, PFMT groups were two times more likely to report cure or improvement than women in the control groups (67% versus 29%; RR 2.39, 95% CI 1.64 to 3.47; 2 trials, 166 women; moderate-quality evidence).\nUI-specific symptoms and quality of life (QoL) at the end of treatment: compared with no treatment or inactive control treatments, women with SUI who were in the PFMT group were more likely to report significant improvement in UI symptoms (7 trials, 376 women; moderate-quality evidence), and to report significant improvement in UI QoL (6 trials, 348 women; low-quality evidence). For any type of UI, women in the PFMT group were more likely to report significant improvement in UI symptoms (1 trial, 121 women; moderate-quality evidence) and to report significant improvement in UI QoL (4 trials, 258 women; moderate-quality evidence). Finally, for women with mixed UI treated with PFMT, there was one small trial (12 women) reporting better QoL.\nLeakage episodes in 24 hours at the end of treatment: PFMT reduced leakage episodes by one in women with SUI (mean difference (MD) 1.23 lower, 95% CI 1.78 lower to 0.68 lower; 7 trials, 432 women; moderate-quality evidence) and in women with all types of UI (MD 1.00 lower, 95% CI 1.37 lower to 0.64 lower; 4 trials, 349 women; moderate-quality evidence).\nLeakage on short clinic-based pad tests at the end of treatment: women with SUI in the PFMT groups lost significantly less urine in short (up to one hour) pad tests. The comparison showed considerable heterogeneity but the findings still favoured PFMT when using a random-effects model (MD 9.71 g lower, 95% CI 18.92 lower to 0.50 lower; 4 trials, 185 women; moderate-quality evidence). For women with all types of UI, PFMT groups also reported less urine loss on short pad tests than controls (MD 3.72 g lower, 95% CI 5.46 lower to 1.98 lower; 2 trials, 146 women; moderate-quality evidence).\nWomen in the PFMT group were also more satisfied with treatment and their sexual outcomes were better. Adverse events were rare and, in the two trials that did report any, they were minor. The findings of the review were largely supported by the 'Summary of findings' tables, but most of the evidence was downgraded to moderate on methodological grounds. The exception was 'participant-perceived cure' in women with SUI, which was rated as high quality.\nAuthors' conclusions\nBased on the data available, we can be confident that PFMT can cure or improve symptoms of SUI and all other types of UI. It may reduce the number of leakage episodes, the quantity of leakage on the short pad tests in the clinic and symptoms on UI-specific symptom questionnaires. The authors of the one economic evaluation identified for the Brief Economic Commentary reported that the cost-effectiveness of PFMT looks promising. The findings of the review suggest that PFMT could be included in first-line conservative management programmes for women with UI. The long-term effectiveness and cost-effectiveness of PFMT needs to be further researched.\n\nGiven the provided abstract, please respond to the following query: \"Why is this question important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Stress incontinence is leaking of urine which cannot be easily controlled (if at all) when performing a physical activity. Physical activities could include coughing, sneezing, sporting activities or suddenly changing position. Urgency incontinence happens with a sudden, strong need to urinate. This can often lead to not making it to the toilet in time to urinate, resulting in leakage. Mixed incontinence is where someone has both stress and urgency incontinence.\nPFMT is a programme of exercise to improve pelvic floor muscle strength, endurance, power, relaxation or a combination of these. It is a widely used treatment for women with stress, urgency and mixed incontinence." } ]

[ { "role": "user", "content": "Abstract: Background\nEczema is a common, chronic, inflammatory skin condition that is frequently associated with atopic conditions, including asthma. Leukotriene receptor antagonists (LTRAs) have a corticosteroid-sparing role in asthma, but their role in eczema remains controversial. Currently available topical therapies for eczema are often poorly tolerated, and use of systemic agents is restricted by their adverse effect profile. A review of alternative treatments was therefore warranted.\nObjectives\nTo assess the possible benefits and harms of leukotriene receptor antagonists for eczema.\nSearch methods\nWe searched the following databases to September 2017: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and the GREAT database. We also searched five trial registries, and handsearched the bibliographies of all extracted studies for further relevant trials.\nSelection criteria\nRandomised controlled trials of LTRAs alone or in combination with other (topical or systemic) treatments compared with other treatments alone such as topical corticosteroids or placebo for eczema in the acute or chronic (maintenance) phase of eczema in adults and children.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. The primary outcome measures were change in disease severity, long-term symptom control, and adverse effects of treatment. Secondary outcomes were change in corticosteroid requirement, reduction of pruritis, quality of life, and emollient requirement. We used GRADE to assess the quality of the evidence for each outcome.\nMain results\nOnly five studies (including a total of 202 participants) met the inclusion criteria, all of which assessed oral montelukast; hence, we found no studies assessing other LTRAs. Treatment ranged from four to eight weeks, and outcomes were assessed at the end of treatment; therefore, we could only report short-term measurements (defined as less than three months follow-up from baseline). Montelukast dosing was 10 mg for adults (age 14 years and above) and 5 mg for children (age 6 years to 14 years). One study included children (aged 6 years and above) among their participants, while the remaining studies only included adults (participant age ranged from 16 to 70 years). The participants were diagnosed with moderate-to-severe eczema in four studies and moderate eczema in one study. The study setting was unclear in two studies, multicentre in two studies, and single centre in one study; the studies were conducted in Europe and Bangladesh. Two studies were industry funded. The comparator was placebo in three studies and conventional treatment in two studies. The conventional treatment comparator was a combination of antihistamines and topical corticosteroids (plus oral antibiotics in one study).\nFour of the studies did not adequately describe their randomisation or allocation concealment method and were considered as at unclear risk of selection bias. Only one study was at low risk of performance and detection bias. However, we judged all studies to be at low risk of attrition and reporting bias.\nWe found no evidence of a difference in disease severity of moderate-to-severe eczema after short-term use of montelukast (10 mg) when compared with placebo. The outcome was assessed using the modified EASI (Eczema Area and Severity Index) score and SASSAD (Six Area, Six Sign Atopic Dermatitis) severity score (standardised mean difference 0.29, with a positive score showing montelukast is favoured, 95% confidence interval (CI) -0.23 to 0.81; 3 studies; n = 131; low-quality evidence).\nWhen short-term montelukast (10 mg) treatment was compared with conventional treatment in one study, the mean improvement in severity of moderate-to-severe eczema was greater in the intervention group (measured using SCORAD (SCORing of Atopic Dermatitis) severity index) (mean difference 10.57, 95% CI 4.58 to 16.56; n = 31); however, another study of 32 participants found no significant difference between groups using the same measure (mean improvement was 25.2 points with montelukast versus 23.9 points with conventional treatment; no further numerical data provided). We judged the quality of the evidence as very low for this outcome, meaning the results are uncertain.\nAll studies reported their adverse event rate during treatment. Four studies (136 participants) reported no adverse events. In one study of 58 participants with moderate eczema who received montelukast 10 mg (compared with placebo), there was one case of septicaemia and one case of dizziness reported in the intervention group, both resulting in study withdrawal, although whether these effects were related to the medication is unclear. Mild side effects (e.g. headache and mild gastrointestinal disturbances) were also noted, but these were fairly evenly distributed between the montelukast and placebo groups. The quality of evidence for this outcome was low.\nNo studies specifically evaluated emollient requirement or quality of life. One study that administered treatment for eight weeks specifically evaluated pruritus improvement at the end treatment and topical corticosteroid use during treatment. We found no evidence of a difference between montelukast (10 mg) and placebo for both outcomes (low-quality evidence, n = 58). No other study assessed these outcomes.\nAuthors' conclusions\nThe findings of this review are limited to montelukast. There was a lack of evidence addressing the review question, and the quality of the available evidence for most of the measured outcomes was low. Some primary and secondary outcomes were not addressed at all, including long-term control.\nWe found no evidence of a difference between montelukast (10 mg) and placebo on disease severity, pruritus improvement, and topical corticosteroid use. Very low-quality evidence means we are uncertain of the effect of montelukast (10 mg) compared with conventional treatment on disease severity. Participants in only one study reported adverse events, which were mainly mild (low-quality evidence).\nThere is no evidence that LTRA is an effective treatment for eczema. Serious limitations were that all studies focused on montelukast and only included people with moderate-to-severe eczema, who were mainly adults; and that each outcome was evaluated with a small sample size, if at all.\nFurther large randomised controlled trials, with a longer treatment duration, of adults and children who have eczema of all severities may help to evaluate the effect of all types of LTRA, especially on eczema maintenance.\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": "Limited available data meant we were unable to draw firm conclusions on the effectiveness of LTRA in eczema. Like other reviews on this topic, this review is unlikely to change how eczema is treated because there is no convincing evidence that montelukast, the only LTRA that could be assessed, is helpful for eczema.\nWe found no evidence of a difference between montelukast and placebo in terms of improving eczema disease severity (low-quality evidence). When montelukast was compared with conventional treatment, participants using montelukast in one study saw an improvement in disease severity, but no difference was observed in another study. We are uncertain about these results because the quality of the evidence was very low.\nNone of the studies looked at long-term eczema control, moisturiser (emollients) use, or quality of life.\nWe found no evidence that montelukast lessened itching or reduced the need for steroid creams during treatment when compared to placebo (low-quality evidence). The studies comparing montelukast with conventional treatments did not assess these outcomes.\nParticipants in four studies did not experience side effects. In one study comparing montelukast with placebo, there were two reported incidents in the montelukast group that resulted in participant withdrawal: one episode of septicaemia (blood poisoning) and one episode of dizziness. However, it was not clear whether these were related to the montelukast treatment. Other mild side effects were reported (e.g. headache, stomach-related disturbances), but by participants in both groups. We therefore found no evidence of a difference between montelukast and placebo or conventional treatments, but this is assessment is based on low-quality evidence." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die from acute respiratory tract infections annually. Among these, pneumonia represents the most frequent cause of mortality, hospitalisation and medical consultation. Azithromycin is a macrolide antibiotic, structurally modified from erythromycin and noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae).\nObjectives\nTo compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication.\nSearch methods\nWe searched CENTRAL (2014, Issue 10), MEDLINE (January 1966 to October week 4, 2014) and EMBASE (January 1974 to November 2014).\nSelection criteria\nRandomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis.\nData collection and analysis\nThe review authors independently assessed all potential studies identified from the searches for methodological quality. We extracted and analysed relevant data separately. We resolved discrepancies through discussion. We initially pooled all types of acute LRTI in the meta-analyses. We investigated the heterogeneity of results using the forest plot and Chi2 test. We also used the index of the I2 statistic to measure inconsistent results among trials. We conducted subgroup and sensitivity analyses.\nMain results\nWe included 16 trials involving 2648 participants. We were able to analyse 15 of the trials with 2496 participants. The pooled analysis of all the trials showed that there was no significant difference in the incidence of clinical failure on about days 10 to 14 between the two groups (risk ratio (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). A subgroup analysis in trials with acute bronchitis participants showed significantly lower clinical failure in the azithromycin group compared to amoxycillin or amoxyclav (RR random-effects 0.63; 95% CI 0.45 to 0.88). A sensitivity analysis showed a non-significant reduction in clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00).\nAuthors' conclusions\nThere is unclear evidence that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxycillin or amoxyclav. However, most studies were of unclear methodological quality and had small sample sizes; future trials of high methodological quality and adequate sizes are needed.\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": "Randomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis." } ]

[ { "role": "user", "content": "Abstract: Background\nAttention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial.\nObjectives\nTo evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults.\nSearch methods\nIn January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches.\nSelection criteria\nRandomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants.\nData collection and analysis\nTwo review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI.\nMain results\nWe included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks.\nIR methylphenidate versus placebo\nWe found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD −20.70, 95% CI −23.97 to −17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD −0.59, 95% CI −1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores).\nThere is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD −0.57, 95% CI −0.85 to −0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD −0.94, 95% CI −1.37 to −0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD −0.20, 95% CI −4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI −0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo.\nIR methylphenidate versus lithium\nCompared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI −3.11 to 4.31; 1 trial, 46 participants; end scores; Conners’ Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD −0.80, 95% CI −4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD −1.20, 95% CI −3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium.\nAdverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively.\nWe considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest.\nAuthors' conclusions\nWe found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.\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": "We found 10 trials, involving 497 adults. Three trials were carried out in Europe and one in Argentina; the remaining trials did not report their location. Six trials compared IR methylphenidate with placebo. In the other trials, IR methylphenidate was compared to an extended-release form of bupropion (an antidepressant), lithium, an extended-release form of methylphenidate named osmotic-release oral system (OROS), and Pycnogenol® (a medicine derived from the bark of a pine tree). People were treated for 6 to 18 weeks. Participants were mainly outpatients; some participants were inpatients for addiction treatment, or individuals willing to attend an intensive outpatient program for cocaine dependence.\nIR methylphenidate versus placebo\nOne trial with 146 participants reported that IR methylphenidate may reduce symptoms of ADHD when judged by the doctors. When participants judge their own symptoms, there may be a moderate positive effect. We are however uncertain about these results and they may change with the addition of more data. IR methylphenidate appears to have little or no effect in reducing symptoms of anxiety and depression. We have concerns about the methods and conflicts of interest presented by this trial and the other nine trials that were evaluated.\nIR methylphenidate versus lithium\nIR methylphenidate may have little or no effect on symptoms of ADHD (judged by the doctors), or anxiety and depression, but the results are uncertain. None of the included trials assessed changes in symptoms of ADHD rated by participants, or the clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium.\nAdverse events\nAdverse events (side effects) were poorly assessed and reported in all trials. Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate reported in these trials increased the risk of digestive complications and loss of appetite. Harm to the heart and circulation was reported, but in a limited and inconsistent manner. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively.\nWe considered almost all trials to have notable concerns related to their sources of funding and conflicts of interest." } ]

[ { "role": "user", "content": "Abstract: Background\nPsoriasis is a chronic skin disease that affects approximately two per cent of the general population. Plaque psoriasis is the most common form: it usually appears as raised, red patches of inflamed skin, covered with silvery white scales. The patches often occur in a symmetrical pattern. Guttate psoriasis is a particular form of psoriasis with widespread, small erythematosquamous lesions. Streptococcal infection is suspected to be a triggering factor for the onset of guttate psoriasis, and flare-up of chronic plaque psoriasis. The previous Cochrane Review on this topic was published in 2000; it required an update because antistreptococcal treatment continues to be used to treat psoriasis, especially for the acute form of guttate psoriasis.\nObjectives\nTo assess the effects of antistreptococcal interventions for guttate and chronic plaque psoriasis.\nSearch methods\nWe searched Cochrane Skin Specialised Register, Cochrane Register of Studies Online, CENTRAL, MEDLINE, Embase, LILACS, and five trials registers (January 2019). We checked the reference lists of included and excluded studies and searched conference proceedings from the American Academy of Dermatology, Society for Investigative Dermatology, and European Academy of Dermatology and Venereology.\nSelection criteria\nWe considered randomised controlled trials (RCTs) assessing antistreptococcal interventions (tonsillectomy or systemic antibiotic treatment) in people with clinically diagnosed acute guttate and chronic plaque psoriasis compared with placebo, no intervention, or each other.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Primary outcome measures were: 1) time-to-resolution; achieving clear or almost clear skin (Physician Global Assessment (PGA) 0 or 1 or Psoriasis Area and Severity Index (PASI) 90 or 100); 2) proportion of participants with adverse effects and severe adverse effects. Secondary outcomes were: 1) proportion of participants achieving clear or almost clear skin; 2) proportion of participants achieving PASI 75 or PGA 1 to 2; 3) risk of having at least one relapse at long-term follow-up. Short-term assessment was defined as within eight weeks of the start of treatment; long-term was at least one year after the start of treatment.\nMain results\nWe included five trials (162 randomised participants); three were conducted in a hospital dermatology department. One study declared funding by a pharmaceutical company. Participants' ages ranged from 12 to 77 years; only two participants were younger than 15 years. Mean PASI score at baseline varied from 5.7 (i.e. mild) to 23 (i.e. severe) in four studies. Twenty-three of 162 participants had streptococcus-positive throat swab culture. We did not perform a meta-analysis due to heterogeneity of participants' characteristics and interventions.\nNone of the trials measured our efficacy primary outcome, time-to-resolution, or the secondary outcome, risk of having at least one relapse at long-term follow-up.\nWe rated the quality of the results as very low-quality evidence, due to high risk of bias (absence of blinding of participants and caregivers, and high risk of outcome reporting bias) and imprecision (single study data with a low number of events). Hence, we are very uncertain about the results presented.\nGuttate psoriasis\nOne three-armed trial (N = 43) assessed penicillin (50,000 international units (IU)/kg/day in three doses) versus erythromycin (250 mg four times per day) versus no treatment (treatment for 14 days, with six-week follow-up from start of treatment). Adverse events and the proportion of participants achieving clear or almost clear skin were not measured.\nOne trial (N = 20) assessed penicillin (1.6 MU (million units) intramuscularly once a day) versus no treatment (six weeks of treatment, with eight-week follow-up from start of treatment). At six-week (short-term) follow-up, no adverse events were observed in either group, and there was no statistically significant difference between the two groups in the proportion of participants with clear or almost clear skin (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.68 to 5.85).\nOne trial (N = 20) assessed rifampicin (300 mg twice daily) versus placebo (14-day treatment duration; six-week follow-up from start of treatment); none of the review outcomes were measured.\nThese trials did not measure the proportion of participants achieving PASI 75 or PGA 1 to 2.\nChronic plaque psoriasis\nOne trial (N = 50) assessed long-term azithromycin treatment (500 mg daily dose) versus vitamin C. Adverse events were reported in the azithromycin group (10 out of 30 had nausea and mild abdominal upset), but not in the vitamin C group. The proportion of participants who achieved clear or almost clear skin was not measured. In the azithromycin group, 18/30 versus 0/20 participants in the vitamin C group reached PASI 75 at the end of 48 weeks of treatment (RR 25.06, 95% CI 1.60 to 393.59).\nOne trial (N = 29) assessed tonsillectomy versus no treatment, with 24-month follow-up after surgery. One participant in the tonsillectomy group had minor bleeding. At eight-week follow-up, 1/15 in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 90; and 3/15 participants in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 75 (RR 6.56, 95% CI 0.37 to 116.7).\nAuthors' conclusions\nWe found only five trials (N = 162), which assessed the effects of five comparisons (systemic antibiotic treatment (penicillin, azithromycin) or tonsillectomy). Two comparisons (erythromycin compared to no treatment, and rifampicin compared to placebo) did not measure any of the outcomes of interest. There was very low-quality evidence for the outcomes that were measured, Therefore, we are uncertain of both the efficacy and safety of antistreptococcal interventions for guttate and chronic plaque psoriasis.\nThe included trials were at unclear or high risk of bias and involved only a small number of unrepresentative participants, with limited measurement of our outcomes of interest. The studies did not allow investigation into the influence of Streptococcal infection, and a key intervention (amoxicillin) was not assessed.\nFurther trials assessing the efficacy and tolerance of penicillin V or amoxicillin are needed in children and young adults with guttate psoriasis.\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": "Many of our main outcomes were not assessed. Those that were assessed were based on very low-quality evidence, meaning we are not sure of their accuracy. The studies were very small, and had a high risk of bias because participants and trial assessors were aware of treatment allocation. More studies are needed to see if antibiotic treatment of Streptococcal infection shortens the duration of acute guttate psoriasis, stopping it from turning into a long-term condition (chronic plaque psoriasis)." } ]

[ { "role": "user", "content": "Abstract: Background\nExcessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling.\nThis is an update of a Cochrane Review published in 2007.\nObjectives\nTo assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews.\nSelection criteria\nWe included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption.\nMain results\nWe included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention.\nWe found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).\nWe found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-20 g/week, 95% CI -40 to 1; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).\nExtended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).\nOnly five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms.\nSources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment.\nAuthors' conclusions\nWe found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.\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": "We aimed to find out whether brief interventions with doctors and nurses in general practices or emergency care can reduce heavy drinking. We assessed the findings from 69 trials that involved a total of 33,642 participants; of these 34 studies (15,197 participants) provided data for the main analysis." } ]

[ { "role": "user", "content": "Abstract: Background\nStress urinary incontinence constitutes a significant health and economic burden to society. Traditional suburethral slings are surgical operations used to treat women with symptoms of stress urinary incontinence.\nObjectives\nTo assess the effectiveness of traditional suburethral sling procedures for treating stress urinary incontinence in women; and summarise the principal findings of relevant economic evaluations.\nSearch methods\nWe searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), as well as MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); we handsearched journals and conference proceedings (searched 27 February 2017) and the reference lists of relevant articles. On 23 January 2019, we updated this search; as a result, several additional reports of studies are awaiting classification.\nSelection criteria\nRandomised or quasi-randomised trials that assessed traditional suburethral slings for treating stress or mixed urinary incontinence.\nData collection and analysis\nAt least two review authors independently extracted data from included trials and assessed risk of bias. When appropriate, a summary statistic was calculated: risk ratio (RR) for dichotomous data, odds ratio (OR) for continence and cure rates that were expected to be high, and mean difference (MD) for continuous data. We adopted the GRADE approach to assess the quality of evidence.\nMain results\nA total of 34 trials involving 3244 women were included. Traditional slings were compared with 10 other treatments and with each other.\nWe did not identify any trials comparing suburethral slings with no treatment or sham treatment, conservative management, anterior repair, or laparoscopic retropubic colposuspension. Most trials did not distinguish between women having surgery for primary or recurrent incontinence. One trial compared traditional slings with bladder neck needle suspension, and another trial compared traditional slings with single-incision slings. Both trials were too small to be informative.\nTraditional suburethral sling operation versus drugs\nOne small trial compared traditional suburethral sling operations with oxybutynin to treat women with mixed urinary incontinence. This trial did not report any of our GRADE-specific outcomes. It is uncertain whether surgery compared with oxybutynin leads to more women being dry (83% vs 0%; OR 195.89, 95% confidence interval (CI) 9.91 to 3871.03) or having less urgency urinary incontinence (13% vs 43%; RR 0.29, 95% CI 0.09 to 0.94) because the quality of this evidence is very low.\nTraditional suburethral sling versus injectables\nOne small trial compared traditional slings with suburethral injectable treatment. The impact of surgery versus injectables is uncertain in terms of the number of continent women (100% were dry with a traditional sling versus 71% with the injectable after the first year; OR 11.57, 95% CI 0.56 to 239.74), the need for repeat surgery for urinary incontinence (RR 0.52, 95% CI 0.05 to 5.36) or the occurrence of perioperative complications (RR 1.57, 95% CI 0.29 to 8.49), as the quality of evidence is very low.\nTraditional suburethral sling versus open abdominal retropubic colposuspension\nEight trials compared slings with open abdominal retropubic colposuspension. Moderate-quality evidence shows that the traditional suburethral sling probably leads to more continent women in the medium term (one to five years) (69% vs 59% after colposuspension: OR 1.70, 95% CI 1.22 to 2.37). High-quality evidence shows that women were less likely to need repeat continence surgery after a traditional sling operation than after colposuspension (RR 0.15, 95% CI 0.05 to 0.42). We found no evidence of a difference in perioperative complications between the two groups, but the CI was very wide and the quality of evidence was very low (RR 1.24, 95% CI 0.83 to 1.86).\nTraditional suburethral sling operation versus mid-urethral slings\nFourteen trials compared traditional sling operations and mid-urethral sling operations. Depending on judgements about what constitutes a clinically important difference between interventions with regard to continence, traditional suburethral slings are probably no better, and may be less effective, than mid-urethral slings in terms of number of women continent in the medium term (one to five years) (67% vs 74%; OR 0.67, 95% CI 0.44 to 1.02; n = 458; moderate-quality evidence). One trial reported more continent women with the traditional sling after 10 years (51% vs 32%: OR 2.22, 95% CI 1.07 to 4.61). Mid-urethral slings may be associated with fewer perioperative complications (RR 1.74, 95% CI 1.16 to 2.60; low-quality evidence).\nOne type of traditional sling operation versus another type of traditional sling operation\nNine trials compared one type of traditional sling operation with another. The different types of traditional slings, along with the number of different materials used, mean that trial results could not be pooled due to clinical heterogeneity. Complications were reported by two trials - one comparing non-absorbable Goretex with a rectus fascia sling, and the second comparing Pelvicol with a rectus fascial sling. The impact was uncertain due to the very low quality of evidence.\nAuthors' conclusions\nLow-quality evidence suggests that women may be more likely to be continent in the medium term (one to five years) after a traditional suburethral sling operation than after colposuspension. It is very uncertain whether there is a difference in urinary incontinence after a traditional suburethral sling compared with a mid-urethral sling in the medium term. However, these findings should be interpreted with caution, as long-term follow-up data were not available from most trials. Long-term follow-up of randomised controlled trials (RCTs) comparing traditional slings with colposuspension and mid-urethral slings is essential. Evidence is insufficient to suggest whether traditional suburethral slings may be better or worse than other management techniques. This review is confined to RCTs and therefore may not identify all of the adverse effects that may be associated with these procedures.\nA brief economic commentary (BEC) identified three eligible economic evaluations, which are not directly comparable due to differences in methods, time horizons, and settings. End users of this review will need to assess the extent to which methods and results of identified economic evaluations may be applicable (or transferable) to their own setting.\n\nGiven the provided abstract, please respond to the following query: \"Study funding sources\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Few trialists reported who had funded their work." } ]

[ { "role": "user", "content": "Abstract: Background\nViruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care.\nObjectives\nTo assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021.\nSelection criteria\nWe included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment.\nData collection and analysis\nWe used standard Cochrane methodology.\nMain results\nWe identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years.\nStudy characteristics and risk of bias\nIn most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains.\nFindings\nWe included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56).\nFour studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty.\nAdverse effects\nAntiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty.\nAuthors' conclusions\nThe evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.\n\nGiven the provided abstract, please respond to the following query: \"How is it treated?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Treatment is usually supportive with cool compresses, artificial tears, and sometimes steroids." } ]

[ { "role": "user", "content": "Abstract: Background\nWorldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite high perfect-use effectiveness rates, typical-use effectiveness rates for shorter-term methods such as oral and injectable contraceptives are much lower. In large part, this disparity reflects difficulties in ongoing adherence to the contraceptive regimen and low continuation rates. Correct use of contraceptives to ensure effectiveness is vital to reducing unintended pregnancy.\nObjectives\nTo determine the effectiveness of strategies aiming to improve adherence to, and continuation of, shorter-term hormonal methods of contraception compared with usual family planning care.\nSearch methods\nWe searched to July 2018 in the following databases (without language restrictions): The Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 7), PubMed via MEDLINE, POPLINE, Web of Science, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP).\nSelection criteria\nWe included randomized controlled trials (RCTs) comparing strategies aimed to facilitate adherence and continuation of shorter-term hormonal methods of contraception (such as oral contraceptives (OCs), injectable depot medroxyprogesterone acetate (DMPA or Depo-Provera), intravaginal ring, or transdermal patch) with usual family planning care in reproductive age women seeking to avoid pregnancy.\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane. Primary outcomes were continuation or discontinuation of contraceptive method, rates of discontinuation due to adverse events (menstrual disturbances and all other adverse events), and adherence to method use as indicated by missed pills and on-time/late injections. Pregnancy was a secondary outcome.\nMain results\nWe included 10 RCTs involving 6242 women. Six trials provided direct in-person counseling using either multiple counseling contacts or multiple components during one visit. Four trials provided intensive reminders of appointments or next dosing, of which two provided additional educational health information as well as reminders. All trials stated 'usual care' as the comparison.\nThe certainty of the evidence ranged from very low to moderate. Main limitations were risk of bias (associated with poor reporting of methodological detail, lack of blinding, and incomplete outcome data), inconsistency, indirectness, and imprecision.\nContinuation of hormonal contraceptive methods\nIt is uncertain whether intensive counseling improves continuation of hormonal contraceptive methods compared with usual care (OR 1.28, 95% CI 1.07 to 1.54; 2624 participants; 6 studies; I2 = 79%; very low certainty evidence). The evidence suggested: if the chance of continuation with usual care is 39%, the chance of continuation with intensive counseling would be between 41% and 50%. The overall pooled OR suggested continuation of improvement, however, when stratified by contraceptive method type, the positive results were restricted to DMPA.\nIt is uncertain whether reminders (+/- educational information) improve continuation of hormonal contraceptive methods compared with usual care (OR 1.33, 95% CI 1.03 to 1.73; 933 participants; 2 studies; I2 = 69%; very low certainty evidence).The evidence suggested: if the chance of continuation with usual care is 52%, the chance of continuation with reminders would be between 52% and 65%.\nDiscontinuation due to adverse events\nThe evidence suggested that counseling may be associated with a decreased rate of discontinuation due to adverse events compared with usual care, with a lower rate of discontinuation due to menstrual disturbances (OR 0.20, 95% CI 0.11 to 0.37; 350 participants; 1 study; low certainty evidence), but may make little or no difference to all other adverse events (OR 0.73, 95% CI 0.36 to 1.47; 350 participants; 1 study; low certainty evidence). The evidence suggested: if the chance of discontinuation with usual care due to menstrual disturbances is 32%, the chance of discontinuation with intensive counseling would be between 5% and 15%; and that if the chance of discontinuation with usual care due to other adverse events is 55%, the chance of discontinuation with intensive counseling would be between 30% and 64%.\nDiscontinuation was not reported among trials that investigated the use of reminders (+/- educational information).\nAdherence\nAdherence was not reported among trials that investigated the use of intensive counseling.\nAmong trials that investigated reminders (+/- educational information), there was no conclusive evidence of a difference in adherence as indicated by missed pills (MD 0.80, 95% CI -1.22 to 2.82; 73 participants; 1 study; moderate certainty evidence) or by on-time injections (OR 0.84, 95% CI 0.54 to 1.29; 350 participants; 2 studies; I2 = 0%; low certainty evidence). The evidence suggested: if the chance of adherence to method use as indicated by on-time injections with usual care is 50%, the chance of adherence with method use as indicated by on-time injections with reminders would be between 35% and 56%.\nPregnancy\nThere was no conclusive evidence of a difference in rates of pregnancy between intensive counseling and usual care (OR 1.24, 95% CI 0.98 to 1.57; 1985 participants; 3 studies; I2 = 0%, very low certainty evidence). The evidence suggested: if the chance of pregnancy with usual care is 18%, the chance of pregnancy with counseling would be between 18% and 25%.\nPregnancy was not reported among trials that investigated the use of reminders (+/- educational information).\nAuthors' conclusions\nDespite the importance of this topic, studies have not been published since the last review in 2013 (nine studies) with only one study added in 2019 that neither changed the results nor improved the certainty of evidence.\nOverall, the certainty of evidence for strategies to improve adherence and continuation of contraceptives is low. Intensive counseling and reminders (with or without educational information) may be associated with improved continuation of shorter-term hormonal contraceptive methods when compared with usual family planning care. However, this should be interpreted with caution due to the low certainty of the evidence. Included trials used a variety of shorter-term hormonal contraceptive methods which may account for the high heterogeneity. It is possible that the effectiveness of strategies for improving adherence and continuation are contingent on the contraceptive method targeted. There was limited reporting of objectively measurable outcomes (e.g. electronic monitoring device) among included studies. Future trials would benefit from standardized definitions and measurements of adherence, and consistent terminology for describing interventions and comparisons. Further research requires larger studies, follow-up of at least one year, and improved reporting of trial methodology.\n\nGiven the provided abstract, please respond to the following query: \"Counseling may\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "· improve continuation of contraception (6 studies; 2624 participants; very low certainty evidence)\n· reduce discontinuation due to menstrual problems (1 study; 350 participants; low certainty evidence)\n· reduce discontinuation due to adverse events (1 study; 350 participants; low certainty evidence)\n· have no effect on pregnancy outcomes (3 studies, 1985 participants; very low certainty evidence)" } ]

[ { "role": "user", "content": "Abstract: Background\nApproximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years of diagnosis. Several different treatments are available, which include endoscopic sclerotherapy, variceal band ligation, beta-blockers, transjugular intrahepatic portosystemic shunt (TIPS), and surgical portocaval shunts, among others. However, there is uncertainty surrounding their individual and relative benefits and harms.\nObjectives\nTo compare the benefits and harms of different initial treatments for secondary prevention of variceal bleeding in adults with previous oesophageal variceal bleeding due to decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for secondary prevention according to their safety and efficacy.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until December 2019 to identify randomised clinical trials in people with cirrhosis and a previous history of bleeding from oesophageal varices.\nSelection criteria\nWe included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and previous history of bleeding from oesophageal varices. We excluded randomised clinical trials in which participants had no previous history of bleeding from oesophageal varices, previous history of bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those who had acute bleeding at the time of treatment, and those who had previously undergone liver transplantation.\nData collection and analysis\nWe performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.\nMain results\nWe included a total of 48 randomised clinical trials (3526 participants) in the review. Forty-six trials (3442 participants) were included in one or more comparisons. The trials that provided the information included people with cirrhosis due to varied aetiologies. The follow-up ranged from two months to 61 months. All the trials were at high risk of bias. A total of 12 interventions were compared in these trials (sclerotherapy, beta-blockers, variceal band ligation, beta-blockers plus sclerotherapy, no active intervention, TIPS (transjugular intrahepatic portosystemic shunt), beta-blockers plus nitrates, portocaval shunt, sclerotherapy plus variceal band ligation, beta-blockers plus nitrates plus variceal band ligation, beta-blockers plus variceal band ligation, sclerotherapy plus nitrates).\nOverall, 22.5% of the trial participants who received the reference treatment (chosen because this was the commonest treatment compared in the trials) of sclerotherapy died during the follow-up period ranging from two months to 61 months. There was considerable uncertainty in the effects of interventions on mortality. Accordingly, none of the interventions showed superiority over another. None of the trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation may result in fewer serious adverse events (number of people) than sclerotherapy (OR 0.19; 95% CrI 0.06 to 0.54; 1 trial; 100 participants).\nBased on low or very low-certainty evidence, the adverse events (number of participants) and adverse events (number of events) may be different across many comparisons; however, these differences are due to very small trials at high risk of bias showing large differences in some comparisons leading to many differences despite absence of direct evidence.\nBased on low-certainty evidence, TIPS may result in large decrease in symptomatic rebleed than variceal band ligation (HR 0.12; 95% CrI 0.03 to 0.41; 1 trial; 58 participants). Based on moderate-certainty evidence, any variceal rebleed was probably lower in sclerotherapy than in no active intervention (HR 0.62; 95% CrI 0.35 to 0.99, direct comparison HR 0.66; 95% CrI 0.11 to 3.13; 3 trials; 296 participants), beta-blockers plus sclerotherapy than sclerotherapy alone (HR 0.60; 95% CrI 0.37 to 0.95; direct comparison HR 0.50; 95% CrI 0.07 to 2.96; 4 trials; 231 participants); TIPS than sclerotherapy (HR 0.18; 95% CrI 0.08 to 0.38; direct comparison HR 0.22; 95% CrI 0.01 to 7.51; 2 trials; 109 participants), and in portocaval shunt than sclerotherapy (HR 0.21; 95% CrI 0.05 to 0.77; no direct comparison) groups.\nBased on low-certainty evidence, beta-blockers alone and TIPS might result in more, other compensation, events than sclerotherapy (rate ratio 2.37; 95% CrI 1.35 to 4.67; 1 trial; 65 participants and rate ratio 2.30; 95% CrI 1.20 to 4.65; 2 trials; 109 participants; low-certainty evidence).\nThe evidence indicates considerable uncertainty about the effect of the interventions including those related to beta-blockers plus variceal band ligation in the remaining comparisons.\nAuthors' conclusions\nThe evidence indicates considerable uncertainty about the effect of the interventions on mortality. Variceal band ligation might result in fewer serious adverse events than sclerotherapy. TIPS might result in a large decrease in symptomatic rebleed than variceal band ligation. Sclerotherapy probably results in fewer 'any' variceal rebleeding than no active intervention. Beta-blockers plus sclerotherapy and TIPS probably result in fewer 'any' variceal rebleeding than sclerotherapy. Beta-blockers alone and TIPS might result in more other compensation events than sclerotherapy. The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons. Accordingly, high-quality randomised comparative clinical trials are needed.\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": "This review looked at adults of any sex, age, and ethnic origin, with advanced liver disease due to various causes and previous bleeding from oesophageal varices. Participants were given different treatments for preventing further bleeding oesophageal varices. The authors excluded studies in people who had bleeding from the stomach, who had no previous bleeding from the oesophageal varices, those who failed to respond to another treatment before study entry, and those who had liver transplantation previously. The average age of participants, when reported, ranged from 40 to 63 years. The treatments used in the trials included endoscopic sclerotherapy (injecting into the enlarged veins by looking through a tube inserted through the mouth), variceal band ligation (inserting bands around the dilated veins by seeing through a tube inserted through the mouth), beta-blockers (drugs that slow the heart and decrease the force of heart pumping resulting in decrease pressure in the blood vessels), and TIPS (transjugular intrahepatic portosystemic shunt; an artificial channel that connects the different blood vessels that carry oxygen-depleted blood (venous system)) within the liver to reduce the pressure built-up in the portal venous system, one of the two venous systems draining the liver), portocaval shunt (performing surgery to create the artificial channel described for TIPS) among others. The review authors wanted to gather and analyse data on death, quality of life, serious and non-serious adverse events, recurrence of bleeding, and development of other complications of advanced liver disease.What were the main results of the review?The 48 studies included a small number of participants (3526 participants). Study data were sparse. Forty-six studies with 3442 participants provided data for analyses. The follow-up of the trial participants ranged from two months to five years.\nThe funding source for the research was unclear in 36 studies; commercial organisations funded five studies. There were no concerns regarding the source of funding for the remaining nine studies.\nThe review shows the following.\n- The evidence indicates considerable uncertainty about the effect of the interventions on the risk of death\n- Variceal band ligation might result in fewer serious adverse events than sclerotherapy\n- The evidence indicates considerable uncertainty about the effect of the interventions on serious and non-serious adverse events\n- Sclerotherapy probably results in decrease in further bleeding than no treatment\n- Beta-blockers plus sclerotherapy and TIPS probably result in a decrease in further bleeding than sclerotherapy alone\n- Portocaval shunt may result in a decrease in further bleeding than sclerotherapy\n- The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons\n- None of the trials reported health-related quality of life\n- Future well-designed trials are needed to find out the best treatment for people with cirrhosis and previous bleeding from oesophageal varices." } ]

[ { "role": "user", "content": "Abstract: Background\nAlthough various solutions have been recommended for cleansing wounds, normal saline is favoured as it is an isotonic solution and is not thought to interfere with the normal healing process. Tap water is commonly used in community settings for cleansing wounds because it is easily accessible, efficient and cost-effective; however, there is an unresolved debate about its use.\nObjectives\nTo assess the effects of water for wound cleansing.\nSearch methods\nFor this fifth update, in May 2021 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched 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\nWe included all randomised controlled trials (RCTs) that assessed wound cleansing using different types of water (e.g. tap water, distilled, boiled) compared with no cleansing or with other solutions (e.g. normal saline). For this update, we excluded quasi-RCTs, thereby removing some studies which had been included in the previous version of the review.\nData collection and analysis\nTwo review authors independently carried out trial selection, data extraction and GRADE assessment of the certainty of evidence.\nMain results\nWe included 13 trials in this update including a total of 2504 participants ranging in age from two to 95 years. Participants in the trials experienced open fractures, surgical wounds, traumatic wounds, anal fissures and chronic wounds. The trials were conducted in six different countries with the majority conducted in India and the USA. Three trials involving 148 participants compared cleansing with tap water with no cleansing. Eight trials involving 2204 participants assessed cleansing with tap water compared with cleansing with normal saline. Two trials involving 152 participants assessed cleansing with distilled water compared with cleansing with normal saline.  One trial involving 51 participants also assessed cleansing with cooled boiled water compared with cleansing with normal saline, and cleansing with distilled water compared with cleansing with cooled boiled water.\nWound infection: no trials reported on wound infection for the comparison cleansing with tap water versus no cleansing. For all wounds, eight trials found the effect of cleansing with tap water compared with normal saline is uncertain (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.59 to 1.19); very low-certainty evidence. Two trials comparing the use of distilled water with normal saline for cleansing open fractures found that the effect on the number of fractures that were infected is uncertain (RR 0.70, 95% CI 0.45 to 1.09); very low-certainty evidence. One trial compared the use of cooled boiled water with normal saline for cleansing open fractures and found that the effect on the number of fractures infected is uncertain (RR 0.83, 95% CI 0.37 to 1.87); very low-certainty evidence. This trial also compared the use of distilled water with cooled boiled water and found that the effect on the number of fractures infected is uncertain (RR 0.59, 95% CI 0.24 to 1.47); very low-certainty evidence.\nWound healing: results from three trials comparing the use of tap water with no wound cleansing demonstrated there may be little or no difference in the number of wounds that did not heal between the groups (RR 1.04, 95% CI 0.95 to 1.14); low-certainty evidence. The effect of tap water compared with normal saline is uncertain; two trials were pooled (RR 0.57, 95% CI 0.30 to 1.07) but the certainty of the evidence is very low. Results from one study comparing the use of distilled water with normal saline for cleansing open fractures found that there may be little or no difference in the number of fractures that healed (RR could not be estimated, all wounds healed); the certainty of the evidence is low.\nReduction in wound size: the effect of cleansing with tap water compared with normal saline on wound size reduction is uncertain (RR 0.97, 95% CI 0.56 to 1.68); the certainty of the evidence is very low.\nRate of wound healing: the effect of cleansing with tap water compared with normal saline on wound healing rate is uncertain (mean difference (MD) -3.06, 95% CI -6.70 to 0.58); the certainty of the evidence is very low.\nCosts: two trials reported cost analyses but the cost-effectiveness of tap water compared with the use of normal saline is uncertain; the certainty of the evidence is very low.\nPain: results from one study comparing the use of tap water with no cleansing for acute and chronic wounds showed that there may be little or no difference in pain scores. The certainty of the evidence is low.\nPatient satisfaction: results from one study comparing the use of tap water with no cleansing for acute and chronic wounds showed that there may be little or no difference in patient satisfaction. The certainty of evidence is low. The effect of cleansing with tap water compared with normal saline is uncertain as the certainty of the evidence is very low.\nAuthors' conclusions\nAll the evidence identified in the review was low or very low certainty. Cleansing with tap water may make little or no difference to wound healing compared with no cleansing; there are no data relating to the impact on wound infection. The effects of cleansing with tap water, cooled boiled water or distilled water compared with cleansing with saline are uncertain, as is the effect of distilled water compared with cooled boiled water. Data for other outcomes are limited across all the comparisons considered and are either uncertain or suggest that there may be little or no difference in the outcome.\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": "Infection can interfere with the normal wound-healing process. In order to reduce the risk of infection, wounds are routinely cleansed to remove dirt, contamination or impurities. In this review, a wound is defined as a break in the skin." } ]

