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[ { "role": "user", "content": "Abstract: Background\nBlood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed.\nObjectives\nTo examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders.\nSearch methods\nWe searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2017, issue 3) in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion Evidence Library (from 1980), and ongoing trial databases (all searches to 3 April 2017).\nSelection criteria\nWe included randomised controlled trials comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid, aprotinin) before, during, or immediately after surgery or after invasive procedures in adults or children.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane.\nMain results\nWe identified 65 completed trials (3874 participants) and four ongoing trials. Of the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on vascular surgery; seven studies were conducted in surgery for other conditions. These trials were conducted between 1986 and 2016, and 11 were funded by pharmaceutical companies or by a party with a commercial interest in the outcome of the trial.\nThe GRADE quality of evidence was very low to moderate across all outcomes. No trial reported quality of life.\nDDAVP versus placebo or no treatment\nTrial results showed considerable heterogeneity between surgical settings for total volume of red cells transfused (low-quality evidence) and for total blood loss (very low-quality evidence) due to large differences in baseline blood loss. Consequently, these outcomes were not pooled and were reported in subgroups.\nCompared with placebo, DDAVP may slightly decrease the total volume of red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units, 95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants), but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI -0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95% CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD -0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants).\nDDAVP probably leads to little or no difference in the total number of participants transfused with blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants) (moderate-quality evidence).\nWhether DDAVP decreases total blood loss in adult cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358 participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53 mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI -1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the quality of evidence is very low.\nDDAVP probably leads to little or no difference in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22 trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to 2.16; 29 trials, 1984 participants) (both low-quality evidence).\nDDAVP versus placebo or no treatment for people with platelet dysfunction\nCompared with placebo, DDAVP may lead to a reduction in the total volume of red cells transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388 participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95% CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality evidence).\nDDAVP probably leads to little or no difference in the total number of participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5 trials, 258 participants) (moderate-quality evidence).\nWhether DDAVP leads to a difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422 participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials, 422 participants) is uncertain because the quality of evidence is very low.\nDDAVP versus tranexamic acid\nCompared with tranexamic acid, DDAVP may increase the volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40 participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2 trials, 115 participants) (both low-quality evidence).\nWhether DDAVP increases or decreases the total number of participants transfused with blood is uncertain because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3 trials, 135 participants).\nNo trial reported all-cause mortality.\nWhether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115 participants).\nDDAVP versus aprotinin\nCompared with aprotinin, DDAVP probably increases the total number of participants transfused with blood (RR 2.41, 95% CI 1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence).\nNo trials reported volume of blood transfused or total blood loss and the single trial that included mortality as an outcome reported no deaths.\nWhether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants).\nAuthors' conclusions\nMost of the evidence derived by comparing DDAVP versus placebo was obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary bypass. In adults undergoing cardiac surgery, the reduction in volume of red cells transfused and total blood loss was small and was unlikely to be clinically important. It is less clear whether DDAVP may be of benefit for children and for those undergoing non-cardiac surgery. A key area for researchers is examining the effects of DDAVP for people with platelet dysfunction. Few trials have compared DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the relative efficacy of these interventions.\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 investigated whether giving DDAVP reduced the need for blood transfusion in people having surgery.\nWe searched the medical literature to 3 April 2017. We identified 65 relevant trials with 3874 participants (adults and children). All trials assessed the effects of giving DDAVP before, during, or immediately after surgery or more minor procedures like biopsies. Most trials focused on adult heart surgery, or bone and joint surgery. Fewer trials focused on heart surgery for children, plastic surgery, surgery on blood vessels, or liver surgery. The trials were conducted between 1986 and 2016. Eleven were funded by pharmaceutical companies or by a party with a commercial interest in the trial’s outcome." } ]

[ { "role": "user", "content": "Abstract: Background\nSeptal surgery is a well-established procedure used to treat nasal obstruction due to deviation of the nasal septum, which is carried out under local or general anaesthesia. Local anaesthesia is used for postoperative pain control, but its effectiveness and safety are unclear.\nObjectives\nTo assess the effectiveness of perioperative local anaesthesia for reducing pain in septal surgery and to evaluate the risk of associated complications.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Trial Register; Central Register of Controlled Trials; Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 9 January 2018.\nSelection criteria\nRandomised controlled trials and cluster-randomised controlled trials involving adults or children (or both) who underwent septal surgery. We included studies comparing local anaesthesia versus no treatment/placebo. We also included studies comparing different types of local anaesthesia to each other (i.e. local injection, the addition of an anaesthetic agent to nasal packing, where used, and sphenopalatine ganglion block).\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. The primary outcome was postoperative pain intensity at 12, 24 and 48 hours measured by visual analogue scale (VAS) or another pain outcome tool including numerical or verbal rating scales. Secondary outcomes were requirement for additional analgesia, duration of hospitalisation and adverse effects (postoperative bleeding and postoperative vomiting). We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.\nMain results\nWe included seven randomised controlled trials involving 493 participants. In all studies the participants were adults undergoing septoplasty. These studies were heterogeneous and the quality of the body of evidence ranged from low to very low. Few of the studies provided reliable data for the primary outcome in this review.\nLocal anaesthetic injection versus no treatment/placebo\nTwo studies (142 participants) compared local anaesthetic injection versus placebo but these studies did not report postoperative pain at 12, 24 or 48 hours. It is unclear whether local anaesthetic injection changed the risk of vomiting (odds ratio (OR) 3.10, 95% confidence interval (CI) 0.12 to 79.23; 60 participants; one study) (low-quality evidence). Neither study reported the requirement for additional analgesia, duration of hospitalisation or uncontrollable postoperative bleeding.\nLocal anaesthetic application via nasal packing versus no packing/packing with placebo\nFour studies (301 participants) used nasal packing postoperatively and compared the addition of local anaesthetic to the pack versus packing with a placebo added. Compared with packing with placebo, the addition of local anaesthetic to nasal packing reduced the pain score on a VAS (ranging from 0 to 100) at 12 hours (mean difference (MD) -16.95, 95% CI -22.27 to -11.62; 151 participants; two studies; I2 = 49%) (low-quality evidence) and at 24 hours postoperatively (MD -7.53, 95% CI -9.76 to -5.29; 268 participants; four studies; I2 = 83%) (very low-quality evidence). These studies did not report postoperative pain at 48 hours. The addition of local anaesthetic to nasal packing decreased the requirement for additional analgesia (OR 0.15, 95% CI 0.07 to 0.34; 151 participants; two studies; I2 = 15%) (moderate-quality evidence). No studies reported duration of hospitalisation, postoperative vomiting or uncontrollable postoperative bleeding.