[ { "role": "user", "content": "Abstract: Background\nTotal knee replacement (TKR) is a common intervention for people with end-stage symptomatic knee osteoarthritis, resulting in significant improvements in pain, function and quality of life within three to six months. It is, however, acutely associated with pain, local oedema and blood loss. Post-operative management may include cryotherapy. This is the application of low temperatures to the skin surrounding the surgical site, through ice or cooled water, often delivered using specialised devices. This is an update of a review published in 2012.\nObjectives\nTo evaluate the effect of cryotherapy in the acute phase after TKR (within 48 hours after surgery) on blood loss, pain, transfusion rate, range of motion, knee function, adverse events and withdrawals due to adverse events.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, as well as reference lists, related links and conference proceedings on 27 May 2022.\nSelection criteria\nWe included randomised controlled trials or controlled clinical trials comparing cryotherapy with or without other treatments (such as compression, regional nerve block or continuous passive motion) to no treatment, or the other treatment alone, following TKR for osteoarthritis.\nData collection and analysis\nTwo review authors independently selected studies for inclusion, extracted data and assessed risk of bias and certainty of evidence using GRADE. We discussed any disagreements and consulted another review author to resolve them, if required. Major outcomes were blood loss, pain, transfusion rate, knee range of motion, knee function, total adverse events and withdrawals from adverse events. Minor outcomes were analgesia use, knee swelling, length of stay, quality of life, activity level and participant-reported global assessment of success.\nMain results\nWe included 22 trials (20 randomised trials and two controlled clinical trials), with 1839 total participants. The mean ages reflected the TKR population, ranging from 64 to 74 years.\nCryotherapy with compression was compared to no treatment in four studies, and to compression alone in nine studies. Cryotherapy without compression was compared to no treatment in eight studies. One study compared cryotherapy without compression to control with compression alone. We combined all control interventions in the primary analysis.\nCertainty of evidence was low for blood loss (downgraded for bias and inconsistency), pain (downgraded twice for bias) and range of motion (downgraded for bias and indirectness). It was very low for transfusion rate (downgraded for bias, inconsistency and imprecision), function (downgraded twice for bias and once for inconsistency), total adverse events (downgraded for bias, indirectness and imprecision) and withdrawals from adverse events (downgraded for bias, indirectness and imprecision). The nature of cryotherapy made blinding difficult and most studies had a high risk of performance and detection bias.\nLow-certainty evidence from 12 trials (956 participants) shows that cryotherapy may reduce blood loss at one to 13 days after surgery. Blood loss was 825 mL with no cryotherapy and 561 mL with cryotherapy: mean difference (MD) 264 mL less (95% confidence interval (CI) 7 mL less to 516 mL less).\nLow-certainty evidence from six trials (530 participants) shows that cryotherapy may slightly improve pain at 48 hours on a 0- to 10-point visual analogue scale (lower scores indicate less pain). Pain was 4.8 points with no cryotherapy and 3.16 points with cryotherapy: MD 1.6 points lower (95% CI 2.3 lower to 1.0 lower).\nWe are uncertain whether cryotherapy improves transfusion rate at zero to 13 days after surgery. The transfusion rate was 37% with no cryotherapy and 79% with cryotherapy (risk ratio (RR) 2.13, 95% CI 0.04 to 109.63; 2 trials, 91 participants; very low-certainty evidence).\nLow-certainty evidence from three trials (174 participants) indicates cryotherapy may improve range of motion at discharge: it was 62.9 degrees with no cryotherapy and 71.2 degrees with cryotherapy: MD 8.3 degrees greater (95% CI 3.6 degrees more to 13.1 degrees more).\nWe are uncertain whether cryotherapy improves function two weeks after surgery. Function was 75.4 points on the 0- to 100-point Dutch Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale (lower score indicates worse function) in the control group and 88.6 points with cryotherapy (MD 13.2 points better, 95% CI 0.5 worse to 27.1 improved; 4 trials, 296 participants; very low-certainty evidence).\nWe are uncertain whether cryotherapy reduces total adverse events: the risk ratio was 1.30 (95% CI 0.53 to 3.20; 16 trials, 1199 participants; very low-certainty evidence). Adverse events included discomfort, local skin reactions, superficial infections, cold-induced injuries and thrombolytic events.\nWe are uncertain whether cryotherapy reduces withdrawals from adverse events (RR 2.71, 95% CI 0.42 to 17.38; 19 trials, 1347 participants; very low-certainty evidence).\nNo significant benefit was found for secondary outcomes of analgesia use, length of stay, activity level or quality of life. Evidence from seven studies (403 participants) showed improved mid-patella swelling between two and six days after surgery (MD 7.32 mm less, 95% CI 11.79 to 2.84 lower), though not at six weeks and three months after surgery. The included studies did not assess participant-reported global assessment of success.\nAuthors' conclusions\nThe certainty of evidence was low for blood loss, pain and range of motion, and very low for transfusion rate, function, total adverse events and withdrawals from adverse events. We are uncertain whether cryotherapy improves transfusion rate, function, total adverse events or withdrawals from adverse events. We downgraded evidence for bias, indirectness, imprecision and inconsistency. Hence, the potential benefits of cryotherapy on blood loss, pain and range of motion may be too small to justify its use. More well-designed randomised controlled trials focusing especially on clinically meaningful outcomes, such as blood transfusion, and patient-reported outcomes, such as knee function, quality of life, activity level and participant-reported global assessment of success, are required.\n\nGiven the provided abstract, please respond to the following query: \"Main results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Blood loss\nBlood loss was 264 mL less with cryotherapy at up to 13 days after surgery.\n• People lost 561 mL of blood with cryotherapy.\n• People lost 825 mL of blood without cryotherapy.\nPain (lower scores mean less pain)\nPain was better by 1.6 points on a 0- to 10-point scale with cryotherapy at 2 days after surgery.\n• People who had cryotherapy rated their pain as 3.2 points.\n• People who had no cryotherapy rated their pain as 4.8 points.\nBlood transfusion\n11% more people had a blood transfusion with cryotherapy, or 11 more out of 100, at up to 13 days after surgery.\n• 79 out of 100 people had a transfusion with cryotherapy.\n• 37 out of 100 people had a transfusion without cryotherapy.\nKnee range of motion\nFlexion (bending of the knee joint) was 8.3 degrees greater with cryotherapy when people left hospital.\n• People who had cryotherapy had 71.2 degrees of flexion.\n• People who had no cryotherapy had 62.9 degrees of flexion.\nKnee function\nKnee function was 13.2 points better on a 0- to 100-point scale with cryotherapy at 2 weeks after surgery.\n• People who had cryotherapy had a function score of 88.6.\n• People who had no cryotherapy had a function score of 75.4\nTotal adverse events\n0% more people reported adverse events with cryotherapy, or 0 more out of 100, up to 30 days after surgery.\n• 2.7 out of 100 people reported adverse events with cryotherapy.\n• 2.1 out of 100 people reported adverse events without cryotherapy.\nWithdrawals due to adverse events\n0% more people withdrew from the study due to adverse events with cryotherapy, or 0 more out of 100, up to 30 days after surgery.\n• 0.4 out of 100 people withdrew due to adverse events with cryotherapy.\n• 0.2 out of 100 people withdrew due to adverse events without cryotherapy." } ]

[ { "role": "user", "content": "Abstract: Background\nAfter decades of decline since 2005, the global prevalence of undernourishment reverted and since 2015 has increased to levels seen in 2010 to 2011. The prevalence is highest in low- and middle-income countries (LMICs), especially Africa and Asia. Food insecurity and associated undernutrition detrimentally affect health and socioeconomic development in the short and long term, for individuals, including children, and societies. Physical and economic access to food is crucial to ensure food security. Community-level interventions could be important to increase access to food in LMICs.\nObjectives\nTo determine the effects of community-level interventions that aim to improve access to nutritious food in LMICs, for both the whole community and for disadvantaged or at-risk individuals or groups within a community, such as infants, children and women; elderly, poor or unemployed people; or minority groups.\nSearch methods\nWe searched for relevant studies in 16 electronic databases, including trial registries, from 1980 to September 2019, and updated the searches in six key databases in February 2020. We applied no language or publication status limits.\nSelection criteria\nWe included randomised controlled trials (RCTs), cluster randomised controlled trials (cRCTs) and prospective controlled studies (PCS). All population groups, adults and children, living in communities in LMICs exposed to community-level interventions aiming to improve food access were eligible for inclusion. We excluded studies that only included participants with specific diseases or conditions (e.g. severely malnourished children).\nEligible interventions were broadly categorised into those that improved buying power (e.g. create income-generation opportunities, cash transfer schemes); addressed food prices (e.g. vouchers and subsidies); addressed infrastructure and transport that affected physical access to food outlets; addressed the social environment and provided social support (e.g. social support from family, neighbours or government).\nData collection and analysis\nTwo authors independently screened titles and abstracts, and full texts of potentially eligible records, against the inclusion criteria. Disagreements were resolved through discussion or arbitration by a third author, if necessary.\nFor each included study, two authors independently extracted data and a third author arbitrated disagreements. However, the outcome data were extracted by one author and checked by a biostatistician.\nWe assessed risk of bias for all studies using the Effective Practice and Organization of Care (EPOC) risk of bias tool for studies with a separate control group.\nWe conducted meta-analyses if there was a minimum of two studies for interventions within the same category, reporting the same outcome measure and these were sufficiently homogeneous. Where we were able to meta-analyse, we used the random-effects model to incorporate any existing heterogeneity. Where we were unable to conduct meta-analyses, we synthesised using vote counting based on effect direction.\nMain results\nWe included 59 studies, including 214 to 169,485 participants, and 300 to 124, 644 households, mostly from Africa and Latin America, addressing the following six intervention types (three studies assessed two different types of interventions).\nInterventions that improved buying power:\nUnconditional cash transfers (UCTs) (16 cRCTs, two RCTs, three PCSs): we found high-certainty evidence that UCTs improve food security and make little or no difference to cognitive function and development and low-certainty evidence that UCTs may increase dietary diversity and may reduce stunting. The evidence was very uncertain about the effects of UCTs on the proportion of household expenditure on food, and on wasting. Regarding adverse outcomes, evidence from one trial indicates that UCTs reduce the proportion of infants who are overweight.\nConditional cash transfers (CCTs) (nine cRCTs, five PCSs): we found high-certainty evidence that CCTs result in little to no difference in the proportion of household expenditure on food and that they slightly improve cognitive function in children; moderate-certainty evidence that CCTs probably slightly improve dietary diversity and low-certainty evidence that they may make little to no difference to stunting or wasting. Evidence on adverse outcomes (two PCSs) shows that CCTs make no difference to the proportion of overweight children.\nIncome generation interventions (six cRCTs, 11 PCSs): we found moderate-certainty evidence that income generation interventions probably make little or no difference to stunting or wasting; and low-certainty evidence that they may result in little to no difference to food security or that they may improve dietary diversity in children, but not for households.\nInterventions that addressed food prices:\nFood vouchers (three cRCTs, one RCT): we found moderate-certainty evidence that food vouchers probably reduce stunting; and low-certainty evidence that that they may improve dietary diversity slightly, and may result in little to no difference in wasting.\nFood and nutrition subsidies (one cRCT, three PCSs): we found low-certainty evidence that food and nutrition subsidies may improve dietary diversity among school children. The evidence is very uncertain about the effects on household expenditure on healthy foods as a proportion of total expenditure on food (very low-certainty evidence).\nInterventions that addressed the social environment:\nSocial support interventions (one cRCT, one PCS): we found moderate-certainty evidence that community grants probably make little or no difference to wasting; low-certainty evidence that they may make little or no difference to stunting. The evidence is very uncertain about the effects of village savings and loans on food security and dietary diversity.\nNone of the included studies addressed the intervention category of infrastructure changes. In addition, none of the studies reported on one of the primary outcomes of this review, namely prevalence of undernourishment.\nAuthors' conclusions\nThe body of evidence indicates that UCTs can improve food security. Income generation interventions do not seem to make a difference for food security, but the evidence is unclear for the other interventions. CCTs, UCTs, interventions that help generate income, interventions that help minimise impact of food prices through food vouchers and subsidies can potentially improve dietary diversity. UCTs and food vouchers may have a potential impact on reducing stunting, but CCTs, income generation interventions or social environment interventions do not seem to make a difference on wasting or stunting. CCTs seem to positively impact cognitive function and development, but not UCTs, which may be due to school attendance, healthcare visits and other conditionalities associated with CCTs.\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": "" } ]

[ { "role": "user", "content": "Abstract: Background\nCentral venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality. This is an update of the Cochrane Review published in 2014.\nObjectives\nTo evaluate the efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC.\nSearch methods\nWe conducted a comprehensive literature search in May 2018 that included a major electronic search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Ovid); handsearching of conference proceedings; checking of references of included studies; searching for ongoing studies; and using the 'related citation' feature in PubMed. This update of the systematic review was based on the findings of a literature search conducted on 14 May 2018.\nSelection criteria\nRandomized controlled trials (RCTs) assessing the benefits and harms of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux or comparing the effects of two of these anticoagulants in people with cancer and a CVC.\nData collection and analysis\nUsing a standardized form, we extracted data and assessed risk of bias. Outcomes included all-cause mortality, symptomatic catheter-related venous thromboembolism (VTE), pulmonary embolism (PE), major bleeding, minor bleeding, catheter-related infection, thrombocytopenia, and health-related quality of life (HRQoL). We assessed the certainty of evidence for each outcome using the GRADE approach (Balshem 2011).\nMain results\nThirteen RCTs (23 papers) fulfilled the inclusion criteria. These trials enrolled 3420 participants. Seven RCTs compared LMWH to no LMWH (six in adults and one in children), six RCTs compared VKA to no VKA (five in adults and one in children), and three RCTs compared LMWH to VKA in adults.\nLMWH versus no LMWH\nSix RCTs (1537 participants) compared LMWH to no LMWH in adults. The meta-analyses showed that LMWH probably decreased the incidence of symptomatic catheter-related VTE up to three months of follow-up compared to no LMWH (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.22 to 0.81; risk difference (RD) 38 fewer per 1000, 95% CI 13 fewer to 52 fewer; moderate-certainty evidence). However, the analysis did not confirm or exclude a beneficial or detrimental effect of LMWH on mortality at three months of follow-up (RR 0.82, 95% CI 0.53 to 1.26; RD 14 fewer per 1000, 95% CI 36 fewer to 20 more; low-certainty evidence), major bleeding (RR 1.49, 95% CI 0.06 to 36.28; RD 0 more per 1000, 95% CI 1 fewer to 35 more; very low-certainty evidence), minor bleeding (RR 1.35, 95% CI 0.62 to 2.92; RD 14 more per 1000, 95% CI 16 fewer to 79 more; low-certainty evidence), and thrombocytopenia (RR 1.03, 95% CI 0.80 to 1.33; RD 5 more per 1000, 95% CI 35 fewer to 58 more; low-certainty evidence).\nVKA versus no VKA\nFive RCTs (1599 participants) compared low-dose VKA to no VKA in adults. The meta-analyses did not confirm or exclude a beneficial or detrimental effect of low-dose VKA compared to no VKA on mortality (RR 0.99, 95% CI 0.64 to 1.55; RD 1 fewer per 1000, 95% CI 34 fewer to 52 more; low-certainty evidence), symptomatic catheter-related VTE (RR 0.61, 95% CI 0.23 to 1.64; RD 31 fewer per 1000, 95% CI 62 fewer to 51 more; low-certainty evidence), major bleeding (RR 7.14, 95% CI 0.88 to 57.78; RD 12 more per 1000, 95% CI 0 fewer to 110 more; low-certainty evidence), minor bleeding (RR 0.69, 95% CI 0.38 to 1.26; RD 15 fewer per 1000, 95% CI 30 fewer to 13 more; low-certainty evidence), premature catheter removal (RR 0.82, 95% CI 0.30 to 2.24; RD 29 fewer per 1000, 95% CI 114 fewer to 202 more; low-certainty evidence), and catheter-related infection (RR 1.17, 95% CI 0.74 to 1.85; RD 71 more per 1000, 95% CI 109 fewer to 356; low-certainty evidence).\nLMWH versus VKA\nThree RCTs (641 participants) compared LMWH to VKA in adults. The available evidence did not confirm or exclude a beneficial or detrimental effect of LMWH relative to VKA on mortality (RR 0.94, 95% CI 0.56 to 1.59; RD 6 fewer per 1000, 95% CI 41 fewer to 56 more; low-certainty evidence), symptomatic catheter-related VTE (RR 1.83, 95% CI 0.44 to 7.61; RD 15 more per 1000, 95% CI 10 fewer to 122 more; very low-certainty evidence), PE (RR 1.70, 95% CI 0.74 to 3.92; RD 35 more per 1000, 95% CI 13 fewer to 144 more; low-certainty evidence), major bleeding (RR 3.11, 95% CI 0.13 to 73.11; RD 2 more per 1000, 95% CI 1 fewer to 72 more; very low-certainty evidence), or minor bleeding (RR 0.95, 95% CI 0.20 to 4.61; RD 1 fewer per 1000, 95% CI 21 fewer to 95 more; very low-certainty evidence). The meta-analyses showed that LMWH probably increased the risk of thrombocytopenia compared to VKA at three months of follow-up (RR 1.69, 95% CI 1.20 to 2.39; RD 149 more per 1000, 95% CI 43 fewer to 300 more; moderate-certainty evidence).\nAuthors' conclusions\nThe evidence was not conclusive for the effect of LMWH on mortality, the effect of VKA on mortality and catheter-related VTE, and the effect of LMWH compared to VKA on mortality and catheter-related VTE. We found moderate-certainty evidence that LMWH reduces catheter-related VTE compared to no LMWH. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.\n\nGiven the provided abstract, please respond to the following query: \"Certainty of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "When comparing injectable blood thinners to no anticoagulation, we judged the certainty of the evidence to be moderate for blood clot at the catheter site, low for mortality, infection at the catheter site and minor bleeding, and very low for major bleeding.\nWhen comparing blood thinner pills to no anticoagulation, we judged the certainty of the evidence to be low for mortality major and minor bleeding, premature catheter removal and catheter-related infection low, and very low for blood clot at the catheter site.\nWhen comparing injectable blood thinners to blood thinner pills, we judged the certainty of the evidence to be low for mortality and blood clots in the limbs and very low for blood clot at the catheter site, major and minor bleeding." } ]

[ { "role": "user", "content": "Abstract: Background\nThere is ongoing debate about the frequency with which patients should attend for a dental check-up and the effects on oral health of the interval between check-ups. Recommendations regarding optimal recall intervals vary between countries and dental healthcare systems, but 6-month dental check-ups have traditionally been advocated by general dental practitioners in many high-income countries.\nThis review updates a version first published in 2005, and updated in 2007 and 2013.\nObjectives\nTo determine the optimal recall interval of dental check-up for oral health in a primary care setting.\nSearch methods\nCochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 17 January 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; in the Cochrane Library, 2019, Issue 12), MEDLINE Ovid (1946 to 17 January 2020), and Embase Ovid (1980 to 17 January 2020). We also searched the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on the language or date of publication when searching.\nSelection criteria\nWe included randomised controlled trials (RCTs) assessing the effects of different dental recall intervals in a primary care setting.\nData collection and analysis\nTwo review authors screened search results against inclusion criteria, extracted data and assessed risk of bias, independently and in duplicate. We contacted study authors for clarification or further information where necessary and feasible. We expressed the estimate of effect as mean difference (MD) with 95% confidence intervals (CIs) for continuous outcomes and risk ratios (RR) with 95% CIs for dichotomous outcomes. We assessed the certainty of the evidence using GRADE.\nMain results\nWe included two studies with data from 1736 participants. One study was conducted in a public dental service clinic in Norway and involved participants under 20 years of age who were regular attenders at dental appointments. It compared 12-month with 24-month recall intervals and measured outcomes at two years. The other study was conducted in UK general dental practices and involved adults who were regular attenders, which was defined as having attended the dentist at least once in the previous two years. It compared the effects of 6-month, 24-month and risk-based recall intervals, and measured outcomes at four years. The main outcomes we considered were dental caries, gingival bleeding and oral-health-related quality of life. Neither study measured other potential adverse effects.\n24-month versus 12-month recall at 2 years' follow-up\nDue to the very low certainty of evidence from one trial, it is unclear if there is an important difference in caries experience between assignment to a 24-month or a 12-month recall. For 3- to 5-year-olds with primary teeth, the mean difference (MD) in dmfs (decayed, missing, and filled tooth surfaces) increment was 0.90 (95% CI −0.16 to 1.96; 58 participants). For 16- to 20-year-olds with permanent teeth, the MD in DMFS increment was 0.86 (95% CI −0.03 to 1.75; 127 participants). The trial did not assess other clinical outcomes of relevance to this review.\nRisk-based recall versus 6-month recall at 4 years' follow-up\nWe found high-certainty evidence from one trial of adults that there is little to no difference between risk-based and 6-month recall intervals for the outcomes: number of tooth surfaces with any caries (ICDAS 1 to 6; MD 0.15, 95% CI −0.77 to 1.08; 1478 participants); proportion of sites with gingival bleeding (MD 0.78%, 95% CI −1.17% to 2.73%; 1472 participants); oral-health-related quality of life (MD in OHIP-14 scores −0.35, 95% CI −1.02 to 0.32; 1551 participants). There is probably little to no difference in the prevalence of moderate to extensive caries (ICDAS 3 to 6) between the groups (RR 1.04, 95% CI 0.99 to 1.09; 1478 participants; moderate-certainty evidence).\n24-month recall versus 6-month recall at 4 years' follow-up\nWe found moderate-certainty evidence from one trial of adults that there is probably little to no difference between 24-month and 6-month recall intervals for the outcomes: number of tooth surfaces with any caries (MD −0.60, 95% CI −2.54 to 1.34; 271 participants); percentage of sites with gingival bleeding (MD −0.91%, 95% CI −5.02% to 3.20%; 271 participants). There may be little to no difference between the groups in the prevalence of moderate to extensive caries (RR 1.05, 95% CI 0.92 to 1.20; 271 participants; low-certainty evidence). We found high-certainty evidence that there is little to no difference in oral-health-related quality of life between the groups (MD in OHIP-14 scores −0.24, 95% CI −1.55 to 1.07; 305 participants).\nRisk-based recall versus 24-month recall at 4 years' follow-up\nWe found moderate-certainty evidence from one trial of adults that there is probably little to no difference between risk-based and 24-month recall intervals for the outcomes: prevalence of moderate to extensive caries (RR 1.06, 95% CI 0.95 to 1.19; 279 participants); number of tooth surfaces with any caries (MD 1.40, 95% CI −0.69 to 3.49; 279 participants). We found high-certainty evidence that there is no important difference between the groups in the percentage of sites with gingival bleeding (MD −0.07%, 95% CI −4.10% to 3.96%; 279 participants); or in oral-health-related quality of life (MD in OHIP-14 scores −0.37, 95% CI −1.69 to 0.95; 298 participants).\nAuthors' conclusions\nFor adults attending dental check-ups in primary care settings, there is little to no difference between risk-based and 6-month recall intervals in the number of tooth surfaces with any caries, gingival bleeding and oral-health-related quality of life over a 4-year period (high-certainty evidence). There is probably little to no difference between the recall strategies in the prevalence of moderate to extensive caries (moderate-certainty evidence).\nWhen comparing 24-month with either 6-month or risk-based recall intervals for adults, there is moderate- to high-certainty evidence that there is little to no difference in the number of tooth surfaces with any caries, gingival bleeding and oral-health-related quality of life over a 4-year period.\nThe available evidence on recall intervals between dental check-ups for children and adolescents is uncertain.\nThe two trials we included in the review did not assess adverse effects of different recall strategies.\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": "Having check-ups every six months might help to keep your mouth healthy and avoid dental problems in future, but could also lead to unnecessary dental treatments. However, having check-ups less often might let dental problems get worse and lead to difficult and expensive treatment and care.\nWe wanted to identify the best time interval to have between dental check-ups." } ]

[ { "role": "user", "content": "Abstract: Background\nCongenital cataracts are lens opacities in one or both eyes of babies or children present at birth. These may cause a reduction in vision severe enough to require surgery. Cataracts are proportionally the most treatable cause of visual loss in childhood, and are a particular problem in low-income countries, where early intervention may not be possible. Paediatric cataracts provide different challenges to those in adults. Intense inflammation, amblyopia (vision is obstructed by cataract from birth which prevents normal development of the visual system), posterior capsule opacification and uncertainty about the final trajectory of ocular growth parameters can affect results of treatment. Two options currently considered for children under 2 years of age with bilateral congenital cataracts are: (i) intraocular lens (IOL) implantation; or (ii) leaving a child with primary aphakia (no lens in the eye), necessitating the need for contact lenses or aphakic glasses. Other important considerations regarding surgery include the prevention of visual axis opacification (VAO), glaucoma and the route used to perform lensectomy.\nObjectives\nTo assess the effectiveness of infant cataract surgery or lensectomy to no surgery for bilateral congenital cataracts in children aged 2 years and under.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 1); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 25 January 2022.\nSelection criteria\nWe included all randomised controlled trials (RCTs) that compared infant cataract surgery or lensectomy to no surgery, in children with bilateral congenital cataracts aged 2 years and younger. This update (of a review published in 2001 and updated in 2006) does not include children over 2 years of age because they have a wider variety of aetiologies, and are therefore managed differently, and have contrasting outcomes.\nData collection and analysis\nWe used standard methods expected by Cochrane. Two review authors extracted data independently. We assessed the risk of bias of included studies using RoB 1 and assessed the certainty of the evidence using GRADE.\nMain results\nWe identified three RCTs that met our inclusion criteria with each trial comparing a different aspect of surgical intervention for this condition. The trials included a total of 79 participants under 2 years of age, were conducted in India and follow-up ranged from 1 to 5 years. Study participants and outcome assessors were not masked in these trials.\nOne study (60 children) compared primary IOL implantation with primary aphakia. The results from this study suggest that there may be little or no difference in visual acuity at 5 years comparing children with pseudophakia (mean logMAR 0.50) and aphakia (mean logMAR 0.59) (mean difference (MD) -0.09 logMAR, 95% confidence intervals (CIs) -0.24 to 0.06; 54 participants; very low-certainty evidence), but the evidence is very uncertain. The evidence is very uncertain as to the effect of IOL implantation compared with aphakia on visual axis opacification (VAO) (risk ratio (RR) 1.29, 95% CI 0.23 to 7.13; 54 participants; very low-certainty evidence). The trial investigators did not report on the cases of amblyopia. There was little evidence of a difference betwen the two groups in cases of glaucoma at 5 years follow-up (RR 0.86, 95% CI 0.24 to 3.10; 54 participants; very low-certainty evidence). Cases of retinal detachment and reoperation rates were not reported. The impact of IOL implantation on adverse effects is very uncertain because of the sparse data available: of the children who were pseudophakic, 1/29  needed a trabeculectomy and 8/29 developed posterior synechiae. In comparison, no trabeculectomies were needed in the aphakic group and 2/25 children had posterior synechiae (54 participants; very low-certainty evidence).\nThe second study (14 eyes of 7 children under 2 years of age) compared posterior optic capture of IOL without vitrectomy versus endocapsular implantations with anterior vitrectomy (commonly called 'in-the-bag surgery'). The authors did not report on visual acuity, amblyopia, glaucoma and reoperation rate. They had no cases of VAO in either group. The evidence is very uncertain as to the effect of in-the-bag implantation in children aged under 1 year. There was a higher incidence of inflammatory sequelae: 4/7 in-the-bag implantation eyes and 1/7 in optic capture eyes (P = 0.04, 7 participants; very low-certainty evidence). We graded the certainty of evidence as low or very low for imprecision in all outcomes because their statistical analysis reported that a sample size of 13 was needed in each group to achieve a power of 80%, whereas their subset of children under the age of 1 year had only 7 eyes in each group.\nThe third study (24 eyes of 12 children) compared a transcorneal versus pars plana route using a 25-gauge transconjunctival sutureless vitrectomy system. The evidence is very uncertain as to the effect of the route chosen on the incidence of VAO, with no cases reported at 1 year follow-up in either group. The investigators did not report on visual acuity, amblyopia, glaucoma, retinal detachment and reoperation rate. The pars plana route had the adverse effects of posterior capsule rupture in 2/12 eyes, and 1/12 eyes needing sutures. Conversely, 1/12 eyes operated on by the transcorneal route needed sutures. We graded the outcomes with very low-certainty because of the small sample size and the absence of a priori sample size calculation.\nAuthors' conclusions\nThere is no high level evidence for the effectiveness of one type of surgery for bilateral congenital cataracts over another, or whether surgery itself is better than primary aphakia. Further RCTs are required to inform modern practice about concerns, including the timing of surgery, age at which surgery should be undertaken, age for implantation of an IOL and development of complications, such as reoperations, glaucoma and retinal detachment. Standardising the methods used to measure visual function, along with objective monitoring of compliance with the use of aphakic glasses/contact lenses would greatly improve the quality of study data and enable more reliable interpretation of outcomes.\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": "Our confidence in the evidence is very low because we found only a few trials, and they differed from each other. The three trials we included used different methods and measured different outcomes. The trials had a small number of participants and were all based in India. This means their results may not be applicable globally.\nStudy limitations include that one study (60 children) reported low compliance with the use of contact lenses after surgery. The other 2 studies (12 and 7 children respectively) did not specify in their methods all the outcomes they were going to measure, which means that their reporting may have been biased. Participants and outcome assessors were also not masked in these studies." } ]

[ { "role": "user", "content": "Abstract: Background\nSurgical site infection rates in the month following surgery vary from 1% to 5%. Due to the large number of surgical procedures conducted annually, the costs of these surgical site infections (SSIs) can be considerable in financial and social terms. Nasal decontamination using antibiotics or antiseptics is performed to reduce the risk of SSIs by preventing organisms from the nasal cavity being transferred to the skin where a surgical incision will be made. Staphylococcus aureus (S aureus) colonises the nasal cavity and skin of carriers and can cause infection in open or unhealed surgical wounds. S aureus is the leading nosocomial (hospital-acquired) pathogen in hospitals worldwide. The potential effectiveness of nasal decontamination of S aureus is thought to be dependent on both the antibiotic/antiseptic used and the dose of application; however, it is unclear whether nasal decontamination actually reduces postoperative wound infection in S aureus carriers.\nObjectives\nTo assess the effects of nasal decontamination on preventing surgical site infections (SSIs) in people who are S aureus carriers undergoing surgery.\nSearch methods\nIn September 2016 we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched three clinical trial registries and the references of included studies and relevant systematic reviews. There were no restrictions based on language, date of publication or study setting.\nSelection criteria\nRandomised controlled trials (RCTs) which enrolled S aureus carriers with any type of surgery and assessed the use of nasal decontamination with antiseptic/antibiotic properties were included in the review.\nData collection and analysis\nTwo review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment.\nMain results\nWe located two studies (291 participants) for inclusion in this review. The trials were clinically heterogeneous with differences in duration of follow-up, and nasal decontamination regimens. One study compared mupirocin (2% contained in a base of polyethylene glycol 400 and polyethylene glycol 3350) with a placebo in elective cardiac surgery patients; and one study compared Anerdian (iodine 0.45% to 0.57% (W/V), chlorhexidine acetate 0.09% to 0.11% (W/V)) with no treatment also in cardiac surgery patients. The trials reported limited outcome data on SSI, adverse events and secondary outcomes (e.g. S aureus SSI, mortality).\nMupirocin compared with placebo\nThis study found no clear difference in SSI risk following use of mupirocin compared with placebo (1 trial, 257 participants); risk ratio (RR) 1.60, 95% confidence interval (CI) 0.79 to 3.25 based on 18/130 events in the mupirocin group and 11/127 in the control group; low-certainty evidence (downgraded twice due to imprecision).\nAnerdian compared with no treatment\nIt is uncertain whether there is a difference in SSI risk following treatment with Anerdian compared with no treatment (1 trial, 34 participants); RR 0.89, 95% CI 0.06 to 13.08 based on 1/18 events in the Anerdian group and 1/16 in the control group; very low certainty evidence (downgraded twice due to imprecision and once due to risk of bias).\nAuthors' conclusions\nThere is currently limited rigorous RCT evidence available regarding the clinical effectiveness of nasal decontamination in the prevention of SSI. This limitation is specific to the focused question our review addresses, looking at nasal decontamination as a single intervention in participants undergoing surgery who are known S aureus carriers. We were only able to identify two studies that met the inclusion criteria for this review and one of these was very small and poorly reported. The potential benefits and harms of using decontamination for the prevention of SSI in this group of people remain uncertain.\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": "It is unclear whether nasal decontamination makes a difference to the rate of SSI in people carrying S aureus bacteria. S aureus SSI was reported in only one trial and the results do not allow us to be certain about differences in infection rates. Some participants in the Anerdian study reported side effects such as itching around the nose, but these were not serious. Mortality was low where reported (one death was directly related to S aureus infection)." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute otitis media (AOM) is one of the most common childhood illnesses. While many children experience sporadic AOM episodes, an important group suffer from recurrent AOM (rAOM), defined as three or more episodes in six months, or four or more in one year. In this subset of children AOM poses a true burden through frequent episodes of ear pain, general illness, sleepless nights and time lost from nursery or school. Grommets, also called ventilation or tympanostomy tubes, can be offered for rAOM.\nObjectives\nTo assess the benefits and harms of bilateral grommet insertion with or without concurrent adenoidectomy in children with rAOM.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL; MEDLINE; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 4 December 2017.\nSelection criteria\nRandomised controlled trials (RCTs) comparing bilateral grommet insertion with or without concurrent adenoidectomy and no ear surgery in children up to age 16 years with rAOM. We planned to apply two main scenarios: grommets as a single surgical intervention and grommets as concurrent treatment with adenoidectomy (i.e. children in both the intervention and comparator groups underwent adenoidectomy). The comparators included active monitoring, antibiotic prophylaxis and placebo medication.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. Primary outcomes were: proportion of children who have no AOM recurrences at three to six months follow-up (intermediate-term) and persistent tympanic membrane perforation (significant adverse event). Secondary outcomes were: proportion of children who have no AOM recurrences at six to 12 months follow-up (long-term); total number of AOM recurrences, disease-specific and generic health-related quality of life, presence of middle ear effusion and other adverse events at short-term, intermediate-term and long-term follow-up. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.\nMain results\nFive RCTs (805 children) with unclear or high risk of bias were included. All studies were conducted prior to the introduction of pneumococcal vaccination in the countries' national immunisation programmes. In none of the trials was adenoidectomy performed concurrently in both groups.\nGrommets versus active monitoring\nGrommets were more effective than active monitoring in terms of:\n- proportion of children who had no AOM recurrence at six months (one study, 95 children, 46% versus 5%; risk ratio (RR) 9.49, 95% confidence interval (CI) 2.38 to 37.80, number needed to treat to benefit (NNTB) 3; low-quality evidence);\n- proportion of children who had no AOM recurrence at 12 months (one study, 200 children, 48% versus 34%; RR 1.41, 95% CI 1.00 to 1.99, NNTB 8; low-quality evidence);\n- number of AOM recurrences at six months (one study, 95 children, mean number of AOM recurrences per child: 0.67 versus 2.17, mean difference (MD) -1.50, 95% CI -1.99 to -1.01; low-quality evidence);\n- number of AOM recurrences at 12 months (one study, 200 children, one-year AOM incidence rate: 1.15 versus 1.70, incidence rate difference -0.55, 95% -0.17 to -0.93; low-quality evidence).\nChildren receiving grommets did not have better disease-specific health-related quality of life (Otitis Media-6 questionnaire) at four (one study, 85 children) or 12 months (one study, 81 children) than those managed by active monitoring (low-quality evidence).\nOne study reported no persistent tympanic membrane perforations among 54 children receiving grommets (low-quality evidence).\nGrommets versus antibiotic prophylaxis\nIt is uncertain whether or not grommets are more effective than antibiotic prophylaxis in terms of:\n- proportion of children who had no AOM recurrence at six months (two studies, 96 children, 60% versus 35%; RR 1.68, 95% CI 1.07 to 2.65, I2 = 0%, fixed-effect model, NNTB 5; very low-quality evidence);\n- number of AOM recurrences at six months (one study, 43 children, mean number of AOM recurrences per child: 0.86 versus 1.38, MD -0.52, 95% CI -1.37 to 0.33; very low-quality evidence).\nGrommets versus placebo medication\nGrommets were more effective than placebo medication in terms of:\n- proportion of children who had no AOM recurrence at six months (one study, 42 children, 55% versus 15%; RR 3.64, 95% CI 1.20 to 11.04, NNTB 3; very low-quality evidence);\n- number of AOM recurrences at six months (one study, 42 children, mean number of AOM recurrences per child: 0.86 versus 2.0, MD -1.14, 95% CI -2.06 to -0.22; very low-quality evidence).\nOne study reported persistent tympanic membrane perforations in 3 of 76 children (4%) receiving grommets (low-quality evidence).\nSubgroup analysis\nThere were insufficient data to determine whether presence of middle ear effusion at randomisation, type of grommet or age modified the effectiveness of grommets.\nAuthors' conclusions\nCurrent evidence on the effectiveness of grommets in children with rAOM is limited to five RCTs with unclear or high risk of bias, which were conducted prior to the introduction of pneumococcal vaccination. Low to very low-quality evidence suggests that children receiving grommets are less likely to have AOM recurrences compared to those managed by active monitoring and placebo medication, but the magnitude of the effect is modest with around one fewer episode at six months and a less noticeable effect by 12 months. The low to very low quality of the evidence means that these numbers need to be interpreted with caution since the true effects may be substantially different. It is uncertain whether or not grommets are more effective than antibiotic prophylaxis. The risk of persistent tympanic membrane perforation after grommet insertion was low.\nWidespread use of pneumococcal vaccination has changed the bacteriology and epidemiology of AOM, and how this might impact the results of prior trials is unknown. New and high-quality RCTs of grommet insertion in children with rAOM are therefore needed. These trials should not only focus on the frequency of AOM recurrences, but also collect data on the severity of AOM episodes, antibiotic consumption and adverse effects of both surgery and antibiotics. This is particularly important since grommets may reduce the severity of AOM recurrences and allow for topical rather than oral antibiotic treatment.\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": "An acute middle ear infection is one of the most common childhood illnesses. While most children have an occasional episode, some suffer from recurring ear infections (three or more infections over a period of a six months, or four or more in a year). Such recurring infections cause considerable distress through frequent ear pain, fever, general illness, sleepless nights and time lost from nursery or school for the child and from work for their carers. Grommets, also known as ventilation or tympanostomy tubes, can be offered as a treatment. They are tiny plastic tubes put into the eardrum by an ENT surgeon during a short operation." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis is a life-limiting inherited condition which affects one in 2500 newborns in the UK and 70,000 children and adults worldwide. The condition is multifaceted and affects many systems in the body. The respiratory system is particularly affected due to a build up of thickened secretions and a predisposition to infection. Inhaled bronchodilators are prescribed for 80% of people with cystic fibrosis in order to widen the airways and alleviate symptoms. Both short- and long-acting inhaled bronchodilators are used to improve respiratory symptoms. Short-acting inhaled bronchodilators take effect in minutes and typically last for four to eight hours (muscarinic antagonists). Long-acting inhaled bronchodilators also take effect within minutes but typically last for around 12 hours and sometimes longer. This review is one of two which are replacing a previously published review of both long- and short-acting inhaled bronchodilators. However, due to the lack of research in this area, we do not envisage undertaking any further updates of this long-acting inhaled bronchodilators review.\nObjectives\nThis review aims to evaluate long-acting inhaled bronchodilators in children and adults with cystic fibrosis in terms of clinical outcomes and safety. If possible, we aimed to assess the optimal drug and dosage regimen.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.\nDate of last search: 10 October 2017.\nWe also carried out a separate search of Embase and the reference lists of included trials. We searched clinical trials registries for any ongoing trials and made contact with pharmaceutical companies for any further trials.\nDate of Embase search: 11 October 2017.\nSelection criteria\nRandomised or quasi-randomised parallel trials comparing long-acting inhaled bronchodilators (beta-2 agonists and muscarinic antagonists) with placebo, no treatment or a different long-acting inhaled bronchodilator in adults and children with cystic fibrosis.\nData collection and analysis\nBoth authors independently assessed trials for inclusion (based on title, abstract and full text). The authors independently assessed the included trials for quality and risk of bias and extracted data. Discrepancies were resolved by a third party.\nMain results\nThe searches identified 195 unique references, of which 155 were excluded on title and abstract. We assessed the full texts of the remaining references, excluded 16 trials (28 references) and included four trials (12 references) in the review with 1082 participants.\nOne trial (n = 16) measuring the effect of beta-2 agonists reported an improvement in forced expiratory volume at one second (FEV1) after treatment (at one month), but the trial was small with an unclear risk of bias so we judged the evidence to be very low quality. The trial did not report on participant-reported outcomes, quality of life or adverse events.\nThree trials (n = 1066) looked at the effects of the muscarinic antagonist tiotropium at doses of 2.5 µg and 5.0 µg in both the short term (up to 28 days) and the longer term (up to three months). Only one of the trials reported the change in FEV1 (L) after 28 days treatment and showed no significant difference between groups; with 2.5 µg tiotropium, mean difference (MD) -0.02 (95% confidence interval (CI) -0.13 to 0.09), or 5.0 µg tiotropium, MD 0.00 (95% CI -0.10 to 0.10) (moderate-quality evidence). All three trials of muscarinic antagonists provided data on adverse events which were found to differ little from placebo at doses of 2.5 µg, risk ratio (RR) 1.01 (95% CI 0.92 to 1.11) or 5.0 µg, RR 0.98 (95% CI 0.90 to 1.06). Very little participant-reported outcome data or quality of life data were available for analysis. Two of the trials were at low risk of bias overall whilst the remaining trial was at an unclear risk overall.\nAuthors' conclusions\nNeither long-acting beta-2 agonists nor long-acting muscarinic antagonist bronchodilators demonstrate improvement in our primary outcome of FEV1. No difference was observed between intervention and placebo in terms of quality of life or adverse events. The quality of evidence for the use of beta-2 agonists was very low. The use of a long-acting inhaled bronchodilator may help to reduce the burden of treatment for people with cystic fibrosis as it is taken less often than a short-acting inhaled bronchodilator, but future trials would benefit from looking at the effects on our primary outcomes (spirometric changes from baseline, quality of life and adverse effects) in the longer term.\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": "The small trial of beta-2 agonists compared to placebo (no active medication) reported some improvement in lung function (forced expiratory volume at one second (FEV1)) after treatment, but did not provide data we could analyse. They did not report on any side effects.\nOnly one of the three trials comparing tiotropium to a placebo reported on FEV1 (measured in litres) and found little difference between treatment and placebo. Two of these trials reported on quality of life, but there was not enough evidence to comment on whether this improved or not. Three trials noted side effects, some of which were seen after treatment with tiotropium, but these symptoms were also seen in the group of people who were given placebo. Future trials would improve our knowledge if they measure side effects and quality of life in a more meaningful way." } ]