\nNo studies compared the addition of local anaesthetic to nasal packing versus no packing.\nSphenopalatine ganglion block versus no treatment/placebo\nOne study (50 participants) compared sphenopalatine ganglion block versus no treatment but this study did not report postoperative pain, requirement for additional analgesia, duration of hospitalisation, vomiting or uncontrollable postoperative bleeding.\nAuthors' conclusions\nThe addition of local anaesthesia to nasal packs (if these are being used) following septal surgery may reduce postoperative pain within the first 12 hours, compared to nasal packing with a placebo added. The effect is uncertain at 24 hours because the quality of the evidence is very low. Evidence was lacking for other outcomes, including adverse effects. There is a lack of evidence about the effects of local anaesthesia added to nasal packing compared to no nasal packing. There is also a lack of evidence about the effects of local anaesthesia given by injection and the effects of sphenopalatine ganglion block.\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 graded the quality of evidence for the use of local anaesthetic injection as low, which means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. We downgraded the quality of the evidence because of the small number of patients and events. We graded the quality of evidence for the use of local anaesthetic applied to nasal packing as low at 12 hours postoperatively and very low at 48 hours. We downgraded the quality of the evidence because of the poor conduct of the studies and because the results were not similar across studies. We did not grade the quality of evidence for the use of regional nerve block because none of our review outcomes were reported by the one study looking at this." } ]

[ { "role": "user", "content": "Abstract: Background\nOtomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used.\nObjectives\nTo evaluate the benefits and harms of topical azole treatments for otomycosis.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020.\nSelection criteria\nWe included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome.\nMain results\nWe included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution).\nA. Topical azoles versus placebo\nNone of the studies assessed this comparison.\nB. Topical azoles versus no treatment\nNone of the studies assessed this comparison.\nC. One type of topical azole versus another type of topical azole\ni) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole)\nThree studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles.\nOne study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence).\nClotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence).\nii) Bifonazole cream versus bifonazole solution\nOne study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence).\nAuthors' conclusions\nWe found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.\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 about the risks and benefits of using topical azoles to treat otomycosis." } ]

[ { "role": "user", "content": "Abstract: Background\nChronic obstructive pulmonary disease (COPD) has been recognised as a global health concern, and one of the leading causes of morbidity and mortality worldwide. Projections of the World Health Organization (WHO) indicate that prevalence rates of COPD continue to increase, and by 2030, it will become the world's third leading cause of death. Depression is a major comorbidity amongst patients with COPD, with an estimate prevalence of up to 80% in severe stages of COPD. Prevalence studies show that patients who have COPD are four times as likely to develop depression compared to those without COPD. Regrettably, they rarely receive appropriate treatment for COPD-related depression. Available findings from trials indicate that untreated depression is associated with worse compliance with medical treatment, poor quality of life, increased mortality rates, increased hospital admissions and readmissions, prolonged length of hospital stay, and subsequently, increased costs to the healthcare system. Given the burden and high prevalence of untreated depression, it is important to evaluate and update existing experimental evidence using rigorous methodology, and to identify effective psychological therapies for patients with COPD-related depression.\nObjectives\nTo assess the effectiveness of psychological therapies for the treatment of depression in patients with chronic obstructive pulmonary disease.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2018, Issue 11), and Ovid MEDLINE, Embase and PsycINFO from June 2016 to 26 November 2018. Previously these databases were searched via the Cochrane Airways and Common Mental Disorders Groups' Specialised Trials Registers (all years to June 2016). We searched ClinicalTrials.gov, the ISRCTN registry, and the World Health Organization International Clinical Trials Registry Platform (ICTRP) to 26 November 2018 to identify unpublished or ongoing trials. Additionally, the grey literature databases and the reference lists of studies initially identified for full-text screening were also searched.\nSelection criteria\nEligible for inclusion were randomised controlled trials that compared the use of psychological therapies with either no intervention, education, or combined with a co-intervention and compared with the same co-intervention in a population of patients with COPD whose depressive symptoms were measured before or at baseline assessment.\nData collection and analysis\nTwo review authors independently assessed the titles and abstracts identified by the search to determine which studies satisfied the inclusion criteria. We assessed two primary outcomes: depressive symptoms and adverse events; and the following secondary outcomes: quality of life, dyspnoea, forced expiratory volume in one second (FEV1), exercise tolerance, hospital length of stay or readmission rate, and cost-effectiveness. Potentially eligible full-text articles were also independently assessed by two review authors. A PRISMA flow diagram was prepared to demonstrate the decision process in detail. We used the Cochrane 'Risk of bias' evaluation tool to examine the risk of bias, and assessed the quality of evidence using the GRADE framework. All outcomes were continuous, therefore, we calculated the pooled standardised mean difference (SMD) or mean difference (MD) with a corresponding 95% confidence interval (CI). We used a random-effects model to calculate treatment effects.\nMain results\nThe findings are based on 13 randomised controlled trials (RCTs), with a total of 1500 participants. In some of the included studies, the investigators did not recruit participants with clinically confirmed depression but applied screening criteria after randomisation. Hence, across the studies, baseline scores for depressive symptoms varied from no symptoms to severe depression. The severity of COPD across the studies was moderate to severe.\nPrimary outcomes\nThere was a small effect showing the effectiveness of psychological therapies in improving depressive symptoms when compared to no intervention (SMD 0.19, 95% CI 0.05 to 0.33; P = 0.009; 6 studies, 764 participants), or to education (SMD 0.23, 95% CI 0.06 to 0.41; P = 0.010; 3 studies, 507 participants).\nTwo studies compared psychological therapies plus a co-intervention versus the co-intervention alone (i.e. pulmonary rehabilitation (PR)). The results suggest that a psychological therapy combined with a PR programme can reduce depressive symptoms more than a PR programme alone (SMD 0.37, 95% CI -0.00 to 0.74; P = 0.05; 2 studies, 112 participants).\nWe rated the quality of evidence as very low. Owing to the nature of psychological therapies, blinding of participants, personnel, and outcome assessment was a concern.\nNone of the included studies measured adverse events.\nSecondary outcomes\nQuality of life was measured in four studies in the comparison with no intervention, and in three studies in the comparison with education. We found inconclusive results for improving quality of life. However, when we pooled data from two studies using the same measure, the result suggested that psychological therapy improved quality of life better than no intervention. One study measured hospital admission rates and cost-effectiveness and showed significant reductions in the intervention group compared to the education group. We rated the quality of evidence as very low for the secondary outcomes.\nAuthors' conclusions\nThe findings from this review indicate that psychological therapies (using a CBT-based approach) may be effective for treating COPD-related depression, but the evidence is limited. Depressive symptoms improved more in the intervention groups compared to: 1) no intervention (attention placebo or standard care), 2) educational interventions, and 3) a co-intervention (pulmonary rehabilitation). However, the effect sizes were small and quality of the evidence very low due to clinical heterogeneity and risk of bias. This means that more experimental studies with larger numbers of participants are needed, to confirm the potential beneficial effects of therapies with a CBT approach for COPD-related depression.\nNew trials should also address the gap in knowledge related to limited data on adverse effects, and the secondary outcomes of quality of life, dyspnoea, forced expiratory volume in one second (FEV1), exercise tolerance, hospital length of stay and frequency of readmissions, and cost-effectiveness. Also, new research studies need to adhere to robust methodology to produce higher quality evidence.\n\nGiven the provided abstract, please respond to the following query: \"Which studies were included in the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review included experimental studies, called randomised controlled trials (RCTs), with participants who had diagnosed COPD." } ]

[ { "role": "user", "content": "Abstract: Background\nSubarachnoid haemorrhage has an incidence of up to nine per 100,000 person-years. It carries a mortality of 30% to 45% and leaves 20% dependent in activities of daily living. The major causes of death or disability after the haemorrhage are delayed cerebral ischaemia and rebleeding. Interventions aimed at lowering blood pressure may reduce the risk of rebleeding, while the induction of hypertension may reduce the risk of delayed cerebral ischaemia. Despite the fact that medical alteration of blood pressure has been clinical practice for more than three decades, no previous systematic reviews have assessed the beneficial and harmful effects of altering blood pressure (induced hypertension or lowered blood pressure) in people with acute subarachnoid haemorrhage.\nObjectives\nTo assess the beneficial and harmful effects of altering arterial blood pressure (induced hypertension or lowered blood pressure) in people with acute subarachnoid haemorrhage.\nSearch methods\nWe searched the following from inception to 8 September 2020 (Chinese databases to 27 January 2019): Cochrane Stroke Group Trials register; CENTRAL; MEDLINE; Embase; five other databases, and five trial registries. We screened reference lists of review articles and relevant randomised clinical trials.\nSelection criteria\nRandomised clinical trials assessing the effects of inducing hypertension or lowering blood pressure in people with acute subarachnoid haemorrhage. We included trials irrespective of publication type, status, date, and language.\nData collection and analysis\nTwo review authors independently extracted data. We assessed the risk of bias of all included trials to control for the risk of systematic errors. We performed trial sequential analysis to control for the risks of random errors. We also applied GRADE. Our primary outcomes were death from all causes and death or dependency. Our secondary outcomes were serious adverse events, quality of life, rebleeding, delayed cerebral ischaemia, and hydrocephalus. We assessed all outcomes closest to three months' follow-up (primary point of interest) and maximum follow-up.\nMain results\nWe included three trials: two trials randomising 61 participants to induced hypertension versus no intervention, and one trial randomising 224 participants to lowered blood pressure versus placebo. All trials were at high risk of bias. The certainty of the evidence was very low for all outcomes.\nInduced hypertension versus control\nTwo trials randomised participants to induced hypertension versus no intervention. Meta-analysis showed no evidence of a difference between induced hypertension versus no intervention on death from all causes (risk ratio (RR) 1.60, 95% confidence interval (CI) 0.57 to 4.42; P = 0.38; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analyses showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.\nMeta-analysis showed no evidence of a difference between induced hypertension versus no intervention on death or dependency (RR 1.29, 95% CI 0.78 to 2.13; P = 0.33; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analyses showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.\nMeta-analysis showed no evidence of a difference between induced hypertension and control on serious adverse events (RR 2.24, 95% CI 1.01 to 4.99; P = 0.05; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.\nOne trial (41 participants) reported quality of life using the Stroke Specific Quality of Life Scale. The induced hypertension group had a median of 47 points (interquartile range 35 to 55) and the no-intervention group had a median of 49 points (interquartile range 35 to 55). The certainty of evidence was very low.\nOne trial (41 participants) reported rebleeding. Fisher's exact test (P = 1.0) showed no evidence of a difference between induced hypertension and no intervention on rebleeding. The certainty of evidence was very low. Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.\nOne trial (20 participants) reported delayed cerebral ischaemia. Fisher's exact test (P = 1.0) showed no evidence of a difference between induced hypertension and no intervention on delayed cerebral ischaemia. The certainty of the evidence was very low. Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.\nNone of the trials randomising participants to induced hypertension versus no intervention reported on hydrocephalus. No subgroup analyses could be conducted for trials randomising participants to induced hypertension versus no intervention.\nLowered blood pressure versus control\nOne trial randomised 224 participants to lowered blood pressure versus placebo. The trial only reported on death from all causes. Fisher's exact test (P = 0.058) showed no evidence of a difference between lowered blood pressure versus placebo on death from all causes. The certainty of evidence was very low.\nAuthors' conclusions\nBased on the current evidence, there is a lack of information needed to confirm or reject minimally important intervention effects on patient-important outcomes for both induced hypertension and lowered blood pressure. There is an urgent need for trials assessing the effects of altering blood pressure in people with acute subarachnoid haemorrhage. Such trials should use the SPIRIT statement for their design and the CONSORT statement for their reporting. Moreover, such trials should use methods allowing for blinded altering of blood pressure and report on patient-important outcomes such as mortality, rebleeding, delayed cerebral ischaemia, quality of life, hydrocephalus, and serious adverse events.\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": "Our aim was to assess the beneficial and harmful effects of altering blood pressure in people with acute subarachnoid haemorrhage." } ]

[ { "role": "user", "content": "Abstract: Background\nSickle cell disease, a common recessively inherited haemoglobin disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean basin, Indian subcontinent, Caribbean and South America. It is associated with complications and a reduced life expectancy. Phytomedicines (medicine derived from plants in their original state) encompass many of the plant remedies from traditional healers which the populations most affected would encounter. Laboratory research and limited clinical trials have suggested positive effects of phytomedicines both in vivo and in vitro. However, there has been little systematic appraisal of their benefits. This is an updated version of a previously published Cochrane Review.\nObjectives\nTo assess the benefits and risks of phytomedicines in people with sickle cell disease of all types, of any age, in any setting.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, the International Standard Randomised Controlled Trial Number Register (ISRCTN), the Allied and Complimentary Medicine Database (AMED), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP).\nDates of most recent searches: Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Trials Register: 17 March 2020; ISRCTN: 19 April 2020; AMED: 18 May 2020; ClinicalTrials.gov: 24 April 2020; and the WHO ICTRP: 27 July 2017.\nSelection criteria\nRandomised or quasi-randomised trials with participants of all ages with sickle cell disease, in all settings, comparing the administration of phytomedicines, by any mode to placebo or conventional treatment, including blood transfusion and hydroxyurea.\nData collection and analysis\nBoth authors independently assessed trial quality and extracted data.\nMain results\nThree trials (212 participants) of three phytomedicines: Niprisan® (also known as Nicosan®), Ciklavit® and a powdered extract of Pfaffia paniculata were included. The Phase IIB (pivotal) trial suggests that Niprisan® may be effective in reducing episodes of severe painful sickle cell disease crisis over a six-month period (low-quality evidence). It did not appear to affect the risk of severe complications or the level of anaemia (low-quality evidence).\nThe single trial of Cajanus cajan (Ciklavit®) reported a possible benefit to individuals with painful crises, and a possible adverse effect (non-significant) on the level of anaemia (low-quality evidence).\nWe are uncertain of the effect of Pfaffia paniculata on the laboratory parameters and symptoms of SCD (very low-quality of evidence).\nNo adverse effects were reported with Niprisan® and Pfaffia paniculata (low- to very low-quality evidence).\nAuthors' conclusions\nWhile Niprisan® appeared to be safe and effective in reducing severe painful crises over a six-month follow-up period, further trials are required to assess its role in managing people with SCD and the results of its multicentre trials are awaited. Currently, no conclusions can be made regarding the efficacy of Ciklavit® and the powdered root extract of Pfaffia paniculata in managing SCD. Based on the published results for Niprisan® and in view of the limitations in data collection and analysis of the three trials, phytomedicines may have a potential beneficial effect in reducing painful crises in SCD. This needs to be further validated in future trials. More trials with improved study design and data collection are required on the safety and efficacy of phytomedicines used in managing SCD.\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 judged the quality of the evidence from this review to be of low to very low quality, depending on the outcome measured." } ]