[ { "role": "user", "content": "Abstract: Background\nOtitis media is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent otitis media.\nObjectives\nTo evaluate whether zinc supplements prevent otitis media in adults and children of different ages.\nSearch methods\nWe searched CENTRAL (2014, Issue 1), MEDLINE (1950 to February week 4, 2014) and EMBASE (1974 to March 2014).\nSelection criteria\nRandomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing otitis media.\nData collection and analysis\nTwo review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate.\nMain results\nNo new trials were identified for inclusion in this update. We identified 12 trials for inclusion, 10 of which contributed outcomes data. There were a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc-supplemented and placebo groups in the numbers of participants experiencing an episode of definite otitis media during follow-up (3191 participants); another trial showed a significantly lower incidence rate of otitis media in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of otitis media (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the supplements. The trial evidence included is generally of good quality, with a low risk of bias.\nAuthors' conclusions\nEvidence on whether zinc supplementation can reduce the incidence of otitis media in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus (severe malnutrition), but this is based on one small trial and should therefore be treated with caution.\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 trial evidence included is generally of good quality, with a low risk of bias. All the included trials included otitis media only as a secondary outcome. Therefore, there was a potential to miss trials which were less publicised or less well indexed within the electronic databases." } ]

[ { "role": "user", "content": "Abstract: Background\nExcessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling.\nThis is an update of a Cochrane Review published in 2007.\nObjectives\nTo assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews.\nSelection criteria\nWe included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption.\nMain results\nWe included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention.\nWe found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).\nWe found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-20 g/week, 95% CI -40 to 1; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).\nExtended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).\nOnly five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms.\nSources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment.\nAuthors' conclusions\nWe found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.\n\nGiven the provided abstract, please respond to the following query: \"Study funding\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Funding sources were reported by 60 (87%) studies. Of these, 58 studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment. Nine studies did not report study funding sources." } ]

[ { "role": "user", "content": "Abstract: Background\nVestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. These unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of interventions have been used, or proposed to be used, as prophylaxis for this condition, to help reduce the frequency of the attacks. Many of these interventions include dietary, lifestyle or behavioural changes, rather than medication.\nObjectives\nTo assess the benefits and harms of non-pharmacological treatments used for prophylaxis of vestibular migraine.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing dietary modifications, sleep improvement techniques, vitamin and mineral supplements, herbal supplements, talking therapies, mind-body interventions or vestibular rehabilitation with either placebo or no treatment. We excluded studies with a cross-over design, unless data from the first phase of the study could be identified.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 3 months, 3 to < 6 months, > 6 to 12 months. We used GRADE to assess the certainty of evidence for each outcome.\nMain results\nWe included three studies in this review with a total of 319 participants. Each study addressed a different comparison and these are outlined below. We did not identify any evidence for the remaining comparisons of interest in this review.\nDietary interventions (probiotics) versus placebo\nWe identified one study with 218 participants (85% female). The use of a probiotic supplement was compared to a placebo and participants were followed up for two years. Some data were reported on the change in vertigo frequency and severity over the duration of the study. However, there were no data regarding improvement of vertigo or serious adverse events.\nCognitive behavioural therapy (CBT) versus no intervention\nOne study compared CBT to no treatment in 61 participants (72% female). Participants were followed up for eight weeks. Data were reported on the change in vertigo over the course of the study, but no information was reported on the proportion of people whose vertigo improved, or on the occurrence of serious adverse events.\nVestibular rehabilitation versus no intervention\nThe third study compared the use of vestibular rehabilitation to no treatment in a group of 40 participants (90% female) and participants were followed up for six months. Again, this study reported some data on change in the frequency of vertigo during the study, but no information on the proportion of participants who experienced an improvement in vertigo or the number who experienced serious adverse events.\nWe are unable to draw meaningful conclusions from the numerical results of these studies, as the data for each comparison of interest come from single, small studies and the certainty of the evidence was low or very low.\nAuthors' conclusions\nThere is a paucity of evidence for non-pharmacological interventions that may be used for prophylaxis of vestibular migraine. Only a limited number of interventions have been assessed by comparing them to no intervention or a placebo treatment, and the evidence from these studies is all of low or very low certainty. We are therefore unsure whether any of these interventions may be effective at reducing the symptoms of vestibular migraine and we are also unsure whether they have the potential to cause harm.\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:\n- whether there was evidence that any non-drug treatments work to prevent attacks of vestibular migraine, or reduce the symptoms when an attack occurs;\n- whether the treatments might cause any harm." } ]

[ { "role": "user", "content": "Abstract: Background\nFor centuries, there has been controversy around whether being upright (sitting, birthing stools, chairs, squatting, kneeling) or lying down (lateral (Sim's) position, semi-recumbent, lithotomy position, Trendelenburg's position) have advantages for women giving birth to their babies. This is an update of a review previously published in 2012, 2004 and 1999.\nObjectives\nTo determine the possible benefits and risks of the use of different birth positions during the second stage of labour without epidural anaesthesia, on maternal, fetal, neonatal and caregiver outcomes.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth's Trials Register (30 November 2016) and reference lists of retrieved studies.\nSelection criteria\nRandomised, quasi-randomised or cluster-randomised controlled trials of any upright position assumed by pregnant women during the second stage of labour compared with supine or lithotomy positions. Secondary comparisons include comparison of different upright positions and the supine position. Trials in abstract form were included.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and assessed trial quality. At least two review authors extracted the data. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach.\nMain results\nResults should be interpreted with caution because risk of bias of the included trials was variable. We included eleven new trials for this update; there are now 32 included studies, and one trial is ongoing. Thirty trials involving 9015 women contributed to the analysis. Comparisons include any upright position, birth or squat stool, birth cushion, and birth chair versus supine positions.\nIn all women studied (primigravid and multigravid), when compared with supine positions, the upright position was associated with a reduction in duration of second stage in the upright group (MD -6.16 minutes, 95% CI -9.74 to -2.59 minutes; 19 trials; 5811 women; P = 0.0007; random-effects; I² = 91%; very low-quality evidence); however, this result should be interpreted with caution due to large differences in size and direction of effect in individual studies. Upright positions were also associated with no clear difference in the rates of caesarean section (RR 1.22, 95% CI 0.81 to 1.81; 16 trials; 5439 women; low-quality evidence), a reduction in assisted deliveries (RR 0.75, 95% CI 0.66 to 0.86; 21 trials; 6481 women; moderate-quality evidence), a reduction in episiotomies (average RR 0.75, 95% CI 0.61 to 0.92; 17 trials; 6148 women; random-effects; I² = 88%), a possible increase in second degree perineal tears (RR 1.20, 95% CI 1.00 to 1.44; 18 trials; 6715 women; I² = 43%; low-quality evidence), no clear difference in the number of third or fourth degree perineal tears (RR 0.72, 95% CI 0.32 to 1.65; 6 trials; 1840 women; very low-quality evidence), increased estimated blood loss greater than 500 mL (RR 1.48, 95% CI 1.10 to 1.98; 15 trials; 5615 women; I² = 33%; moderate-quality evidence), fewer abnormal fetal heart rate patterns (RR 0.46, 95% CI 0.22 to 0.93; 2 trials; 617 women), no clear difference in the number of babies admitted to neonatal intensive care (RR 0.79, 95% CI 0.51 to 1.21; 4 trials; 2565 infants; low-quality evidence). On sensitivity analysis excluding trials with high risk of bias, these findings were unchanged except that there was no longer a clear difference in duration of second stage of labour (MD -4.34, 95% CI -9.00 to 0.32; 21 trials; 2499 women; I² = 85%).\nThe main reasons for downgrading of GRADE assessment was that several studies had design limitations (inadequate randomisation and allocation concealment) with high heterogeneity and wide CIs.\nAuthors' conclusions\nThe findings of this review suggest several possible benefits for upright posture in women without epidural anaesthesia, such as a very small reduction in the duration of second stage of labour (mainly from the primigravid group), reduction in episiotomy rates and assisted deliveries. However, there is an increased risk blood loss greater than 500 mL and there may be an increased risk of second degree tears, though we cannot be certain of this. In view of the variable risk of bias of the trials reviewed, further trials using well-designed protocols are needed to ascertain the true benefits and risks of various birth positions.\n\nGiven the provided abstract, please respond to the following query: \"What is the issue?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Women often give birth in upright positions like kneeling, standing or squatting. Some women give birth on their backs in what are known as ‘supine’ positions - including dorsal (the woman flat on her back), lateral (the woman lying on her side), semi-recumbent (where the woman is angled partly upright) or lithotomy (where the woman’s legs are held up in stirrups). Birth position can be influenced by many different factors including setting, mother's choice, caregiver preference, or medical intervention. This Cochrane review assessed the possible benefits and risks to the mother and baby, by giving birth in upright positions compared with supine positions and also looked at some individual upright positions for benefits and harms." } ]

[ { "role": "user", "content": "Abstract: Background\nBacterial infections occurring during labour, childbirth, and the puerperium may be associated with considerable maternal and perinatal morbidity and mortality. Antibiotic prophylaxis might reduce wound infection incidence after an episiotomy, particularly in situations associated with a higher risk of postpartum perineal infection, such as midline episiotomy, extension of the incision, or in settings where the baseline risk of infection after vaginal birth is high. However, available evidence is unclear concerning the role of prophylactic antibiotics in preventing infections after an episiotomy.\nObjectives\nTo assess whether routine antibiotic prophylaxis before or immediately after incision or repair of episiotomy for women with an uncomplicated vaginal birth, compared with either placebo or no antibiotic prophylaxis, prevents maternal infectious morbidities and improves outcomes.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth's Trials Register, LILACS, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) on 24 July 2017, and screened reference lists of retrieved studies.\nSelection criteria\nWe considered randomised controlled trials, quasi-randomised trials, and cluster-randomised trials that compared the use of routine antibiotic prophylaxis for incision or repair of an episiotomy for women with otherwise normal vaginal births, compared with either placebo or no antibiotic prophylaxis.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We only found one quasi-randomised trial that met the inclusion criteria and was included in the analysis, therefore, we did not perform a meta-analysis.\nMain results\nWe included one quasi-RCT (with data from 73 women) in the review. The trial, which was conducted in a public hospital in Brazil, compared oral chloramphenicol 500 mg four times daily for 72 hours after episiotomy repair (N = 34) and no treatment (N = 39). We assessed most of the domains at high risk of bias because women were randomised according to even and odd numbers, allocation concealment was based on protocol number, there was no treatment or placebo administered in the control group, we were unclear about the blinding of outcome assessments, and outcomes were incompletely reported. We considered the other domains to be at low risk of bias. We downgraded the quality of the evidence for very serious design limitations (related to lack of random sequence generation, allocation concealment, and blinding) and imprecision of effect estimates (small sample sizes and wide confidence intervals (CI) of effect estimates).\nWe found very low-quality evidence, from one trial of 73 women, that there was no clear indication that prophylactic antibiotics reduced the incidence of episiotomy wound dehiscence with infection (risk ratio (RR) 0.13, 95% CI 0.01 to 2.28), or without infection (RR 0.82, 95% CI 0.29 to 2.34). No cases of other puerperal infections (e.g. endometritis) were reported in either the antibiotic or control group.\nThe trial did not report on any of the secondary outcomes of interest for this review, including severe maternal infectious morbidity, discomfort or pain at the episiotomy wound site, sexual function postpartum, adverse effects of antibiotics, costs of care, women's satisfaction with care, and individual antimicrobial resistance.\nAuthors' conclusions\nThere was insufficient evidence to assess the clinical benefits or harms of routine antibiotic prophylaxis for episiotomy repair after normal birth. The only trial included in this review had several methodological limitations, with very serious limitations in design, and imprecision of effect estimates. In addition, the trial tested an antibiotic with limited application in current clinical practice. There is a need for a careful and rigorous assessment of the comparative benefits and harms of prophylactic antibiotics on infection morbidity after episiotomy, in well-designed randomised controlled trials, using common antibiotics and regimens in current obstetric practice.\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": "The review assessed whether routine use of antibiotics at the time of an episiotomy prevented infection for women with an uncomplicated vaginal birth, compared with either placebo, or no antibiotics. We searched for evidence (24 July 2017) from randomised controlled trials in the medical literature. We only identified one small trial that was conducted in a public hospital in Brazil and provided very low-quality data from 73 women. The trial showed no clear difference between the groups, with or without antibiotics, of the number of women who experienced infection or breakdown of the episiotomy wound. No women developed infection of the lining of the uterus in either group. The trial did not report on any other outcomes of interest for this review." } ]

[ { "role": "user", "content": "Abstract: Background\nInhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review.\nObjectives\nTo determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis.\nSearch methods\nWe identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.\nDate of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 28 February 2019.\nSelection criteria\nAny trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author.\nData collection and analysis\nBoth authors independently assessed the trials identified by the search for potential inclusion in the review. The certainty of the evidence was assessed using GRADE.\nMain results\nThe searches identified 104 trial reports which represented 51 trials, of which three cross-over trials (providing data on 77 participants) met our inclusion criteria. We present three comparisons: inhalation before versus during airway clearance techniques; inhalation before versus after airway clearance techniques; and inhalation during versus after airway clearance techniques. One trial (50 participants), given its three-arm design, was eligible for all three comparisons. No trials compared morning versus evening inhalation of hypertonic saline.\nThe evidence from the three trials was judged to be of low quality downgraded for limitations (high risk of bias due to blinding) and indirectness (all participants are adults, and therefore not applicable to children). Intervention periods ranged from one treatment to three treatments in one day. There were no clinically important differences between the timing regimens of inhaling hypertonic saline before, during or after airway clearance techniques in the mean amount of improvement in lung function or symptom scores (77 participants), with the between-group comparisons being non-significant (low-certainty evidence). While there may be little or no difference in the rating of satisfaction when hypertonic saline was inhaled before versus during the airway clearance techniques (64 participants) (with the 95% confidence interval including the possibility of both a higher and lower rating of satisfaction), satisfaction may be lower on a 100-mm scale when inhaled after the airway clearance techniques compared to before: mean difference (MD) 20.38 mm (95% confidence interval (CI) 12.10 to 28.66) and when compared to during the techniques, MD 14.80 mm (95% CI 5.70 to 23.90). Perceived effectiveness showed similar results: little or no difference for inhalation before versus during airway clearance techniques (64 participants); may be lower when inhaled after the airway clearance techniques compared to before, MD 10.62 (95% CI 2.54 to 18.70); and also when compared to during the techniques, MD 15.60 (95% CI 7.55 to 23.65). There were no quality of life or adverse events reported in any of the trials.\nAuthors' conclusions\nTiming of hypertonic saline inhalation makes little or no difference to lung function (low-certainty evidence). However, inhaling hypertonic saline before or during airway clearance techniques may maximise perceived efficacy and satisfaction. The long-term efficacy of hypertonic saline has only been established for twice-daily inhalations; however, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available.\nThe identified trials were all of very short intervention periods, so longer-term research could be conducted to establish the effects arising from regular use, which would incorporate the influence of changes in adherence with long-term use, as well as generating data on any adverse effects that occur with long-term use.\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 about whether the timing (in relation to airway clearance techniques or in relation to time of day) of hypertonic saline (a strong, sterile, salt water solution) through a nebuliser improves the physical properties of sputum, stimulates cough, improves clinical outcomes (such as lung function), and improves the perceived effect of airway clearance techniques in cystic fibrosis. This is an update of a previously published Cochrane Review." } ]

[ { "role": "user", "content": "Abstract: Background\nAutogenic drainage is an airway clearance technique that was developed by Jean Chevaillier in 1967. The technique is characterised by breathing control using expiratory airflow to mobilise secretions from smaller to larger airways. Secretions are cleared independently by adjusting the depth and speed of respiration in a sequence of controlled breathing techniques during exhalation. The technique requires training, concentration and effort from the individual but it has previously been shown to be an effective treatment option for those who are seeking techniques to support and promote independence.  However, at a time where the trajectory and demographics of the disease are changing, it is important to systematically review the evidence demonstrating that autogenic drainage is an effective intervention for people with cystic fibrosis.\nObjectives\nTo compare the clinical effectiveness of autogenic drainage in people with cystic fibrosis with other physiotherapy airway clearance techniques.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews, as well as two ongoing trials registers (02 February 2021).\nDate of most recent search of the Cochrane Cystic Fibrosis Trials Register: 06 July 2021.\nSelection criteria\nWe identified randomised and quasi-randomised controlled studies comparing autogenic drainage to another airway clearance technique or no therapy in people with cystic fibrosis for at least two treatment sessions.\nData collection and analysis\nData extraction and assessments of risk of bias were independently performed by three authors. The authors assessed the quality of the evidence using the GRADE system. The authors contacted seven teams of investigators for further information pertinent to their published studies.\nMain results\nSearches retrieved 64 references to 37 individual studies, of which eight (n = 212) were eligible for inclusion. One study was of parallel design with the remaining seven being cross-over in design; participant numbers ranged from 4 to 75. The total study duration varied between four days and two years. The age of participants ranged between seven and 63 years with a wide range of disease severity reported. Six studies enrolled participants who were clinically stable, whilst participants in two studies received treatment whilst hospitalised with an infective exacerbation. All studies compared autogenic drainage to one (or more) other recognised airway clearance technique. Exercise is commonly used as an alternative therapy by people with cystic fibrosis; however, there were no studies identified comparing exercise with autogenic drainage.\nThe certainty of the evidence was generally low or very low. The main reasons for downgrading the level of evidence were the frequent use of a cross-over design, outcome reporting bias and the inability to blind participants.\nThe review's primary outcome, forced expiratory volume in one second, was the most common outcome measured and was reported by all eight studies; only three studies reported on quality of life (also a primary outcome of the review). One study reported on adverse events and described a decrease in oxygen saturation levels whilst performing active cycle of breathing techniques, but not with autogenic drainage. Seven of the eight included studies measured forced vital capacity and three of the studies used mid peak expiratory flow (per cent predicted) as an outcome. Six studies reported sputum weight. Less commonly used outcomes included oxygen saturation levels, personal preference, hospital admissions, intravenous antibiotics and pseudomonas gene expression. There were no statistically significant differences found between any of the techniques used with respect to the outcomes measured except when autogenic drainage was described as being the preferred technique of the participants in one study over postural drainage and percussion.\nAuthors' conclusions\nAutogenic drainage is a challenging technique that requires commitment from the individual. As such, this intervention merits systematic review to ensure its effectiveness for people with cystic fibrosis, particularly in an era where treatment options are changing rapidly. From the studies assessed, autogenic drainage was not found to be superior to any other form of airway clearance technique. Larger studies are required to better evaluate autogenic drainage in comparison to other airway clearance techniques in view of the relatively small number of participants in this review and the complex study designs. The studies recruited a range of participants and were not powered to assess non-inferiority. The varied length and design of the studies made the analysis of pooled data challenging.\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 the literature for studies comparing at least two sessions of autogenic drainage with other breathing techniques and devices which help to clear the lungs of mucus. We included eight studies in the review involving 212 people with cystic fibrosis, aged between seven and 63 years of age. People were randomly selected for one physiotherapy treatment or the other. The number of people in the studies ranged from 4 to 75, and had a wide range of disease severity. The studies lasted from four days to two years in total." } ]

[ { "role": "user", "content": "Abstract: Background\nPreterm birth (PTB) is a major factor contributing to global rates of neonatal death and to longer-term health problems for surviving infants. Both the World Health Organization and the United Nations consider prevention of PTB as central to improving health care for pregnant women and newborn babies. Current preventative clinical strategies show varied efficacy in different populations of pregnant women, frustrating women and health providers alike, while researchers call for better understanding of the underlying mechanisms that lead to PTB.\nObjectives\nWe aimed to summarise all evidence for interventions relevant to the prevention of PTB as reported in Cochrane systematic reviews (SRs). We intended to highlight promising interventions and to identify SRs in need of an update.\nMethods\nWe searched the Cochrane Database of Systematic Reviews (2 November 2017) with key words to capture any Cochrane SR that prespecified or reported a PTB outcome. Inclusion criteria focused on pregnant women without signs of preterm labour or ruptured amniotic membranes. We included reviews of interventions for pregnant women irrespective of their risk status. We followed standard Cochrane methods.\nWe applied GRADE criteria to evaluate the quality of SR evidence. We assigned graphic icons to classify the effectiveness of interventions as: clear evidence of benefit; clear evidence of harm; clear evidence of no effect or equivalence; possible benefit; possible harm; or unknown benefit or harm. We defined clear evidence of benefit and clear evidence of harm to be GRADE moderate- or high-quality evidence with a confidence interval (CI) that does not cross the line of no effect. Clear evidence of no effect or equivalence is GRADE moderate- or high-quality evidence with a narrow CI crossing the line of no effect. Possible benefit and possible harm refer to GRADE low-quality evidence with a clear effect (CI does not cross the line of no effect) or GRADE moderate- or high-quality evidence with a wide CI. Unknown harm or benefit refers to GRADE low- or very low-quality evidence with a wide CI.\nMain results\nWe included 83 SRs; 70 had outcome data. Below we highlight key results from a subset of 36 SRs of interventions intended to prevent PTB.\nOutcome: preterm birth\nClear evidence of benefit\nFour SRs reported clear evidence of benefit to prevent specific populations of pregnant women from giving birth early, including midwife-led continuity models of care versus other models of care for all women; screening for lower genital tract infections for pregnant women less than 37 weeks' gestation and without signs of labour, bleeding or infection; and zinc supplementation for pregnant women without systemic illness. Cervical cerclage showed clear benefit for women with singleton pregnancy and high risk of PTB only.\nClear evidence of harm\nNo included SR reported clear evidence of harm.\nNo effect or equivalence\nFor pregnant women at high risk of PTB, bedrest for women with singleton pregnancy and antibiotic prophylaxis during the second and third trimester were of no effect or equivalent to a comparator.\nPossible benefit\nFour SRs found possible benefit in: group antenatal care for all pregnant women; antibiotics for pregnant women with asymptomatic bacteriuria; pharmacological interventions for smoking cessation for pregnant women who smoke; and vitamin D supplements alone for women without pre-existing conditions such as diabetes.\nPossible harm\nOne SR reported possible harm (increased risk of PTB) with intramuscular progesterone, but this finding is only relevant to women with multiple pregnancy and high risk of PTB. Another review found possible harm with vitamin D, calcium and other minerals for pregnant women without pre-existing conditions.\nOutcome: perinatal death\nClear evidence of benefit\nTwo SRs reported clear evidence of benefit to reduce pregnant women's risk of perinatal death: midwife-led continuity models of care for all pregnant women; and fetal and umbilical Doppler for high-risk pregnant women.\nClear evidence of harm\nNo included SR reported clear evidence of harm.\nNo effect or equivalence\nFor pregnant women at high risk of PTB, antibiotic prophylaxis during the second and third trimester was of no effect or equivalent to a comparator.\nPossible benefit\nOne SR reported possible benefit with cervical cerclage for women with singleton pregnancy and high risk of PTB.\nPossible harm\nOne SR reported possible harm associated with a reduced schedule of antenatal visits for pregnant women at low risk of pregnancy complications; importantly, these women already received antenatal care in settings with limited resources.\nOutcomes: preterm birth and perinatal death\nUnknown benefit or harm\nFor pregnant women at high risk of PTB for any reason including multiple pregnancy, home uterine monitoring was of unknown benefit or harm. For pregnant women at high risk due to multiple pregnancy: bedrest, prophylactic oral betamimetics, vaginal progesterone and cervical cerclage were all of unknown benefit or harm.\nAuthors' conclusions\nImplications for practice\nThe overview serves as a map and guide to all current evidence relevant to PTB prevention published in the Cochrane Library. Of 70 SRs with outcome data, we identified 36 reviews of interventions with the aim of preventing PTB. Just four of these SRs had evidence of clear benefit to women, with an additional four SRs reporting possible benefit. No SR reported clear harm, which is an important finding for women and health providers alike.\nThe overview summarises no evidence for the clinically important interventions of cervical pessary, cervical length assessment and vaginal progesterone because these Cochrane Reviews were not current. These are active areas for PTB research.\nThe graphic icons we assigned to SR effect estimates do not constitute clinical guidance or an endorsement of specific interventions for pregnant women. It remains critical for pregnant women and their healthcare providers to carefully consider whether specific strategies to prevent PTB will be of benefit for individual women, or for specific populations of women.\nImplications for research\nFormal consensus work is needed to establish standard language for overviews of reviews and to define the limits of their interpretation.\nClinicians, researchers and funders must address the lack of evidence for interventions relevant to women at high risk of PTB due to multiple pregnancy.\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 included 83 systematic reviews with evidence about whether or not the intervention was able to reduce pregnant women's chance of having a preterm birth or a baby death. Seventy of these reviews had information about preterm birth. We categorised the evidence we found as: clear benefit or harm; no effect; possible benefit or harm; or unknown effect." } ]

[ { "role": "user", "content": "Abstract: Background\nPrimary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain.\nObjectives\nTo assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10), which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the WHO ICTRP. The date of the most recent search was 10 October 2021.\nSelection criteria\nRandomized or quasi-randomized controlled trials that compared iridotomy with no iridotomy in primary angle-closure suspects, people with primary angle-closure, or people with primary angle-closure glaucoma in one or both eyes were eligible.\nData collection and analysis\nWe used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach.\nMain results\nWe identified four studies (3086 eyes of 1543 participants) that compared iridotomy with no iridotomy in participants (range of mean age 59.6 to 62.9 years) who were primary angle-closure suspects from China, Singapore, or the UK. Study investigators randomized one eye of each participant to iridotomy and the other to no iridotomy. Two studies provided long-term (five or more years) results. We judged the certainty of the evidence as moderate to low across the prespecified outcomes, downgrading for high risk of bias (e.g. performance and detection biases) and imprecision of results.\nMeta-analyses of data from two studies suggest that iridotomy probably results in little to no difference in IOP compared with no iridotomy at one year (mean difference (MD) 0.04 mm Hg, 95% confidence interval (CI) −0.17 to 0.24; I2 = 65%; 2598 eyes of 1299 participants; moderate certainty evidence) and five years (MD 0.12 mm Hg, 95% CI −0.11 to 0.35; I2 = 0%; 2016 eyes of 1008 participants), and in best-corrected visual acuity measured as logMAR at one year (MD 0.00, 95% CI −0.01 to 0.01; I2 = 69%; 2596 eyes of 1298 participants; moderate certainty evidence) and five years (MD 0.01, 95% CI −0.01 to 0.03; I2 = 0%; 2002 eyes of 1001 participants). In terms of gonioscopic findings, eyes treated with iridotomy likely had wider angles in Shaffer grading scale (MD 4.93 units, 95% CI 4.73 to 5.12; I2 = 59%; 2598 eyes of 1299 participants at one year; MD 5.07, 95% CI 4.78 to 5.36; I2 = 97%; 2016 eyes of 1008 participants at five years; moderate certainty evidence) and experienced fewer peripheral anterior synechiae (PAS) than eyes that received no iridotomy at five years (risk ratio (RR) 0.41, 95% CI 0.24 to 0.67; I2 = 28%; 2 studies, 2738 eyes of 1369 participants), but the evidence was less conclusive at one year (RR 0.62, 95% CI 0.25 to 1.54; I2 = 57%; 3 studies, 2896 eyes of 1448 participants; low certainty evidence). No studies reported data on the proportion of participants with progressive visual field loss during follow-up (the primary outcome of this review), mean number of medications to control IOP, or quality of life outcomes. Low certainty evidence suggests that iridotomy may result in little to no difference in the incidence of acute angle-closure (RR 0.29, 95% CI 0.07 to 1.20; I2 = 0%; 3 studies, 3006 eyes of 1503 participants). Other ocular adverse events (e.g. eye pain, dry eye, redness of eyes, and ocular discomfort), although rare, were more common in eyes treated with iridotomy than in eyes in the control group.\nAuthors' conclusions\nWe did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. No study reported on progressive visual field loss, the primary outcome of this review. Although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits.\n\nGiven the provided abstract, please respond to the following query: \"What were the main results of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We collected and analyzed all relevant clinical trials and identified four eligible trials (3086 eyes of 1543 participants) comparing iridotomy with no iridotomy that addressed our review question.\nThe four included trials recruited participants from China, Singapore, or the UK who were suspected of having primary angle-closure. One eye of each participant received iridotomy, and the other eye did not receive iridotomy.\nTwo large studies found that eyes treated with iridotomy likely had wider angles at one year and five years after the treatment, and had less scarring of the drainage channels, which may reduce outflow of aqueous humor (the clear liquid inside the front part of the eye), than eyes that received no iridotomy at five years. The evidence for the effect of iridotomy on drainage channels at one year was uncertain. Our confidence in the evidence for eye pressure and visual acuity is only moderate because of concerns about study design. Unwanted effects related to the treatment, although rare, appeared to be more common in iridotomy-treated eyes than in non-treated eyes.\nNo studies measured:\n• how visual field was affected;\n• the number of medications needed to control eye pressure; or\n• people's well-being (quality of life)." } ]

[ { "role": "user", "content": "Abstract: Background\nSickle cell disease is the most common hemoglobinopathy occurring worldwide and sickle cell intrahepatic cholestasis is a complication long recognized in this population. Cholestatic liver diseases are characterized by impaired formation or excretion (or both) of bile from the liver. There is a need to assess the clinical benefits and harms of the interventions used to treat intrahepatic cholestasis in people with sickle cell disease. This is an update of a previously published Cochrane Review.\nObjectives\nTo assess the benefits and harms of the interventions for treating intrahepatic cholestasis in people with sickle cell disease.\nSearch methods\nWe searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 21 January 2020), the WHO International Clinical Trials Registry Platform Search Portal and ClinicalTrials.gov (21 January 2020).\nDate of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 25 November 2019.\nSelection criteria\nWe searched for published or unpublished randomised controlled trials.\nData collection and analysis\nEach author intended to independently extract data, assess the risk of bias of the trials by standard Cochrane methodologies and assess the quality of the evidence using the GRADE criteria; however, no trials were included in the review.\nMain results\nWe did not identify any randomised controlled trials.\nAuthors' conclusions\nThis updated Cochrane Review did not identify any randomised controlled trials assessing interventions for treating intrahepatic cholestasis in people with sickle cell disease. Randomised controlled trials are needed to establish the optimum treatment for this condition.\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 aimed to review the evidence for treating intrahepatic cholestasis (liver diseases where bile is either not formed or excreted properly (or both)) in people with sickle cell disease. This is an update of a previously published Cochrane Review." } ]

[ { "role": "user", "content": "Abstract: Background\nLong-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma.\nObjectives\nTo assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration.\nSearch methods\nWe searched the Cochrane Airways Group Asthma Trials Register until January 2015.\nSelection criteria\nWe included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals.\nData collection and analysis\nTwo review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible.\nMain results\nWe included in this review a total of 33 trials representing 39 control-intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS.\nLABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV1) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies.\nThere was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate-quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate-quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate-quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low-quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV1 (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low-quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD -0.07 puffs/d, 95% CI -0.11 to -0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD -0.08 puffs/d, 95% CI -0.13 to -0.03, three studies, 672 children). No significant group difference was noted in exercise-induced % fall in FEV1, symptom-free days, asthma symptom score, quality of life, use of reliever medication and adverse events.\nA total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV1 was ≥ 80% of predicted. All trials enrolled participants who were inadequately controlled on a baseline inhaled steroid dose equivalent to 400 µg/d of beclomethasone equivalent or less.\nThere was no significant group differences in risk of exacerbation requiring oral steroids with the combination of LABA and ICS versus a double dose of ICS (RR 1.69, 95% CI 0.85 to 3.32, three studies, 581 children; moderate-quality evidence) nor in risk of hospital admission (RR 1.90, 95% CI 0.65 to 5.54, four studies, 1008 children; moderate-quality evidence).\nNo statistical significant group difference was noted in serious adverse events (RR 1.54, 95% CI 0.81 to 2.94, seven studies, N = 1343; moderate-quality evidence) and no statistically significant differences in overall risk of all-cause withdrawals (RR 0.96, 95% CI 0.67 to 1.37, eight studies, 1491 children; moderate-quality evidence). Compared with double the dose of ICS, use of LABA was associated with significantly greater improvement in morning PEF (MD 8.73 L/min, 95% CI 5.15 to 12.31, five studies, 1283 children; moderate-quality evidence), but data were insufficient to aggregate on other markers of asthma symptoms, rescue medication use and nighttime awakening. There was no group difference in risk of overall adverse effects, A significant group difference was observed in linear growth over 12 months, clearly indicating lower growth velocity in the higher ICS dose group (two studies: MD 1.21 cm/y, 95% CI 0.72 to 1.70).\nAuthors' conclusions\nIn children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring.\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": "From available evidence until January 2015, we found 39 eligible studies evaluating the combination of LABA and ICS in children with persistent asthma. Of these, 28 studies compared LABA with the same dose of ICS, and the remaining studies compared LABA with a larger dose of ICS.\nThe number of people who had an exacerbation (worsening of symptoms) that required treatment with oral steroids was not significantly different. However, lung function improved in people taking LABA and steroids compared with the same dose of steroids only or larger doses of steroids. No evidence suggested increased serious adverse events or adverse events (also known as side effects) with the addition of LABA.\nCompared with the same dose of ICS, people used less of their rescue/relief bronchodilator treatment. There was no benefit for control of asthma symptoms when LABA added to ICS was compared with higher doses of ICS. The higher dose of ICS was associated with 1.2 cm per year lower growth than was observed with the combination of LABA and a lower dose of ICS." } ]

[ { "role": "user", "content": "Abstract: Background\nOcular discomfort is the leading cause of permanent discontinuation of soft contact lens (SCL) wear. Silicone hydrogel and hydrogel materials are the two major categories of SCLs, with silicone hydrogel materials being newer and more breathable than hydrogel materials. Whether comfort is associated with SCL material is controversial despite numerous studies. Similarly, the difference between these materials in terms of safety outcomes (e.g. frequency of microbial keratitis) is unclear.\nObjectives\nTo evaluate the comparative effectiveness and safety of silicone hydrogel compared with hydrogel SCLs on self-reported comfort, dry eye test results, and adverse events in SCL-wearing adults 18 years of age or older.\nSearch methods\nThe Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials (RCTs). There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We also searched the reference lists of identified studies, review articles, and guidelines for information about relevant studies that may not have been identified by our search strategy. Furthermore, we contacted investigators regarding ongoing trials. The most recent database search was conducted on 24 June 2022.\nSelection criteria\nOur search selection criteria included RCTs, quasi-RCTs, and cross-over RCTs.\nData collection and analysis\nWe applied standard Cochrane methodology.\nMain results\nWe included seven parallel-group RCTs conducted in the USA, the UK, Australia, Germany, India, and Turkey. A total of 1371 participants were randomized. The duration of SCL wear ranged from one to 52 weeks.\nStudy characteristics and risk of bias\nThe median number of participants per trial was 120 (interquartile range: 51 to 314), and the average age ranged from 20.7 to 33.0 years. Women represented the majority of participants (range 55% to 74.9%; 5 RCTs). Collectively, the included trials compared eight different silicone hydrogel SCLs with three different hydrogel SCLs. Five trials compared daily disposable SCLs, and two compared extended wear SCLs (worn for seven days and six nights). New SCL wearers were enrolled in three trials. Two trials included both new and established SCL wearers, and two trials did not report participants' history of SCL use. Five trials were sponsored by industry. We judged the overall risk of bias to be 'high' or 'some concerns' for the safety and efficacy outcomes.\nFindings\nOne trial reported Ocular Surface Disease Index (OSDI) results, with the evidence being very uncertain about the effects of SCL material on OSDI scores (mean difference −1.20, 95% confidence interval [CI] −10.49 to 8.09; 1 RCT, 47 participants; very low certainty evidence). Three trials reported visual analog scale comfort score results, with no clear difference in comfort between materials, but the evidence was of very low certainty; trial results could not be combined because the three trials reported results at different time points. The evidence is very uncertain about the effect of SCL material on discontinuation of contact lens wear (risk ratio [RR] 0.64, 95% CI 0.11 to 3.74; 1 RCT, 248 participants). None of the included trials reported Contact Lens Dry Eye Questionnaire (CLDEQ-8) or Standard Patient Evaluation of Eye Dryness (SPEED) scores.\nThere was no evidence of a clinically meaningful difference (> 0.5 unit) between daily disposable silicone hydrogel and hydrogel SCLs in corneal staining, conjunctival staining, or conjunctival redness (very low certainty evidence).\nAdverse events\nVery low certainty evidence from two trials comparing daily disposable SCLs suggested no evidence of a difference between lens materials in the risk of vision-threatening adverse events at one to four weeks (RR 0.68, 95% CI 0.08 to 5.51; 2 RCTs, 368 participants). Two trials comparing extended wear SCLs indicated that hydrogel SCLs may have a 2.03 times lower risk of adverse events at 52 weeks compared with silicone hydrogel SCLs (RR 2.03, 95% CI 1.38 to 2.99; 815 participants), but the certainty of evidence was very low.\nAuthors' conclusions\nThe overall evidence for a difference between all included silicone hydrogel and hydrogel SCLs was of very low certainty, with most trials at high overall risk of bias. The majority of studies did not assess comfort using a validated instrument. There was insufficient evidence to support recommending one SCL material over the other. For extended wear, hydrogel SCL may have a lower risk of adverse events at 52 weeks compared to silicon hydrogel. Future well-designed trials are needed to generate high certainty evidence to further clarify differences in SCL material comfort and safety.\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 if silicone hydrogel SCLs can decrease eye discomfort and complications such as eye infections compared with hydrogel SCLs." } ]