[ { "role": "user", "content": "Abstract: Background\nGlaucoma is a leading cause of irreversible blindness. A number of minimally-invasive surgical techniques have been introduced as a treatment to prevent glaucoma from progressing; ab interno trabecular bypass surgery with the Schlemm's canal Hydrus microstent is one of them.\nObjectives\nTo evaluate the efficacy and safety of ab interno trabecular bypass surgery with the Hydrus microstent in treating people with open angle glaucoma (OAG).\nSearch methods\nOn 7 May 2019, we searched CENTRAL (2019, Issue 5), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP.\nSelection criteria\nWe searched for randomised controlled trials (RCTs) of the Hydrus microstent, alone or with cataract surgery, compared to other surgical treatments (cataract surgery alone, other minimally-invasive glaucoma device techniques, trabeculectomy), laser treatment, or medical treatment.\nData collection and analysis\nA minimum of three authors independently extracted data from reports of included studies, using a data collection form and analysed data, based on standard Cochrane methods.\nMain results\nWe included three published studies, with 808 people randomised. Two studies had multiple international recruitment centres in the USA and other countries. The third study had several sites based in Europe. All three studies were sponsored by the Hydrus manufacturer Ivantis Inc. All studies included participants with mainly mild or moderate OAG (mean deviation between -3.6 dB (decibel) and -8.4 dB in all study arms), which was controlled with medication in many participants (mean medicated intraocular pressure (IOP) 17.9 mmHg to 19.1 mmHg). There were no concerns regarding allocation concealment bias, but masking of outcome assessors was high or unclear risk in all studies; masking of participants was achieved, and losses to follow-up were not a concern.\nTwo studies compared the Hydrus microstent combined with cataract surgery to cataract surgery alone, in participants with visually significant cataracts and OAG.\nWe found moderate-certainty evidence that adding the Hydrus microstent to cataract surgery increased the proportion of participants who were medication-free from about half to more than three quarters at 12-month, short-term follow-up (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.39 to 1.83; 2 studies, 639 participants; I² = 0%; and 24-month, medium-term follow-up (RR 1.63, 95% CI 1.40 to 1.88; 2 studies, 619 participants; I² = 0%).\nThe Hydrus microstent combined with cataract surgery reduced the medium-term mean change in unmedicated IOP (after washout) by 2 mmHg more compared to cataract surgery alone (mean difference (MD) -2.00, 95% CI -2.69 to -1.31; 2 studies, 619 participants; I² = 0%; moderate-certainty evidence), and the mean change in IOP-lowering drops (MD -0.41, 95% CI -0.56 to -0.27; 2 studies, 619 participants; I² = 0%; low-certainty evidence). We also found low-certainty evidence that adding a Hydrus microstent to cataract surgery reduced the need for secondary glaucoma surgery from about 2.5% to less than 1% (RR 0.17, 95% CI 0.03 to 0.86; 2 studies, 653 participants; I² = 27%; low-certainty evidence).\nIntraocular bleeding, loss of 2 or more visual acuity (VA) lines, and IOP spikes of 10 mmHg or more were rare in both groups; estimates were imprecise, and included both beneficial and harmful effects. There were no cases of endophthalmitis in either group.\nNo data were available on the proportion of participants achieving IOP less than 21 mmHg, 17 mmHg, or 14 mmHg; health-related quality of life (HRQOL), or visual field progression.\nOne study provided short-term data for the Hydrus microstent compared with the iStent trabecular micro-bypass stent (iStent: implantation of two devices in a single procedure) in 152 participants with OAG (148 in analyses). Use of the Hydrus increased the proportion of medication-free participants from about a quarter to about half compared to those who received iStent, but this estimate was imprecise (RR 1.94, 95% CI 1.21 to 3.11; low-certainty evidence). Use of the Hydrus microstent reduced unmedicated IOP (after washout) by about 3 mmHg more than the iStent (MD -3.10, 95% CI -4.17 to -2.03; moderate-certainty evidence), and the use of IOP-lowering medication (MD -0.60, 95% CI -0.99 to -0.21; low-certainty evidence). Both devices achieved a final IOP < 21 mmHg in most participants (Hydrus microstent: 91.8%; iStent: 84%; RR 1.09, 95% CI 0.97 to 1.23; low-certainty evidence).\nNone of the participants who received the Hydrus microstent (N = 74) required additional glaucoma surgery; two participants who received the iStent (N = 76) did.\nFew adverse events were found in either group.\nNo data were available on the proportion of participants achieving IOP less than 17 mmHg or 14 mmHg, or on HRQOL.\nAuthors' conclusions\nIn people with cataracts and generally mild to moderate OAG, there is moderate-certainty evidence that the Hydrus microstent with cataract surgery compared to cataract surgery alone, likely increases the proportion of participants who do not require IOP lowering medication, and may further reduce IOP at short- and medium-term follow-up.\nThere is moderate-certainty evidence that the Hydrus microstent is probably more effective than the iStent in lowering IOP of people with OAG in the short-term.\nFew studies were available on the effects of the Hydrus microstent, therefore the results of this review may not be applicable to all people with OAG, particularly in selected people with medically uncontrolled glaucoma, since IOP was controlled with medication in many participants in the included studies. Complications may be rare using the Hydrus microstent, as well as the comparator iStent, but larger studies are needed to investigate its safety.\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": "Glaucoma is a common eye condition and can cause blindness if left untreated. In glaucoma, the optic nerve (which connects the eye to the brain) is damaged, often due to increased pressure in the eye as a result of build-up of fluid. Ab interno trabecular bypass surgery with a Hydrus microstent is a type of surgery in which doctors implant the Hydrus (a small device that opens up a channel in the main fluid canal called Schlemm's) and improves the flow of fluid through this canal. This may lead to lower eye pressure and a lower chance of damage to the optic nerve. This type of surgery is less invasive, and may lead to fewer complications and faster healing times than other types of surgery for glaucoma." } ]