[ { "role": "user", "content": "Abstract: Background\nOvarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common kind, accounting for 90% of cases. First-line therapy for women with epithelial ovarian cancer consists of a combination of cytoreductive surgery and platinum and taxane-based chemotherapy. However, more than 50% of women with epithelial ovarian cancer will experience a relapse and require further chemotherapy and at some point develop resistance to platinum-based drugs.\nCurrently, guidance on the use of most chemotherapy drugs, including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly regimens (at a lower dose) or three-weekly regimens (at a higher dose), which may have differences in the severity of side effects and effectiveness. As relapsed disease suggests incurable disease, it is all the more important to consider side effects and the impact of treatment schedules, as well as quality of life, and not only the life-prolonging effects of treatment.\nObjectives\nTo assess the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal or primary peritoneal cancer.\nSearch methods\nWe searched CENTRAL, MEDLINE and Embase, up to 22 March 2022. Other related databases and trial registries were searched as well as grey literature and no additional studies were identified. A total of 1500 records were identified.\nSelection criteria\nWe included randomised controlled trials of taxane monotherapy for adult women diagnosed with recurrent epithelial ovarian, tubal or primary peritoneal cancer, previously treated with platinum-based chemotherapy. We included trials comparing two or more taxane monotherapy regimens. Participants could be experiencing their first recurrence of disease or any line of recurrence.\nData collection and analysis\nTwo review authors screened, independently assessed studies, and extracted data from the included studies. The clinical outcomes we examined were overall survival, response rate, progression-free survival, neurotoxicity, neutropenia, alopecia, and quality of life. We performed statistical analyses using fixed-effect and random-effects models following standard Cochrane methodology. We rated the certainty of evidence according to the GRADE approach.\nMain results\nOur literature search yielded 1500 records of 1466 studies; no additional studies were identified by searching grey literature or handsearching. We uploaded the search results into Covidence. After the exclusion of 92 duplicates, we screened titles and abstracts of 1374 records. Of these, we identified 24 studies for full-text screening. We included four parallel-group randomised controlled trials (RCTs). All trials were multicentred and conducted in a hospital setting. The studies included 981 eligible participants with recurrent epithelial ovarian cancer, tubal or primary peritoneal cancer with a median age ranging between 56 to 62 years of age. All participants had a WHO (World Health Organization) performance status of between 0 to 2. The proportion of participants with serous histology ranged between 56% to 85%. Participants included women who had platinum-sensitive (71%) and platinum-resistant (29%) relapse. Some participants were taxane pre-treated (5.6%), whilst the majority were taxane-naive (94.4%). No studies were classified as having a high risk of bias for any of the domains in the Cochrane risk of bias tool.\nWe found that there may be little or no difference in overall survival (OS) between weekly paclitaxel and three-weekly paclitaxel, but the evidence is very uncertain (risk ratio (RR) of 0.94, 95% confidence interval (CI) 0.66 to 1.33, two studies, 263 participants, very low-certainty evidence). Similarly, there may be little or no difference in response rate (RR of 1.07, 95% CI 0.78 to 1.48, two studies, 263 participants, very low-certainty evidence) and progression-free survival (PFS) (RR of 0.83, 95% CI 0.46 to 1.52, two studies, 263 participants, very low-certainty evidence) between weekly and three-weekly paclitaxel, but the evidence is very uncertain.\nWe found differences in the chemotherapy-associated adverse events between the weekly and three-weekly paclitaxel regimens. The weekly paclitaxel regimen may result in a reduction in neutropenia (RR 0.51, 95% 0.27 to 0.95, two studies, 260 participants, low-certainty evidence) and alopecia (RR 0.58, 95% CI 0.46 to 0.73, one study, 205 participants, low-certainty evidence). There may be little or no difference in neurotoxicity, but the evidence was very low-certainty and we cannot exclude an effect (RR 0.53, 95% CI 0.19 to 1.45, two studies, 260 participants).\nWhen examining the effect of paclitaxel dosage in the three-weekly regimen, the 250 mg/m2 paclitaxel regimen probably causes more neurotoxicity compared to the 175 mg/m2 regimen (RR 0.41, 95% CI 0.21 to 0.80, one study, 330 participants, moderate-certainty evidence).\nQuality-of-life data were not extractable from any of the included studies.\nAuthors' conclusions\nFewer people may experience neutropenia when given weekly rather than three-weekly paclitaxel (low-certainty evidence), although it may make little or no difference to the risk of developing neurotoxicity (very low-certainty evidence). This is based on the participants receiving lower doses of drug more often. However, our confidence in this result is low and the true effect may be substantially different from the estimate of the effect. Weekly paclitaxel probably reduces the risk of alopecia, although the rates in both arms were high (46% versus 79%) (low-certainty evidence). A change to weekly from three-weekly chemotherapy could be considered to reduce the likelihood of toxicity, as it may have little or no negative impact on response rate (very low-certainty evidence), PFS (very low-certainty evidence) or OS (very low-certainty evidence).\nThree-weekly paclitaxel, given at a dose of 175 mg/m2 compared to a higher dose,probably reduces the risk of neurotoxicity.We are moderately confident in this result; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. A change to 175 mg/m2 paclitaxel (from a higher dose), if a three-weekly regimen is used, probably has little or no negative impact on PFS or OS (very low-certainty evidence).\n\nGiven the provided abstract, please respond to the following query: \"Different doses of taxane given three-weekly\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Women who received a lower dose of taxane every three weeksprobably had less neurotoxicity and we have moderate certainty in this result. We found that there are probably few or no differences in how long women survived or how long it took for their cancer to progress after treatment between the groups." } ]

[ { "role": "user", "content": "Abstract: Background\nMedicinal plant products are used orally for treating osteoarthritis. Although their mechanisms of action have not yet been elucidated in full detail, interactions with common inflammatory mediators provide a rationale for using them to treat osteoarthritic complaints.\nObjectives\nTo update a previous Cochrane review to assess the benefits and harms of oral medicinal plant products in treating osteoarthritis.\nSearch methods\nWe searched electronic databases (CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, World Health Organization Clinical Trials Registry Platform) to 29 August 2013, unrestricted by language, and the reference lists from retrieved trials.\nSelection criteria\nRandomised controlled trials of orally consumed herbal interventions compared with placebo or active controls in people with osteoarthritis were included. Herbal interventions included any plant preparation but excluded homeopathy or aromatherapy products, or any preparation of synthetic origin.\nData collection and analysis\nTwo authors used standard methods for trial selection and data extraction, and assessed the quality of the body of evidence using the GRADE approach for major outcomes (pain, function, radiographic joint changes, quality of life, withdrawals due to adverse events, total adverse events, and serious adverse events).\nMain results\nForty-nine randomised controlled studies (33 interventions, 5980 participants) were included. Seventeen studies of confirmatory design (sample and effect sizes pre-specified) were mostly at moderate risk of bias. The remaining 32 studies of exploratory design were at higher risk of bias. Due to differing interventions, meta-analyses were restricted to Boswellia serrata (monoherbal) and avocado-soyabean unsaponifiables (ASU) (two herb combination) products.\nFive studies of three different extracts from Boswellia serrata were included. Moderate-quality evidence from two studies (85 participants) indicated that 90 days treatment with 100 mg of enriched Boswellia serrata extract improved symptoms compared to placebo. Mean pain was 40 points on a 0 to 100 point VAS scale (0 is no pain) with placebo, enriched Boswellia serrata reduced pain by a mean of 17 points (95% confidence interval (CI) 8 to 26); number needed to treat for an additional beneficial outcome (NNTB) 2; the 95% CIs did not exclude a clinically significant reduction of 15 points in pain. Physical function was 33 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 0 to 100 point subscale (0 is no loss of function) with placebo, enriched Boswellia serrata improved function by 8 points (95% CI 2 to 14); NNTB 4. Assuming a minimal clinically important difference of 10 points, we cannot exclude a clinically important benefit in some people. Moderate-quality evidence (one study, 96 participants) indicated that adverse events were probably reduced with enriched Boswellia serrata (18/48 events versus 30/48 events with placebo; relative risk (RR) 0.60, 95% CI 0.39 to 0.92). Possible benefits of other Boswellia serrata extracts over placebo were confirmed in moderate-quality evidence from two studies (97 participants) of Boswellia serrata (enriched) 100 mg plus non-volatile oil, and low-quality evidence from small single studies of a 999 mg daily dose of Boswellia serrata extract and 250 mg daily dose of enrichedBoswellia serrata. It was uncertain if a 99 mg daily dose of Boswellia serrata offered benefits over valdecoxib due to the very low-quality evidence from a small single study. It was uncertain if there was an increased risk of adverse events or withdrawals with Boswellia serrata extract due to variable reporting of results across studies. The studies reported no serious adverse events. Quality of life and radiographic joint changes were not measured.\nSix studies examined the ASU product Piasclidine®. Moderate-quality evidence from four studies (651 participants) indicated that ASU 300 mg produced a small and clinically questionable improvement in symptoms, and probably no increased adverse events compared to placebo after three to 12 months treatment. Mean pain with placebo was 40.5 points on a VAS 0 to 100 scale (0 is no pain), ASU 300 mg reduced pain by a mean of 8.5 points (95% CI 1 to 16 points); NNTB 8. ASU 300 mg improved function (standardised mean difference (SMD) -0.42, 95% CI -0.73 to -0.11). Function was estimated as 47 mm (0 to 100 mm scale, where 0 is no loss of function) with placebo, ASU 300 mg improved function by a mean of 7 mm (95% CI 2 to 12 mm); NNTB 5 (3 to 19). There were no differences in adverse events (5 studies, 1050 participants) between ASU (53%) and placebo (51%) (RR 1.04, 95% CI 0.97 to 1.12); withdrawals due to adverse events (1 study, 398 participants) between ASU (17%) and placebo (15%) (RR 1.14, 95% CI 0.73 to 1.80); or serious adverse events (1 study, 398 participants) between ASU (40%) and placebo (33%) (RR 1.22, 95% CI 0.94 to 1.59). Radiographic joint changes, measured as change in joint space width (JSW) in two studies (453 participants) did not differ between ASU 300 mg treatment (-0.53 mm) and placebo (-0.65 mm); mean difference of -0.12 (95% CI -0.43 to 0.19). Moderate-quality evidence from a single study (156 participants) confirmed possible benefits of ASU 600 mg over placebo, with no increased adverse events. Low-quality evidence (1 study, 357 participants) indicated there may be no differences in symptoms or adverse events between ASU 300 mg and chondroitin sulphate. Quality of life was not measured.\nAll other herbal interventions were investigated in single studies, limiting conclusions. No serious side effects related to any plant product were reported.\nAuthors' conclusions\nEvidence for the proprietary ASU product Piasclidine® in the treatment of osteoarthritis symptoms seems moderate for short term use, but studies over a longer term and against an apparently active control are less convincing. Several other medicinal plant products, including extracts of Boswellia serrata, have moderate-quality evidence for trends of benefits that warrant further investigation in light of the fact that the risk of adverse events appear low.\nThere is no evidence that Piasclidine® significantly improves joint structure, and limited evidence that it prevents joint space narrowing. Structural changes were not tested for with any other herbal intervention.\nFurther investigations are required to determine optimum daily doses producing clinical benefits without adverse events.\n\nGiven the provided abstract, please respond to the following query: \"Quality of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "There is moderate-quality evidence that in people with osteoarthritis Boswellia serrata slightly improved pain and function. Further research may change the estimates.\nThere is moderate-quality evidence that avocado-soybean unsaponifiables (ASU) probably improved pain and function slightly, but may not preserve joint space. Further research may change the estimates.\nWe are uncertain whether other oral herbal products improve osteoarthritis pain or function, or slow progression of joint structure damage because the available evidence is limited to single studies or studies that cannot be pooled, and some of these studies are of low to very low quality. Quality of life was not measured.\nHerbal therapies may cause side effects, however we are uncertain if there is an increased risk of these." } ]

[ { "role": "user", "content": "Abstract: Background\nCorneal endothelial transplantation has become the gold standard for the treatment of corneal endothelial dysfunctions, replacing full thickness transplantation, known as penetrating keratoplasty. Corneal endothelial transplantation has been described using two different techniques: Descemet’s membrane endothelial keratoplasty (DMEK) and Descemet’s stripping automated endothelial keratoplasty (DSAEK). Both are still performed worldwide.\nObjectives\nTo compare the effectiveness and safety of Descemet's membrane endothelial keratoplasty (DMEK) versus Descemet's stripping automated endothelial keratoplasty (DSAEK) for the treatment of corneal endothelial failure in people with Fuch’s endothelial dystropy (FED) and pseudophakic bullous keratopathy (PBK).\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 7); MEDLINE Ovid; Embase Ovid; LILACS BIREME; the ISRCTN registry; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the search was 11 August 2017.\nSelection criteria\nWe included randomised controlled trials (RCTs) and non-randomised paired, contralateral-eye studies in any setting where DMEK was compared with DSAEK to treat people with corneal endothelial failure.\nData collection and analysis\nTwo review authors independently screened the search results, assessed trial quality and extracted data using the standard methodological procedures expected by Cochrane. Our primary outcome was best corrected visual acuity (BCVA) measured in logarithm of the Minimum Angle of Resolution (logMAR). Secondary outcomes were endothelial cell count, graft rejection, primary graft failure and graft dislocation. We graded the risk of bias of non-randomised studies (NRSs) using ROBINS-I.\nMain results\nWe did not identify any RCTs but found four non-randomised studies (NRSs) including 72 participants (144 eyes), who had received DSAEK in the first eye followed by DMEK in the fellow eye. All the studies included adult participants where there was evidence of FED and endothelial failure requiring a corneal transplant for the treatment of visual impairment. We did not find any studies that included PBK. The trials were published between 2011 and 2015, and we assessed them as high risk of bias due to potential unknown confounding factors since DSAEK preceded DMEK in all participants. Two studies reported results at 12 months, one at 6 months, and one between 6 and 24 months. At one year, using DMEK in cases of endothelial failure may result in better BCVA compared with DSAEK (mean difference (MD) -0.14, 95% confidence interval (CI) -0.18 to -0.10 logMAR, 4 studies, 140 eyes, low-certainty evidence). None of the participants had severe visual loss (BCVA of 1.0 logMAR or more; very low-certainty evidence). Regarding endothelial cell count data (4 studies, 134 eyes) it is hard to draw any conclusions since two studies suggested no difference and the other two reported that DMEK provides a higher cell density at one year (very low-certainty evidence). No primary graft failure and only one graft rejection were recorded over four studies (144 eyes) (very low-certainty evidence). The most common complications reported were graft dislocations, which were recorded in one or two out of 100 participants with DSAEK but were more common using DMEK, although this difference could not be precisely estimated (risk ratio (RR) 5.40, 95% CI 1.51 to 19.3; 4 studies, 144 eyes, very low-certainty evidence).\nAuthors' conclusions\nThis review included studies conducted on people with corneal endothelium failure due to FED for whom both DMEK and DSAEK can be considered, and found low-certainty evidence that DMEK provides some advantage in terms of final BCVA, at the cost of more graft dislocations needing 're-bubbling' (very low-certainty of evidence).\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": "Cochrane Review authors searched for studies that had been published up to August 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nDressings are part of the routine postoperative management of people after transtibial amputation. Two types of dressings are commonly used; soft dressings (e.g. elastic bandages, crepe bandages) and rigid dressings (e.g. non-removable rigid dressings, removable rigid dressings, immediate postoperative protheses). Soft dressings are the conventional dressing choice as they are cheap and easy to apply, while rigid dressings are costly, more time consuming to apply and require skilled personnel to apply the dressings. However, rigid dressings have been suggested to result in faster wound healing due to the hard exterior providing a greater degree of compression to the stump.\nObjectives\nTo assess the benefits and harms of rigid dressings versus soft dressings for treating transtibial amputations.\nSearch methods\nIn December 2018 we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, EBSCO CINAHL Plus, Ovid AMED and PEDro to identify relevant trials. To identify further published, unpublished and ongoing studies, we also searched clinical trial registries, the grey literature, the reference lists of relevant studies and reviews identified in prior searches. We used the Cited Reference Search facility on ThomsonReuters Web of Science and contacted relevant individuals and organisations. There were no restrictions with respect to language, date of publication or study setting.\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs that enrolled people with transtibial amputations. There were no restrictions on the age of participants and reasons for amputation. Trials that compared the effectiveness of rigid dressings with soft dressings were the main focus of this review.\nData collection and analysis\nTwo review authors independently screened titles, abstracts and full-text publications for eligible studies. Two review authors also independently extracted data on study characteristics and outcomes, and performed risk of bias and GRADE assessments.\nMain results\nWe included nine RCTs and quasi-RCTs involving 436 participants (441 limbs). All studies recruited participants from acute and/or rehabilitation hospitals from seven different countries (the USA, Australia, Indonesia, Thailand, Canada, France and the UK). In all but one study, it was clearly stated that amputations were secondary to vascular conditions.\nPrimary outcomes\nWound healing\nWe are uncertain whether rigid dressings decrease the time to wound healing compared with soft dressings (MD -25.60 days; 95% CI -49.08 to -2.12; one study, 56 participants); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision. It is not clear whether rigid dressings increase the proportion of wounds healed compared with soft dressings (RR 1.14; 95% CI 0.74 to 1.76; one study, 51 participants); very low-certainty evidence, downgraded twice for very high risk of bias and twice for very serious imprecision.\nAdverse events\nIt is not clear whether rigid dressings increase the proportion of skin-related adverse events compared with soft dressings (RR 0.65; 95% CI 0.32 to 1.32; I2 = 0%; six studies, 336 participants (340 limbs)); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision.\nIt is not clear whether rigid dressings increase the proportion of non skin-related adverse events compared with soft dressings (RR 1.09; 95% CI 0.60 to 1.99; I2 = 0%; six studies, 342 participants (346 limbs)); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision. In addition, we are uncertain whether rigid dressings decrease the time to no pain compared with soft dressings (MD -0.35 weeks; 95% CI -2.11 to 1.41; one study of 23 participants); very low-certainty evidence, downgraded twice for very high risk of bias and twice for very serious imprecision.\nSecondary outcomes\nWe are uncertain whether rigid dressings decrease the time to walking compared with soft dressings (MD -3 days; 95% CI -9.96 to 3.96; one study, 56 participants); very low-certainty evidence, downgraded twice for very high risk of bias and twice for very serious imprecision. We are also uncertain whether rigid dressings decrease the length of hospital stay compared with soft dressings (MD -30.10 days; 95% CI -49.82 to -10.38; one study, 56 participants); very low-certainty evidence, downgraded twice for very high risk of bias and once for serious imprecision. It is also not clear whether rigid dressings decrease the time to readiness for prosthetic prescription and swelling compared with soft dressings, as results are based on very low-certainty evidence, downgraded twice for very high risk of bias and once/twice for serious/very serious imprecision. None of the studies reported outcomes on patient comfort, quality of life and cost.\nAuthors' conclusions\nWe are uncertain of the benefits and harms of rigid dressings compared with soft dressings for people undergoing transtibial amputation due to limited and very low-certainty evidence. It is not clear if rigid dressings are superior to soft dressings for improving outcomes related to wound healing, adverse events, prosthetic prescription, walking function, length of hospital stay and swelling. Clinicians should exercise clinical judgement as to which type of dressing they use, and consider the pros and cons of each for patients (e.g. patients with high risk of falling may benefit from the protection offered by a rigid dressing, and patients with poor skin integrity may have less risk of skin breakdown from a soft dressing).\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": "We studied the effects of rigid dressings such as plaster casts or fibreglass dressings on outcomes including wound healing, adverse events, prescription of prosthetics, physical function, length of hospital stay, patient comfort, quality of life, cost and swelling in people following transtibial amputations. Rigid dressings were compared with soft dressings such as gauze or elastic bandages in all included studies." } ]

[ { "role": "user", "content": "Abstract: Background\nExperiencing anxiety and depression is very common in people living with dementia and mild cognitive impairment (MCI). There is uncertainty about the best treatment approach. Drug treatments may be ineffective and associated with adverse effects. Guidelines recommend psychological treatments. In this updated systematic review, we investigated the effectiveness of different psychological treatment approaches.\nObjectives\nPrimary objective\nTo assess the clinical effectiveness of psychological interventions in reducing depression and anxiety in people with dementia or MCI.\nSecondary objectives\nTo determine whether psychological interventions improve individuals' quality of life, cognition, activities of daily living (ADL), and reduce behavioural and psychological symptoms of dementia, and whether they improve caregiver quality of life or reduce caregiver burden.\nSearch methods\nWe searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases, and three trials registers on 18 February 2021.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared a psychological intervention for depression or anxiety with treatment as usual (TAU) or another control intervention in people with dementia or MCI.\nData collection and analysis\nA minimum of two authors worked independently to select trials, extract data, and assess studies for risk of bias. We classified the included psychological interventions as cognitive behavioural therapies (cognitive behavioural therapy (CBT), behavioural activation (BA), problem-solving therapy (PST)); 'third-wave' therapies (such as mindfulness-based cognitive therapy (MBCT)); supportive and counselling therapies; and interpersonal therapies. We compared each class of intervention with control. We expressed treatment effects as standardised mean differences or risk ratios. Where possible, we pooled data using a fixed-effects model. We used GRADE methods to assess the certainty of the evidence behind each result.\nMain results\nWe included 29 studies with 2599 participants. They were all published between 1997 and 2020. There were 15 trials of cognitive behavioural therapies (4 CBT, 8 BA, 3 PST), 11 trials of supportive and counselling therapies, three trials of MBCT, and one of interpersonal therapy. The comparison groups received either usual care, attention-control education, or enhanced usual care incorporating an active control condition that was not a specific psychological treatment. There were 24 trials of people with a diagnosis of dementia, and five trials of people with MCI. Most studies were conducted in community settings. We considered none of the studies to be at low risk of bias in all domains.\nCognitive behavioural therapies (CBT, BA, PST)\nCognitive behavioural therapies are probably slightly better than treatment as usual or active control conditions for reducing depressive symptoms (standardised mean difference (SMD) -0.23, 95% CI -0.37 to -0.10; 13 trials, 893 participants; moderate-certainty evidence). They may also increase rates of depression remission at the end of treatment (risk ratio (RR) 1.84, 95% CI 1.18 to 2.88; 2 studies, with one study contributing 2 independent comparisons, 146 participants; low-certainty evidence). We were very uncertain about the effect of cognitive behavioural therapies on anxiety at the end of treatment (SMD -0.03, 95% CI -0.36 to 0.30; 3 trials, 143 participants; very low-certainty evidence). Cognitive behavioural therapies probably improve patient quality of life (SMD 0.31, 95% CI 0.13 to 0.50; 7 trials, 459 participants; moderate-certainty evidence) and activities of daily living at end of treatment compared to treatment as usual or active control (SMD -0.25, 95% CI -0.40 to -0.09; 7 trials, 680 participants; moderate-certainty evidence).\nSupportive and counselling interventions\nMeta-analysis showed that supportive and counselling interventions may have little or no effect on depressive symptoms in people with dementia compared to usual care at end of treatment (SMD -0.05, 95% CI -0.18 to 0.07; 9 trials, 994 participants; low-certainty evidence). We were very uncertain about the effects of these treatments on anxiety, which was assessed only in one small pilot study.\nOther interventions\nThere were very few data and very low-certainty evidence on MBCT and interpersonal therapy, so we were unable to draw any conclusions about the effectiveness of these interventions.\nAuthors' conclusions\nCBT-based treatments added to usual care probably slightly reduce symptoms of depression for people with dementia and MCI and may increase rates of remission of depression. There may be important effect modifiers (degree of baseline depression, cognitive diagnosis, or content of the intervention). CBT-based treatments probably also have a small positive effect on quality of life and activities of daily living. Supportive and counselling interventions may not improve symptoms of depression in people with dementia. Effects of both types of treatment on anxiety symptoms are very uncertain. We are also uncertain about the effects of other types of psychological treatments, and about persistence of effects over time. To inform clinical guidelines, future studies should assess detailed components of these interventions and their implementation in different patient populations and in different settings.\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": "We could be moderately certain about the small positive effects of CBT-based treatments on depression, quality of life and daily activities, but were less certain about other results. Most people in the review had dementia of mild to moderate severity so the results may not apply to people with MCI or more severe dementia. Very few studies included only people who had significant levels of depression before treatment, although these are the people most likely to be offered treatment in practice. There is not yet enough evidence to be able to say which people are most likely to benefit from which psychological treatments." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with venous thromboembolism (VTE) generally are treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (LMWH), followed by three months of vitamin K antagonists (VKAs). Treatment with VKAs requires regular laboratory measurements and carries risk of bleeding; some patients have contraindications to such treatment. Treatment with LMWH has been proposed to minimise the risk of bleeding complications. This is the second update of a review first published in 2001.\nObjectives\nThe purpose of this review was to evaluate the efficacy and safety of long term treatment (three months) with LMWH versus long term treatment (three months) with VKAs for symptomatic VTE.\nSearch methods\nFor this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), The Cochrane Vascular Information Specialistalso searched clinical trials registries for ongoing studies.\nSelection criteria\nRandomised controlled trials comparing LMWH versus VKA for long treatment (three months) of symptomatic VTE. Two review authors independently evaluated trials for inclusion and methodological quality.\nData collection and analysis\nReview authors independently extracted data and assessed risk of bias. We resolved disagreements by discussion and performed meta-analysis using fixed-effect models with Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs). Outcomes of interest were recurrent VTE, major bleeding, and mortality. We used GRADE to assess the overall quality of evidence supporting these outcomes.\nMain results\nSixteen trials, with a combined total of 3299 participants fulfilled our inclusion criteria. According to GRADE, the quality of evidence was moderate for recurrent VTE, low for major bleeding, and moderate for mortality. We downgraded the quality of the evidence for imprecision (recurrent VTE, mortality) and for risk of bias and inconsistency (major bleeding).\nWe found no clear differences in recurrent VTE between LMWH and VKA (Peto OR 0.83, 95% confidence interval (CI) 0.60 to 1.15; P = 0.27; 3299 participants; 16 studies; moderate-quality evidence). We found less bleeding with LMWH than with VKA (Peto OR 0.51, 95% CI 0.32 to 0.80; P = 0.004; 3299 participants; 16 studies; low-quality evidence). However, when comparing only high-quality studies for bleeding, we observed no clear differences between LMWH and VKA (Peto OR 0.62, 95% CI 0.36 to 1.07; P = 0.08; 1872 participants; seven studies). We found no clear differences between LMWH and VKA in terms of mortality (Peto OR 1.08, 95% CI 0.75 to 1.56; P = 0.68; 3299 participants; 16 studies; moderate-quality evidence).\nAuthors' conclusions\nModerate-quality evidence shows no clear differences between LMWH and VKA in preventing symptomatic VTE and death after an episode of symptomatic DVT. Low-quality evidence suggests fewer cases of major bleeding with LMWH than with VKA. However, comparison of only high-quality studies for bleeding shows no clear differences between LMWH and VKA. LMWH may represent an alternative for some patients, for example, those residing in geographically inaccessible areas, those who are unable or reluctant to visit the thrombosis service regularly, and those with contraindications to VKA.\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": "Blood clots (venous thromboembolism) sometimes cause blockages in veins after surgery, during bed rest, or spontaneously. These clots can be fatal when they travel to the lungs. Vitamin K antagonists (VKAs), 99% of which consist of warfarin, are effective in preventing renewed blood clot formation, because they thin the blood. Low-molecular-weight heparins (LMWHs) are drugs that thin the blood and are used for people who are at risk of major bleeding, people who cannot take vitamin K antagonists, and pregnant women." } ]

[ { "role": "user", "content": "Abstract: Background\nMajor depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have a negative impact in terms of quality of life, compliance with anticancer treatment, suicide risk and possibly the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results.\nObjectives\nTo evaluate the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage).\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was November 2022.\nSelection criteria\nWe included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis).\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcome was 1. efficacy as a continuous outcome. Our secondary outcomes were 2. efficacy as a dichotomous outcome, 3. Social adjustment, 4. health-related quality of life and 5. dropouts. We used GRADE to assess certainty of evidence for each outcome.\nMain results\nWe identified 14 studies (1364 participants), 10 of which contributed to the meta-analysis for the primary outcome. Six of these compared antidepressants and placebo, three compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update, we included four additional studies, three of which contributed data for the primary outcome.\nFor acute-phase treatment response (six to 12 weeks), antidepressants may reduce depressive symptoms when compared with placebo, even though the evidence is very uncertain. This was true when depressive symptoms were measured as a continuous outcome (standardised mean difference (SMD) −0.52, 95% confidence interval (CI) −0.92 to −0.12; 7 studies, 511 participants; very low-certainty evidence) and when measured as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.74, 95% CI 0.57 to 0.96; 5 studies, 662 participants; very low-certainty evidence). No studies reported data on follow-up response (more than 12 weeks). In head-to-head comparisons, we retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs) and for mirtazapine versus TCAs. There was no difference between the various classes of antidepressants (continuous outcome: SSRI versus TCA: SMD −0.08, 95% CI −0.34 to 0.18; 3 studies, 237 participants; very low-certainty evidence; mirtazapine versus TCA: SMD −4.80, 95% CI −9.70 to 0.10; 1 study, 25 participants).\nThere was a potential beneficial effect of antidepressants versus placebo for the secondary efficacy outcomes (continuous outcome, response at one to four weeks; very low-certainty evidence). There were no differences for these outcomes when comparing two different classes of antidepressants, even though the evidence was very uncertain.\nIn terms of dropouts due to any cause, we found no difference between antidepressants compared with placebo (RR 0.85, 95% CI 0.52 to 1.38; 9 studies, 889 participants; very low-certainty evidence), and between SSRIs and TCAs (RR 0.83, 95% CI 0.53 to 1.22; 3 studies, 237 participants).\nWe downgraded the certainty of the evidence because of the heterogeneous quality of the studies, imprecision arising from small sample sizes and wide CIs, and inconsistency due to statistical or clinical heterogeneity.\nAuthors' conclusions\nDespite the impact of depression on people with cancer, the available studies were few and of low quality. This review found a potential beneficial effect of antidepressants against placebo in depressed participants with cancer. However, the certainty of evidence is very low and, on the basis of these results, it is difficult to draw clear implications for practice. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which drug to prescribe may be based on the data on antidepressant efficacy in the general population of people with major depression, also taking into account that data on people with other serious medical conditions suggest a positive safety profile for the SSRIs. Furthermore, this update shows that the usage of the newly US Food and Drug Administration-approved antidepressant esketamine in its intravenous formulation might represent a potential treatment for this specific population of people, since it can be used both as an anaesthetic and an antidepressant. However, data are too inconclusive and further studies are needed. We conclude that to better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.\n\nGiven the provided abstract, please respond to the following query: \"What are the conclusions?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Despite the impact of depression on people with cancer, the available studies were very few and of low quality. We observed a small potential beneficial effect of antidepressants in treating depressive symptoms in people with cancer. However, this finding was supported by very low-quality evidence. To better inform doctors and patients, we need larger studies that randomly assign people to different treatments. Currently, it is difficult to draw reliable conclusions about the effects of antidepressants on depression in people with cancer. Our review seems to indicate that people with cancer should be treated in a similar way to the general population for the management of depressive symptoms." } ]

[ { "role": "user", "content": "Abstract: Background\nOpen-angle glaucoma (OAG) is an important cause of blindness worldwide. Laser trabeculoplasty, a treatment modality, still does not have a clear position in the treatment sequence.\nObjectives\nTo assess the effects of laser trabeculoplasty for treating OAG and ocular hypertension (OHT) when compared to medication, glaucoma surgery or no intervention. We also wished to compare the effectiveness of different laser trabeculoplasty technologies for treating OAG and OHT.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; LILACS, ClinicalTrials.gov and the WHO ICTRP. The date of the search was 28 October 2021. We also contacted researchers in the field.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing laser trabeculoplasty with no intervention, with medical treatment, or with surgery in people with OAG or OHT. We also included trials comparing different types of laser trabeculoplasty technologies.\nData collection and analysis\nWe used standard methods expected by Cochrane. Two authors screened search results and extracted data independently. We considered the following outcomes at 24 months: failure to control intraocular pressure (IOP), failure to stabilise visual field progression, failure to stabilise optic neuropathy progression, adverse effects, quality of life, and costs. We graded the 'certainty' of the evidence using GRADE.\nMain results\nWe included 40 studies (5613 eyes of 4028 people) in this review. The majority of the studies were conducted in Europe and in the USA. Most of the studies were at risk of performance and/or detection bias as they were unmasked. None of the studies were judged as having low risk of bias for all domains. We did not identify any studies of laser trabeculoplasty alone versus no intervention.\nLaser trabeculoplasty versus medication\nFourteen studies compared laser trabeculoplasty with medication in either people with primary OAG (7 studies) or primary or secondary OAG (7 studies); five of the 14 studies also included participants with OHT. Six studies used argon laser trabeculoplasty and eight studies used selective laser trabeculoplasty. There was considerable clinical and methodological diversity in these studies leading to statistical heterogeneity in results for the primary outcome \"failure to control IOP\" at 24 months.  Risk ratios (RRs) ranged from 0.43 in favour of laser trabeculoplasty to 1.87 in favour of medication (5 studies, I2 = 89%). Studies of argon laser compared with medication were more likely to show a beneficial effect compared with studies of selective laser (test for interaction P = 0.0001) but the argon laser studies were older and the medication comparator group in those studies may have been less effective. We considered this to be low-certainty evidence because the trials were at risk of bias (they were not masked) and there was unexplained heterogeneity. There was evidence from two studies (624 eyes) that argon laser treatment was associated with less failure to stabilise visual field progression compared with medication (7% versus 11%, RR 0.70, 95% CI 0.42 to 1.16) at 24 months and one further large recent study of selective laser also reported a reduced risk of failure at 48 months (17% versus 26%) RR 0.65, 95% CI 0.52 to 0.81, 1178 eyes). We judged this outcome as moderate-certainty evidence, downgrading for risk of bias. There was only very low-certainty evidence on optic neuropathy progression. Adverse effects were more commonly seen in the laser trabeculoplasty group including peripheral anterior synechiae (PAS) associated with argon laser (32% versus 26%, RR 11.74, 95% CI 5.94 to 23.22; 624 eyes; 2 RCTs; low-certainty evidence); 5% of participants treated with laser in three studies of selective laser group had early IOP spikes (moderate-certainty evidence). One UK-based study provided moderate-certainty evidence that laser trabeculoplasty was more cost-effective.\nLaser trabeculoplasty versus trabeculectomy\nThree studies compared laser trabeculoplasty with trabeculectomy. All three studies enrolled participants with OAG (primary or secondary) and used argon laser. People receiving laser trabeculoplasty may have a higher risk of uncontrolled IOP at 24 months compared with people receiving trabeculectomy (16% versus 8%, RR 2.12, 95% CI 1.44 to 3.11; 901 eyes; 2 RCTs). We judged this to be low-certainty evidence because of risk of bias (trials were not masked) and there was inconsistency between the two trials (I2 = 68%). There was limited evidence on visual field progression suggesting a higher risk of failure with laser trabeculoplasty. There was no information on optic neuropathy progression, quality of life or costs. PAS formation and IOP spikes were not reported but in one study trabeculectomy was associated with an increased risk of cataract (RR 1.78, 95% CI 1.46 to 2.16) (very low-certainty evidence).\nAuthors' conclusions\nLaser trabeculoplasty may work better than topical medication in slowing down the progression of open-angle glaucoma (rate of visual field loss) and may be similar to modern eye drops in controlling eye pressure at a lower cost. It is not associated with serious unwanted effects, particularly for the newer types of trabeculoplasty, such as selective laser trabeculoplasty.\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": "Some of the studies were not masked and were not large enough to provide a reliable answer to the question. There have been changes over time in both laser and eye drops which meant that, for some outcomes, there were different effects in different studies." } ]

[ { "role": "user", "content": "Abstract: Background\nThis review is an update of a rapid review undertaken in 2020 to identify relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control. The rapid review was published when little was known about transmission, treatment or future vaccination, and when physical distancing measures (isolation, quarantine, contact tracing, crowd avoidance, work and school measures) were the cornerstone of public health responses globally.\nThis updated review includes more recent evidence to extend what we know about effective pandemic public health communication. This includes considerations of changes needed over time to maintain responsiveness to pandemic transmission waves, the (in)equities and variable needs of groups within communities due to the pandemic, and highlights again the critical role of effective communication as integral to the public health response.\nObjectives\nTo update the evidence on the question 'What are relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control?', our primary focus was communication approaches to promote and support acceptance, uptake and adherence to physical distancing.\nSecondary objective: to explore and identify key elements of effective communication for physical distancing measures for different (diverse) populations and groups.\nSearch methods\nWe searched MEDLINE, Embase and Cochrane Library databases from inception, with searches for this update including the period 1 January 2020 to 18 August 2021. Systematic review and study repositories and grey literature sources were searched in August 2021 and guidelines identified for the eCOVID19 Recommendations Map were screened (November 2021).\nSelection criteria\nGuidelines or reviews focusing on communication (information, education, reminders, facilitating decision-making, skills acquisition, supporting behaviour change, support, involvement in decision-making) related to physical distancing measures for prevention and/or control of COVID-19 or selected other diseases (sudden acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, Ebola virus disease (EVD) or tuberculosis (TB)) were included. New evidence was added to guidelines, reviews and primary studies included in the 2020 review.\nData collection and analysis\nMethods were based on the original rapid review, using methods developed by McMaster University and informed by Cochrane rapid review guidance.\nScreening, data extraction, quality assessment and synthesis were conducted by one author and checked by a second author. Synthesis of results was conducted using modified framework analysis, with themes from the original review used as an initial framework.\nMain results\nThis review update includes 68 studies, with 17 guidelines and 20 reviews added to the original 31 studies.\nSynthesis identified six major themes, which can be used to inform policy and decision-making related to planning and implementing communication about a public health emergency and measures to protect the community.\nTheme 1: Strengthening public trust and countering misinformation: essential foundations for effective public health communication\nRecognising the key role of public trust is essential. Working to build and maintain trust over time underpins the success of public health communications and, therefore, the effectiveness of public health prevention measures.\nTheme 2: Two-way communication: involving communities to improve the dissemination, accessibility and acceptability of information\nTwo-way communication (engagement) with the public is needed over the course of a public health emergency: at first, recognition of a health threat (despite uncertainties), and regularly as public health measures are introduced or adjusted. Engagement needs to be embedded at all stages of the response and inform tailoring of communications and implementation of public health measures over time.\nTheme 3: Development of and preparation for public communication: target audience, equity and tailoring\nCommunication and information must be tailored to reach all groups within populations, and explicitly consider existing inequities and the needs of disadvantaged groups, including those who are underserved, vulnerable, from diverse cultural or language groups, or who have lower educational attainment. Awareness that implementing public health measures may magnify existing or emerging inequities is also needed in response planning, enactment and adjustment over time.\nTheme 4: Public communication features: content, timing and duration, delivery\nPublic communication needs to be based on clear, consistent, actionable and timely (up-to-date) information about preventive measures, including the benefits (whether for individual, social groupings or wider society), harms (likewise) and rationale for use, and include information about supports available to help follow recommended measures. Communication needs to occur through multiple channels and/or formats to build public trust and reach more of the community.\nTheme 5: Supporting behaviour change at individual and population levels\nSupporting implementation of public health measures with practical supports and services (e.g. essential supplies, financial support) is critical. Information about available supports must be widely disseminated and well understood. Supports and communication related to them require flexibility and tailoring to explicitly consider community needs, including those of vulnerable groups. Proactively monitoring and countering stigma related to preventive measures (e.g. quarantine) is also necessary to support adherence.\nTheme 6: Fostering and sustaining receptiveness and responsiveness to public health communication\nEfforts to foster and sustain public receptiveness and responsiveness to public health communication are needed throughout a public health emergency. Trust, acceptance and behaviours change over time, and communication needs to be adaptive and responsive to these changing needs. Ongoing community engagement efforts should inform communication and public health response measures.\nAuthors' conclusions\nImplications for practice\nEvidence highlights the critical role of communication throughout a public health emergency. Like any intervention, communication can be done well or poorly, but the consequences of poor communication during a pandemic may mean the difference between life and death.\nThe approaches to effective communication identified in this review can be used by policymakers and decision-makers, working closely with communication teams, to plan, implement and adjust public communications over the course of a public health emergency like the COVID-19 pandemic.\nImplications for research\nDespite massive growth in research during the COVID-19 period, gaps in the evidence persist and require high-quality, meaningful research. This includes investigating the experiences of people at heightened COVID-19 risk, and identifying barriers to implementing public communication and protective health measures particular to lower- and middle-income countries, and how to overcome these.\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 which ways of communicating with the public are best to increase people's understanding and use of physical distancing measures to protect themselves and limit the spread of COVID-19 and other similar diseases. We also wanted to find out whether there were ways of communicating that worked better for certain groups in the community, including people who experience disadvantage." } ]

[ { "role": "user", "content": "Abstract: Background\nWomen with a prior caesarean delivery have an increased risk of uterine rupture and for women subsequently requiring induction of labour it is unclear which method is preferable to avoid adverse outcomes. This is an update of a review that was published in 2013.\nObjectives\nTo assess the benefits and harms associated with different methods used to induce labour in women who have had a previous caesarean birth.\nSearch methods\nWe searched Cochrane Pregnancy and Childbirth's Trials Register (31 August 2016) and reference lists of retrieved studies.\nSelection criteria\nRandomised controlled trials (RCTs) comparing any method of third trimester cervical ripening or labour induction, with placebo/no treatment or other methods in women with prior caesarean section requiring labour induction in a subsequent pregnancy.\nData collection and analysis\nTwo review authors independently assessed studies for inclusion and trial quality, extracted data, and checked them for accuracy.\nMain results\nEight studies (data from 707 women and babies) are included in this updated review. Meta-analysis was not possible because studies compared different methods of labour induction. All included studies had at least one design limitation (i.e. lack of blinding, sample attrition, other bias, or reporting bias). One study stopped prematurely due to safety concerns.\nVaginal PGE2 versus intravenous oxytocin (one trial, 42 women): no clear differences for caesarean section (risk ratio (RR) 0.67, 95% confidence interval (CI) 0.22 to 2.03, evidence graded low), serious neonatal morbidity or perinatal death (RR 3.00, 95% CI 0.13 to 69.70, evidence graded low), serious maternal morbidity or death (RR 3.00, 95% CI 0.13 to 69.70, evidence graded low). Also no clear differences between groups for the reported secondary outcomes. The GRADE outcomes vaginal delivery not achieved within 24 hours, and uterine hyperstimulation with fetal heart rate changes were not reported.\nVaginal misoprostol versus intravenous oxytocin (one trial, 38 women): this trial stopped early because one woman who received misoprostol had a uterine rupture (RR 3.67, 95% CI 0.16 to 84.66) and one had uterine dehiscence. No other outcomes (including GRADE outcomes) were reported.\nFoley catheter versus intravenous oxytocin (one trial, subgroup of 53 women): no clear difference between groups for vaginal delivery not achieved within 24 hours (RR 1.47, 95% CI 0.89 to 2.44, evidence graded low), uterine hyperstimulation with fetal heart rate changes (RR 3.11, 95% CI 0.13 to 73.09, evidence graded low), and caesarean section (RR 0.93, 95% CI 0.45 to 1.92, evidence graded low). There were also no clear differences between groups for the reported secondary outcomes. The following GRADE outcomes were not reported: serious neonatal morbidity or perinatal death, and serious maternal morbidity or death.\nDouble-balloon catheter versus vaginal PGE2 (one trial, subgroup of 26 women): no clear difference in caesarean section (RR 0.97, 95% CI 0.41 to 2.32, evidence graded very low). Vaginal delivery not achieved within 24 hours, uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death were not reported.\nOral mifepristone versus Foley catheter (one trial, 107 women): no primary/GRADE outcomes were reported. Fewer women induced with mifepristone required oxytocin augmentation (RR 0.54, 95% CI 0.38 to 0.76). There were slightly fewer cases of uterine rupture among women who received mifepristone, however this was not a clear difference between groups (RR 0.29, 95% CI 0.08 to 1.02). No other secondary outcomes were reported.\nVaginal isosorbide mononitrate (IMN) versus Foley catheter (one trial, 80 women): fewer women induced with IMN achieved a vaginal delivery within 24 hours (RR 2.62, 95% CI 1.32 to 5.21, evidence graded low). There was no difference between groups in the number of women who had a caesarean section (RR 1.00, 95% CI 0.39 to 2.59, evidence graded very low). More women induced with IMN required oxytocin augmentation (RR 1.65, 95% CI 1.17 to 2.32). There were no clear differences in the other reported secondary outcomes. The following GRADE outcomes were not reported: uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death.\n80 mL versus 30 mL Foley catheter (one trial, 154 women): no clear difference between groups for the primary outcomes: vaginal delivery not achieved within 24 hours (RR 1.05, 95% CI 0.91 to 1.20, evidence graded moderate) and caesarean section (RR 1.05, 95% CI 0.89 to 1.24, evidence graded moderate). However, more women induced using a 30 mL Foley catheter required oxytocin augmentation (RR 0.81, 95% CI 0.66 to 0.98). There were no clear differences between groups for other secondary outcomes reported. Several GRADE outcomes were not reported: uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death.\nVaginal PGE2 pessary versus vaginal PGE2 tablet (one trial, 200 women): no difference between groups for caesarean section (RR 1.09, 95% CI 0.74 to 1.60, evidence graded very low), or any of the reported secondary outcomes. Several GRADE outcomes were not reported: vaginal delivery not achieved within 24 hours, uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death.\nAuthors' conclusions\nRCT evidence on methods of induction of labour for women with a prior caesarean section is inadequate, and studies are underpowered to detect clinically relevant differences for many outcomes. Several studies reported few of our prespecified outcomes and reporting of infant outcomes was especially scarce. The GRADE level for quality of evidence was moderate to very low, due to imprecision and study design limitations.\nHigh-quality, adequately-powered RCTs would be the best approach to determine the optimal method for induction of labour in women with a prior caesarean birth. However, such trials are unlikely to be undertaken due to the very large numbers needed to investigate the risk of infrequent but serious adverse outcomes (e.g. uterine rupture). Observational studies (cohort studies), including different methods of cervical ripening, may be the best alternative. Studies could compare methods believed to provide effective induction of labour with low risk of serious harm, and report the outcomes listed in this review.\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": "There is not enough information available from randomised controlled trials to advise on the best methods of labour induction in women with a previous caesarean birth. More high-quality randomised controlled trials are needed to find out which method is best for mothers and babies. However, such trials are unlikely to be carried out because they would need a very large number of participants in order to study the risk of infrequent but serious outcomes (such as rupture of the woman's uterus). Other types of studies (i.e. non-randomised controlled trials) might be the best alternative. Future research could focus on those methods of induction that are believed to be effective and have a low risk of serious harm. The outcomes identified as important in this review could be utilised in future studies." } ]

[ { "role": "user", "content": "Abstract: Background\nAnimal-derived surfactants have been shown to have several advantages over the first generation synthetic surfactants and are the most commonly used surfactant preparations. The animal-derived surfactants in clinical use are minced or lavaged and modified or purified from bovine or porcine lungs. It is unclear whether significant differences in clinical outcome exist among the available bovine (modified minced or lavage) and porcine (minced or lavage) surfactant extracts.\nObjectives\nTo compare the effect of administration of different animal-derived surfactant extracts on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having respiratory distress syndrome (RDS).\nSearch methods\nWe used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (1966 to July 31, 2015), EMBASE (1980 to July 31, 2015), and CINAHL (1982 to July 31, 2015). 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\nRandomized or quasi-randomized controlled trials that compared the effect of animal-derived surfactant extract treatment administered to preterm infants at risk for or having RDS to prevent complications of prematurity and mortality.\nData collection and analysis\nData regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on gestational age, surfactant dosing and schedule, treatment severity and treatment strategy. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group.\nMain results\nSixteen randomized controlled trials were included in the analysis.\nBovine lung lavage surfactant extract to modified bovine minced lung surfactant extract: Seven treatment studies and two prevention studies compared bovine lung lavage surfactant extract to modified bovine minced lung surfactant extract. The meta-analysis did not demonstrate any significant differences in death or chronic lung disease in the prevention trials (typical RR 1.02, 95% CI 0.89 to 1.17; typical RD 0.01, 95% CI −0.05 to 0.06; 2 studies and 1123 infants; high quality evidence) or treatment trials (typical RR 0.95, 95% CI 0.86 to 1.06; typical RD −0.02 , 95% CI −0.06 to 0.02; 3 studies and 2009 infants; high quality evidence)\nModified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract: Nine treatment studies compared modified bovine minced lung surfactant extract to porcine minced lung surfactant extract. Meta-analysis of these trials demonstrate a significant increase in the risk of mortality prior to hospital discharge (typical RR 1.44, 95% CI 1.04 to 2.00; typical RD 0.05, 95% CI 0.01 to 0.10; NNTH 20, 95% CI 10 to 100; 9 studies and 901 infants; moderate quality evidence), death or oxygen requirement at 36 weeks' postmenstrual age (typical RR 1.30, 95% CI 1.04 to 1.64; typical RD 0.11, 95% CI 0.02 to 0.20; NNTH 9, 95% CI 5 to 50; 3 studies and 448 infants; moderate quality evidence), receiving more than one dose of surfactant (typical RR 1.57, 95% CI 1.29 to 1.92; typical RD 0.14, 95% CI 0.08 to 0.20; NNTH 7, 95% CI 5 to 13; 6 studies and 786 infants), and patent ductus arteriosus (PDA) requiring treatment (typical RR 1.86, 95% CI 1.28 to 2.70; typical RD 0.28, 95% CI 0.13 to 0.43; NNTH 4, 95% CI 2 to 8; 3 studies and 137 infants) in infants treated with modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract. In the subgroup analysis based on initial dose of surfactant, improvement in mortality prior to discharge (typical RR 1.62, 95% CI 1.11 to 2.38; typical RD 0.06, 95% CI 0.01 to 0.11; NNTH 16, 95% CI 9 to 100) and risk of death or oxygen requirement at 36 weeks' postmenstrual age (typical RR 1.39, 95% CI 1.08 to 1.79; typical RD 0.13, 95% 0.03 to 0.23; NNTH 7, 95% CI 4 to 33) was limited to higher initial dose of porcine minced lung surfactant (> 100 mg/kg).\nOther comparisons: No difference in outcome was noted between bovine lung lavage surfactant extract versus porcine minced lung surfactant extract. There were no studies comparing bovine lung lavage surfactant extract versus porcine lung lavage surfactant; or porcine minced lung surfactant extract versus porcine lung lavage surfactant.\nAuthors' conclusions\nSignificant differences in clinical outcome were noted in the comparison trials of modified minced lung surfactant extract (beractant) compared with porcine minced lung surfactant extract (poractant alfa) including a significant increase in the risk of mortality prior to discharge, death or oxygen requirement at 36 weeks' postmenstrual age, PDA requiring treatment and \"receiving > 1 dose of surfactant\" in infants treated with modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract. The difference in these outcomes was limited to studies using a higher initial dose of porcine minced lung surfactant extract. It is uncertain whether the observed differences are from differences in dose or from source of extraction (porcine vs. bovine) because of the lack of dose-equivalent comparison groups with appropriate sample size. No differences in clinical outcomes were observed in comparative trials between bovine lung lavage surfactant and modified bovine minced lung surfactants.\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": "Does the use of one animal-derived surfactant preparation compared with an alternative animal-derived surfactant preparation lead to improved outcome in infants at risk for or having respiratory distress syndrome?" } ]

[ { "role": "user", "content": "Abstract: Background\nMuscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety. This review was first published in 2010 and searches were updated in 2014.\nObjectives\nTo assess the efficacy and safety of quinine-based agents in treating muscle cramps.\nSearch methods\nOn 27 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. We searched reference lists of articles up to 2014. We also searched for ongoing trials in November 2014.\nSelection criteria\nRandomised controlled trials of people of all ages with muscle cramps in any location and of any cause, treated with quinine or its derivatives.\nData collection and analysis\nThree review authors independently selected trials for inclusion, assessed risk of bias and extracted data. We contacted study authors for additional information. For comparisons including more than one trial, we assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).\nMain results\nWe identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n = 1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg). We found no new trials for inclusion when searches were updated in 2014.\nThe risk of bias in the trials varied considerably. All 23 trials claimed to be randomised, but only a minority described randomisation and allocation concealment adequately.\nCompared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected.\nA significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference (RD) 3%, 95% confidence interval (CI) 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (RD 0%, 95% CI -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine.\nA quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events.\nAuthors' conclusions\nThere is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials, but because serious adverse events can be rarely fatal, in some countries prescription of quinine is severely restricted.\nEvidence from single trials suggests that theophylline combined with quinine improves cramps more than quinine alone, and the effects of xylocaine injections into gastrocnemius are not significantly different to quinine across all outcomes. Low or moderate quality evidence shows no significant difference between quinine and vitamin E or quinine and quinine-vitamin E mixture. Further research into these alternatives, as well other pharmacological and non-pharmacological treatments, is thus warranted.\nThere is no evidence to judge optimal dosage or duration of quinine treatment. Further studies using different dosages and measurement of serum quinine levels will allow a therapeutic range to be defined for muscle cramp. Because serious adverse events are not common, large population studies are required to more accurately inform incidence. Longer lengths of follow-up in future trials will help determine the duration of action following cessation of quinine as well as long-term adverse events. The search for new therapies, pharmacological and nonpharmacological, should continue and further trials should compare vitamin E, quinine-vitamin E combination, and quinine-theophylline mixture with quinine.\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": "Muscle cramps can occur anywhere and in anyone; however, leg cramps are especially common in older people. Quinine is a medicine which has been used to treat cramps for many years. There is conflicting evidence for its ability to reduce cramps. Quinine can cause serious, even fatal adverse events, especially in overdosage." } ]

[ { "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: \"Quality of evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Quality ratings for the evidence ranged from very low to moderate, the main limitation being imprecision due to insufficient data. When the review authors checked the effect of using an alternative method of analysis the findings suggested higher rates of clinical pregnancy with standard IVF than with natural cycle IVF." } ]

[ { "role": "user", "content": "Abstract: Background\nBeta blockers are commonly used to treat hypertension. The blood pressure reading is the primary tool for physicians and patients to assess the efficacy of the treatment. The blood pressure lowering effect of beta-1 selective blockers is not known.\nObjectives\nTo quantify the dose-related effects of various doses and types of beta-1 selective adrenergic receptor blockers on systolic and diastolic blood pressure versus placebo in people with primary hypertension.\nSearch methods\nWe searched the Database of Abstracts of Reviews of Effectiveness (DARE) for related reviews.\nWe searched the following databases for primary studies: the Cochrane Hypertension Specialised Register (All years to 15 October 2015), CENTRAL via the Cochrane Register of Studies Online (2015, Issue 10), Ovid MEDLINE (1946 to 15 October 2015), Ovid EMBASE (1974 to 15 October 2015) and ClinicalTrials.gov (all years to 15 October 2015).\nThe Hypertension Group Specialised Register includes controlled trials from searches of CAB Abstracts, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, Food Science and Technology Abstracts (FSTA), Global Health, LILACS, MEDLINE, ProQuest Dissertations & Theses, PsycINFO, Web of Science and the WHO International Clinical Trials Registry Platform (ICTRP).\nElectronic databases were searched using a strategy combining the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity-maximizing version (2008 revision) with selected MeSH terms and free text terms. No language restrictions were used. The MEDLINE search strategy was translated into CENTRAL, EMBASE, the Hypertension Group Specialised Register and ClinicalTrials.gov using the appropriate controlled vocabulary as applicable. Full strategies are in Appendix 1.\nSelection criteria\nRandomised, double-blind, placebo-controlled parallel or cross-over trials. Studies had to contain a beta blocker monotherapy arm with fixed dose. People enrolled into the studies had to have primary hypertension at baseline. Duration of studies had to be between 3 weeks to 12 weeks. Drugs in this class of beta blockers are atenolol, betaxolol, bevantolol, bisoprolol, esmolol, metoprolol, nebivolol, pafenolol, practolol.\nData collection and analysis\nTwo authors confirmed the inclusion of studies and extracted the data independently. Review Manager (RevMan) 5.3.5 was used to synthesise data.\nMain results\nWe identified 56 RCTs (randomised controlled trials) that examined the blood pressure (BP) lowering efficacy of beta-1 selective blockers (beta-1 blocker) in 7812 primary hypertensive patients. Among the included trials, 26 RCTs were parallel studies and 30 RCTs were cross-over studies, examining eight beta-1 blockers. Overall, the majority of beta-1 blockers studied significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP). In people with mild to moderate hypertension, beta-1 selective blockers lowered BP by an average of -10/-8 mmHg and reduced heart rate by 11 beats per minute. The maximum BP reduction of beta-1 blockers occurred at twice the starting dose. Individual beta-1 blockers did not exhibit a graded dose-response effect on SBP and DBP over the recommended dose range.\nMost beta-1 blockers tested significantly lowered heart rate. A graded dose-response of beta-1 blockers on heart rate was evident. Higher dose beta-1 blockers lowered heart rate more than lower doses. Individually and overall beta-1 blockers did not affect pulse pressure, which distinguishes them from other classes of drugs.\nAuthors' conclusions\nThis review provides low quality evidence that in people with mild to moderate hypertension, beta-1 selective blockers lowered BP by an average of -10/-8 mmHg and reduced heart rate by 11 beats per minute as compared to placebo. The effect of beta-1 blockers at peak hours, -12/-9 mmHg, was greater than the reduction at trough hours, -8/-7 mmHg. Beta-1 selective blockers lowered BP by a greater magnitude than dual receptor beta-blockers and partial agonist beta-blockers, lowered BP similarly to nonselective beta-blockers. Beta-1 selective blockers lowered SBP by a similar degree and lowered DBP by a greater degree than diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Because DBP is lowered by a similar extent to SBP, beta-1 selective blockers do not reduce pulse pressure.\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 quality of the evidence was judged to be low due to various types of bias that could exaggerate the effect. A low quality of evidence means future research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate." } ]

[ { "role": "user", "content": "Abstract: Background\nThis review focuses on non-dispensing services from pharmacists, i.e. pharmacists in community, primary or ambulatory-care settings, to non-hospitalised patients, and is an update of a previously-published Cochrane Review.\nObjectives\nTo examine the effect of pharmacists' non-dispensing services on non-hospitalised patient outcomes.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, two other databases and two trial registers in March 2015, together with reference checking and contact with study authors to identify additional studies. We included non-English language publications. We ran top-up searches in January 2018 and have added potentially eligible studies to 'Studies awaiting classification'.\nSelection criteria\nRandomised trials of pharmacist services compared with the delivery of usual care or equivalent/similar services with the same objective delivered by other health professionals.\nData collection and analysis\nWe used standard methodological procedures of Cochrane and the Effective Practice and Organisation of Care Group. Two review authors independently checked studies for inclusion, extracted data and assessed risks of bias. We evaluated the overall certainty of evidence using GRADE.\nMain results\nWe included 116 trials comprising 111 trials (39,729 participants) comparing pharmacist interventions with usual care and five trials (2122 participants) comparing pharmacist services with services from other healthcare professionals. Of the 116 trials, 76 were included in meta-analyses. The 40 remaining trials were not included in the meta-analyses because they each reported unique outcome measures which could not be combined. Most trials targeted chronic conditions and were conducted in a range of settings, mostly community pharmacies and hospital outpatient clinics, and were mainly but not exclusively conducted in high-income countries. Most trials had a low risk of reporting bias and about 25%-30% were at high risk of bias for performance, detection, and attrition. Selection bias was unclear for about half of the included studies.\nCompared with usual care, we are uncertain whether pharmacist services reduce the percentage of patients outside the glycated haemoglobin target range (5 trials, N = 558, odds ratio (OR) 0.29, 95% confidence interval (CI) 0.04 to 2.22; very low-certainty evidence). Pharmacist services may reduce the percentage of patients whose blood pressure is outside the target range (18 trials, N = 4107, OR 0.40, 95% CI 0.29 to 0.55; low-certainty evidence) and probably lead to little or no difference in hospital attendance or admissions (14 trials, N = 3631, OR 0.85, 95% CI 0.65 to 1.11; moderate-certainty evidence). Pharmacist services may make little or no difference to adverse drug effects (3 trials, N = 590, OR 1.65, 95% CI 0.84 to 3.24) and may slightly improve physical functioning (7 trials, N = 1329, mean difference (MD) 5.84, 95% CI 1.21 to 10.48; low-certainty evidence). Pharmacist services may make little or no difference to mortality (9 trials, N = 1980, OR 0.79, 95% CI 0.56 to 1.12, low-certaintly evidence).\nOf the five studies that compared services delivered by pharmacists with other health professionals, no studies evaluated the impact of the intervention on the percentage of patients outside blood pressure or glycated haemoglobin target range, hospital attendance and admission, adverse drug effects, or physical functioning.\nAuthors' conclusions\nThe results demonstrate that pharmacist services have varying effects on patient outcomes compared with usual care. We found no studies comparing services delivered by pharmacists with other healthcare professionals that evaluated the impact of the intervention on the six main outcome measures. The results need to be interpreted cautiously because there was major heterogeneity in study populations, types of interventions delivered and reported outcomes.There was considerable heterogeneity within many of the meta-analyses, as well as considerable variation in the risks of bias.\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": "We found 116 relevant studies which involved 41,851 participants. Studies were conducted in 25 countries with the USA, UK, Canada and Australia contributing most studies. Many were conducted in community pharmacies (chemist shops) and hospital outpatient clinics. The studies compared services delivered by pharmacists with either usual care or with care delivered by other health professionals. The studies were of overall high quality, although some had problems because they did not include all the relevant information needed to assess quality.\nOf the 111 studies that compared pharmacist services with usual care, 47 studies reported the most important outcomes. Compared with usual care, pharmacist services may reduce the percentage of patients whose blood pressure is outside the target range. It is uncertain whether services delivered by pharmacists reduce the number of patients with glycated haemoglobin levels outside the target range, because the certainty of the evidence is very low. Pharmacist services may make little or no difference to hospital attendance or admissions or to adverse drug effects or to death rates. Pharmacist services may slightly improve physical functioning.\nWe found no studies comparing services delivered by pharmacists with other healthcare professionals that evaluated the impact of the intervention on the six main outcome measures." } ]

[ { "role": "user", "content": "Abstract: Background\nIntermittent claudication (IC) is the classic symptomatic form of peripheral arterial disease affecting an estimated 4.5% of the general population aged 40 years and older. Patients with IC experience limitations in their ambulatory function resulting in functional disability and impaired quality of life (QoL). Endovascular revascularisation has been proposed as an effective treatment for patients with IC and is increasingly performed.\nObjectives\nThe main objective of this systematic review is to summarise the (added) effects of endovascular revascularisation on functional performance and QoL in the management of IC.\nSearch methods\nFor this review the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (February 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). The CIS also searched trials registries for details of ongoing and unpublished studies.\nSelection criteria\nRandomised controlled trials (RCTs) comparing endovascular revascularisation (± conservative therapy consisting of supervised exercise or pharmacotherapy) versus no therapy (except advice to exercise) or versus conservative therapy (i.e. supervised exercise or pharmacotherapy) for IC.\nData collection and analysis\nTwo review authors independently selected studies, extracted data, and assessed the methodological quality of studies. Given large variation in the intensity of treadmill protocols to assess walking distances and use of different instruments to assess QoL, we used standardised mean difference (SMD) as treatment effect for continuous outcome measures to allow standardisation of results and calculated the pooled SMD as treatment effect size in meta-analyses. We interpreted pooled SMDs using rules of thumb (< 0.40 = small, 0.40 to 0.70 = moderate, > 0.70 = large effect) according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated the pooled treatment effect size for dichotomous outcome measures as odds ratio (OR).\nMain results\nWe identified ten RCTs (1087 participants) assessing the value of endovascular revascularisation in the management of IC. These RCTs compared endovascular revascularisation versus no specific treatment for IC or conservative therapy or a combination therapy of endovascular revascularisation plus conservative therapy versus conservative therapy alone. In the included studies, conservative treatment consisted of supervised exercise or pharmacotherapy with cilostazol 100 mg twice daily. The quality of the evidence ranged from low to high and was downgraded mainly owing to substantial heterogeneity and small sample size.\nComparing endovascular revascularisation versus no specific treatment for IC (except advice to exercise) showed a moderate effect on maximum walking distance (MWD) (SMD 0.70, 95% confidence interval (CI) 0.31 to 1.08; 3 studies; 125 participants; moderate-quality evidence) and a large effect on pain-free walking distance (PFWD) (SMD 1.29, 95% CI 0.90 to 1.68; 3 studies; 125 participants; moderate-quality evidence) in favour of endovascular revascularisation. Long-term follow-up in two studies (103 participants) showed no clear differences between groups for MWD (SMD 0.67, 95% CI -0.30 to 1.63; low-quality evidence) and PFWD (SMD 0.69, 95% CI -0.45 to 1.82; low-quality evidence). The number of secondary invasive interventions (OR 0.81, 95% CI 0.12 to 5.28; 2 studies; 118 participants; moderate-quality evidence) was also not different between groups. One study reported no differences in disease-specific QoL after two years.\nData from five studies (n = 345) comparing endovascular revascularisation versus supervised exercise showed no clear differences between groups for MWD (SMD -0.42, 95% CI -0.87 to 0.04; moderate-quality evidence) and PFWD (SMD -0.05, 95% CI -0.38 to 0.29; moderate-quality evidence). Similarliy, long-term follow-up in three studies (184 participants) revealed no differences between groups for MWD (SMD -0.02, 95% CI -0.36 to 0.32; moderate-quality evidence) and PFWD (SMD 0.11, 95% CI -0.26 to 0.48; moderate-quality evidence). In addition, high-quality evidence showed no difference between groups in the number of secondary invasive interventions (OR 1.40, 95% CI 0.70 to 2.80; 4 studies; 395 participants) and in disease-specific QoL (SMD 0.18, 95% CI -0.04 to 0.41; 3 studies; 301 participants).\nComparing endovascular revascularisation plus supervised exercise versus supervised exercise alone showed no clear differences between groups for MWD (SMD 0.26, 95% CI -0.13 to 0.64; 3 studies; 432 participants; moderate-quality evidence) and PFWD (SMD 0.33, 95% CI -0.26 to 0.93; 2 studies; 305 participants; moderate-quality evidence). Long-term follow-up in one study (106 participants) revealed a large effect on MWD (SMD 1.18, 95% CI 0.65 to 1.70; low-quality evidence) in favour of the combination therapy. Reports indicate that disease-specific QoL was comparable between groups (SMD 0.25, 95% CI -0.05 to 0.56; 2 studies; 330 participants; moderate-quality evidence) and that the number of secondary invasive interventions (OR 0.27, 95% CI 0.13 to 0.55; 3 studies; 457 participants; high-quality evidence) was lower following combination therapy.\n\nTwo studies comparing endovascular revascularisation plus pharmacotherapy (cilostazol) versus pharmacotherapy alone provided data showing a small effect on MWD (SMD 0.38, 95% CI 0.08 to 0.68; 186 participants; high-quality evidence), a moderate effect on PFWD (SMD 0.63, 95% CI 0.33 to 0.94; 186 participants; high-quality evidence), and a moderate effect on disease-specific QoL (SMD 0.59, 95% CI 0.27 to 0.91; 170 participants; high-quality evidence) in favour of combination therapy. Long-term follow-up in one study (47 participants) revealed a moderate effect on MWD (SMD 0.72, 95% CI 0.09 to 1.36; P = 0.02) in favour of combination therapy and no clear differences in PFWD between groups (SMD 0.54, 95% CI -0.08 to 1.17; P = 0.09). The number of secondary invasive interventions was comparable between groups (OR 1.83, 95% CI 0.49 to 6.83; 199 participants; high-quality evidence).\nAuthors' conclusions\nIn the management of patients with IC, endovascular revascularisation does not provide significant benefits compared with supervised exercise alone in terms of improvement in functional performance or QoL. Although the number of studies is small and clinical heterogeneity underlines the need for more homogenous and larger studies, evidence suggests that a synergetic effect may occur when endovascular revascularisation is combined with a conservative therapy of supervised exercise or pharmacotherapy with cilostazol: the combination therapy seems to result in greater improvements in functional performance and in QoL scores than are seen with conservative therapy alone.\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": "Overall, reviewers rated the quality of evidence for outcomes in the comparison of endovascular revascularisation versus no specific therapy for intermittent claudication as low to moderate mainly owing to small study sample sizes and the possibility of serious risk of bias in these studies. For comparisons of endovascular revascularisation versus conservative therapy, and the combination therapy of endovascular revascularisation and conservative therapy versus conservative therapy alone, reviewers generally rated the quality of evidence for outcomes as moderate to high mainly owing to substantial differences between studies." } ]

[ { "role": "user", "content": "Abstract: Background\nHandwashing is important to reduce the spread and transmission of infectious disease. Ash, the residue from stoves and fires, is a material used for cleaning hands in settings where soap is not widely available.\nObjectives\nTo assess the benefits and harms of hand cleaning with ash compared with hand cleaning using soap or other materials for reducing the spread of viral and bacterial infections.\nSearch methods\nOn 26 March 2020 we searched CENTRAL, MEDLINE, Embase, WHO Global Index Medicus, and the WHO International Clinical Trials Registry Platform.\nSelection criteria\nWe included all types of studies, in any population, that examined hand cleaning with ash compared to hand cleaning with any other material.\nData collection and analysis\nTwo review authors independently screened titles and full texts, and one review author extracted outcome data and assessed risk of bias, which another review author double-checked. We used the ROBINS-I tool for observational studies, we used RoB 2.0 for three interventional studies, and we used GRADE to assess the certainty of the evidence. We planned to synthesise data with random-effects meta-analyses. Our prespecified outcome measures were overall mortality, number of cases of infections (as defined in the individual studies), severity of infectious disease, harms (as reported in the individual studies), and adherence.\nMain results\nWe included 14 studies described in 19 records using eight different study designs, but only one randomised trial. The studies were primarily conducted in rural settings in low- and lower-middle-income countries. Six studies reported outcome data relevant to our review.\nA retrospective case-control study and a cohort study assessed diarrhoea in children under the age of five years and self-reported reproductive tract symptoms in women, respectively. It was very uncertain whether the rate of hospital contacts for moderate-to-severe diarrhoea in children differed between households that cleaned hands using ash compared with households cleaning hands using soap (RR 0.97, 95% CI 0.84 to 1.11; very low-certainty evidence). Similarly, it was very uncertain whether the rate of women experiencing symptoms of reproductive tract infection differed between women cleaning hands with ash compared with cleaning hands using soap (RR 0.48, 95% CI 0.12 to 1.86; very low-certainty evidence) or when compared with handwashing with water only or not washing hands (RR 0.50, 95% CI 0.13 to 1.96; very low-certainty evidence).\nFour studies reported on bacteriological counts after hand wash. We rated all four studies at high risk of bias, and we did not synthesise data due to methodological heterogeneity and unclear outcome reporting.\nAuthors' conclusions\nBased on the available evidence, the benefits and harms of hand cleaning with ash compared with soap or other materials for reducing the spread of viral or bacterial infections are uncertain.\n\nGiven the provided abstract, please respond to the following query: \"Certainty of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Our certainty (confidence) in the evidence was limited because we found few studies; those we did find had unreliable methods and different kinds of participants, and none of the studies we found reliably examined whether participants got infections." } ]

[ { "role": "user", "content": "Abstract: Background\nTerminally ill people experience a variety of symptoms in the last hours and days of life, including delirium, agitation, anxiety, terminal restlessness, dyspnoea, pain, vomiting, and psychological and physical distress. In the terminal phase of life, these symptoms may become refractory, and unable to be controlled by supportive and palliative therapies specifically targeted to these symptoms. Palliative sedation therapy is one potential solution to providing relief from these refractory symptoms. Sedation in terminally ill people is intended to provide relief from refractory symptoms that are not controlled by other methods. Sedative drugs such as benzodiazepines are titrated to achieve the desired level of sedation; the level of sedation can be easily maintained and the effect is reversible.\nObjectives\nTo assess the evidence for the benefit of palliative pharmacological sedation on quality of life, survival, and specific refractory symptoms in terminally ill adults during their last few days of life.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 11), MEDLINE (1946 to November 2014), and EMBASE (1974 to December 2014), using search terms representing the sedative drug names and classes, disease stage, and study designs.\nSelection criteria\nWe included randomised controlled trials (RCTs), quasi-RCTs, non-RCTs, and observational studies (e.g. before-and-after, interrupted-time-series) with quantitative outcomes. We excluded studies with only qualitative outcomes or that had no comparison (i.e. no control group or no within-group comparison) (e.g. single arm case series).\nData collection and analysis\nTwo review authors independently screened titles and abstracts of citations, and full text of potentially eligible studies. Two review authors independently carried out data extraction using standard data extraction forms. A third review author acted as arbiter for both stages. We carried out no meta-analyses due to insufficient data for pooling on any outcome; therefore, we reported outcomes narratively.\nMain results\nThe searches resulted in 14 included studies, involving 4167 adults, of whom 1137 received palliative sedation. More than 95% of people had cancer. No studies were randomised or quasi-randomised. All were consecutive case series, with only three having prospective data collection. Risk of bias was high, due to lack of randomisation. No studies measured quality of life or participant well-being, which was the primary outcome of the review. Five studies measured symptom control, using four different methods, so pooling was not possible. The results demonstrated that despite sedation, delirium and dyspnoea were still troublesome symptoms in these people in the last few days of life. Control of other symptoms appeared to be similar in sedated and non-sedated people. Only one study measured unintended adverse effects of sedative drugs and found no major events; however, four of 70 participants appeared to have drug-induced delirium. The study noticed no respiratory suppression. Thirteen of the 14 studies measured survival time from admission or referral to death, and all demonstrated no statistically significant difference between sedated and non-sedated groups.\nAuthors' conclusions\nThere was insufficient evidence about the efficacy of palliative sedation in terms of a person's quality of life or symptom control. There was evidence that palliative sedation did not hasten death, which has been a concern of physicians and families in prescribing this treatment. However, this evidence comes from low quality studies, so should be interpreted with caution. Further studies that specifically measure the efficacy and quality of life in sedated people, compared with non-sedated people, and quantify adverse effects are required.\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 studies were not randomised controlled trials (where people are randomly allocated to one of two or more treatment groups), and so we judged the quality of the evidence as poor." } ]

[ { "role": "user", "content": "Abstract: Background\nBasal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First-line treatment is usually surgical excision, but alternatives are available. New published studies and the development of non-surgical treatments meant an update of our Cochrane Review (first published in 2003, and previously updated in 2007) was timely.\nObjectives\nTo assess the effects of interventions for BCC in immunocompetent adults.\nSearch methods\nWe updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS.\nSelection criteria\nRandomised controlled trials (RCTs) of interventions for BCC in immunocompetent adults with histologically-proven, primary BCC. Eligible comparators were placebo, active treatment, other treatments, or no treatment.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Primary outcome measures were recurrence at three years and five years (measured clinically) (we included recurrence data outside of these time points if there was no measurement at three or five years) and participant- and observer-rated good/excellent cosmetic outcome. Secondary outcomes included pain during and after treatment, early treatment failure within six months, and adverse effects (AEs). We used GRADE to assess evidence certainty for each outcome.\nMain results\nWe included 52 RCTs (26 new) involving 6690 participants (median 89) in this update. All studies recruited from secondary care outpatient clinics. More males than females were included. Study duration ranged from six weeks to 10 years (average 13 months). Most studies (48/52) included only low-risk BCC (superficial (sBCC) and nodular (nBCC) histological subtypes). The majority of studies were at low or unclear risk of bias for most domains. Twenty-two studies were industry-funded: commercial sponsors conducted most of the studies assessing imiquimod, and just under half of the photodynamic therapy (PDT) studies.\nOverall, surgical interventions have the lowest recurrence rates. For high-risk facial BCC (high-risk histological subtype or located in the facial 'H-zone' or both), there may be slightly fewer recurrences with Mohs micrographic surgery (MMS) compared to surgical excision (SE) at three years (1.9% versus 2.9%, respectively) (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.16 to 2.64; 1 study, 331 participants; low-certainty evidence) and at five years (3.2% versus 5.2%, respectively) (RR 0.61, 95% CI 0.18 to 2.04; 1 study, 259 participants; low-certainty evidence). However, the 95% CI also includes the possibility of increased risk of recurrence and no difference between treatments. There may be little to no difference regarding improvement of cosmetic outcomes between MMS and SE, judged by participants and observers 18 months post-operatively (one study; low-certainty evidence); however, no raw data were available for this outcome.\nWhen comparing imiquimod and SE for nBCC or sBCC at low-risk sites, imiquimod probably results in more recurrences than SE at three years (16.4% versus 1.6%, respectively) (RR 10.30, 95% CI 3.22 to 32.94; 1 study, 401 participants; moderate-certainty evidence) and five years (17.5% versus 2.3%, respectively) (RR 7.73, 95% CI 2.81 to 21.3; 1 study, 383 participants; moderate-certainty evidence). There may be little to no difference in the number of participant-rated good/excellent cosmetic outcomes (RR 1.00, 95% CI 0.94 to 1.06; 1 study, 326 participants; low-certainty evidence). However, imiquimod may result in greater numbers of good/excellent cosmetic outcomes compared to SE when observer-rated (60.6% versus 35.6%, respectively) (RR 1.70, 95% CI 1.35 to 2.15; 1 study, 344 participants; low-certainty evidence). Both cosmetic outcomes were measured at three years.\nBased on one study of 347 participants with high- and low-risk primary BCC of the face, radiotherapy may result in more recurrences compared to SE under frozen section margin control at three years (5.2% versus 0%, respectively) (RR 19.11, 95% CI 1.12 to 325.78; low-certainty evidence) and at four years (6.4% versus 0.6%, respectively) (RR 11.06, 95% CI 1.44 to 84.77; low-certainty evidence). Radiotherapy probably results in a smaller number of participant- (RR 0.76, 95% CI 0.63 to 0.91; 50.3% versus 66.1%, respectively) or observer-rated (RR 0.48, 95% CI 0.37 to 0.62; 28.9% versus 60.3%, respectively) good/excellent cosmetic outcomes compared to SE, when measured at four years, where dyspigmentation and telangiectasia can occur (both moderate-certainty evidence).\nMethyl-aminolevulinate (MAL)-PDT may result in more recurrences compared to SE at three years (36.4% versus 0%, respectively) (RR 26.47, 95% CI 1.63 to 429.92; 1 study; 68 participants with low-risk nBCC in the head and neck area; low-certainty evidence). There were no useable data for measurement at five years. MAL-PDT probably results in greater numbers of participant- (RR 1.18, 95% CI 1.09 to 1.27; 97.3% versus 82.5%) or observer-rated (RR 1.87, 95% CI 1.54 to 2.26; 87.1% versus 46.6%) good/excellent cosmetic outcomes at one year compared to SE (2 studies, 309 participants with low-risk nBCC and sBCC; moderate-certainty evidence).\nBased on moderate-certainty evidence (single low-risk sBCC), imiquimod probably results in fewer recurrences at three years compared to MAL-PDT (22.8% versus 51.6%, respectively) (RR 0.44, 95% CI 0.32 to 0.62; 277 participants) and five years (28.6% versus 68.6%, respectively) (RR 0.42, 95% CI 0.31 to 0.57; 228 participants). There is probably little to no difference in numbers of observer-rated good/excellent cosmetic outcomes at one year (RR 0.98, 95% CI 0.84 to 1.16; 370 participants). Participant-rated cosmetic outcomes were not measured for this comparison.\nAEs with surgical interventions include wound infections, graft necrosis and post-operative bleeding. Local AEs such as itching, weeping, pain and redness occur frequently with non-surgical interventions. Treatment-related AEs resulting in study modification or withdrawal occurred with imiquimod and MAL-PDT.\nAuthors' conclusions\nSurgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for high-risk facial primary BCC (low-certainty evidence). Non-surgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Of the non-surgical treatments, imiquimod has the best evidence to support its efficacy.\nOverall, evidence certainty was low to moderate. Priorities for future research include core outcome measures and studies with longer-term follow-up.\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": "We found 52 studies that involved a total of 6690 adults with BCC. Most studies (48 out of 52) included hospital outpatients with small, superficial or nodular BCC. Studies lasted for between six weeks and 10 years (average duration: 13 months). Twenty-two studies were funded by pharmaceutical companies.\nOur confidence in the evidence presented here is low to moderate, mainly because many studies were small.\nComparison between different surgical treatments\n- Mohs micrographic surgery (a specialised surgical approach that removes less skin) may slightly decrease recurrence rates at three and five years compared to surgical excision (one of the most common surgical treatments for BCC).\n-There may be little to no difference in how well scars heal between these two surgical treatments according to patients and observers (one study).\nSurgery versus non-surgical treatments\nCompared against surgical excision:\n- Imiquimod (an anti-cancer cream) probably increases BCC recurrence rates at three and five years. There may be little to no difference in scar healing according to patients, although imiquimod may increase chances of scars healing well when healing is rated by an observer (one study).\n- Radiotherapy may increase BCC recurrence rates at three and four years, and probably decreases chances of scars healing well (one study).\n- MAL-PDT, a type of photodynamic therapy (that uses a light source and light-sensitive medicine to kill cancer cells), may increase BCC recurrence rates at three years. MAL-PDT probably increases chances of scars healing well (two studies).\nComparison of different non-surgical treatments\nCompared against imiquimod:\n- MAL-PDT probably increases BCC recurrence rates at three and five years. There is probably little to no difference in scar healing (one study);" } ]

[ { "role": "user", "content": "Abstract: Background\nArt therapy is defined by the British Association of Art Therapists as: “a form of psychotherapy that uses art media as its primary mode of communication. Clients who are referred to an art therapist need not have experience or skill in art. The art therapist is not primarily concerned with making an aesthetic or diagnostic assessment of the client’s image. The overall aim of its practitioners is to enable a client to change and grow on a personal level through the use of art materials in a safe and facilitating environment”. Historically, drawings and paintings have been recognised as a useful part of therapeutic processes within psychiatric and psychological specialties, and this has been acknowledged within medical and neurology-based disciplines.\nArts-based therapies are generally considered as interventions managing manifestations of dementia, as they may help to slow cognitive deterioration, address symptoms related to psychosocially challenging behaviours and improve quality of life.\nObjectives\nTo review the effects of art therapy as an adjunctive treatment for dementia compared with standard care and other non-pharmacological interventions.\nSearch methods\nWe identified trials from ALOIS - the Cochrane Dementia and Cognitive Improvement Group’s Specialised Register - on 12 May 2014, 20 March 2015, 15 January 2016, 4 November 2016, and 4 October 2017. We also handsearched the grey literature and contacted specialists in the field and authors of relevant reviews or studies to enquire about other sources of relevant information.\nSelection criteria\nAll randomised controlled trials examining art therapy as an intervention for dementia.\nData collection and analysis\nTwo review authors independently extracted data. We examined scales measuring cognition, affect and emotional well-being, social functioning, behaviour and quality of life.\nMain results\nWe found two studies that met the inclusion criteria, incorporating data on a total of 60 participants (from 88 randomised), in experimental groups (n = 29) and active control groups (n = 31). One study compared group art therapy with simple calculation activities over 12 weeks. The other study compared group art therapy with recreational activities over 40 weeks. It was not possible to pool the data for analysis from the included studies, due to heterogeneity in terms of differences in the interventions, control treatments and choice of outcome measures.\nIn both studies there were no clear changes reported between the intervention group and the control group in the important outcome measures. According to GRADE ratings, we judged the quality of evidence for these outcome measures to be 'very low'.\nAuthors' conclusions\nThere is insufficient evidence about the efficacy of art therapy for people with dementia. More adequately-powered and high-quality studies using relevant outcome measures are needed.\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 at research trials of people with dementia doing art therapy, compared with usual care and other activities. We looked at effects of art therapy on memory and thinking, emotions, well-being, social behaviour and quality of life. We also looked at negative effects and costs of art therapy. We found two research studies with a total of 88 older people taking part. There were results for 60 people. One study compared groups doing art therapy or simple calculation activities over 12 weeks. The other study compared groups doing art therapy or recreational activities over 40 weeks. The evidence is current to October 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nPrimary healthcare (PHC) workers often work alone or in isolation. Healthcare managerial supervision is recommended to help assure quality; but this requires skilled supervisors and takes time and resources. It is therefore important to assess to what extent supervision is beneficial and the ways in which it can be implemented.\nObjectives\nTo review the effects of managerial supervision of health workers to improve the quality of PHC (such as adherence to guidance or coverage of services) in low- and middle-income countries.\nSearch methods\nWe searched The Cochrane Central Register of Controlled Trials (CENTRAL) 2011, Issue 1, part of The Cochrane Library. www.thecochranelibrary.com, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register (searched 10 March 2011); MEDLINE, Ovid 1950 to March Week 1 2011 (searched 08 March 2011); EMBASE, Ovid 1980 to 2011 Week 12 (searched 08 March 2011); CINAHL, Ebsco 1981 – present (searched 10 March 2011); LILACS, VHL (searched 10 March 2011).\nSelection criteria\nRandomised controlled trials, controlled before-and-after studies, and interrupted time series studies, conducted in PHC in low- and middle-income countries. Supervision includes site visits from a central level of the health system, plus at least one supervisory activity. We excluded studies aimed solely at improving the clinical skills of PHC workers.\nData collection and analysis\nWe extracted data using a predefined form and assessed for risk of bias using the EPOC risk of bias criteria. Data are presented in a narrative way without pooling the effects on the outcomes as studies and outcomes were diverse.\nMain results\nNine studies met the inclusion criteria: three compared supervision with no supervision, five compared enhanced supervision with routine supervision, and one study compared less intensive supervision with routine supervision. Most outcomes were scores relating to providers’ practice, knowledge and provider or user satisfaction. The majority of the outcomes were measured within nine months after the interventions were introduced. In two studies comparing supervision with no supervision, small benefits on provider practice and knowledge were found. For methods of enhancing supervision, we identified five studies, and two studies of frequent supportive supervision demonstrated small benefits on workers performance. The one study examining the impact of less intensive supervision found no evidence that reducing the frequency of visits had any effect on the utilisation of services. The GRADE evidence quality for all comparisons and outcomes was \"low\" or \"very low\".\nAuthors' conclusions\nIt is uncertain whether supervision has a substantive, positive effect on the quality of primary health care in low- and middle-income countries. The long term effectiveness of supervision is unknown.\n\nGiven the provided abstract, please respond to the following query: \"Health worker supervision\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Supervision from higher levels of the health system, such as district headquarters, to the local level is widely recommended. Supervision is seen as a way of supporting often isolated primary health care workers and ensuring the quality of the health services they provide. However, supervisory visits need certain logistics including time and transport, and can be relatively costly.\nThe studies in this review took place in nine countries in Africa, Asia and Latin America, in both rural and urban areas. Most of the studies looked at the supervision of health care professionals (including nurses, midwives, health officers and physicians), while two studies examined the effect of supervision on community or lay health workers. The number of supervisory visits generally varied from one to six over a period of up to nine months." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of a Cochrane Review, first published in 2005.\nHemifacial spasm (HFS) is characterised by unilateral, involuntary contractions of the muscles innervated by the facial nerve. It is a chronic disorder, and spontaneous recovery is very rare. The two treatments routinely available are microvascular decompression and intramuscular injections with botulinum toxin type A (BtA).\nObjectives\nTo compare the efficacy, safety, and tolerability of BtA versus placebo in people with HFS.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. We ran the electronic database search, with no language restrictions, in July 2020.\nSelection criteria\nDouble-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with HFS.\nData collection and analysis\nTwo review authors independently assessed records. We planned to select included studies, extract data using a paper pro forma, and evaluate the risk of bias. We resolved disagreements by consensus, or by consulting a third review author. We planned to perform meta-analyses. The primary efficacy outcome was HFS-specific improvement. The primary safety outcome was the proportion of participants with any adverse event.\nMain results\nWe found no parallel-group randomised controlled trials comparing BtA and placebo in HFS.\nAuthors' conclusions\nWe did not find any randomised trials that evaluated the efficacy and safety of botulinum toxin type A in people with hemifacial spasm, so we are unable to draw any conclusions. Observational data show a strong association between BtA treatment and symptom improvement, and a favourable safety profile. While it is unlikely that future placebo-controlled RCTs will evaluate absolute efficacy and safety, they should address relevant questions for both people with HFS (such as long-term effects, quality of life, and other patient-reported outcomes), and clinicians (such as relative effectiveness of different BtA formulations and schemes of treatment) to better guide clinical practice.\n\nGiven the provided abstract, please respond to the following query: \"Certainty in the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The clinical benefit of BtA treatment for HFS has not been properly addressed in randomised clinical trials.\nWe did not systematically search for data from other sources of evidence, which, by definition, are more prone to bias and carry a higher level of uncertainty. Observational studies suggest that BtA is effective and safe in this setting. Future randomised studies should evaluate the impact on outcomes that are relevant for people with HFS, and help to guide clinical practice in the selection of the BtA formulation, dose, and technique of administration" } ]