[ { "role": "user", "content": "Abstract: Background\nAge-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as populations age, AMD remains incurable and there are no treatments for most patients. Mounting genetic and molecular evidence implicates complement system overactivity as a key driver of AMD development and progression. The last decade has seen the development of several novel therapeutics targeting complement in the eye for the treatment of AMD. This review update encompasses the results of the first randomised controlled trials in this field.\nObjectives\nTo assess the effects and safety of complement inhibitors in the prevention or treatment of AMD.\nSearch methods\nWe searched CENTRAL on the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, ISRCTN registry, ClinicalTrials.gov, and the WHO ICTRP to 29 June 2022 with no language restrictions. We also contacted companies running clinical trials for unpublished data.\nSelection criteria\nWe included randomised controlled trials (RCTs) with parallel groups and comparator arms that studied complement inhibition for advanced AMD prevention/treatment.\nData collection and analysis\nTwo authors independently assessed search results and resolved discrepancies through discussion. Outcome measures evaluated at one year included change in best-corrected visual acuity (BCVA), untransformed and square root-transformed geographic atrophy (GA) lesion size progression, development of macular neovascularisation (MNV) or exudative AMD, development of endophthalmitis, loss of ≥ 15 letters of BCVA, change in low luminance visual acuity, and change in quality of life. We assessed risk of bias and evidence certainty using Cochrane risk of bias and GRADE tools.\nMain results\nTen RCTs with 4052 participants and eyes with GA were included. Nine evaluated intravitreal (IVT) administrations against sham, and one investigated an intravenous agent against placebo. Seven studies excluded patients with prior MNV in the non-study eye, whereas the three pegcetacoplan studies did not. The risk of bias in the included studies was low overall. We also synthesised results of two intravitreal agents (lampalizumab, pegcetacoplan) at monthly and every-other-month (EOM) dosing intervals.\nEfficacy and safety of IVT lampalizumab versus sham for GA\nFor 1932 participants in three studies, lampalizumab did not meaningfully change BCVA given monthly (+1.03 letters, 95% confidence interval (CI) −0.19 to 2.25) or EOM (+0.22 letters, 95% CI −1.00 to 1.44) (high-certainty evidence). For 1920 participants, lampalizumab did not meaningfully change GA lesion growth given monthly (+0.07 mm², 95% CI −0.09 to 0.23; moderate-certainty due to imprecision) or EOM (+0.07 mm², 95% CI −0.05 to 0.19; high-certainty). For 2000 participants, lampalizumab may have also increased MNV risk given monthly (RR 1.77, 95% CI 0.73 to 4.30) and EOM (RR 1.70, 95% CI 0.67 to 4.28), based on low-certainty evidence. The incidence of endophthalmitis in patients treated with monthly and EOM lampalizumab was 4 per 1000 (0 to 87) and 3 per 1000 (0 to 62), respectively, based on moderate-certainty evidence.\nEfficacy and safety of IVT pegcetacoplan versus sham for GA\nFor 242 participants in one study, pegcetacoplan probably did not meaningfully change BCVA given monthly (+1.05 letters, 95% CI −2.71 to 4.81) or EOM (−1.42 letters, 95% CI −5.25 to 2.41), as supported by moderate-certainty evidence. In contrast, for 1208 participants across three studies, pegcetacoplan meaningfully reduced GA lesion growth when given monthly (−0.38 mm², 95% CI −0.57 to −0.19) and EOM (−0.29 mm², 95% CI −0.44 to −0.13), with high certainty. These reductions correspond to 19.2% and 14.8% versus sham, respectively. A post hoc analysis showed possibly greater benefits in 446 participants with extrafoveal GA given monthly (−0.67 mm², 95% CI −0.98 to −0.36) and EOM (−0.60 mm², 95% CI −0.91 to −0.30), representing 26.1% and 23.3% reductions, respectively. However, we did not have data on subfoveal GA growth to undertake a formal subgroup analysis. In 1502 participants, there is low-certainty evidence that pegcetacoplan may have increased MNV risk when given monthly (RR 4.47, 95% CI 0.41 to 48.98) or EOM (RR 2.29, 95% CI 0.46 to 11.35). The incidence of endophthalmitis in patients treated with monthly and EOM pegcetacoplan was 6 per 1000 (1 to 53) and 8 per 1000 (1 to 70) respectively, based on moderate-certainty evidence.\nEfficacy and safety of IVT avacincaptad pegol versus sham for GA\nIn a study of 260 participants with extrafoveal or juxtafoveal GA, monthly avacincaptad pegol probably did not result in a clinically meaningful change in BCVA at 2 mg (+1.39 letters, 95% CI −5.89 to 8.67) or 4 mg (−0.28 letters, 95% CI −8.74 to 8.18), based on moderate-certainty evidence. Despite this, the drug was still found to have probably reduced GA lesion growth, with estimates of 30.5% reduction at 2 mg (−0.70 mm², 95% CI −1.99 to 0.59) and 25.6% reduction at 4 mg (−0.71 mm², 95% CI −1.92 to 0.51), based on moderate-certainty evidence. Avacincaptad pegol may have also increased the risk of developing MNV (RR 3.13, 95% CI 0.93 to 10.55), although this evidence is of low certainty. There were no cases of endophthalmitis reported in this study.\nAuthors' conclusions\nDespite confirmation of the negative findings of intravitreal lampalizumab across all endpoints, local complement inhibition with intravitreal pegcetacoplan meaningfully reduces GA lesion growth relative to sham at one year. Inhibition of complement C5 with intravitreal avacincaptad pegol is also an emerging therapy with probable benefits on anatomical endpoints in the extrafoveal or juxtafoveal GA population. However, there is currently no evidence that complement inhibition with any agent improves functional endpoints in advanced AMD; further results from the phase 3 studies of pegcetacoplan and avacincaptad pegol are eagerly awaited. Progression to MNV or exudative AMD is a possible emergent adverse event of complement inhibition, requiring careful consideration should these agents be used clinically. Intravitreal administration of complement inhibitors is probably associated with a small risk of endophthalmitis, which may be higher than that of other intravitreal therapies. Further research is likely to have an important impact on our confidence in the estimates of adverse effects and may change these. The optimal dosing regimens, treatment duration, and cost-effectiveness of such therapies are yet to be established.\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 are confident in our results for lampalizumab and pegcetacoplan to treat geographic atrophy. People in the studies were randomly placed into the different treatment groups. This means that differences between the groups are due to differences between the treatments rather than between the people. More information is needed to increase our confidence in the anatomical benefits of avacincaptad pegol, but early evidence is encouraging.\nThese findings relate only to treatment with intravitreal medicines for up to one year at most. Not all studies provided data about everything that patients and their clinicians may be interested in. Participants in the studies had severe ‘dry’ AMD, so our results may not be useful for people whose AMD is less severe or those who have the ‘wet’ form of AMD." } ]

[ { "role": "user", "content": "Abstract: Background\nStillbirth is generally defined as a death prior to birth at or after 22 weeks' gestation. It remains a major public health concern globally. Antenatal interventions may reduce stillbirths and improve maternal and neonatal outcomes in settings with high rates of stillbirth. There are several key antenatal strategies that aim to prevent stillbirth including nutrition, and prevention and management of infections.\nObjectives\nTo summarise the evidence from Cochrane systematic reviews on the effects of antenatal interventions for preventing stillbirth for low risk or unselected populations of women.\nMethods\nWe collaborated with Cochrane Pregnancy and Childbirth's Information Specialist to identify all their published reviews that specified or reported stillbirth; and we searched the Cochrane Database of Systematic Reviews (search date: 29 Feburary 2020) to identify reviews published within other Cochrane groups. The primary outcome measure was stillbirth but in the absence of stillbirth data, we used perinatal mortality (both stillbirth and death in the first week of life), fetal loss or fetal death as outcomes. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm; clear evidence of no effect or equivalence; possible benefit or harm; or unknown benefit or harm or no effect or equivalence.\nMain results\nWe identified 43 Cochrane Reviews that included interventions in pregnant women with the potential for preventing stillbirth; all of the included reviews reported our primary outcome 'stillbirth' or in the absence of stillbirth, 'perinatal death' or 'fetal loss/fetal death'. AMSTAR quality was high in 40 reviews with scores ranging from 8 to 11 and moderate in three reviews with a score of 7.\nNutrition interventions\nClear evidence of benefit: balanced energy/protein supplementation versus no supplementation suggests a probable reduction in stillbirth (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.94, 5 randomised controlled trials (RCTs), 3408 women; moderate-certainty evidence).\nClear evidence of no effect or equivalence for stillbirth or perinatal death: vitamin A alone versus placebo or no treatment; and multiple micronutrients with iron and folic acid versus iron with or without folic acid.\nUnknown benefit or harm or no effect or equivalence: for all other nutrition interventions examined the effects were uncertain.\nPrevention and management of infections\nPossible benefit for fetal loss or death: insecticide-treated anti-malarial nets versus no nets (RR 0.67, 95% CI 0.47 to 0.97, 4 RCTs; low-certainty).\nUnknown evidence of no effect or equivalence: drugs for preventing malaria (stillbirth RR 1.02, 95% CI 0.76 to 1.36, 5 RCTs, 7130 women, moderate certainty in women of all parity; perinatal death RR 1.24, 95% CI 0.94 to 1.63, 4 RCTs, 5216 women, moderate-certainty in women of all parity).