[ { "role": "user", "content": "Abstract: Background\nAlthough helicopters are presently an integral part of trauma systems in most developed nations, previous reviews and studies to date have raised questions about which groups of traumatically injured people derive the greatest benefit.\nObjectives\nTo determine if helicopter emergency medical services (HEMS) transport, compared with ground emergency medical services (GEMS) transport, is associated with improved morbidity and mortality for adults with major trauma.\nSearch methods\nWe ran the most recent search on 29 April 2015. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library (Cochrane Central Register of Controlled Trials; CENTRAL), MEDLINE (OvidSP), EMBASE Classic + EMBASE (OvidSP), CINAHL Plus (EBSCOhost), four other sources, and clinical trials registers. We screened reference lists.\nSelection criteria\nEligible trials included randomized controlled trials (RCTs) and nonrandomized intervention studies. We also evaluated nonrandomized studies (NRS), including controlled trials and cohort studies. Each study was required to have a GEMS comparison group. An Injury Severity Score (ISS) of at least 15 or an equivalent marker for injury severity was required. We included adults age 16 years or older.\nData collection and analysis\nThree review authors independently extracted data and assessed the risk of bias of included studies. We applied the Downs and Black quality assessment tool for NRS. We analyzed the results in a narrative review, and with studies grouped by methodology and injury type. We constructed 'Summary of findings' tables in accordance with the GRADE Working Group criteria.\nMain results\nThis review includes 38 studies, of which 34 studies examined survival following transportation by HEMS compared with GEMS for adults with major trauma. Four studies were of inter-facility transfer to a higher level trauma center by HEMS compared with GEMS. All studies were NRS; we found no RCTs. The primary outcome was survival at hospital discharge. We calculated unadjusted mortality using data from 282,258 people from 28 of the 38 studies included in the primary analysis. Overall, there was considerable heterogeneity and we could not determine an accurate estimate of overall effect.\nBased on the unadjusted mortality data from six trials that focused on traumatic brain injury, there was no decreased risk of death with HEMS. Twenty-one studies used multivariate regression to adjust for confounding. Results varied, some studies found a benefit of HEMS while others did not. Trauma-Related Injury Severity Score (TRISS)-based analysis methods were used in 14 studies; studies showed survival benefits in both the HEMS and GEMS groups as compared with MTOS. We found no studies evaluating the secondary outcome, morbidity, as assessed by quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs). Four studies suggested a small to moderate benefit when HEMS was used to transfer people to higher level trauma centers. Road traffic and helicopter crashes are adverse effects which can occur with either method of transport. Data regarding safety were not available in any of the included studies. Overall, the quality of the included studies was very low as assessed by the GRADE Working Group criteria.\nAuthors' conclusions\nDue to the methodological weakness of the available literature, and the considerable heterogeneity of effects and study methodologies, we could not determine an accurate composite estimate of the benefit of HEMS. Although some of the 19 multivariate regression studies indicated improved survival associated with HEMS, others did not. This was also the case for the TRISS-based studies. All were subject to a low quality of evidence as assessed by the GRADE Working Group criteria due to their nonrandomized design. The question of which elements of HEMS may be beneficial has not been fully answered. The results from this review provide motivation for future work in this area. This includes an ongoing need for diligent reporting of research methods, which is imperative for transparency and to maximize the potential utility of results. Large, multicenter studies are warranted as these will help produce more robust estimates of treatment effects. Future work in this area should also examine the costs and safety of HEMS, since multiple contextual determinants must be considered when evaluating the effects of HEMS for adults with major trauma.\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": "Overall, the quality of the included studies was low. It is possible that HEMS may be better than GEMS for people with certain characteristics. There are various reasons why HEMS may be better, such as staff having more specialty training in managing major injuries. But more research is required to determine what elements of helicopter transport improve survival. Some studies did not describe the care available to people in the GEMS group. Due to this poor reporting it is impossible to compare the treatments people received." } ]

[ { "role": "user", "content": "Abstract: Background\nPneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily zinc supplements have been reported to prevent acute lower respiratory tract infection (LRTI) and reduce child mortality. This is an update of a review first published in 2010.\nObjectives\nTo evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months.\nSearch methods\nWe searched CENTRAL (Issue 21 October 2016), MEDLINE (1966 to October 2016), Embase (1974 to October 2016), LILACS (1982 to October 2016), CINAHL (1981 to October 2016), Web of Science (1985 to October 2016) and IMSEAR (1980 to October 2016).\nSelection criteria\nRandomised controlled trials (RCTs) evaluating zinc supplementation for the prevention of pneumonia in children aged from 2 months to 59 months.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data.\nMain results\nWe did not identify any new studies for inclusion in this update. We included six studies that involved 5193 participants.\nAnalysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (fixed-effect risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, six studies, low-quality evidence) and prevalence of pneumonia by 41% (random-effects RR 0.59; 95% CI 0.35 to 0.99, one study, n = 609, low-quality evidence). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (fixed-effect RR 0.79; 95% CI 0.71 to 0.88, four studies, n = 3261), but had no effect on lower specificity pneumonia case definition (i.e. age-specific fast breathing with or without lower chest indrawing) (fixed-effect RR 0.95; 95% CI 0.86 to 1.06, four studies, n = 1932).\nAuthors' conclusions\nZinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia.\n\nGiven the provided abstract, please respond to the following query: \"Study funding sources\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "All included studies were funded. Of these, three explicitly mentioned that funding agencies had no role in the design and results of the study." } ]

[ { "role": "user", "content": "Abstract: Background\nClinicians typically select the antibiotics used to treat pulmonary infections in people with cystic fibrosis based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis. This is an update of a previously published Cochrane Review.\nObjectives\nTo compare biofilm antimicrobial susceptibility testing-driven therapy to conventional antimicrobial susceptibility testing-driven therapy in the treatment of Pseudomonas aeruginosa infection in people with cystic fibrosis.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Most recent search: 07 April 2020.\nWe also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 07 April 2020 and 05 September 2017.\nSelection criteria\nRandomized controlled trials (RCTs) of antibiotic therapy based on biofilm antimicrobial susceptibility testing compared to antibiotic therapy based on conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infection in people with cystic fibrosis.\nData collection and analysis\nTwo authors independently selected RCTs, assessed their risk of bias and extracted data from eligible trials. Additionally, the review authors contacted the trial investigators to obtain further information. The quality of the evidence was assessed using the GRADE criteria.\nMain results\nThe searches identified two multicentre, double-blind RCTs eligible for inclusion in the review with a total of 78 participants (adults and children); one RCT was undertaken in people who were clinically stable, the second was in people experiencing pulmonary exacerbations. Both RCTs prospectively assessed whether the use of biofilm antimicrobial susceptibility testing improved microbiological and clinical outcomes in participants with cystic fibrosis who were infected with Pseudomonas aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa density from the beginning to the end of antibiotic therapy.\nAlthough the intervention was shown to be safe, the data from these two RCTs did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes. One of the trials also measured risk and time to subsequent exacerbation as well as quality of life measures and did not demonstrate any difference between groups in these outcomes. Both RCTs had an overall low risk of bias and the quality of the evidence using GRADE criteria was deemed to be moderate to high for the outcomes selected.\nAuthors' conclusions\nThe current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Biofilm antimicrobial susceptibility testing may be more appropriate in the development of newer, more effective formulations of drugs which can then be tested in clinical trials.\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": "Long-term lung infection is the main cause of death in people with cystic fibrosis. Antibiotic treatments for these infections have helped people with cystic fibrosis live longer. Doctors usually choose which antibiotics to use after on testing them against bacteria grown from samples taken from the infected person. These bacteria are grown in a liquid in the laboratory; but in real life bacteria such as Pseudomonas aeruginosa do not grow in liquid in the lungs of people with cystic fibrosis, instead they grow in a slime layer called a biofilm. Laboratory testing of antibiotics against Pseudomonas aeruginosa grown in a biofilm rather than in a liquid may give results that lead to better antibiotic choices with better clinical outcomes when treating lung infections in people with cystic fibrosis." } ]

[ { "role": "user", "content": "Abstract: Background\nLumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a corticosteroid dose into the epidural space, with the aim of reducing the local inflammatory process and, consequently, relieving the symptoms of lumbosacral radicular pain. This Cochrane Review is an update of a review published in Annals of Internal Medicine in 2012. Some placebo-controlled trials have been published recently, which highlights the importance of updating the previous review.\nObjectives\nTo investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection on pain and disability in patients with lumbosacral radicular pain.\nSearch methods\nWe searched the following databases without language limitations up to 25 September 2019: Cochrane Back and Neck group trial register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and two trial registers. We also performed citation tracking of included studies and relevant systematic reviews in the field.\nSelection criteria\nWe included studies that compared epidural corticosteroid injections of any corticosteroid drug to placebo injections in patients with lumbosacral radicular pain. We accepted all three anatomical approaches (caudal, interlaminar, and transforaminal) to delivering corticosteroids into the epidural space. We considered trials that included a placebo treatment as delivery of an inert substance (i.e. one with no pharmacologic activity), an innocuous substance (e.g. normal saline solution), or a pharmacologically active substance but not one considered to provide sustained benefit (e.g. local anaesthetic), either into the epidural space (i.e. to mimic epidural corticosteroid injection) or adjacent spinal tissue (i.e. subcutaneous, intramuscular, or interspinous tissue). We also included trials in which a local anaesthetic with a short duration of action was used as a placebo and injected together with corticosteroid in the intervention group.\nData collection and analysis\nTwo authors independently performed the screening, data extraction, and 'Risk of bias' assessments. In case of insufficient information, we contacted the authors of the original studies or estimated the data. We grouped the outcome data into four time points of assessment: immediate (≤ 2 weeks), short term (> 2 weeks but ≤ 3 months), intermediate term (> 3 months but < 12 months), and long term (≥ 12 months). We assessed the overall quality of evidence for each outcome and time point using the GRADE approach.\nMain results\nWe included 25 clinical trials (from 29 publications) investigating the effects of epidural corticosteroid injections compared to placebo in patients with lumbosacral radicular pain. The included studies provided data for a total of 2470 participants with a mean age ranging from 37.3 to 52.8 years. Seventeen studies included participants with lumbosacral radicular pain with a diagnosis based on clinical assessment and 15 studies included participants with mixed duration of symptoms. The included studies were conducted mainly in North America and Europe. Fifteen studies did not report funding sources, five studies reported not receiving funding, and five reported receiving funding from a non-profit or government source. Eight trials reported data on pain intensity, 12 reported data on disability, and eight studies reported data on adverse events. The duration of the follow-up assessments ranged from 12 hours to 1 year. We considered eight trials to be of high quality because we judged them as having low risk of bias in four out of the five bias domains. We identified one ongoing trial in a trial registry.\nEpidural corticosteroid injections were probably slightly more effective compared to placebo in reducing leg pain at short-term follow-up (mean difference (MD) −4.93, 95% confidence interval (CI) −8.77 to –1.09 on a 0 to 100 scale; 8 trials, n = 949; moderate-quality evidence (downgraded for risk of bias)). For disability, epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing disability at short-term follow-up (MD −4.18, 95% CI −6.04 to −2.17, on a 0 to 100 scale; 12 trials, n = 1367; moderate-quality evidence (downgraded for risk of bias)). The treatment effects are small, however, and may not be considered clinically important by patients and clinicians (i.e. MD lower than 10%).\nMost trials provided insufficient information on how or when adverse events were assessed (immediate or short-term follow-up) and only reported adverse drug reactions — that is, adverse events that the trialists attributed to the study treatment. We are very uncertain that epidural corticosteroid injections make no difference compared to placebo injection in the frequency of minor adverse events (risk ratio (RR) 1.14, 95% CI 0.91 to 1.42; 8 trials, n = 877; very low quality evidence (downgraded for risk of bias, inconsistency and imprecision)). Minor adverse events included increased pain during or after the injection, non-specific headache, post-dural puncture headache, irregular periods, accidental dural puncture, thoracic pain, non-local rash, sinusitis, vasovagal response, hypotension, nausea, and tinnitus. One study reported a major drug reaction for one patient on anticoagulant therapy who had a retroperitoneal haematoma as a complication of the corticosteroid injection.\nAuthors' conclusions\nThis study found that epidural corticosteroid injections probably slightly reduced leg pain and disability at short-term follow-up in people with lumbosacral radicular pain. In addition, no minor or major adverse events were reported at short-term follow-up after epidural corticosteroid injections or placebo injection. Although the current review identified additional clinical trials, the available evidence still provides only limited support for the use of epidural corticosteroid injections in people with lumbosacral radicular pain as the treatment effects are small, mainly evident at short-term follow-up and may not be considered clinically important by patients and clinicians (i.e. mean difference lower than 10%). According to GRADE, the quality of the evidence ranged from very low to moderate, suggesting that further studies are likely to play an important role in clarifying the efficacy and tolerability of this treatment. We recommend that further trials should attend to methodological features such as appropriate allocation concealment and blinding of care providers to minimise the potential for biased estimates of treatment and harmful effects.\n\nGiven the provided abstract, please respond to the following query: \"How injections of anti-inflammatory steroids directly into the spinal region might work\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "" } ]

[ { "role": "user", "content": "Abstract: Background\nNon-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion.\nPeople with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use.\nObjectives\nTo compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDβT:\n1. HbF inducers versus usual care or placebo;\n2. single HbF inducer with another HbF inducer, and single dose with another dose; and\n3. combination of HbF inducers versus usual care or placebo, or single HbF inducer.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was 21 August 2022.\nSelection criteria\nWe included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDβT, quality of life and adverse events.\nMain results\nWe included seven RCTs involving 291 people with NTDβT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved.\nHbF inducer against placebo or usual care\nThree HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI −0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001.\nAdverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP.\nHbF inducer versus another HbF inducer\nFour studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence).\nDifferent doses of the same HbF inducer\nTwo studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD −2.39 g/dL, 95% CI −2.80 to −1.98; very low-certainty evidence; HbF: MD −10.20%, 95% CI −16.28% to −4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects.\nA combination of HbF inducers versus a single HbF inducer\nTwo studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported.\nHydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD −0.74 g/dL, 95% CI −1.45 to −0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions.\nWe are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group.\nNone of the comparisons reported the outcome of HbF.\nAuthors' conclusions\nWe are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDβT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.\n\nGiven the provided abstract, please respond to the following query: \"How up to date is this evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence is current to 21 August 2022." } ]

[ { "role": "user", "content": "Abstract: Background\nLay health workers (LHWs) are widely used to provide care for a broad range of health issues. Little is known, however, about the effectiveness of LHW interventions.\nObjectives\nTo assess the effects of LHW interventions in primary and community health care on maternal and child health and the management of infectious diseases.\nSearch methods\nFor the current version of this review we searched The Cochrane Central Register of Controlled Trials (including citations uploaded from the EPOC and the CCRG registers) (The Cochrane Library 2009, Issue 1 Online) (searched 18 February 2009); MEDLINE, Ovid (1950 to February Week 1 2009) (searched 17 February 2009); MEDLINE In-Process & Other Non-Indexed Citations, Ovid (February 13 2009) (searched 17 February 2009); EMBASE, Ovid (1980 to 2009 Week 05) (searched 18 February 2009); AMED, Ovid (1985 to February 2009) (searched 19 February 2009); British Nursing Index and Archive, Ovid (1985 to February 2009) (searched 17 February 2009); CINAHL, Ebsco 1981 to present (searched 07 February 2010); POPLINE (searched 25 February 2009); WHOLIS (searched 16 April 2009); Science Citation Index and Social Sciences Citation Index (ISI Web of Science) (1975 to present) (searched 10 August 2006 and 10 February 2010). We also searched the reference lists of all included papers and relevant reviews, and contacted study authors and researchers in the field for additional papers.\nSelection criteria\nRandomised controlled trials of any intervention delivered by LHWs (paid or voluntary) in primary or community health care and intended to improve maternal or child health or the management of infectious diseases. A 'lay health worker' was defined as any health worker carrying out functions related to healthcare delivery, trained in some way in the context of the intervention, and having no formal professional or paraprofessional certificate or tertiary education degree. There were no restrictions on care recipients.\nData collection and analysis\nTwo review authors independently extracted data using a standard form and assessed risk of bias. Studies that compared broadly similar types of interventions were grouped together. Where feasible, the study results were combined and an overall estimate of effect obtained.\nMain results\nEighty-two studies met the inclusion criteria. These showed considerable diversity in the targeted health issue and the aims, content, and outcomes of interventions. The majority were conducted in high income countries (n = 55) but many of these focused on low income and minority populations. The diversity of included studies limited meta-analysis to outcomes for four study groups. These analyses found evidence of moderate quality of the effectiveness of LHWs in promoting immunisation childhood uptake (RR 1.22, 95% CI 1.10 to 1.37; P = 0.0004); promoting initiation of breastfeeding (RR = 1.36, 95% CI 1.14 to 1.61; P < 0.00001), any breastfeeding (RR 1.24, 95% CI 1.10 to 1.39; P = 0.0004), and exclusive breastfeeding (RR 2.78, 95% CI 1.74 to 4.44; P <0.0001); and improving pulmonary TB cure rates (RR 1.22 (95% CI 1.13 to 1.31) P <0.0001), when compared to usual care. There was moderate quality evidence that LHW support had little or no effect on TB preventive treatment completion (RR 1.00, 95% CI 0.92 to 1.09; P = 0.99). There was also low quality evidence that LHWs may reduce child morbidity (RR 0.86, 95% CI 0.75 to 0.99; P = 0.03) and child (RR 0.75, 95% CI 0.55 to 1.03; P = 0.07) and neonatal (RR 0.76, 95% CI 0.57 to 1.02; P = 0.07) mortality, and increase the likelihood of seeking care for childhood illness (RR 1.33, 95% CI 0.86 to 2.05; P = 0.20). For other health issues, the evidence is insufficient to draw conclusions regarding effectiveness, or to enable the identification of specific LHW training or intervention strategies likely to be most effective.\nAuthors' conclusions\nLHWs provide promising benefits in promoting immunisation uptake and breastfeeding, improving TB treatment outcomes, and reducing child morbidity and mortality when compared to usual care. For other health issues, evidence is insufficient to draw conclusions about the effects of LHWs.\n\nGiven the provided abstract, please respond to the following query: \"What is a lay health worker?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "A lay health worker is a member of the community who has received some training to promote health or to carry out some healthcare services, but is not a healthcare professional. In the studies in this review, lay health workers carried out different tasks. These included giving help and advice about issues such as child health, child illnesses, and medicine taking. In some studies, lay health workers also treated people for particular health problems.\nThe studies took place in different settings. In many of the studies, lay health workers worked among people on low incomes in wealthy countries, or among people living in poor countries." } ]

[ { "role": "user", "content": "Abstract: Background\nCerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose-related magnitude of effect of cerivastatin on blood lipids is not known.\nObjectives\nPrimary objective\nTo quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease.\nThe aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose-related effect and variability of the effect of cerivastatin on surrogate markers.\nSecondary objectives\nTo quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.\nSearch methods\nThe Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.\nSelection criteria\nRCTs and controlled before-and-after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.\nData collection and analysis\nTwo review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.\nMain results\nFifty trials (19 RCTs and 31 before-and-after studies) evaluated the dose-related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on LDL cholesterol, total cholesterol and triglycerides.\nWhen compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin at reducing LDL cholesterol; 233-fold more potent than fluvastatin, 18-fold more potent than atorvastatin and six-fold more potent than rosuvastatin at reducing total cholesterol; and 125-fold more potent than fluvastatin, 11-fold more potent than atorvastatin and 13-fold more potent than rosuvastatin at reducing triglycerides. There was no dose-related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short-term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74).\nAuthors' conclusions\nThe LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin in reducing LDL cholesterol, and 233-fold greater potency than fluvastatin, 18-fold greater potency than atorvastatin and six-fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.\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 looked at research up to March 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nDysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life, and longer hospital stay. Treatments provided to improve dysphagia are aimed at accelerating recovery of swallowing function and reducing these risks. This is an update of the review first published in 1999 and updated in 2012.\nObjectives\nTo assess the effects of swallowing therapy on death or dependency among stroke survivors with dysphagia within six months of stroke onset.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (26 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 26 June 2018), MEDLINE (26 June 2018), Embase (26 June 2018), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (26 June 2018), Web of Science Core Collection (26 June 2018), SpeechBITE (28 June 2016), ClinicalTrials.Gov (26 June 2018), and the World Health Organization International Clinical Trials Registry Platform (26 June 2018). We also searched Google Scholar (7 June 2018) and the reference lists of relevant trials and review articles.\nSelection criteria\nWe sought to include randomised controlled trials (RCTs) of interventions for people with dysphagia and recent stroke (within six months).\nData collection and analysis\nTwo review authors independently applied the inclusion criteria, extracted data, assessed risk of bias, used the GRADE approach to assess the quality of evidence, and resolved disagreements through discussion with the third review author (PB). We used random-effects models to calculate odds ratios (ORs), mean differences (MDs), and standardised mean differences (SMDs), and provided 95% confidence intervals (CIs) for each.\nThe primary outcome was functional outcome, defined as death or dependency (or death or disability), at the end of the trial. Secondary outcomes were case fatality at the end of the trial, length of inpatient stay, proportion of participants with dysphagia at the end of the trial, swallowing ability, penetration aspiration score, or pneumonia, pharyngeal transit time, institutionalisation, and nutrition.\nMain results\nWe added 27 new studies (1777 participants) to this update to include a total of 41 trials (2660 participants).\nWe assessed the efficacy of swallowing therapy overall and in subgroups by type of intervention: acupuncture (11 studies), behavioural interventions (nine studies), drug therapy (three studies), neuromuscular electrical stimulation (NMES; six studies), pharyngeal electrical stimulation (PES; four studies), physical stimulation (three studies), transcranial direct current stimulation (tDCS; two studies), and transcranial magnetic stimulation (TMS; nine studies).\nSwallowing therapy had no effect on the primary outcome (death or dependency/disability at the end of the trial) based on data from one trial (two data sets) (OR 1.05, 95% CI 0.63 to 1.75; 306 participants; 2 studies; I² = 0%; P = 0.86; moderate-quality evidence). Swallowing therapy had no effect on case fatality at the end of the trial (OR 1.00, 95% CI 0.66 to 1.52; 766 participants; 14 studies; I² = 6%; P = 0.99; moderate-quality evidence). Swallowing therapy probably reduced length of inpatient stay (MD -2.9, 95% CI -5.65 to -0.15; 577 participants; 8 studies; I² = 11%; P = 0.04; moderate-quality evidence). Researchers found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.54). Swallowing therapy may have reduced the proportion of participants with dysphagia at the end of the trial (OR 0.42, 95% CI 0.32 to 0.55; 1487 participants; 23 studies; I² = 0%; P = 0.00001; low-quality evidence). Trial results show no evidence of a subgroup effect based on testing for subgroup differences (P = 0.91). Swallowing therapy may improve swallowing ability (SMD -0.66, 95% CI -1.01 to -0.32; 1173 participants; 26 studies; I² = 86%; P = 0.0002; very low-quality evidence). We found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.09). We noted moderate to substantial heterogeneity between trials for these interventions. Swallowing therapy did not reduce the penetration aspiration score (i.e. it did not reduce radiological aspiration) (SMD -0.37, 95% CI -0.74 to -0.00; 303 participants; 11 studies; I² = 46%; P = 0.05; low-quality evidence). Swallowing therapy may reduce the incidence of chest infection or pneumonia (OR 0.36, 95% CI 0.16 to 0.78; 618 participants; 9 studies; I² = 59%; P = 0.009; very low-quality evidence).\nAuthors' conclusions\nModerate- and low-quality evidence suggests that swallowing therapy did not have a significant effect on the outcomes of death or dependency/disability, case fatality at the end of the trial, or penetration aspiration score. However, swallowing therapy may have reduced length of hospital stay, dysphagia, and chest infections, and may have improved swallowing ability. However, these results are based on evidence of variable quality, involving a variety of interventions. Further high-quality trials are needed to test whether specific interventions are effective.\n\nGiven the provided abstract, please respond to the following query: \",\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": ",and the evidence is current to June 2018. Swallowing therapy comprises several different treatment types, and we looked at eight of these: acupuncture (11 studies), behavioural interventions (nine studies), drug therapy (three studies), neuromuscular electrical stimulation (NMES; six studies), pharyngeal electrical stimulation (PES; four studies), physical stimulation (three studies), transcranial direct current stimulation (tDCS; two studies), and transcranial magnetic stimulation (TMS; nine studies)." } ]

[ { "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 did we want to find out?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Cutaneous melanoma is a very aggressive form of skin cancer. It is generally fatal if detected at an advanced stage. Earlier treatment may allow for surgical removal of the tumour and an improved chance of long-term survival. Neoadjuvant treatment is drug treatment administered before surgery, to reduce the tumour size so that it is easier to remove, to reduce complications of surgery, and to reduce the risk of spread of the disease. New drug types, immunotherapies and targeted treatments, have been developed which may be effective for neoadjuvant use.\nWe wanted to find out if neoadjuvant treatment of stage III or IV melanoma helps people live longer, and to compare adverse (unwanted) effects with neoadjuvant treatment and routine care." } ]

[ { "role": "user", "content": "Abstract: Background\nSince the early 2010s, there has been a push to enhance the capacity to effectively treat wasting in children through community-based service delivery models and thus reduce morbidity and mortality.\nObjectives\nTo assess the effectiveness of identification and treatment of moderate and severe wasting in children aged five years or under by lay health workers working in the community compared with health providers working in health facilities.\nSearch methods\nWe searched MEDLINE, CENTRAL, two other databases, and two ongoing trials registers to 24 September 2021. We also screened the reference lists of related systematic reviews and all included studies.\nSelection criteria\nWe included randomised controlled trials (RCTs) and non-randomised studies in children aged five years or under with moderate wasting (defined as weight-for-height Z-score (WHZ) below −2 but no lower than ≥ −3, or mid-upper-arm circumference (MUAC) below 125 mm but no lower than 115 mm, and no nutritional oedema) or severe wasting (WHZ below −3 or MUAC below 115 mm or nutritional oedema).\nEligible interventions were:\n• identification by lay health workers (LHWs) of children with wasting (intervention 1);\n• identification by LHWs of children with wasting and medical complications needing referral (intervention 2); and\n• identification by LHWs of children with wasting without medical complications needing referral (intervention 3).\nEligible comparators were:\n• identification and treatment of wasting by health professionals such as nurses or doctors (at health facilities); and\n• identification and treatment of wasting by health facility-based teams, including health professionals and LHWs.\nData collection and analysis\nTwo review authors independently screened trials, extracted data and assessed risk of bias using the Cochrane risk of bias tool (RoB 2) and Cochrane Effective Practice and Organisation of Care (EPOC) guidelines. We used a random-effects model to meta-analyse data, producing risk ratios (RRs) for dichotomous outcomes in trials with individual allocation, adjusted RRs for dichotomous outcomes in trials with cluster allocation (using the generic inverse variance method in Review Manager 5), and mean differences (MDs) for continuous outcomes. We used the GRADE approach to assess the certainty of the evidence.\nMain results\nWe included two RCTs and five non-RCTs. Six studies were from African countries, and one was from Pakistan. Six studies included children with severe wasting, and one included children with moderate wasting. All studies offered home-based ready-to-use therapeutic food treatment and monitoring. Children received antibiotics in three studies, vitamins or micronutrients in three studies, and deworming treatment in two studies. In three studies, the comparison arm involved LHWs screening children for malnutrition and referring them to health facilities for diagnosis and treatment.\nAll the non-randomised studies had a high overall risk of bias.\nInterventions 1 and 2\nIdentification and referral for treatment by LHWs, compared with treatment by health professionals following self-referral, may result in little or no difference in the percentage of children who recover from moderate or severe wasting (MD 1.00%, 95% confidence interval (CI) −2.53 to 4.53; 1 RCT, 29,475 households; low certainty).\nIntervention 3\nCompared with treatment by health professionals following identification by LHWs, identification and treatment of severe wasting in children by LHWs:\n• may slightly reduce improvement from severe wasting (RR 0.93, 95% CI 0.86 to 0.99; 1 RCT, 789 participants; low certainty);\n• may slightly increase non-response to treatment (RR 1.44, 95% CI 1.04 to 2.01; 1 RCT, 789 participants; low certainty);\n• may result in little or no difference in the number of children with WHZ above −2 on discharge (RR 0.94, 95% CI 0.28 to 3.18; 1 RCT, 789 participants; low certainty);\n• probably results in little or no difference in the number of children with WHZ between −3 and −2 on discharge (RR 1.09, 95% CI 0.87 to 1.36; 1 RCT, 789 participants; moderate certainty);\n• probably results in little or no difference in the number of children with WHZ below −3 (severe wasting) on discharge (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT, 789 participants; moderate certainty);\n• probably results in little or no difference in the number of children with MUAC equal to or greater than 115 mm on discharge (RR 0.99, 95% CI 0.93 to 1.06; 1 RCT, 789 participants; moderate certainty);\n• results in little or no difference in weight gain per day (mean weight gain 0.50 g/kg/day higher, 95% CI 1.74 lower to 2.74 higher; 1 RCT, 571 participants; high certainty);\n• probably has little or no effect on relapse of severe wasting (RR 1.03, 95% CI 0.69 to 1.54; 1 RCT, 649 participants; moderate certainty);\n• may have little or no effect on mortality among children with severe wasting (RR 0.46, 95% CI 0.04 to 5.98; 1 RCT, 829 participants; low certainty);\n• probably has little or no effect on the transfer of children with severe wasting to inpatient care (RR 3.71, 95% CI 0.36 to 38.23; 1 RCT, 829 participants; moderate certainty); and\n• probably has little or no effect on the default of children with severe wasting (RR 1.48, 95% CI 0.65 to 3.40; 1 RCT, 829 participants; moderate certainty).\nThe evidence was very uncertain for total MUAC gain, MUAC gain per day, total weight gain, treatment coverage, and transfer to another LHW site or health facility.\nNo studies examined sustained recovery, deterioration to severe wasting, appropriate identification of children with wasting or oedema, appropriate referral of children with moderate or severe wasting, adherence, or adverse effects and other harms.\nAuthors' conclusions\nIdentification and treatment of severe wasting in children who do not require inpatient care by LHWs, compared with treatment by health professionals, may lead to similar or slightly poorer outcomes. We found only two RCTs, and the evidence from non-randomised studies was of very low certainty for all outcomes due to serious risks of bias and imprecision. No studies included children aged under 6 months. Future studies must address these methodological issues.\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": "Identification and referral of children with wasting by lay health professionals, compared with treatment by health professionals after self-referral, may make little or no difference to the number of children who recover from moderate or severe wasting.\nIdentification and treatment of children with severe wasting by lay health workers, compared with treatment by health professionals after identification and referral by lay health workers:\n• may slightly reduce response to treatment (60 fewer children per 1000 responding to treatment);\n• may have little or no effect on the number of children who gain weight;\n• probably has little or no effect on the amount of weight gained;\n• probably has little or no effect on the number of children who relapse;\n• probably has little or no effect on the number of children who are transferred to inpatient care;\n• probably has little or no effect on the number of children who drop out of treatment; and\n• may have little or no effect on the number of children who die." } ]

[ { "role": "user", "content": "Abstract: Background\nPreterm infants are susceptible to hyperglycaemia and hypoglycaemia, which may lead to adverse neurodevelopment. The use of continuous glucose monitoring (CGM) devices might help in keeping glucose levels in the normal range, and reduce the need for blood sampling. However, the use of CGM might be associated with harms in the preterm infant.\nObjectives\nTo assess the benefits and harms of CGM versus intermittent modalities to measure glycaemia in preterm infants 1. at risk of hypoglycaemia or hyperglycaemia; 2. with proven hypoglycaemia; or 3. with proven hyperglycaemia.\nSearch methods\nWe searched CENTRAL (2021, Issue 4); PubMed; Embase; and CINAHL in April 2021. We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs.\nSelection criteria\nWe included RCTs and quasi-RCTs comparing the use of CGM versus intermittent modalities to measure glycaemia in preterm infants at risk of hypoglycaemia or hyperglycaemia; with proven hypoglycaemia; or with proven hyperglycaemia.\nData collection and analysis\nWe assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) with 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of the evidence.\nMain results\nWe included four trials enrolling 300 infants in our updated review. We included one new study and excluded another previously included study (because the inclusion criteria of the review have been narrowed). We compared the use of CGM to intermittent modalities in preterm infants at risk of hypoglycaemia or hyperglycaemia; however, one of these trials was analyzed separately because CGM was used as a standalone device, without being coupled to a control algorithm as in the other trials. We identified no studies in preterm infants with proven hypoglycaemia or hyperglycaemia.\nNone of the four included trials reported the neurodevelopmental outcome (i.e. the primary outcome of this review), or seizures. The effect of the use of CGM on mortality during hospitalization is uncertain (RR 0.59, 95% CI 0.16 to 2.13; RD −0.02, 95% CI −0.07 to 0.03; 230 participants; 2 studies; very low-certainty evidence). The certainty of the evidence was very low for all outcomes because of limitations in study design, and imprecision of estimates. One study is ongoing (estimated sample size 60 infants) and planned to be completed in 2022.\nAuthors' conclusions\nThere is insufficient evidence to determine if CGM affects preterm infant mortality or morbidities.  We are very uncertain of the safety of CGM and the available management algorithms, and many morbidities remain unreported. Preterm infants at risk of hypoglycaemia or hyperglycaemia were enrolled in all four included studies. No studies have been conducted in preterm infants with proven hypoglycaemia or hyperglycaemia. Long-term outcomes were not reported. Events of necrotizing enterocolitis, reported in the study published in 2021, were lower in the CGM group. However, the effect of CGM on this outcome remains very uncertain. Clinical trials are required to determine the most effective CGM and glycaemic management regimens in preterm infants before larger studies can be performed to assess the efficacy of CGM for reducing mortality, morbidity, and long-term neurodevelopmental impairments.\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 collected and analyzed all relevant studies to answer the review question, and found four studies enrolling 300 babies. These studies compared the use of CGM to intermittent measurements in infants at risk of too high or too low ​​​​​​ levels of blood glucose." } ]

[ { "role": "user", "content": "Abstract: Background\nPolycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions.\nObjectives\nTo assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS.\nSearch methods\nWe searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied.\nSelection criteria\nRandomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS.\nData collection and analysis\nTwo authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD).\nMain results\nWe included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.\nLifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence).\nAuthors' conclusions\nLifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.\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": "There were no studies that investigated the effect of a healthy lifestyle on live birth, miscarriage or regularity of menstrual cycles. Adopting a healthy lifestyle may result in weight loss or reduction in male hormone levels in some individuals. Diet and exercise may not have an effect on the body's ability to maintain normal blood glucose levels." } ]

[ { "role": "user", "content": "Abstract: Background\nIt is well known that physical exercise can trigger asthma symptoms and can induce bronchial obstruction in people without clinical asthma. International guidelines on asthma management recommend the use of beta2-agonists at any stage of the disease. At present, however, no consensus has been reached about the efficacy and safety of beta2-agonists in the pretreatment of exercise-induced asthma and exercise-induced bronchoconstriction. For the purpose of the present review, both of these conditions are referred to by the acronymous EIA, independently from the presence of an underlying chronic clinical disease.\nObjectives\nTo assess the effects of inhaled short- and long-acting beta2-agonists, compared with placebo, in the pretreatment of children and adults with exercise-induced asthma (or exercise-induced bronchoconstriction).\nSearch methods\nTrials were identified by electronic searching of the Cochrane Airways Group Specialised Register of Trials and by handsearching of respiratory journals and meetings. Searches are current as of August 2013.\nSelection criteria\nWe included randomised, double-blind, placebo-controlled trials of any study design, published in full text, that assessed the effects of inhaled beta2-agonists on EIA in adults and children. We excluded studies that did not clearly state diagnostic criteria for EIA.\nData collection and analysis\nWe used standard methodological procedures as expected by The Cochrane Collaboration.\nMain results\nWe included 53 trials consisting of 1139 participants. Forty-eight studies used a cross-over design, and five were performed in accordance with a parallel-group design. Forty-five studies addressed the effect of a single beta2-agonist administration, and eight focused on long-term treatment. We addressed these two different intervention regimens as different comparisons.\nAmong primary outcomes for short-term administration, data on maximum fall in forced expiratory volume in 1 second (FEV1) showed a significant protective effect for both short-acting beta-agonists (SABA) and long-acting beta-agonists (LABA) compared with placebo, with a mean difference of -17.67% (95% confidence interval (CI) -19.51% to -15.84%, P = 0.00001, 799 participants from 72 studies). The subgroup analysis of studies performed in adults compared with those performed in children showed high heterogeneity confined to children, despite the comparable mean bronchoprotective effect.\nSecondary outcomes on other pulmonary function parameters confirmed a more positive and protective effect of beta2-agonists on EIA compared with placebo. Occurrence of side effects was not significantly different between beta2-agonists and placebo.\nOverall evaluation of the included long-term studies suggests a beta2-agonist bronchoprotective effect for the first dose of treatment. However, long-term use of both SABA and LABA induced the onset of tolerance and decreased the duration of drug effect, even after a short treatment period.\nAuthors' conclusions\nEvidence of low to moderate quality shows that beta2-agonists, both SABA and LABA, when administered in a single dose, are effective and safe in preventing EIA.\nLong-term regular administration of inhaled beta2-agonists induces tolerance and lacks sufficient safety data. This finding appears to be of particular clinical relevance in view of the potential for prolonged regular use of beta2-agonists as monotherapy in the pretreatment of EIA, despite the warnings of drug agencies (FDA, EMA) regarding LABA.\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 53 trials consisting of 1139 participants. Forty-eight studies used a cross-over design, which meant that each person in the trial received two or more treatments－one or more active treatments, the beta-agonist and a placebo in random order. The rest were parallel-group trials, meaning that people received either the active treatment or a placebo. Most of the studies addressed the effect of a giving a single beta2-agonist treatment before exercise and recorded the effect on lung function following exercise. Only eight focused on longer treatment－longer treatments would be needed to assess whether these treatments were harmful over the longer term." } ]

[ { "role": "user", "content": "Abstract: Background\nBasilar skull fractures predispose patients to meningitis because of the possible direct contact of bacteria in the paranasal sinuses, nasopharynx or middle ear with the central nervous system (CNS). Cerebrospinal fluid (CSF) leakage has been associated with a greater risk of contracting meningitis. Antibiotics are often given prophylactically, although their role in preventing bacterial meningitis has not been established.\nObjectives\nTo evaluate the effectiveness of prophylactic antibiotics for preventing meningitis in patients with basilar skull fractures.\nSearch methods\nWe searched CENTRAL (2014, Issue 5), MEDLINE (1966 to June week 1, 2014), EMBASE (1974 to June 2014) and LILACS (1982 to June 2014). We also performed an electronic search of meeting proceedings from the American Association of Neurological Surgeons (1997 to September 2005) and handsearched the abstracts of meeting proceedings of the European Association of Neurosurgical Societies (1995, 1999 and 2003).\nSelection criteria\nRandomised controlled trials (RCTs) comparing any antibiotic versus placebo or no intervention. We also identified non-RCTs to perform a separate meta-analysis in order to compare results.\nData collection and analysis\nThree review authors independently screened and selected trials, assessed risk of bias and extracted data. We sought clarification with trial authors when needed. We pooled risk ratios (RRs) for dichotomous data with their 95% confidence intervals (CIs) using a random-effects model. We assessed the overall quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.\nMain results\nIn this update we did not identify any new trials for inclusion. We included five RCTs with 208 participants in the review and meta-analysis. We also identified 17 non-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention in patients with basilar skull fractures. Most trials presented insufficient methodological detail. All studies included meningitis in their primary outcome. When we evaluated the five included RCTs, there were no significant differences between antibiotic prophylaxis groups and control groups in terms of reduction of the frequency of meningitis, all-cause mortality, meningitis-related mortality and need for surgical correction in patients with CSF leakage. There were no reported adverse effects of antibiotic administration, although one of the five RCTs reported an induced change in the posterior nasopharyngeal flora towards potentially more pathogenic organisms resistant to the antibiotic regimen used in prophylaxis. We performed a subgroup analysis to evaluate the primary outcome in patients with and without CSF leakage. We also completed a meta-analysis of all the identified controlled non-RCTs (enrolling a total of 2168 patients), which produced results consistent with the randomised data from the included studies.\nUsing the GRADE approach, we assessed the quality of trials as moderate.\nAuthors' conclusions\nCurrently available evidence from RCTs does not support prophylactic antibiotic use in patients with basilar skull fractures, whether there is evidence of CSF leakage or not. Until more research is available, the effectiveness of antibiotics in patients with basilar skull fractures cannot be determined because studies published to date are flawed by biases. Large, appropriately designed RCTs are needed.\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": "Is it beneficial for patients with basilar skull fractures to receive a course of intravenous antibiotics?" } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with serious mental illness not only experience an erosion of functioning in day-to-day life over a protracted period of time, but evidence also suggests that they have a greater risk of experiencing oral disease and greater oral treatment needs than the general population. Poor oral hygiene has been linked to coronary heart disease, diabetes, and respiratory disease and impacts on quality of life, affecting everyday functioning such as eating, comfort, appearance, social acceptance, and self esteem. Oral health, however, is often not seen as a priority in people suffering with serious mental illness.\nObjectives\nTo review the effects of oral health education (advice and training) with or without monitoring for people with serious mental illness.\nSearch methods\nWe searched the Cochrane Schizophrenia Group's Trials Register (5 November 2015), which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the register.\nSelection criteria\nAll randomised clinical trials focusing on oral health education (advice and training) with or without monitoring for people with serious mental illness.\nData collection and analysis\nWe extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.\nMain results\nWe included three randomised controlled trials (RCTs) involving 1358 participants. None of the studies provided useable data for the key outcomes of not having seen a dentist in the past year, not brushing teeth twice a day, chronic pain, clinically important adverse events, and service use. Data for leaving the study early and change in plaque index scores were provided.\nOral health education compared with standard care\nWhen 'oral health education' was compared with 'standard care', there was no clear difference between the groups for numbers leaving the study early (1 RCT, n = 50, RR 1.67, 95% CI 0.45 to 6.24, moderate-quality evidence), while for dental state: no clinically important change in plaque index, an effect was found. Although this was statistically significant and favoured the intervention group, it is unclear if it was clinically important (1 RCT, n = 40, MD - 0.50 95% CI - 0.62 to - 0.38, very low quality evidence).These limited data may have implications regarding improvement in oral hygiene.\nMotivational interview + oral health education compared with oral health education\nSimilarly, when 'motivational interview + oral health education' was compared with 'oral health education', there was no clear difference for the outcome of leaving the study early (1 RCT, n = 60 RR 3.00, 95% CI 0.33 to 27.23, moderate-quality evidence), while for dental state: no clinically important change in plaque index, an effect favouring the intervention group was found (1 RCT, n = 56, MD - 0.60 95% CI - 1.02 to - 0.18 very low-quality evidence). These limited, clinically opaque data may or may not have implications regarding improvement in oral hygiene.\nMonitoring compared with no monitoring\nFor this comparison, only data for leaving the study early were available. We found a difference in numbers leaving early, favouring the 'no monitoring' group (1 RCT, n = 1682, RR 1.07, 95% CI 1.00 to 1.14, moderate-quality evidence). However, these data are problematic. The control denominator is implied and not clear, and follow-up did not depend only on individual participants, but also on professional caregivers and organisations - the latter changing frequently resulting in poor follow-up, but not a good reflection of the acceptability of the monitoring to patients. For this comparison, no data were available for 'no clinically important change in plaque index'.\nAuthors' conclusions\nWe found no evidence from trials that oral health advice helps people with serious mental illness in terms of clinically meaningful outcomes. It makes sense to follow guidelines and recommendations such as those put forward by the British Society for Disability and Oral Health working group until better evidence is generated. Pioneering trialists have shown that evaluative studies relevant to oral health advice for people with serious mental illness are possible.\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 mental health problems have an increased likelihood of oral disease (affecting the teeth, mouth, and gums) and can require more dental treatment than the general population. Oral health is currently not a priority for service users and mental health professionals, even though tooth decay, discolouration, sensitivity, and gum disease can affect such aspects of everyday life as eating, comfort, appearance, feelings of being accepted by others, and self esteem. While unlikely in itself to be fatal, poor dental health can contribute to other physical health problems such as heart disease. Some medications used to treat serious mental illness can cause side effects that lead to oral disease.\nOral health advice from a healthcare professional may encourage people with mental health problems to brush their teeth more regularly, have regular check-ups with their dentist, and seek dental care if suffering from painful tooth decay, increased sensitivity, or gum disease. Advice may include information or counsel that enables the individual to think about and be aware of their dental health. It should educate and inform, aim at preventing problems, and empower people to take better care of their mouth and teeth." } ]

[ { "role": "user", "content": "Abstract: Background\nSpecific diagnostic tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resulting COVID-19 disease are not always available and take time to obtain results. Routine laboratory markers such as white blood cell count, measures of anticoagulation, C-reactive protein (CRP) and procalcitonin, are used to assess the clinical status of a patient. These laboratory tests may be useful for the triage of people with potential COVID-19 to prioritize them for different levels of treatment, especially in situations where time and resources are limited.\nObjectives\nTo assess the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19.\nSearch methods\nOn 4 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.\nSelection criteria\nWe included both case-control designs and consecutive series of patients that assessed the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19. The reference standard could be reverse transcriptase polymerase chain reaction (RT-PCR) alone; RT-PCR plus clinical expertise or and imaging; repeated RT-PCR several days apart or from different samples; WHO and other case definitions; and any other reference standard used by the study authors.\nData collection and analysis\nTwo review authors independently extracted data from each included study. They also assessed the methodological quality of the studies, using QUADAS-2. We used the 'NLMIXED' procedure in SAS 9.4 for the hierarchical summary receiver operating characteristic (HSROC) meta-analyses of tests for which we included four or more studies. To facilitate interpretation of results, for each meta-analysis we estimated summary sensitivity at the points on the SROC curve that corresponded to the median and interquartile range boundaries of specificities in the included studies.\nMain results\nWe included 21 studies in this review, including 14,126 COVID-19 patients and 56,585 non-COVID-19 patients in total. Studies evaluated a total of 67 different laboratory tests. Although we were interested in the diagnotic accuracy of routine tests for COVID-19, the included studies used detection of SARS-CoV-2 infection through RT-PCR as reference standard. There was considerable heterogeneity between tests, threshold values and the settings in which they were applied. For some tests a positive result was defined as a decrease compared to normal vaues, for other tests a positive result was defined as an increase, and for some tests both increase and decrease may have indicated test positivity. None of the studies had either low risk of bias on all domains or low concerns for applicability for all domains. Only three of the tests evaluated had a summary sensitivity and specificity over 50%. These were: increase in interleukin-6, increase in C-reactive protein and lymphocyte count decrease.\nBlood count\nEleven studies evaluated a decrease in white blood cell count, with a median specificity of 93% and a summary sensitivity of 25% (95% CI 8.0% to 27%; very low-certainty evidence). The 15 studies that evaluated an increase in white blood cell count had a lower median specificity and a lower corresponding sensitivity. Four studies evaluated a decrease in neutrophil count. Their median specificity was 93%, corresponding to a summary sensitivity of 10% (95% CI 1.0% to 56%; low-certainty evidence). The 11 studies that evaluated an increase in neutrophil count had a lower median specificity and a lower corresponding sensitivity. The summary sensitivity of an increase in neutrophil percentage (4 studies) was 59% (95% CI 1.0% to 100%) at median specificity (38%; very low-certainty evidence). The summary sensitivity of an increase in monocyte count (4 studies) was 13% (95% CI 6.0% to 26%) at median specificity (73%; very low-certainty evidence). The summary sensitivity of a decrease in lymphocyte count (13 studies) was 64% (95% CI 28% to 89%) at median specificity (53%; low-certainty evidence). Four studies that evaluated a decrease in lymphocyte percentage showed a lower median specificity and lower corresponding sensitivity. The summary sensitivity of a decrease in platelets (4 studies) was 19% (95% CI 10% to 32%) at median specificity (88%; low-certainty evidence).\nLiver function tests\nThe summary sensitivity of an increase in alanine aminotransferase (9 studies) was 12% (95% CI 3% to 34%) at median specificity (92%; low-certainty evidence). The summary sensitivity of an increase in aspartate aminotransferase (7 studies) was 29% (95% CI 17% to 45%) at median specificity (81%) (low-certainty evidence). The summary sensitivity of a decrease in albumin (4 studies) was 21% (95% CI 3% to 67%) at median specificity (66%; low-certainty evidence). The summary sensitivity of an increase in total bilirubin (4 studies) was 12% (95% CI 3.0% to 34%) at median specificity (92%; very low-certainty evidence).\nMarkers of inflammation\nThe summary sensitivity of an increase in CRP (14 studies) was 66% (95% CI 55% to 75%) at median specificity (44%; very low-certainty evidence). The summary sensitivity of an increase in procalcitonin (6 studies) was 3% (95% CI 1% to 19%) at median specificity (86%; very low-certainty evidence). The summary sensitivity of an increase in IL-6 (four studies) was 73% (95% CI 36% to 93%) at median specificity (58%) (very low-certainty evidence).\nOther biomarkers\nThe summary sensitivity of an increase in creatine kinase (5 studies) was 11% (95% CI 6% to 19%) at median specificity (94%) (low-certainty evidence). The summary sensitivity of an increase in serum creatinine (four studies) was 7% (95% CI 1% to 37%) at median specificity (91%; low-certainty evidence). The summary sensitivity of an increase in lactate dehydrogenase (4 studies) was 25% (95% CI 15% to 38%) at median specificity (72%; very low-certainty evidence).\nAuthors' conclusions\nAlthough these tests give an indication about the general health status of patients and some tests may be specific indicators for inflammatory processes, none of the tests we investigated are useful for accurately ruling in or ruling out COVID-19 on their own. Studies were done in specific hospitalized populations, and future studies should consider non-hospital settings to evaluate how these tests would perform in people with milder symptoms.\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": "Routine laboratory tests cannot distinguish between COVID-19 and other diseases as the cause of infection, inflammation or tissue damage. None of the tests performed well enough to be a standalone diagnostic test for COVID-19 nor to prioritize patients for treatment. They will mainly be used to provide an overall picture about the health status of the patient. The final COVID-19 diagnosis has to be made based on other tests." } ]

[ { "role": "user", "content": "Abstract: Background\nThe role of cardiac catheterization in pediatrics has progressed significantly over the last two decades, evolving from a primary diagnostic tool to a primary treatment modality in children with congenital heart disease. Vascular complications, particularly arterial thrombosis, are among the most common unwanted post-cardiac catheterization events. In 1974, unfractionated heparin proved to be superior to placebo in decreasing the incidence of arterial thrombosis in pediatric patients. However, the optimal dose of unfractionated heparin to be utilized in this setting remains a matter of controversy. This is an update of the review first published in 2014.\nObjectives\nTo evaluate the use of low-dose (< 100 units/kg) versus high-dose (≥ 100 units/kg) unfractionated heparin administered as an intravenous bolus at the time of initiation of cardiac catheterization (that is, immediately after arterial puncture), with or without subsequent heparin maintenance doses, for the prevention of post-procedural arterial thrombosis in children.\nSearch methods\nThe Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 15 October 2019. We planned to undertake reference checking of identified trials to identify additional studies. No language restrictions were applied.\nSelection criteria\nWe included randomized or quasi-randomized trials that compared low dose to high dose unfractionated heparin administered prior to cardiac catheterization. We selected studies conducted in children aged 0 to 18 years.\nData collection and analysis\nThe first screening of potentially eligible studies was conducted by one of the authors (MLA). The second screening, risk of bias assessment and data extraction were independently conducted by two authors (MLA, LRB). Outcomes (thrombotic events, bleeding complications, other complications) were treated as dichotomous variables. The effect measures used were risk ratio (RR), risk difference (RD) and number needed to treat (NNT), with 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach.\nMain results\nWe identified no new studies for inclusion in this review. In total, two studies with a total of 492 participants were included. We had concerns about risk of bias for one of the two studies. The certainty of the evidence for our key outcomes was downgraded to moderate due to risk of bias concerns and imprecision. The confidence interval for the risk of arterial thrombotic events was compatible with benefits of either high or low unfractionated heparin dose regimens (RR low-dose versus high-dose 1.06, 95% CI 0.58 to 1.92). Only one of the studies reported the frequency of bleeding events and found no clear difference in the incidence of major or minor bleeding events between arms (RR low-dose versus high-dose 2.96, 95% CI 0.12 to 71.34 for major bleeding events; RR low-dose versus high-dose 1.38, 95% CI 0.46 to 4.13 for minor bleeding). This study also reported on the incidence of deep vein thrombosis when comparing the high versus low dose of heparin and reported a non-significant difference (RR low-dose versus high-dose 0.34, 95% CI 0.01 to 8.28). The other study lacked information about bleeding. Additional side effects of heparin other than bleeding events were not reported in either of the studies.\nAuthors' conclusions\nDue to the limitations of the current evidence, small number of included studies, and lack of details reported in one study, we are unable to determine the effects of different dosing regimens of unfractionated heparin for the prevention of vascular thrombosis during cardiac catheterization in children. Further adequately powered, randomized clinical trials are needed.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review included two small randomized controlled trials with a total of 492 participants (current until 15 October 2019). These two studies found imprecise evidence that the risk of arterial clots was similar in both the low-dose and high-dose heparin groups. Only one study reported bleeding and the frequency of clots in veins, which were also not different between groups. Side effects of heparin other than bleeding were not reported in either of the studies." } ]

[ { "role": "user", "content": "Abstract: Background\nChorioamnionitis is a common infection that affects both mother and infant. Infant complications associated with chorioamnionitis include early neonatal sepsis, pneumonia, and meningitis. Chorioamnionitis can also result in maternal morbidity such as pelvic infection and septic shock.\nClinical chorioamnionitis is estimated to occur in 1% to 2% of term births and in 5% to 10% of preterm births; histologic chorioamnionitis is found in nearly 20% of term births and in 50% of preterm births. Women with chorioamnionitis have a two to three times higher risk for cesarean delivery and a three to four times greater risk for endomyometritis, wound infection, pelvic abscess, bacteremia, and postpartum hemorrhage.\nObjectives\nTo assess the effects of administering antibiotic regimens for intra-amniotic infection on maternal and perinatal morbidity and mortality and on infection-related complications.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 October 2014), CENTRAL, MEDLINE, Embase, LILACS, and the WHO ICTRP (September 2014). We also searched reference lists of retrieved studies and contacted experts in the field.\nSelection criteria\nRandomized controlled trials (RCTs) that included women who experienced intra-amniotic infection. Trials were included if they compared antibiotic treatment with placebo or no treatment (if applicable), treatment with different antibiotic regimens, or timing of antibiotic therapy (intrapartum and/or postpartum). Therefore, this review assesses trials evaluating intrapartum antibiotics, intrapartum and postpartum antibiotic regimens, and postpartum antibiotics. Diagnosis of intra-amniotic infection was based on standard criteria (clinical/test), and no limit was placed on gestational age.\nData collection and analysis\nTwo review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data and checked them for accuracy. We assessed the quality of the evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and included a 'Summary of findings' table.\nMain results\nOur prespecified primary outcomes were maternal and neonatal mortality, maternal and neonatal severe infection, and duration of maternal and neonatal hospital stay.\nWe included 11 studies (involving 1296 women) and assessed them as having low to moderate risk of bias - mainly because allocation concealment methods were not adequately reported, most studies were open, and outcome reporting was incomplete. The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. The following antibiotics were assessed in the included trials: ampicillin, ampicillin/sulbactam, gentamicin, clindamycin, and cefotetan.\nDuring labor: meta-analysis of two studies found no clear differences in rates of neonatal sepsis (163 neonates; risk ratio (RR) 1.07, 95% confidence interval (CI) 0.40 to 2.86; I² = 9%; low quality of evidence), treatment failure (endometritis) (163 participants; RR 0.86, 95% CI 0.27 to 2.70; I² = 0%; low quality of evidence), and postpartum hemorrhage (RR 1.39, 95% CI 0.76 to 2.56; I² = 0%; low quality of evidence) when two different dosages/regimens of gentamicin were assessed. No clear differences between groups were found for any reported maternal or neonatal outcomes. The review did not identify data for a comparison of antibiotics versus no treatment/placebo.\nPostpartum: meta-analysis of two studies that evaluated use of antibiotics versus placebo after vaginal delivery showed no significant differences between groups in rates of treatment failure or postpartum endometritis. No significant differences were found in rates of neonatal death and postpartum endometritis when use of antibiotics was compared with no treatment. Four trials assessing two different dosages/regimens of gentamicin or dual-agent therapy versus triple-agent therapy, or comparing antibiotics, found no significant differences in most reported neonatal or maternal outcomes; the duration of hospital stay showed a difference in favor of the group of women who received short-duration antibiotics (one study, 292 women; mean difference (MD) -0.90 days, 95% CI -1.64 to -0.16; moderate quality of evidence).\nIntrapartum versus postpartum: one small study (45 women) evaluating use of ampicillin/gentamicin during intrapartum versus immediate postpartum treatment found significant differences favoring the intrapartum group in the mean number of days of maternal postpartum hospital stay (one trial, 45 women; MD -1.00 days, 95% CI -1.94 to - 0.06; very low quality of evidence) and the mean number of neonatal hospital stay days (one trial, 45 neonates; MD -1.90 days, 95% CI -3.91 to -0.49; very low quality of evidence). Although no significant differences were found in the rate of maternal bacteremia or early neonatal sepsis, for the outcome of neonatal pneumonia or sepsis we observed a significant difference favoring intrapartum treatment (one trial, 45 neonates; RR 0.06, 95% CI 0.00 to 0.95; very low quality of evidence).\nAuthors' conclusions\nThis review included 11 studies (having low to moderate risk of bias). The quality of the evidence was low to very low for most outcomes, as per the GRADE approach. Only one outcome (duration of hospital stay) was considered to provide moderate quality of evidence when antibiotics (short duration) were compared with antibiotics (long duration) during postpartum management of intra-amniotic infection. Our main reasons for downgrading the quality of evidence were limitations in study design or execution (risk of bias), imprecision, and inconsistency of results.\nCurrently, limited evidence is available to reveal the most appropriate antimicrobial regimen for the treatment of patients with intra-amniotic infection; whether antibiotics should be continued during the postpartum period; and which antibiotic regimen or what treatment duration should be used. Also, no evidence was found on adverse effects of the intervention (not reported in any of the included studies). One small RCT showed that use of antibiotics during the intrapartum period is superior to their use during the postpartum period in reducing the number of days of maternal and neonatal hospital stay.\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 was ranked low to very low, mainly because many studies had methodological limitations with outcome results based on limited numbers of trials and included participants that could be pooled." } ]

[ { "role": "user", "content": "Abstract: Background\nSeptic arthritis is an acute infection of the joints characterised by erosive disruption of the articular space. It is the most common non-degenerative articular disease in developing countries. The most vulnerable population for septic arthritis includes infants and preschoolers, especially boys. Septic arthritis disproportionately affects populations of low socioeconomic status. Systemic corticosteroids and antibiotic therapy may be beneficial for treatment of septic arthritis. Even if the joint infection is eradicated by antibiotic treatment, the inflammatory process may produce residual joint damage and sequelae.\nObjectives\nTo determine the benefits and harms of corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis.\nSearch methods\nWe searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, Latin American Caribbean Health Sciences Literature (LILACS), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/), ClinicalTrials.gov (www.ClinicalTrials.gov), and Google Scholar. We searched all databases from their inception to 17 April 2018, with no restrictions on language of publication.\nSelection criteria\nWe included randomised controlled trials (RCTs) with patients from two months to 18 years of age with a diagnosis of septic arthritis who were receiving corticosteroids in addition to antibiotic therapy or as an adjuvant to other therapies such as surgical drainage, intra-articular puncture, arthroscopic irrigation, or debridement.\nData collection and analysis\nTwo review authors independently assessed eligibility, data extraction, and evaluation of risk of bias. We considered as major outcomes the presence of pain, activities of daily living, normal physical joint function, days of antibiotic treatment, length of hospital stay, and numbers of total and serious adverse events. We used standard methodological procedures expected by Cochrane. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.\nMain results\nWe included two RCTs involving a total of 149 children between three months and 18 years of age who were receiving antibiotics for septic arthritis. The most commonly affected joints were hips and knees. These studies were performed in Costa Rica and Israel. In both studies, dexamethasone administered intravenously (ranging from 0.15 to 0.2 mg/kg/dose every six to eight hours) during four days was the corticosteroid, and the comparator was placebo. Trials excluded patients with any degree of immunodeficiency or immunosuppression. The longest follow-up was one year. Trials did not report activities of daily living nor length of hospital stay. Both studies used adequate processes for randomisation, allocation concealment, and blinding, and review authors judged them to have low risk of selection and performance bias. Losses to follow-up were substantive in both studies, and we judged them to have high risk of attrition bias and of selective outcome reporting. We graded all outcomes as low quality due to concerns about study limitations and imprecision.\nThe risk ratio (RR) for absence of pain at 12 months of follow-up was 1.33, favouring corticosteroids (95% confidence interval (CI) 1.03 to 1.72; P = 0.03; number needed to treat for an additional beneficial outcome (NNTB) = 13, 95% CI 6 to 139; absolute risk difference 24%, 95% CI 5% to 43%).\nThe RR for normal function of the affected joint at 12 months of follow-up was 1.32, favouring corticosteroids (95% CI 1.12 to 1.57; P = 0.001; NNTB = 13, 95% CI 7 to 33; absolute risk difference 24%, 95% CI 11% to 37%).\nWe found a reduction in the number of days of intravenous antibiotic treatment favouring corticosteroids (mean difference (MD) -2.77, 95% CI -4.16 to -1.39) based on two trials with 149 participants.\nResearchers did not report length of hospital stay. One trial (49 participants) reported that treatment with dexamethasone was associated with a shorter duration of IV antibiotic treatment, leading to a shorter hospital stay, and although duration of hospitalisation was a primary outcome of the study, study authors did not provide data on the duration of hospitalisation. We downgraded the quality by one level for concerns about study limitations (high risk of attrition bias and selective reporting), and by another level for imprecision.\nIn one trial of 49 participants, researchers followed 29 children for 12 months, and parents reported that no children demonstrated adverse effects of the intervention.\nAuthors' conclusions\nEvidence for corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis is of low quality and is derived from the findings of two trials (N = 149). Corticosteroids may increase the proportion of patients without pain and the proportion of patients with normal function of the affected joint at 12 months, and may also reduce the number of days of antibiotic treatment. However, we cannot draw strong conclusions based upon these trial results. Additional randomised clinical trials in children with relevant outcomes are needed.\n\nGiven the provided abstract, please respond to the following query: \"Normal physical joint function\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "1. 24 more of 100 children who received corticosteroids had normal function of the joint after 12 months (24% absolute improvement)\n2. 98 of 100 children experienced absence of pain compared to 74 of 100 children who received a placebo" } ]

[ { "role": "user", "content": "Abstract: Background\nTraditionally, amalgam has been used for filling cavities in posterior teeth, and it continues to be the restorative material of choice in some low- and middle-income countries due to its effectiveness and relatively low cost. However, there are concerns over the use of amalgam restorations (fillings) with regard to mercury release in the body and the environmental impact of mercury disposal. Dental composite resin materials are an aesthetic alternative to amalgam, and their mechanical properties have developed sufficiently to make them suitable for restoring posterior teeth. Nevertheless, composite resin materials may have potential for toxicity to human health and the environment.\nThe United Nations Environment Programme has established the Minamata Convention on Mercury, which is an international treaty that aims \"to protect the [sic] human health and the environment from anthropogenic emissions and releases of mercury and mercury compounds\". It entered into force in August 2017, and as of February 2021 had been ratified by 127 governments. Ratification involves committing to the adoption of at least two of nine proposed measures to phase down the use of mercury, including amalgam in dentistry. In light of this, we have updated a review originally published in 2014, expanding the scope of the review by undertaking an additional search for harms outcomes. Our review synthesises the results of studies that evaluate the long-term effectiveness and safety of amalgam versus composite resin restorations, and evaluates the level of certainty we can have in that evidence.\nObjectives\nTo examine the effects (i.e. efficacy and safety) of direct composite resin fillings versus amalgam fillings.\nSearch methods\nAn information specialist searched five bibliographic databases up to 16 February 2021 and used additional search methods to identify published, unpublished and ongoing studies\nSelection criteria\nTo assess efficacy, we included randomised controlled trials (RCTs) comparing dental composite resin with amalgam restorations in permanent posterior teeth that assessed restoration failure or survival at follow-up of at least three years.\nTo assess safety, we sought non-randomised studies in addition to RCTs that directly compared composite resin and amalgam restorative materials and measured toxicity, sensitivity, allergy, or injury.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane.\nMain results\nWe included a total of eight studies in this updated review, all of which were RCTs. Two studies used a parallel-group design, and six used a split-mouth design. We judged all of the included studies to be at high risk of bias due to lack of blinding and issues related to unit of analysis. We identified one new trial since the previous version of this review (2014), as well as eight additional papers that assessed safety, all of which related to the two parallel-group studies that were already included in the review.\nFor our primary meta-analyses, we combined data from the two parallel-group trials, which involved 1645 composite restorations and 1365 amalgam restorations in 921 children. We found low-certainty evidence that composite resin restorations had almost double the risk of failure compared to amalgam restorations (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.52 to 2.35; P < 0.001), and were at much higher risk of secondary caries (RR 2.14, 95% CI 1.67 to 2.74; P < 0.001). We found low-certainty evidence that composite resin restorations were not more likely to result in restoration fracture (RR 0.87, 95% CI 0.46 to 1.64; P = 0.66).\nSix trials used a split-mouth design. We considered these studies separately, as their reliability was compromised due to poor reporting, unit of analysis errors, and variability in methods and findings. Subgroup analysis showed that the findings were consistent with the results of the parallel-group studies.\nThree trials investigated possible harms of dental restorations. Higher urinary mercury levels were reported amongst children with amalgam restorations in two trials, but the levels were lower than what is known to be toxic. Some differences between amalgam and composite resin groups were observed on certain measures of renal, neuropsychological, and psychosocial function, physical development, and postoperative sensitivity; however, no consistent or clinically important harms were found. We considered that the vast number of comparisons made false-positive results likely. There was no evidence of differences between the amalgam and composite resin groups in neurological symptoms, immune function, and urinary porphyrin excretion. The evidence is of very low certainty, with most harms outcomes reported in only one trial.\nAuthors' conclusions\nLow-certainty evidence suggests that composite resin restorations may have almost double the failure rate of amalgam restorations. The risk of restoration fracture does not seem to be higher with composite resin restorations, but there is a much higher risk of developing secondary caries. Very low-certainty evidence suggests that there may be no clinically important differences in the safety profile of amalgam compared with composite resin dental restorations.\nThis review supports the utility of amalgam restorations, and the results may be particularly useful in parts of the world where amalgam is still the material of choice to restore posterior teeth with proximal caries. Of note, however, is that composite resin materials have undergone important improvements in the years since the trials informing the primary analyses for this review were conducted. The global phase-down of dental amalgam via the Minamata Convention on Mercury is an important consideration when deciding between amalgam and composite resin dental materials. The choice of which dental material to use will depend on shared decision-making between dental providers and patients in the clinic setting, and local directives and protocols.\n\nGiven the provided abstract, please respond to the following query: \"Implications of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Overall, the evidence suggests that amalgam restorations are effective, enduring, and safe, while composite resin restorations are more likely to fail and lead to secondary caries. However, the studies in this review were quite old, and composite resin materials have likely improved since the included studies were conducted. Patients and dental providers can discuss together which material they want to use when permanent teeth in the back of the mouth require fillings in the dental clinic. Governments around the world are trying to reduce the use of dental amalgam (according to the Minamata Convention on Mercury), and so each local area will have their own regulations and guidance." } ]

[ { "role": "user", "content": "Abstract: Background\nPotential benefits of rapamycin or rapalogs for treating people with tuberous sclerosis complex (TSC) have been shown. Currently everolimus (a rapalog) is only approved for TSC-associated renal angiomyolipoma and subependymal giant cell astrocytoma (SEGA), but not other manifestations of TSC. A systematic review needs to establish evidence for rapamycin or rapalogs for various manifestations in TSC. This is an updated review.\nObjectives\nTo determine the effectiveness of rapamycin or rapalogs in people with TSC for decreasing tumour size and other manifestations and to assess the safety of rapamycin or rapalogs in relation to their adverse effects.\nSearch methods\nWe identified relevant studies from the Cochrane-Central-Register-of-Controlled-Trials (CENTRAL), Ovid MEDLINE and ongoing trials registries with no language restrictions. We searched conference proceedings and abstract books of conferences.\nDate of the last searches: 15 July 2022.\nSelection criteria\nRandomised controlled trials (RCTs) or quasi-RCTs of rapamycin or rapalogs in people with TSC.\nData collection and analysis\nTwo review authors independently extracted data and assessed the risk of bias of each study; a third review author verified the extracted data and risk of bias decisions. We assessed the certainty of the evidence using GRADE.\nMain results\nThe current update added seven RCTs, bringing the total number to 10 RCTs (with 1008 participants aged 3 months to 65 years; 484 males). All TSC diagnoses were by consensus criteria as a minimum. In parallel studies, 645 participants received active interventions and 340 placebo. Evidence is low-to-high certainty and study quality is mixed; mostly a low risk of bias across domains, but one study had a high risk of performance bias (lack of blinding) and three studies had a high risk of attrition bias. Manufacturers of the investigational products supported eight studies.\nSystemic administration\nSix studies (703 participants) administered everolimus (rapalog) orally. More participants in the intervention arm reduced renal angiomyolipoma size by 50% (risk ratio (RR) 24.69, 95% confidence interval (CI) 3.51 to 173.41; P = 0.001; 2 studies, 162 participants, high-certainty evidence). In the intervention arm, more participants in the intervention arm reduced SEGA tumour size by 50% (RR 27.85, 95% CI 1.74 to 444.82; P = 0.02; 1 study; 117 participants; moderate-certainty evidence) ,and reported more skin responses (RR 5.78, 95% CI 2.30 to 14.52; P = 0.0002; 2 studies; 224 participants; high-certainty evidence). In one 18-week study (366 participants), the intervention led to 25% fewer seizures (RR 1.63, 95% CI 1.27 to 2.09; P = 0.0001) or 50% fewer seizures (RR 2.28, 95% CI 1.44 to 3.60; P = 0.0004); but there was no difference in numbers being seizure-free (RR 5.30, 95% CI 0.69 to 40.57; P = 0.11) (moderate-certainty evidence). One study (42 participants) showed no difference in neurocognitive, neuropsychiatry, behavioural, sensory and motor development (low-certainty evidence).\nTotal adverse events (AEs) did not differ between groups (RR 1.09, 95% CI 0.97 to 1.22; P = 0.16; 5 studies; 680 participants; high-certainty evidence). However, the intervention group experienced more AEs resulting in withdrawal, interruption of treatment, or reduced dose (RR 2.61, 95% CI 1.58 to 4.33; P = 0.0002; 4 studies; 633 participants; high-certainty evidence and also reported more severe AEs (RR 2.35, 95% CI 0.99 to 5.58; P = 0.05; 2 studies; 413 participants; high-certainty evidence).\nTopical (skin) administration\nFour studies (305 participants) administered rapamycin topically. More participants in the intervention arm showed a response to skin lesions (RR 2.72, 95% CI 1.76 to 4.18; P < 0.00001; 2 studies; 187 participants; high-certainty evidence) and more participants in the placebo arm reported a deterioration of skin lesions (RR 0.27, 95% CI 0.15 to 0.49; 1 study; 164 participants; high-certainty evidence). More participants in the intervention arm responded to facial angiofibroma at one to three months (RR 28.74, 95% CI 1.78 to 463.19; P = 0.02) and three to six months (RR 39.39, 95% CI 2.48 to 626.00; P = 0.009; low-certainty evidence). Similar results were noted for cephalic plaques at one to three months (RR 10.93, 95% CI 0.64 to 186.08; P = 0.10) and three to six months (RR 7.38, 95% CI 1.01 to 53.83; P = 0.05; low-certainty evidence). More participants on placebo showed a deterioration of skin lesions (RR 0.27, 95% CI 0.15 to 0.49; P < 0.0001; 1 study; 164 participants; moderate-certainty evidence). The intervention arm reported a higher general improvement score (MD -1.01, 95% CI -1.68 to -0.34; P < 0.0001), but no difference specifically in the adult subgroup (MD -0.75, 95% CI -1.58 to 0.08; P = 0.08; 1 study; 36 participants; moderate-certainty evidence). Participants in the intervention arm reported higher satisfaction than with placebo (MD -0.92, 95% CI -1.79 to -0.05; P = 0.04; 1 study; 36 participants; low-certainty evidence), although again with no difference among adults (MD -0.25, 95% CI -1.52 to 1.02; P = 0.70; 1 study; 18 participants; low-certainty evidence). Groups did not differ in change in quality of life at six months (MD 0.30, 95% CI -1.01 to 1.61; P = 0.65; 1 study; 62 participants; low-certainty evidence).\nTreatment led to a higher risk of any AE compared to placebo (RR 1.72, 95% CI 1.10, 2.67; P = 0.02; 3 studies; 277 participants; moderate-certainty evidence); but no difference between groups in severe AEs (RR 0.78, 95% CI 0.19 to 3.15; P = 0.73; 1 study; 179 participants; moderate-certainty evidence).\nAuthors' conclusions\nOral everolimus reduces the size of SEGA and renal angiomyolipoma by 50%, reduces seizure frequency by 25% and 50% and implements beneficial effects on skin lesions with no difference in the total number of AEs compared to placebo; however, more participants in the treatment group required a dose reduction, interruption or withdrawal and marginally more experienced serious AEs compared to placebo.\nTopical rapamycin increases the response to skin lesions and facial angiofibroma, an improvement score, satisfaction and the risk of any AE, but not severe adverse events.\nWith caution regarding the risk of severe AEs, this review supports oral everolimus for renal angiomyolipoma, SEGA, seizure, and skin lesions, and topical rapamycin for facial angiofibroma.\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: 15 July 2022." } ]

[ { "role": "user", "content": "Abstract: Background\nCardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. This is an update of a review previously published in 2009 and 2015.\nObjectives\nTo compare the effect of home-based and supervised centre-based cardiac rehabilitation on mortality and morbidity, exercise-capacity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease.\nSearch methods\nWe updated searches from the previous Cochrane Review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) on 21 September 2016. We also searched two clinical trials registers as well as previous systematic reviews and reference lists of included studies. No language restrictions were applied.\nSelection criteria\nWe included randomised controlled trials, including parallel group, cross-over or quasi-randomised designs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation.\nData collection and analysis\nTwo review authors independently screened all identified references for inclusion based on pre-defined inclusion criteria. Disagreements were resolved through discussion or by involving a third review author. Two authors independently extracted outcome data and study characteristics and assessed risk of bias. Quality of evidence was assessed using GRADE principles and a Summary of findings table was created.\nMain results\nWe included six new studies (624 participants) for this update, which now includes a total of 23 trials that randomised a total of 2890 participants undergoing cardiac rehabilitation. Participants had an acute myocardial infarction, revascularisation or heart failure. A number of studies provided insufficient detail to enable assessment of potential risk of bias, in particular, details of generation and concealment of random allocation sequencing and blinding of outcome assessment were poorly reported.\nNo evidence of a difference was seen between home- and centre-based cardiac rehabilitation in clinical primary outcomes up to 12 months of follow up: total mortality (relative risk (RR) = 1.19, 95% CI 0.65 to 2.16; participants = 1505; studies = 11/comparisons = 13; very low quality evidence), exercise capacity (standardised mean difference (SMD) = -0.13, 95% CI -0.28 to 0.02; participants = 2255; studies = 22/comparisons = 26; low quality evidence), or health-related quality of life up to 24 months (not estimable). Trials were generally of short duration, with only three studies reporting outcomes beyond 12 months (exercise capacity: SMD 0.11, 95% CI -0.01 to 0.23; participants = 1074; studies = 3; moderate quality evidence). However, there was evidence of marginally higher levels of programme completion (RR 1.04, 95% CI 1.00 to 1.08; participants = 2615; studies = 22/comparisons = 26; low quality evidence) by home-based participants.\nAuthors' conclusions\nThis update supports previous conclusions that home- and centre-based forms of cardiac rehabilitation seem to be similarly effective in improving clinical and health-related quality of life outcomes in patients after myocardial infarction or revascularisation, or with heart failure. This finding supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme may reflect local availability and consider the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in the included short-term trials can be confirmed in the longer term and need to consider adequately powered non-inferiority or equivalence study designs.\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 up to September 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nInflammatory bowel disease (IBD) is a life-long condition for which currently there is no cure. Patient educational interventions deliver structured information to their recipients. Evidence suggests patient education can have positive effects in other chronic diseases.\nObjectives\nTo identify the different types of educational interventions, how they are delivered, and to determine their effectiveness and safety in people with IBD.\nSearch methods\nOn 27 November 2022, we searched CENTRAL, Embase, MEDLINE, ClinicalTrials.gov, and WHO ICTRP with no limitations to language, date, document type, or publication status. Any type of formal or informal educational intervention, lasting for any time, that had content focused directly on knowledge about IBD or skills needed for direct management of IBD or its symptoms was included. Delivery methods included face-to-face or remote educational sessions, workshops, guided study via the use of printed or online materials, the use of mobile applications, or any other method that delivers information to patients.\nSelection criteria\nAll published, unpublished and ongoing randomised control trials (RCTs) that compare educational interventions targeted at people with IBD to any other type of intervention or no intervention.\nData collection and analysis\nTwo review authors independently conducted data extraction and risk of bias assessment of the included studies. We analysed data using Review Manager Web. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE methodology.\nMain results\nWe included 14 studies with a total of 2708 randomised participants, aged 11 to 75 years. Two studies examined populations who all had ulcerative colitis (UC); the remaining studies examined a mix of IBD patients (UC and Crohn's disease). Studies considered a range of disease activity states. The length of the interventions ranged from 30 minutes to 12 months. Education was provided in the form of in-person workshops/lectures, and remotely via printed materials or multimedia, smartphones and internet learning.\nThirteen studies compared patient education interventions plus standard care against standard care alone. The interventions included seminars, information booklets, text messages, e-learning, a multi professional group-based programme, guidebooks, a staff-delivered programme based on an illustrated book, a standardised programme followed by group session, lectures alternating with group therapy, educational sessions based on an IBD guidebook, internet blog access and text messages, a structured education programme, and interactive videos.\nRisk of bias findings were concerning in all judgement areas across all studies. No single study was free of unclear or high of bias judgements.\nReporting of most outcomes in a homogeneous fashion was limited, with quality of life at study end reported most commonly in six of the 14 studies which allowed for meta-analysis, with all other outcomes reported in a more heterogeneous manner that limited wider analysis. Two studies provided data on disease activity. There was no clear difference in disease activity when patient education (n = 277) combined with standard care was compared to standard care (n = 202). Patient education combined with standard care is probably equivalent to standard care in reducing disease activity in patients with IBD (standardised mean difference (SMD) -0.03, 95% CI -0.25 to 0.20), moderate-certainty evidence.\nTwo studies provided continuous data on flare-up/relapse. There was no clear difference for flare-ups or relapse when patient education (n = 515) combined with standard care was compared to standard care (n = 507), as a continuous outcome. Patient education combined with standard care is probably equivalent to standard care in reducing flare-ups or relapse in patients with IBD (MD -0.00, 95% CI -0.06 to 0.05; moderate-certainty evidence).\nThree studies provided dichotomous data on flare-up/relapse. The evidence is very uncertain on whether patient education combined with standard care (n = 157) is different to standard care (n = 150) in reducing flare-ups or relapse in patients with IBD (RR 0.94, 95% CI 0.41 to 2.18; very low-certainty evidence).\nSix studies provided data on quality of life. There was no clear difference in quality of life when patient education combined with standard care (n = 721) was compared to standard care (n = 643). Patient education combined with standard care is probably equivalent to standard care in improving quality of life in patients with IBD (SMD 0.08, 95% CI -0.03 to 0.18; moderate-certainty evidence).\nThe included studies did not report major differences on healthcare access. Medication adherence, patient knowledge and change in quality of life showed conflicting results that varied between no major differences and differences in favour of the educational interventions.\nOnly five studies reported on adverse events. Four reported zero total adverse events and one reported one case of breast cancer and two cases of surgery in their interventions groups, and zero adverse events in their control group.\nTwo studies compared delivery methods of patient education, specifically: web-based patient education interventions versus colour-printed books or text messages; and one study compared frequency of patient education, specifically: weekly educational text messages versus once every other week educational text messages. These did not show major differences for disease activity and quality of life.\nOther outcomes were not reported.\nAuthors' conclusions\nThe ways in which patient educational support surrounding IBD may impact on disease outcomes is complex.\nThere is evidence that education added to standard care is probably of no benefit to disease activity or quality of life when compared with standard care, and may be of no benefit for occurrence of relapse when compared with standard care. However, as there was a paucity of specific information regarding the components of education or standard care, the utility of these findings is questionable.\nFurther research on the impact of education on our primary outcomes of disease activity, flare-ups/relapse and quality of life is probably not indicated. However, further research is necessary, which should focus on reporting details of the educational interventions and study outcomes that educational interventions could be directly targeted to address, such as healthcare access and medication adherence. These should be informed by direct engagement with stakeholders and people affected by Crohn's and colitis.\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": "It is possible that education programmes may benefit people with IBD. The education can be delivered face-to-face, with the patient and educator being at the same or different locations, such as in live lectures, seminars and workshops, or at a distance without live communication, such as with the use of the Internet, smartphones, books and videos.\nWe wanted to find out if education programmes for patients with IBD can have benefits for disease improvement, relapses or flare-ups, and quality of life. We also wanted to find out about their effects on healthcare access, missing medications, or overall patient knowledge of IBD. Additionally, we wanted to find out how safe the education programmes are, even though safety issues were unlikely." } ]