\nPrevention, detection and management of other morbidities\nClear evidence of benefit: the following interventions suggest a reduction: midwife-led models of care in settings where the midwife is the primary healthcare provider particularly for low-risk pregnant women (overall fetal loss/neonatal death reduction RR 0.84, 95% CI 0.71 to 0.99, 13 RCTs, 17,561 women; high-certainty), training versus not training traditional birth attendants in rural populations of low- and middle-income countries (stillbirth reduction odds ratio (OR) 0.69, 95% CI 0.57 to 0.83, 1 RCT, 18,699 women, moderate-certainty; perinatal death reduction OR 0.70, 95% CI 0.59 to 0.83, 1 RCT, 18,699 women, moderate-certainty).\nClear evidence of harm: a reduced number of antenatal care visits probably results in an increase in perinatal death (RR 1.14 95% CI 1.00 to 1.31, 5 RCTs, 56,431 women; moderate-certainty evidence).\nClear evidence of no effect or equivalence: there was evidence of no effect in the risk of stillbirth/fetal loss or perinatal death for the following interventions and comparisons: psychosocial interventions; and providing case notes to women.\nPossible benefit: community-based intervention packages (including community support groups/women's groups, community mobilisation and home visitation, or training traditional birth attendants who made home visits) may result in a reduction of stillbirth (RR 0.81, 95% CI 0.73 to 0.91, 15 RCTs, 201,181 women; low-certainty) and perinatal death (RR 0.78, 95% CI 0.70 to 0.86, 17 RCTs, 282,327 women; low-certainty).\nUnknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined.\nScreening and management of fetal growth and well-being\nClear evidence of benefit: computerised antenatal cardiotocography for assessing infant's well-being in utero compared with traditional antenatal cardiotocography (perinatal mortality reduction RR 0.20, 95% CI 0.04 to 0.88, 2 RCTs, 469 women; moderate-certainty).\nUnknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined.\nAuthors' conclusions\nWhile most interventions were unable to demonstrate a clear effect in reducing stillbirth or perinatal death, several interventions suggested a clear benefit, such as balanced energy/protein supplements, midwife-led models of care, training versus not training traditional birth attendants, and antenatal cardiotocography. Possible benefits were also observed for insecticide-treated anti-malarial nets and community-based intervention packages, whereas a reduced number of antenatal care visits were shown to be harmful. However, there was variation in the effectiveness of interventions across different settings, indicating the need to carefully understand the context in which these interventions were tested.\nFurther high-quality RCTs are needed to evaluate the effects of antenatal preventive interventions and which approaches are most effective to reduce the risk of stillbirth. Stillbirth (or fetal death), perinatal and neonatal death need to be reported separately in future RCTs of antenatal interventions to allow assessment of different interventions on these rare but important outcomes and they need to clearly define the target populations of women where the intervention is most likely to be of benefit. As the high burden of stillbirths occurs in low- and middle-income countries, further high-quality trials need to be conducted in these settings as a priority.\n\nGiven the provided abstract, please respond to the following query: \"Why is this important?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Stillbirth can be very upsetting for families. It is most common in low- and middle-income countries but also affects people in high-income countries. Numbers of stillbirths have not fallen much in the last 20 years and, despite the high numbers, it is not widely recognised as a global health problem. It is important to raise awareness of effective methods of preventing stillbirths, particularly in low- and middle-income countries." } ]

[ { "role": "user", "content": "Abstract: Background\nGabapentin is commonly used to treat neuropathic pain (pain due to nerve damage). This review updates a review published in 2014, and previous reviews published in 2011, 2005 and 2000.\nObjectives\nTo assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain in adults.\nSearch methods\nFor this update we searched CENTRAL), MEDLINE, and Embase for randomised controlled trials from January 2014 to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trials registries.\nSelection criteria\nWe included randomised, double-blind trials of two weeks' duration or longer, comparing gabapentin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.\nData collection and analysis\nTwo review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). We performed a pooled analysis for any substantial or moderate benefit. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables.\nMain results\nWe included four new studies (530 participants), and excluded three previously included studies (126 participants). In all, 37 studies provided information on 5914 participants. Most studies used oral gabapentin or gabapentin encarbil at doses of 1200 mg or more daily in different neuropathic pain conditions, predominantly postherpetic neuralgia and painful diabetic neuropathy. Study duration was typically four to 12 weeks. Not all studies reported important outcomes of interest. High risk of bias occurred mainly due to small size (especially in cross-over studies), and handling of data after study withdrawal.\nIn postherpetic neuralgia, more participants (32%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (17%) (RR 1.8 (95% CI 1.5 to 2.1); NNT 6.7 (5.4 to 8.7); 8 studies, 2260 participants, moderate-quality evidence). More participants (46%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (25%) (RR 1.8 (95% CI 1.6 to 2.0); NNT 4.8 (4.1 to 6.0); 8 studies, 2260 participants, moderate-quality evidence).\nIn painful diabetic neuropathy, more participants (38%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (23%) (RR 1.7 (95% CI 1.4 to 2.0); NNT 6.6 (5.0 to 10); 6 studies, 1331 participants, moderate-quality evidence). More participants (52%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (37%) (RR 1.4 (95% CI 1.3 to 1.6); NNT 6.6 (4.9 to 9.9); 7 studies, 1439 participants, moderate-quality evidence).\nFor all conditions combined, adverse event withdrawals were more common with gabapentin (11%) than with placebo (8.2%) (RR 1.4 (95% CI 1.1 to 1.7); NNH 30 (20 to 65); 22 studies, 4346 participants, high-quality evidence). Serious adverse events were no more common with gabapentin (3.2%) than with placebo (2.8%) (RR 1.2 (95% CI 0.8 to 1.7); 19 studies, 3948 participants, moderate-quality evidence); there were eight deaths (very low-quality evidence). Participants experiencing at least one adverse event were more common with gabapentin (63%) than with placebo (49%) (RR 1.3 (95% CI 1.2 to 1.4); NNH 7.5 (6.1 to 9.6); 18 studies, 4279 participants, moderate-quality evidence). Individual adverse events occurred significantly more often with gabapentin. Participants taking gabapentin experienced dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (14%).\nAuthors' conclusions\nGabapentin at doses of 1800 mg to 3600 mg daily (1200 mg to 3600 mg gabapentin encarbil) can provide good levels of pain relief to some people with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is very limited. The outcome of at least 50% pain intensity reduction is regarded as a useful outcome of treatment by patients, and the achievement of this degree of pain relief is associated with important beneficial effects on sleep interference, fatigue, and depression, as well as quality of life, function, and work. Around 3 or 4 out of 10 participants achieved this degree of pain relief with gabapentin, compared with 1 or 2 out of 10 for placebo. Over half of those treated with gabapentin will not have worthwhile pain relief but may experience adverse events. Conclusions have not changed since the previous update of this review.\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": "Neuropathic pain comes from damaged nerves. It is different from pain messages that are carried along healthy nerves from damaged tissue (for example, from a fall or cut, or arthritic knee). Neuropathic pain is often treated by different medicines (drugs) to those used for pain from damaged tissue, which we often think of as painkillers. Medicines that are sometimes used to treat depression or epilepsy can be effective in some people with neuropathic pain. One of these is gabapentin. Our definition of a good result was someone with a high level of pain relief and able to keep taking the medicine without side effects making them stop." } ]

[ { "role": "user", "content": "Abstract: Background\nTeeth that have suffered trauma can fuse to the surrounding bone in a process called dental ankylosis. Ankylosed permanent front teeth fail to erupt during facial growth and can become displaced, thus resulting in functional and aesthetic problems. Dental ankylosis is also associated with root resorption, which may eventually lead to the loss of affected teeth. Different interventions for the management of ankylosed permanent front teeth have been described, but it is unclear which are the most effective.\nObjectives\nTo evaluate the effectiveness of any intervention that can be used in the treatment of ankylosed permanent front teeth.\nSearch methods\nThe following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 3 August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 7), MEDLINE via OVID (1946 to 3 August 2015), EMBASE via OVID (1980 to 3 August 2015) and LILACS via BIREME (1982 to 3 August 2015). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.\nSelection criteria\nWe included randomised controlled trials (RCTs) comparing any intervention for treating displaced ankylosed permanent front teeth in individuals of any age. Treatments could be compared with one another, with placebo or with no treatment.\nData collection and analysis\nTwo independent review authors screened studies independently. Full papers were obtained for potentially relevant trials. Although no study was included, the authors had planned to extract data independently and to analyse the data according to the Cochrane Handbook for Systematic Reviews of Interventions.\nMain results\nNo randomised controlled trials that met the inclusion criteria were identified.\nAuthors' conclusions\nWe were unable to identify any reports of randomised controlled trials regarding the efficacy of different treatment options for ankylosed permanent front teeth. The lack of high level evidence for the management of this health problem emphasises the need for well designed clinical trials on this topic, which conform to the CONSORT statement (www.consort-statement.org/).\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": "Sometimes teeth can fuse to the bone of the jaws after an injury to the tooth, such as when the tooth is knocked and pushed up into the jawbone. This fusion is called 'ankylosis'. Usually the roots of fused ('ankylosed') teeth are resorbed by the body and replaced by the surrounding bone. For some individuals, this can lead to the fused teeth falling out. These teeth do not grow with the normal growth of the jawbones, so can become gradually moved if the injury occurs during childhood. It is not clear which treatment is best for these fused teeth, which is why we have undertaken this review." } ]

[ { "role": "user", "content": "Abstract: Background\nSore throat is a common reason for people to present for medical care and to be prescribed antibiotics. Overuse of antibiotics in primary medicine is a concern, hence it is important to establish their efficacy in treating sore throat and preventing secondary complications.\nObjectives\nTo assess the effects of antibiotics for reducing symptoms of sore throat for child and adult patients.\nSearch methods\nWe searched CENTRAL 2021, Issue 2, MEDLINE (January 1966 to April week 1, 2021), Embase (January 1990 to April 2021), and two trial registries (searched 6 April 2021).\nSelection criteria\nRandomised controlled trials (RCTs) or quasi-RCTs of antibiotics versus control assessing typical sore throat symptoms or complications amongst children and adults seeking medical care for sore throat symptoms.\nData collection and analysis\nWe used standard methodological procedures as recommended by Cochrane. Two review authors independently screened studies for inclusion and extracted data, resolving any differences in opinion by discussion. We contacted the trial authors from three studies for additional information. We used GRADE to assess the certainty of the evidence for the efficacy of antibiotics on our primary outcomes (sore throat at day three and one week) and secondary outcomes (fever and headache symptoms and incidence of acute rheumatic fever, acute glomerulonephritis, acute otitis media, acute sinusitis, and quinsy).\nMain results\nWe included 29 trials with 15,337 cases of sore throat. The majority of included studies were conducted in the 1950s, during which time the rates of serious complications (especially acute rheumatic fever) were much higher than today. Although clinical antibiotic trials for sore throat and respiratory symptoms are still being conducted, it is unusual for them to include placebo or 'no treatment' control arms, which is a requirement for inclusion in the review.\nThe age of participants ranged from younger than one year to older than 50 years, but most participants across all studies were adults. Although all studies recruited patients presenting with symptoms of sore throat, few of them distinguished between bacterial and viral aetiology. Bias may have been introduced through non-clarity in treatment allocation procedures and lack of blinding in some studies. Harms from antibiotics were poorly or inconsistently reported, and were thus not quantified for this review.\n1. Symptoms\nThroat soreness and headache at day three were reduced by using antibiotics, although 82% of participants in the placebo or no treatment group were symptom-free by one week. The reduction in sore throat symptoms at day three (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.60 to 0.80; 16 studies, 3730 participants; moderate-certainty evidence) was greater than at one week in absolute numbers (RR 0.50, 95% CI 0.34 to 0.75; 14 studies, 3083 participants; moderate-certainty evidence) due to many cases in both treatment groups having resolved by this time. The number needed to treat for an additional beneficial outcome (NNTB) to prevent one sore throat at day three was less than six; at week one it was 18. Compared with placebo or no treatment, antibiotics did not significantly reduce fever at day three (RR 0.75, 95% CI 0.53 to 1.07; 8 studies, 1443 participants; high-certainty evidence), but did reduce headache at day three (RR 0.49, 95% CI 0.34 to 0.70; 4 studies, 1020 participants; high-certainty evidence).\n2. Suppurative complications\nWhilst the prevalence of suppurative complications was low, antibiotics reduced the incidence of acute otitis media within 14 days (Peto odds ratio (OR) 0.21, 95% CI 0.11 to 0.40; 10 studies, 3646 participants; high-certainty evidence) and quinsy within two months (Peto OR 0.16, 95% CI 0.07 to 0.35; 8 studies, 2433 participants; high-certainty evidence) compared to those receiving placebo or no treatment, but not acute sinusitis within 14 days (Peto OR 0.46, 95% CI 0.10 to 2.05; 8 studies, 2387 participants; high-certainty evidence).\n3. Non-suppurative complications\nThere were too few cases of acute glomerulonephritis to determine whether there was a protective effect of antibiotics compared with placebo against this complication (Peto OR 0.07, 95% CI 0.00 to 1.32; 10 studies, 5147 participants; low-certainty evidence). Antibiotics reduced acute rheumatic fever within two months when compared to the control group (Peto OR 0.36, 95% CI 0.26 to 0.50; 18 studies, 12,249 participants; moderate-certainty evidence). It should be noted that the overall prevalence of acute rheumatic fever was very low, particularly in the later studies.\nAuthors' conclusions\nAntibiotics probably reduce the number of people experiencing sore throat, and reduce the likelihood of headache, and some sore throat complications. As the effect on symptoms can be small, clinicians must judge on an individual basis whether it is clinically justifiable to use antibiotics to produce this effect, and whether the underlying cause of the sore throat is likely to be of bacterial origin. Furthermore, the balance between modest symptom reduction and the potential hazards of antimicrobial resistance must be recognised. Few trials have attempted to measure symptom severity. If antibiotics reduce the severity as well as the duration of symptoms, their benefit will have been underestimated in this meta-analysis. Additionally, more trials are needed in low-income countries, in socio-economically deprived sections of high-income countries, as well as in children.\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": "Many of the early studies were funded by the United States Armed Forces and recruited young, adult male military personnel. Later studies were mostly supported by governmental research grants, with a small number funded by private pharmaceutical companies." } ]