[ { "role": "user", "content": "Abstract: Background\nSickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. This is an update of a previously published review.\nObjectives\nTo determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of the Cochrane Library) and quarterly searches of MEDLINE. We also searched trial registries for ongoing trials up to April 2020.\nDate of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 December 2019.\nSelection criteria\nRandomized controlled and quasi-randomized trials that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting.\nData collection and analysis\nNo trials were eligible for inclusion in the review.\nMain results\nWe identified 12 potentially-eligible trials by the searches; we excluded 11 of these and the remaining trial is an ongoing trial that may be eligible for inclusion in a future version of the review.\nAuthors' conclusions\nReports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. We did not find any eligible randomized controlled trials assessing the benefit or risk of hematopoietic stem cell transplantations. However, there is an ongoing quasi-randomized trial comparing hematopoietic stem cell transplantation with standard care, Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease.\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": "There are no trials included in the review. There is one ongoing trial which may, in the future, be eligible for inclusion." } ]

[ { "role": "user", "content": "Abstract: Background\nIndacaterol is an inhaled long-acting beta2-agonist that is administered once daily and has been investigated as a treatment for chronic obstructive pulmonary disease (COPD). Four different doses have been investigated (75 mcg, 150 mcg, 300 mcg and 600 mcg). The relative effects of different doses of once-daily indacaterol in the management of patients with COPD are uncertain.\nObjectives\nTo compare the efficacy and safety of indacaterol versus placebo and alternative twice-daily long-acting beta2-agonists for the treatment of patients with stable COPD.\nSearch methods\nWe identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), handsearched respiratory journals and meeting abstracts and searched the Novartis trials registry and ClinicalTrials.gov. The date of the most recent search was 8 November 2014.\nSelection criteria\nWe included all randomised controlled trials comparing indacaterol at any dose versus placebo or alternative long-acting beta2-agonists. Trials were required to be of at least 12 weeks' duration and had to include adults older than 18 years with a confirmed spirometric diagnosis of COPD.\nData collection and analysis\nTwo review authors (JBG, EJD) independently assessed for possible inclusion all citations identified as a result of the search. Disagreements were resolved through discussion or, if required, through resolution by a third review author (RWB). One review author (JBG) extracted data from trials identified by the search and entered these data into Review Manager 5.1 for statistical analysis. Data entry was cross-checked by a second review author (EJD, CJC).\nMain results\nA total of 13 trials with 9961 participants were included in the review. Ten trials with a total of 8562 participants involved an indacaterol versus placebo comparison. Five trials with a total of 4133 participants involved an indacaterol versus twice-daily beta2-agonist comparison. The comparator beta2-agonists were salmeterol, formoterol and eformoterol. One of these trials, with a total of 90 participants, provided no data that could be used in this review. Two trials included both indacaterol versus placebo and indacaterol versus twice-daily beta2-agonist comparisons. Trials were between 12 weeks and 52 weeks in duration. Overall the quality of the evidence was strong, and risk of significant bias was minimal in most of the included studies. Enrolled participants had stable COPD across a range of spirometric severities. Forced expiratory volume in 1 second (FEV1) was generally between 30% and 80% predicted, and a mean FEV1 of approximately 50% was predicted in most studies. Patients with concurrent respiratory disease, including asthma, were excluded. Concomitant use of inhaled corticosteroids was permitted.\nThe primary objectives were to compare trough FEV1 at the end of dosing, exacerbation rates and quality of life. Significant adverse events, mortality and dyspnoea were included as secondary outcomes. Compared with placebo, a significant and clinically relevant improvement in trough FEV1 was noted with indacaterol (mean difference (MD) 149.11, 95% confidence interval (CI) 137.09 to 161.12). In addition, compared with placebo, a significant improvement in mean St George Respiratory Questionaire (SGRQ) score (MD -3.60, 95% CI -4.36 to -2.83) was reported, and the proportion of participants experiencing clinically relevant improvement in SGRQ score was significantly greater (odds ratio (OR) 1.64, 95% CI 1.46 to 1.845. Compared with twice-daily beta2-agonists, a small but statistically significant increase in trough FEV1 was seen with indacaterol (MD 61.71 mL, 95% CI 41.24 to 82.17). Differences between indacaterol and twice-daily beta2-agonists in mean SGRQ scores (MD -0.81, 95% CI -2.28 to 0.66) and in the proportions of participants achieving clinically relevant improvements in SGRQ scores (OR 1.07, 95% CI 0.87 to 1.32) were not statistically significant, but the confidence intervals are too wide to permit the conclusion that the treatments were equivalent.\nAuthors' conclusions\nFor patients with stable COPD, use of indacaterol versus placebo results in statistically significant and clinically meaningful improvements in lung function and quality of life. The clinical benefit for lung function is at least as good as that seen with twice-daily long-acting beta2-agonists, but the comparative effect on quality of life remains uncertain, as important differences cannot be excluded.\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": "Overall the quality of the evidence was judged to be high." } ]

[ { "role": "user", "content": "Abstract: Background\nNeonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures.\nOptions for pain management include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported.\nObjectives\nTo evaluate the benefits and harms of opioids in term or preterm neonates exposed to procedural pain, compared to placebo or no drug, non-pharmacological intervention, other analgesics or sedatives, other opioids, or the same opioid administered by a different route.\nSearch methods\nWe used standard, extensive Cochrane search methods. The latest search date was December 2021.\nSelection criteria\nWe included randomized controlled trials conducted in preterm and term infants of a postmenstrual age (PMA) up to 46 weeks and 0 days exposed to procedural pain where opioids were compared to 1) placebo or no drug; 2) non-pharmacological intervention; 3) other analgesics or sedatives; 4) other opioids; or 5) the same opioid administered by a different route.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were pain assessed with validated methods and any harms. We used a fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, and their confidence intervals (CI). We used GRADE to assess the certainty of the evidence for each outcome.\nMain results\nWe included 13 independent studies (enrolling 823 newborn infants): seven studies compared opioids to no treatment or placebo (the main comparison in this review), two studies to oral sweet solution or non-pharmacological intervention, and five studies (of which two were part of the same study) to other analgesics and sedatives. All studies were performed in a hospital setting.\nOpioids compared to placebo or no drug\nCompared to placebo, opioids probably reduce pain score assessed with the Premature Infant Pain Profile (PIPP)/PIPP-Revised (PIPP-R) scale during the procedure (MD −2.58, 95% CI −3.12 to −2.03; 199 participants, 3 studies; moderate-certainty evidence); may reduce Neonatal Infant Pain Scale (NIPS) during the procedure (MD −1.97, 95% CI −2.46 to −1.48; 102 participants, 2 studies; low-certainty evidence); and may result in little to no difference in pain score assessed with the Douleur Aiguë du Nouveau-né (DAN) scale one to two hours after the procedure (MD −0.20, 95% CI −2.21 to 1.81; 42 participants, 1 study; low-certainty evidence). The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R scale up to 30 minutes after the procedure (MD 0.14, 95% CI −0.17 to 0.45; 123 participants, 2 studies; very low-certainty evidence) or one to two hours after the procedure (MD −0.83, 95% CI −2.42 to 0.75; 54 participants, 2 studies; very low-certainty evidence). The evidence is very uncertain about the effect of opioids on episodes of bradycardia (RR 3.19, 95% CI 0.14 to 72.69; 172 participants, 3 studies; very low-certainty evidence). Opioids may result in an increase in episodes of apnea compared to placebo (RR 3.15, 95% CI 1.08 to 9.16; 199 participants, 3 studies; low-certainty evidence): with one study reporting a concerning increase in severe apnea (RR 7.44, 95% CI 0.42 to 132.95; 31 participants, 1 study; very low-certainty). The evidence is very uncertain about the effect of opioids on episodes of hypotension (RR not estimable, risk difference 0.00, 95% CI −0.06 to 0.06; 88 participants, 2 studies; very low-certainty evidence). No studies reported parent satisfaction with care provided in the neonatal intensive care unit (NICU).\nOpioids compared to non-pharmacological intervention\nThe evidence is very uncertain about the effect of opioids on pain score assessed with the Crying Requires oxygen Increased vital signs Expression Sleep (CRIES) scale during the procedure when compared to facilitated tucking (MD −4.62, 95% CI −6.38 to −2.86; 100 participants, 1 study; very low-certainty evidence) or sensorial stimulation (MD 0.32, 95% CI −1.13 to 1.77; 100 participants, 1 study; very low-certainty evidence). The other main outcomes were not reported.\nOpioids compared to other analgesics or sedatives\nThe evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R during the procedure (MD −0.29, 95% CI −1.58 to 1.01; 124 participants, 2 studies; very low-certainty evidence); up to 30 minutes after the procedure (MD −1.10, 95% CI −2.82 to 0.62; 12 participants, 1 study; very low-certainty evidence); and one to two hours after the procedure (MD −0.17, 95% CI −2.22 to 1.88; 12 participants, 1 study; very low-certainty evidence). No studies reported any harms. The evidence is very uncertain about the effect of opioids on episodes of apnea during (RR 3.27, 95% CI 0.85 to 12.58; 124 participants, 2 studies; very low-certainty evidence) and after the procedure (RR 2.71, 95% CI 0.11 to 64.96; 124 participants, 2 studies; very low-certainty evidence) and on hypotension (RR 1.34, 95% CI 0.32 to 5.59; 204 participants, 3 studies; very low-certainty evidence). The other main outcomes were not reported.\nWe identified no studies comparing different opioids (e.g. morphine versus fentanyl) or different routes for administration of the same opioid (e.g. morphine enterally versus morphine intravenously).\nAuthors' conclusions\nCompared to placebo, opioids probably reduce pain score assessed with PIPP/PIPP-R scale during the procedure; may reduce NIPS during the procedure; and may result in little to no difference in DAN one to two hours after the procedure. The evidence is very uncertain about the effect of opioids on pain assessed with other pain scores or at different time points. The evidence is very uncertain about the effect of opioids on episodes of bradycardia, hypotension or severe apnea. Opioids may result in an increase in episodes of apnea. No studies reported parent satisfaction with care provided in the NICU. The evidence is very uncertain about the effect of opioids on any outcome when compared to non-pharmacological interventions or to other analgesics. We identified no studies comparing opioids to other opioids or comparing different routes of administration of the same opioid.\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": "We searched for studies up to December 2021." } ]

[ { "role": "user", "content": "Abstract: Background\nAcute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially among infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over- and under-hydration are associated with adverse outcomes. This is the latest update of a review first published in 2005 and updated in 2008 and 2014.\nObjectives\nTo evaluate treatment of acute bacterial meningitis with differing volumes of initial fluid administration (up to 72 hours after first presentation) and the effects on death and neurological sequelae.\nSearch methods\nFor this 2016 update we searched the following databases up to March 2016: the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, CINAHL, Global Health, and Web of Science.\nSelection criteria\nRandomised controlled trials (RCTs) of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion.\nData collection and analysis\nAll four of the original review authors extracted data and assessed trials for quality in the first publication of this review (one author, ROW, has passed away since the original review; see Acknowledgements). The current authors combined data for meta-analysis using risk ratios (RRs) for dichotomous data or mean difference (MD) for continuous data. We used a fixed-effect statistical model. We assessed the overall quality of evidence using the GRADE approach.\nMain results\nWe included three trials with a total of 420 children; there were no trials in adult populations. The largest of the three trials was conducted in settings with high mortality rates and was judged to have low risk of bias for all domains, except performance bias which was high risk. The other two smaller trials were not of high quality.The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% confidence interval (CI) 0.53 to 1.27; 407 participants; low quality of evidence) or acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08; 407 participants; low quality of evidence). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group for spasticity (RR 0.50, 95% CI 0.27 to 0.93; 357 participants); and seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants). There was very low quality of evidence favouring maintenance fluid over restrictive fluid for chronic severe neurological sequelae at three months follow-up (RR 0.42, 95% CI 0.20 to 0.89; 351 participants).\nAuthors' conclusions\nThe quality of evidence regarding fluid therapy in children with acute bacterial meningitis is low to very low and more RCTs need to be conducted. There is insufficient evidence to guide practice as to whether maintenance fluids should be chosen over restricted fluids in the treatment of acute bacterial meningitis.\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": "The evidence is current to March 2016. We did not find any trials in adult populations and included three trials involving 420 children. All trials were set in countries where death rates for meningitis are high. In one study no funding source was mentioned. The remaining two studies were funded jointly by pharmaceutical concerns with government agencies and a charitable agency." } ]

[ { "role": "user", "content": "Abstract: Background\nInvasive aspergillosis (IA) is a life-threatening opportunistic mycosis that occurs in some people with a compromised immune system. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) rapidly gained widespread acceptance as part of the diagnostic work-up of a patient suspected of IA. Due to its non-invasive nature, it can be used as a routine screening test. The ELISA can also be performed on bronchoalveolar lavage (BAL), allowing sampling of the immediate vicinity of the infection. The invasive nature of acquiring BAL, however, changes the role of the galactomannan test significantly, for example by precluding its use as a routine screening test.\nObjectives\nTo assess the diagnostic accuracy of galactomannan detection in BAL for the diagnosis of IA in people who are immunocompromised, at different cut-off values for test positivity, in accordance with the Cochrane Diagnostic Test Accuracy Handbook.\nSearch methods\nWe searched three bibliographic databases including MEDLINE on 9 September 2016 for aspergillosis and galactomannan as text words and subject headings where appropriate. We checked reference lists of included studies for additional studies.\nSelection criteria\nWe included cohort studies that examined the accuracy of BAL galactomannan for the diagnosis of IA in immunocompromised patients if they used the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) classification as reference standard.\nData collection and analysis\nTwo review authors assessed study quality and extracted data. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for quality assessment.\nMain results\nWe included 17 studies in our review. All studies except one had a high risk of bias in two or more domains. The diagnostic performance of an optical density index (ODI) of 0.5 as cut-off value was reported in 12 studies (with 1123 patients). The estimated sensitivity was 0.88 (95% confidence interval (CI) 0.75 to 1.00) and specificity 0.81 (95% CI 0.71 to 0.91). The performance of an ODI of 1.0 as cut-off value could be determined in 11 studies (with 648 patients). The sensitivity was 0.78 (95% CI 0.61 to 0.95) and specificity 0.93 (95% CI 0.87 to 0.98). At a cut-off ODI of 1.5 or higher, the heterogeneity in specificity decreased significantly and was invariably >90%.\nAuthors' conclusions\nThe optimal cut-off value depends on the local incidence and clinical pathway. At a prevalence of 12% a hypothetical population of 1000 patients will consist of 120 patients with IA. At a cut-off value of 0.5 14 patients with IA will be missed and there will be 167 patients incorrectly diagnosed with IA. If we use the test at a cut-off value of 1.0, we will miss 26 patients with IA. And there will be 62 patients incorrectly diagnosed with invasive aspergillosis. The populations and results were very heterogeneous. Therefore, interpretation and extrapolation of these results has to be performed with caution. A test result of 1.5 ODI or higher appears a strong indicator of IA.\n\nGiven the provided abstract, please respond to the following query: \"What are the main results of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Imagine a group of 1000 people with an impaired immune system where 120 (12%) have invasive aspergillosis. The results of this review indicate that in theory, if the BAL galactomannan test were to be used using an ODI of 0.5 or higher to decide which results are positive:\n- an estimated 273 will have a test result indicating that they probably have invasive aspergillosis, and of these 167 will be incorrectly classified as having invasive aspergillosis; and\n- of the 727 people with a result indicating that invasive aspergillosis is not likely to be present, 14 will be incorrectly classified as not having invasive aspergillosis.\nIf a higher cut-off value is used to determine test positivity, then more patients will have a false-negative result and fewer patients will have a false-positive result." } ]

[ { "role": "user", "content": "Abstract: Background\nCorruption is the abuse or complicity in abuse, of public or private position, power or authority to benefit oneself, a group, an organisation or others close to oneself; where the benefits may be financial, material or non-material. It is wide-spread in the health sector and represents a major problem.\nObjectives\nOur primary objective was to systematically summarise empirical evidence of the effects of strategies to reduce corruption in the health sector. Our secondary objective was to describe the range of strategies that have been tried and to guide future evaluations of promising strategies for which there is insufficient evidence.\nSearch methods\nWe searched 14 electronic databases up to January 2014, including: CENTRAL; MEDLINE; EMBASE; sociological, economic, political and other health databases; Human Resources Abstracts up to November 2010; Euroethics up to August 2015; and PubMed alerts from January 2014 to June 2016. We searched another 23 websites and online databases for grey literature up to August 2015, including the World Bank, the International Monetary Fund, the U4 Anti-Corruption Resource Centre, Transparency International, healthcare anti-fraud association websites and trial registries. We conducted citation searches in Science Citation Index and Google Scholar, and searched PubMed for related articles up to August 2015. We contacted corruption researchers in December 2015, and screened reference lists of articles up to May 2016.\nSelection criteria\nFor the primary analysis, we included randomised trials, non-randomised trials, interrupted time series studies and controlled before-after studies that evaluated the effects of an intervention to reduce corruption in the health sector. For the secondary analysis, we included case studies that clearly described an intervention to reduce corruption in the health sector, addressed either our primary or secondary objective, and stated the methods that the study authors used to collect and analyse data.\nData collection and analysis\nOne review author extracted data from the included studies and a second review author checked the extracted data against the reports of the included studies. We undertook a structured synthesis of the findings. We constructed a results table and 'Summaries of findings' tables. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence.\nMain results\nNo studies met the inclusion criteria of the primary analysis. We included nine studies that met the inclusion criteria for the secondary analysis.\nOne study found that a package of interventions coordinated by the US Department of Health and Human Services and Department of Justice recovered a large amount of money and resulted in hundreds of new cases and convictions each year (high certainty of the evidence). Another study from the USA found that establishment of an independent agency to investigate and enforce efforts against overbilling might lead to a small reduction in overbilling, but the certainty of this evidence was very low. A third study from India suggested that the impacts of coordinated efforts to reduce corruption through increased detection and enforcement are dependent on continued political support and that they can be limited by a dysfunctional judicial system (very low certainty of the evidence).\nOne study in South Korea and two in the USA evaluated increased efforts to investigate and punish corruption in clinics and hospitals without establishing an independent agency to coordinate these efforts. It is unclear whether these were effective because the evidence is of very low certainty.\nOne study from Kyrgyzstan suggested that increased transparency and accountability for co-payments together with reduction of incentives for demanding informal payments may reduce informal payments (low certainty of the evidence).\nOne study from Germany suggested that guidelines that prohibit hospital doctors from accepting any form of benefits from the pharmaceutical industry may improve doctors’ attitudes about the influence of pharmaceutical companies on their choice of medicines (low certainty of the evidence).\nA study in the USA, evaluated the effects of introducing a law that required pharmaceutical companies to report the gifts they gave to healthcare workers. Another study in the USA evaluated the effects of a variety of internal control mechanisms used by community health centres to stop corruption. The effects of these strategies is unclear because the evidence was of very low certainty.\nAuthors' conclusions\nThere is a paucity of evidence regarding how best to reduce corruption. Promising interventions include improvements in the detection and punishment of corruption, especially efforts that are coordinated by an independent agency. Other promising interventions include guidelines that prohibit doctors from accepting benefits from the pharmaceutical industry, internal control practices in community health centres, and increased transparency and accountability for co-payments combined with reduced incentives for informal payments. The extent to which increased transparency alone reduces corruption is uncertain. There is a need to monitor and evaluate the impacts of all interventions to reduce corruption, including their potential adverse effects.\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": "The review authors searched for studies that had been published up to 06 June 2016." } ]

[ { "role": "user", "content": "Abstract: Background\nVenous thromboembolism (VTE), although rare, is a major cause of maternal mortality and morbidity. Some women are at increased risk of VTE during pregnancy and the early postnatal period (e.g. caesarean section, family history of VTE, or thrombophilia), and so prophylaxis may be considered. As some methods of prophylaxis carry risks of adverse effects, and risk of VTE is often low, benefits of thromboprophylaxis may be outweighed by harms.\nObjectives\nTo assess the effects of thromboprophylaxis during pregnancy and the early postnatal period on the risk of venous thromboembolic disease and adverse effects in women at increased risk of VTE.\nSearch methods\nWe searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (18 October 2019). In addition, we searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for unpublished, planned and ongoing trial reports (18 October 2019).\nSelection criteria\nRandomised trials comparing one method of thromboprophylaxis with placebo or no treatment, or two (or more) methods of thromboprophylaxis.\nData collection and analysis\nAt least two review authors assessed trial eligibility, extracted data, assessed risk of bias, and judged certainty of evidence for selected critical outcomes (using GRADE). We conducted fixed-effect meta-analysis and reported data (all dichotomous) as summary risk ratios (RRs) with 95% confidence intervals (CIs).\nMain results\nTwenty-nine trials (involving 3839 women), overall at moderate to high risk of bias were included. Trials were conducted across the antenatal, peripartum and postnatal periods, with most in high-income countries. Interventions included types and regimens of heparin (low molecular weight heparin (LMWH) and unfractionated heparin (UFH)), hydroxyethyl starch (HES), and compression stockings or devices. Data were limited due to a small number of trials in comparisons and/or few or no events reported. All critical outcomes (assessed for comparisons of heparin versus no treatment/placebo, and LMWH versus UFH) were considered to have very low-certainty evidence, downgraded mainly for study limitations and imprecise effect estimates.  Maternal death was not reported in most studies.\nAntenatal (± postnatal) prophylaxis\nFor the primary outcomes symptomatic thromboembolic events pulmonary embolism (PE) and/or deep vein thrombosis (DVT), and the critical outcome of adverse effects sufficient to stop treatment, the evidence was very uncertain.\nSymptomatic thromboembolic events:\n- heparin versus no treatment/placebo (RR 0.39; 95% CI 0.08 to 1.98; 4 trials, 476 women; very low-certainty evidence);\n- LMWH versus UFH (RR 0.47; 95% CI 0.09 to 2.49; 4 trials, 404 women; very low-certainty evidence);\nSymptomatic PE:\n- heparin versus no treatment/placebo (RR 0.33; 95% CI 0.02 to 7.14; 3 trials, 187 women; very low-certainty evidence);\n- LMWH versus UFH (no events; 3 trials, 287 women);\nSymptomatic DVT:\n- heparin versus no treatment/placebo (RR 0.33; 95% CI 0.04 to 3.10; 4 trials, 227 women; very low-certainty evidence);\n- LMWH versus UFH (no events; 3 trials, 287 women);\nAdverse effects sufficient to stop treatment:\n- heparin versus no treatment/placebo (RR 0.49; 95% CI 0.05 to 5.31; 1 trial, 139 women; very low-certainty evidence);\n- LMWH versus UFH (RR 0.07; 95% CI 0.01 to 0.54; 2 trials, 226 women; very low-certainty evidence).\nPeripartum/postnatal prophylaxis\nVaginal or caesarean birth\nWhen UFH and no treatment were compared, the effects on symptomatic thromboembolic events (RR 0.16; 95% CI 0.02 to 1.36; 1 trial, 210 women; very low-certainty evidence), symptomatic PE (RR 0.16; 95% CI 0.01 to 3.34; 1 trial, 210 women; very low-certainty evidence), and symptomatic DVT  (RR 0.27; 95% CI 0.03 to 2.55; 1 trial, 210 women; very low-certainty evidence) were very uncertain.  Maternal death and adverse effects sufficient to stop treatment were not reported.\nCaesarean birth\nSymptomatic thromboembolic events:\n- heparin versus no treatment/placebo (RR 1.30; 95% CI 0.39 to 4.27; 4 trials, 840 women; very low-certainty evidence);\n- LMWH versus UFH (RR 0.33; 95% CI 0.01 to 7.99; 3 trials, 217 women; very low-certainty evidence);\nSymptomatic PE:\n- heparin versus no treatment/placebo (RR 1.10; 95% CI 0.25 to 4.87; 4 trials, 840 women; very low-certainty evidence);\n- LMWH versus UFH (no events; 3 trials, 217 women);\nSymptomatic DVT:\n- heparin versus no treatment/placebo (RR 1.30; 95% CI 0.24 to 6.94; 5 trials, 1140 women; very low-certainty evidence); LMWH versus UFH (RR 0.33; 95% CI 0.01 to 7.99; 3 trials, 217 women; very low-certainty evidence);\nMaternal death:\n- heparin versus placebo (no events, 1 trial, 300 women);\nAdverse effects sufficient to stop treatment:\n- heparin versus placebo (no events;  1 trial, 140 women).\nPostnatal prophylaxis\nNo events were reported for LMWH versus no treatment/placebo for: symptomatic thromboembolic events, symptomatic PE and symptomatic DVT (all 2 trials, 58 women), or maternal death (1 trial, 24 women). Adverse effects sufficient to stop treatment were not reported.\nWe were unable to conduct subgroup analyses due to lack of data.\nSensitivity analysis including the nine studies at low risk of bias did not impact overall findings.\nAuthors' conclusions\nThe evidence is very uncertain about benefits and harms of VTE thromboprophylaxis in women during pregnancy and the early postnatal period at increased risk of VTE. Further high-quality very large-scale randomised trials are needed to determine effects of currently used treatments in women with different VTE risk factors. As sufficiently large definitive trials are unlikely to be funded, secondary data analyses based on high-quality registry data are important.\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 very uncertain if the benefits of treatments used to prevent deep vein clots in high-risk women during pregnancy and around the time of childbirth outweigh any harms. Small numbers of studies were included in the comparisons with a range of outcomes measured and low numbers of events. Some studies had design limitations and definitions of blood clotting risk factors and outcomes were not always clear. More, large, high-quality studies are needed." } ]

[ { "role": "user", "content": "Abstract: Background\nA key aim of asthma care is to empower each person to take control of his or her own condition. A personalised asthma action plan (PAAP), also known as a written action plan, an individualised action plan, or a self-management action plan, contributes to this endeavour. A PAAP includes individualised self-management instructions devised collaboratively with the patient to help maintain asthma control and regain control in the event of an exacerbation. A PAAP includes baseline characteristics (such as lung function), maintenance medication and instructions on how to respond to increasing symptoms and when to seek medical help.\nObjectives\nTo evaluate the effectiveness of PAAPs used alone or in combination with education, for patient-reported outcomes, resource use and safety among adults with asthma.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register of trials, clinical trial registers, reference lists of included studies and review articles, and relevant manufacturers’ websites up to 14 September 2016.\nSelection criteria\nWe included parallel randomised controlled trials (RCTs), both blinded and unblinded, that evaluated written PAAPs in adults with asthma. Included studies compared PAAP alone versus no PAAP, and/or PAAP plus education versus education alone.\nData collection and analysis\nTwo review authors independently extracted study characteristics and outcome data and assessed risk of bias for each included study. Primary outcomes were number of participants reporting at least one exacerbation requiring an emergency department (ED) visit or hospitalisation, asthma symptom scores on a validated scale and adverse events (all causes). Secondary outcomes were quality of life measured on a validated scale, number of participants reporting at least one exacerbation requiring systemic corticosteroids, respiratory function and days lost from work or study. We used a random-effects model for all analyses and standard Cochrane methods throughout.\nMain results\nWe identified 15 studies described in 27 articles that met our inclusion criteria. These 15 included studies randomised a total of 3062 participants (PAAP vs no PAAP: 2602 participants; PAAP plus education vs education alone: 460 participants). Ten studies (eight PAAP vs no PAAP; two PAAP plus education vs education alone) provided outcome data that contributed to quantitative analyses. The overall quality of evidence was rated as low or very low.\nFourteen studies lasted six months or longer, and the remaining study lasted for 14 weeks. When reported, mean age ranged from 22 to 49 years and asthma severity ranged from mild to severe/high risk.\nPAAP alone compared with no PAAP\nResults showed no clear benefit or harm associated with PAAPs in terms of the number of participants requiring an ED visit or hospitalisation for an exacerbation (odds ratio (OR) 0.75, 95% confidence interval (CI) 0.45 to 1.24; 1385 participants; five studies; low-quality evidence), change from baseline in asthma symptoms (mean difference (MD) -0.16, 95% CI -0.25 to - 0.07; 141 participants; one study; low-quality evidence) or the number of serious adverse events, including death (OR 3.26, 95% CI 0.33 to 32.21; 125 participants; one study; very low-quality evidence). Data revealed a statistically significant improvement in quality of life scores for those receiving PAAP compared with no PAAP (MD 0.18, 95% CI 0.05 to 0.30; 441 participants; three studies; low-quality evidence), but this was below the threshold for a minimum clinically important difference (MCID). Results also showed no clear benefit or harm associated with PAAPs on the number of participants reporting at least one exacerbation requiring oral corticosteroids (OR 1.45, 95% CI 0.84 to 2.48; 1136 participants; three studies; very low-quality evidence) nor on respiratory function (change from baseline forced expiratory volume in one second (FEV1): MD -0.04 L, 95% CI -0.25L to 0.17 L; 392 participants; three studies; low-quality evidence). In one study, PAAPs were associated with significantly fewer days lost from work or study (MD -6.20, 95% CI -7.32 to - 5.08; 74 participants; low-quality evidence).\nPAAP plus education compared with education alone\nResults showed no clear benefit or harm associated with adding a PAAP to education in terms of the number of participants requiring an ED visit or hospitalisation for an exacerbation (OR 1.08, 95% CI 0.27 to 4.32; 70 participants; one study; very low-quality evidence), change from baseline in asthma symptoms (MD -0.10, 95% CI -0.54 to 0.34; 70 participants; one study; low-quality evidence), change in quality of life scores from baseline (MD 0.13, 95% CI -0.13 to 0.39; 174 participants; one study; low-quality evidence) and number of participants requiring oral corticosteroids for an exacerbation (OR 0.28, 95% CI 0.07 to 1.12; 70 participants; one study; very low-quality evidence). No studies reported serious adverse events, respiratory function or days lost from work or study.\nAuthors' conclusions\nAnalysis of available studies was limited by variable reporting of primary and secondary outcomes; therefore, it is difficult to draw firm conclusions related to the effectiveness of PAAPs in the management of adult asthma. We found no evidence from randomised controlled trials of additional benefit or harm associated with use of PAAP versus no PAAP, or PAAP plus education versus education alone, but we considered the quality of the evidence to be low or very low, meaning that we cannot be confident in the magnitude or direction of reported treatment effects. In the context of this caveat, we found no observable effect on the primary outcomes of hospital attendance with an asthma exacerbation, asthma symptom scores or adverse events. We recommend further research with a particular focus on key patient-relevant outcomes, including exacerbation frequency and quality of life, in a broad spectrum of adults, including those over 60 years of age.\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": "People with asthma may be given a written personalised action plan for managing their asthma. This plan provides information on which medicines they should take and when. Other people may be given education on how they should look after their asthma. This review set out to see if using a plan on its own or with education helps improve outcomes for people with asthma." } ]

[ { "role": "user", "content": "Abstract: Background\nThe World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine.\nObjectives\nTo assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate:\n• the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and\n• the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.\nSearch methods\nWe searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials.\nSelection criteria\nRandomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen.\nData collection and analysis\nTwo review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting.\nMain results\nSix trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria.\nTwo trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo.\nStudy participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes.\nWhen compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I2 statistic = 0%; moderate-certainty evidence). IPTp-mefloquine increased drug-related vomiting (RR 4.76, 95% CI 4.13 to 5.49; 6272 participants, 2 studies; high-certainty evidence) and dizziness (RR 4.21, 95% CI 3.36 to 5.27; participants = 6272, 2 studies; moderate-certainty evidence).\nWhen compared with cotrimoxazole, IPTp-mefloquine plus cotrimoxazole probably results in a 48% reduction in maternal peripheral parasitaemia at delivery (RR 0.52, 95% CI 0.30 to 0.93; 989 participants, 2 studies; moderate-certainty evidence) and a 72% reduction in placental malaria (RR 0.28, 95% CI 0.14 to 0.57; 977 participants, 2 studies; moderate-certainty evidence) but has little or no effect on the incidence of clinical malaria episodes during pregnancy (IRR 0.76, 95% CI 0.33 to 1.76, 1 study; high-certainty evidence) and probably no effect on maternal anaemia at delivery (RR 0.94, 95% CI 0.73 to 1.20; 1197 participants, 2 studies; moderate-certainty evidence), low birth weight rates (RR 1.20, 95% CI 0.89 to 1.60; 1220 participants, 2 studies; moderate-certainty evidence), and rates of spontaneous abortion and stillbirth (RR 1.12, 95% CI 0.42 to 2.98; 1347 participants, 2 studies; very low-certainty evidence). Mefloquine was associated with higher risks of drug-related vomiting (RR 7.95, 95% CI 4.79 to 13.18; 1055 participants, one study; high-certainty evidence) and dizziness (RR 3.94, 95% CI 2.85 to 5.46; 1055 participants, 1 study; high-certainty evidence).\nAuthors' conclusions\nMefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women.\n\nGiven the provided abstract, please respond to the following query: \"Key messages\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The antimalarial drug mefloquine is efficacious for malaria prevention in pregnant women. The drug has been found to be safe in terms of adverse pregnancy outcomes, such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations. However, it is worse tolerated than other antimalarial drugs." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis is a life-limiting inherited condition which affects one in 2500 newborns in the UK and 70,000 children and adults worldwide. The condition is multifaceted and affects many systems in the body. The respiratory system is particularly affected due to a build up of thickened secretions and a predisposition to infection. Inhaled bronchodilators are prescribed for 80% of people with cystic fibrosis in order to widen the airways and alleviate symptoms. Both short- and long-acting inhaled bronchodilators are used to improve respiratory symptoms. Short-acting inhaled bronchodilators take effect in minutes and typically last for four to eight hours (muscarinic antagonists). Long-acting inhaled bronchodilators also take effect within minutes but typically last for around 12 hours and sometimes longer. This review is one of two which are replacing a previously published review of both long- and short-acting inhaled bronchodilators. However, due to the lack of research in this area, we do not envisage undertaking any further updates of this long-acting inhaled bronchodilators review.\nObjectives\nThis review aims to evaluate long-acting inhaled bronchodilators in children and adults with cystic fibrosis in terms of clinical outcomes and safety. If possible, we aimed to assess the optimal drug and dosage regimen.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.\nDate of last search: 10 October 2017.\nWe also carried out a separate search of Embase and the reference lists of included trials. We searched clinical trials registries for any ongoing trials and made contact with pharmaceutical companies for any further trials.\nDate of Embase search: 11 October 2017.\nSelection criteria\nRandomised or quasi-randomised parallel trials comparing long-acting inhaled bronchodilators (beta-2 agonists and muscarinic antagonists) with placebo, no treatment or a different long-acting inhaled bronchodilator in adults and children with cystic fibrosis.\nData collection and analysis\nBoth authors independently assessed trials for inclusion (based on title, abstract and full text). The authors independently assessed the included trials for quality and risk of bias and extracted data. Discrepancies were resolved by a third party.\nMain results\nThe searches identified 195 unique references, of which 155 were excluded on title and abstract. We assessed the full texts of the remaining references, excluded 16 trials (28 references) and included four trials (12 references) in the review with 1082 participants.\nOne trial (n = 16) measuring the effect of beta-2 agonists reported an improvement in forced expiratory volume at one second (FEV1) after treatment (at one month), but the trial was small with an unclear risk of bias so we judged the evidence to be very low quality. The trial did not report on participant-reported outcomes, quality of life or adverse events.\nThree trials (n = 1066) looked at the effects of the muscarinic antagonist tiotropium at doses of 2.5 µg and 5.0 µg in both the short term (up to 28 days) and the longer term (up to three months). Only one of the trials reported the change in FEV1 (L) after 28 days treatment and showed no significant difference between groups; with 2.5 µg tiotropium, mean difference (MD) -0.02 (95% confidence interval (CI) -0.13 to 0.09), or 5.0 µg tiotropium, MD 0.00 (95% CI -0.10 to 0.10) (moderate-quality evidence). All three trials of muscarinic antagonists provided data on adverse events which were found to differ little from placebo at doses of 2.5 µg, risk ratio (RR) 1.01 (95% CI 0.92 to 1.11) or 5.0 µg, RR 0.98 (95% CI 0.90 to 1.06). Very little participant-reported outcome data or quality of life data were available for analysis. Two of the trials were at low risk of bias overall whilst the remaining trial was at an unclear risk overall.\nAuthors' conclusions\nNeither long-acting beta-2 agonists nor long-acting muscarinic antagonist bronchodilators demonstrate improvement in our primary outcome of FEV1. No difference was observed between intervention and placebo in terms of quality of life or adverse events. The quality of evidence for the use of beta-2 agonists was very low. The use of a long-acting inhaled bronchodilator may help to reduce the burden of treatment for people with cystic fibrosis as it is taken less often than a short-acting inhaled bronchodilator, but future trials would benefit from looking at the effects on our primary outcomes (spirometric changes from baseline, quality of life and adverse effects) in the longer term.\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": "Only 16 people took part in the trial of the beta-2 agonist which only lasted for 28 days, which makes the results less reliable. The trials of muscarinic antagonists included 1066 people and the trials appeared to be well run. We don't think any design factors will have influenced the results in a negative way.\nNone of the trials ran for more than 12 weeks which makes it difficult to comment on the effects over a longer time period." } ]

[ { "role": "user", "content": "Abstract: Background\nNeonatal healthcare-associated infections (HAIs) result in increased morbidity and mortality, as well as increased healthcare costs. Patient isolation measures, i.e. single-room isolation or the cohorting of patients with similar infections, remain a recommended and commonly used practice for preventing horizontal spread of infections in the neonatal intensive care unit (NICU).\nObjectives\nOur primary objective was to assess the effect of single-room isolation or cohorting, or both for preventing transmission of HAIs or colonization with HAI-causing pathogens in newborn infants less than six months of age admitted to the neonatal intensive care unit (NICU).\nOur secondary objective was to assess the effect of single-room isolation or cohorting, or both on neonatal mortality and perceived or documented adverse effects in newborn infants admitted to the NICU.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, the WHO ICTRP and ClinicalTrials.gov trials registries. There were no restrictions to date, language or publication type. We also checked the reference lists of studies identified for full-text review.\nSelection criteria\nTypes of studies: cluster-randomized or quasi-randomized trials at the level of the cluster (where clusters may be defined by NICU, hospital, ward, or other subunits of the hospital). We also included cross-over trials with a washout period of more than four months (arbitrarily defined).\nTypes of participants: newborn infants less than six months of age in neonatal units that implemented patient isolation or cohorting as infection control measures to prevent HAIs.\nTypes of interventions: patient isolation measures (single-room isolation or cohorting, or both of infants with similar colonization or infections) compared to routine isolation measures.\nTypes of outcome measures: the primary outcome was the rate of transmission of HAIs as estimated by the infection and colonization rates in the NICU. Secondary outcomes included all-cause mortality during hospital stay at 28 days of age, length of hospital stay, as well as potential adverse effects of isolation or cohorting measures, or both.\nData collection and analysis\nThe standard methods of Cochrane Neonatal were used to identify studies and assess the methodological quality of eligible cluster-randomized trials. The certainty of the evidence was to be assessed by the GRADE method as evidence of high, moderate, low, or very low certainty. Infection and colonization rates were to be expressed as rate ratios for each trial and if appropriate for meta-analysis, the generic inverse variance method in RevMan was to be used.\nMain results\nWe did not identify any published or ongoing trials to include in the review.\nAuthors' conclusions\nThe review found no evidence from randomized trials to either support or refute the use of patient isolation measures (single-room isolation or cohorting) in neonates with HAIs. Risks secondary to infection control measures need to be balanced against the benefits of decreasing horizontal transmission in the neonatal unit for optimal neonatal outcomes. There is an urgent need to research the effectiveness of patient isolation measures for preventing the transmission of HAIs in neonatal units. Well-designed trials randomizing clusters of units or hospitals to a type of patient isolation method intervention are warranted.\n\nGiven the provided abstract, please respond to the following query: \"How up-to-date is this evidence?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence is up-to-date to November 2022." } ]