[ { "role": "user", "content": "Abstract: Background\nGuidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence.\nObjectives\nOur primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects.\nSearch methods\nWe searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature.\nSelection criteria\nWe included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients.\nData collection and analysis\nWe examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes.\nMain results\nWe included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients.\nNo trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence).\nNo trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence).\nAuthors' conclusions\nThere were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.\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 for the effectiveness and safety of antipsychotics for treatment of delirium in hospitalised patients, not including those in intensive care units (specialised wards for caring for very sick patients)." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of a previously published version of the review (Issue 10, 2011).\nEpithelial ovarian cancer (EOC) is the seventh most common cause of cancer death among women worldwide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy. Between 55% and 75% of women who respond to first-line therapy experience relapse within two years. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Improved understanding about the molecular basis of EOC has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and anti-EGFR antibodies.\nObjectives\nTo compare the effectiveness and harmful effects of interventions that target the epidermal growth factor receptor in the treatment of epithelial ovarian cancer (EOC).\nSearch methods\nWe searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2010, Issue 4), MEDLINE, and Embase up to October 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field. This update includes further searches up to September 2017.\nSelection criteria\nRandomised controlled trials (RCTs) comparing anti-EGFR agents with or without conventional chemotherapy versus conventional chemotherapy alone or no treatment in women with histologically proven EOC.\nData collection and analysis\nTwo review authors independently abstracted data, assessed risk of bias, and performed GRADE assessment.\nMain results\nFrom 6105 references obtained through the literature search and an additional 15 references derived from grey literature searches, we identified seven RCTs that met our inclusion criteria and included 1725 participants. Trial results show that after first-line chemotherapy is provided, maintenance treatment with erlotinib (EGFR tyrosine kinase inhibitor (TKI)) probably makes little or no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.81 to 1.20; one study; 835 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 1.05, 95% CI 0.90 to 1.23; one study; 835 participants; very low-certainty evidence). Less than 50% of participants provided quality of life data, and study authors reported these results incompletely. The certainty of evidence is very low, but treatment may reduce quality of life compared to observation.\nTreatment with an EGFR TKI (vandetanib) for women with relapsed EOC may make little or no difference in overall survival (HR 1.25, 95% CI 0.80 to 1.95; one study; 129 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 0.99, 95% CI 0.69 to 1.42; one study; 129 participants; very low-certainty evidence). In treating patients with relapse, giving EGFR TKI may slightly increase some toxicities, such as severe rash (risk ratio (RR) 13.63, 95% CI 0.78 to 236.87; one study; 125 participants; very low-certainty evidence). Quality of life data were not available for meta-analysis.\nAnti-EGFR antibody treatment in relapsed EOC may or may not make a difference to overall survival (HR 0.93, 95% CI 0.74 to 1.18; four studies; 658 participants; moderate-certainty evidence) and may or may not have any effect on progression-free survival (HR 0.90, 95% CI 0.70 to 1.16; four studies; 658 participants; low-certainty evidence). Anti-EGFR antibody treatment may or may not increase side effects, including severe nausea and/or vomiting (RR 1.27, 95% CI 0.56 to 2.89; three studies; 503 participants; low-certainty evidence), severe fatigue (RR 1.06, 95% CI 0.66 to 1.73; I² = 0%; four studies; 652 participants; low-certainty evidence), and hypokalaemia (RR 2.01, 95% CI 0.80 to 5.06; I² = 0%; three studies; 522 participants; low-certainty evidence). Severe diarrhoea rates were heterogeneous across studies (RR 2.87, 95% CI 0.59 to 13.89; four studies; 652 participants; low-certainty evidence), and subgroup analysis revealed that severe diarrhoea was more likely with pertuzumab (RR 6.37, 95% CI 1.89 to 21.45; I² = 0%; three studies; 432 participants; low-certainty evidence) than with seribantumab treatment (RR 0.38, 95% CI 0.07 to 2.23; I² = 0%; one study; 220 participants; very low-certainty evidence). Quality of life data were incompletely reported, and we were unable to combine them in a meta-analysis.\nAuthors' conclusions\nCurrent evidence suggests that an anti-EGFR single-agent biological treatment (EGFR TKI or anti-EGFR antibody) makes little or no difference to survival, either as maintenance treatment after first-line chemotherapy or in association with chemotherapy in recurrent cancer. Anti-EGFR therapy may increase some side effects and may or may not reduce quality of life.\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": "Approximately a quarter of gynaecological cancers are of ovarian origin, although they account for half of all deaths related to gynaecological cancers. The annual incidence worldwide is about 6.6 cases per 100,000 women, with an annual mortality rate of four deaths per 100,000 women, as three-quarters of these cases are diagnosed at an advanced stage. Treatment usually consists of a combination of surgery to remove as much of the visible cancer as possible (debulking surgery) and platinum-based chemotherapy. Most cases of EOC (70% to 80%) respond to chemotherapy. Unfortunately, most women with advanced disease experience relapse and ultimately die because of resistance to chemotherapy.\nEGFR is involved in controlling cell growth. High EGFR activity is linked to development of EOC and to poor outcomes. Preventing EGFR activity is an attractive target for novel therapeutic agents. Anti-EGFR agents have been developed and have been tried in combination with chemotherapy or as maintenance treatment after chemotherapy." } ]

[ { "role": "user", "content": "Abstract: Background\nSpecialised disease management programmes for heart failure aim to improve care, clinical outcomes and/or reduce healthcare utilisation. Since the last version of this review in 2010, several new trials of structured telephone support and non-invasive home telemonitoring have been published which have raised questions about their effectiveness.\nObjectives\nTo review randomised controlled trials (RCTs) of structured telephone support or non-invasive home telemonitoring compared to standard practice for people with heart failure, in order to quantify the effects of these interventions over and above usual care.\nSearch methods\nWe updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology AsseFssment Database (HTA) on the Cochrane Library; MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index- Science (CPCI-S) on Web of Science (Thomson Reuters), AMED, Proquest Theses and Dissertations, IEEE Xplore and TROVE in January 2015. We handsearched bibliographies of relevant studies and systematic reviews and abstract conference proceedings. We applied no language limits.\nSelection criteria\nWe included only peer-reviewed, published RCTs comparing structured telephone support or non-invasive home telemonitoring to usual care of people with chronic heart failure. The intervention or usual care could not include protocol-driven home visits or more intensive than usual (typically four to six weeks) clinic follow-up.\nData collection and analysis\nWe present data as risk ratios (RRs) with 95% confidence intervals (CIs). Primary outcomes included all-cause mortality, all-cause and heart failure-related hospitalisations, which we analysed using a fixed-effect model. Other outcomes included length of stay, health-related quality of life, heart failure knowledge and self care, acceptability and cost; we described and tabulated these. We performed meta-regression to assess homogeneity (the null hypothesis) in each subgroup analysis and to see if the effect of the intervention varied according to some quantitative variable (such as year of publication or median age).\nMain results\nWe include 41 studies of either structured telephone support or non-invasive home telemonitoring for people with heart failure, of which 17 were new and 24 had been included in the previous Cochrane review. In the current review, 25 studies evaluated structured telephone support (eight new studies, plus one study previously included but classified as telemonitoring; total of 9332 participants), 18 evaluated telemonitoring (nine new studies; total of 3860 participants). Two of the included studies trialled both structured telephone support and telemonitoring compared to usual care, therefore 43 comparisons are evident.\nNon-invasive telemonitoring reduced all-cause mortality (RR 0.80, 95% CI 0.68 to 0.94; participants = 3740; studies = 17; I² = 24%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.71, 95% CI 0.60 to 0.83; participants = 2148; studies = 8; I² = 20%, GRADE: moderate-quality evidence). Structured telephone support reduced all-cause mortality (RR 0.87, 95% CI 0.77 to 0.98; participants = 9222; studies = 22; I² = 0%, GRADE: moderate-quality evidence) and heart failure-related hospitalisations (RR 0.85, 95% CI 0.77 to 0.93; participants = 7030; studies = 16; I² = 27%, GRADE: moderate-quality evidence).\nNeither structured telephone support nor telemonitoring demonstrated effectiveness in reducing the risk of all-cause hospitalisations (structured telephone support: RR 0.95, 95% CI 0.90 to 1.00; participants = 7216; studies = 16; I² = 47%, GRADE: very low-quality evidence; non-invasive telemonitoring: RR 0.95, 95% CI 0.89 to 1.01; participants = 3332; studies = 13; I² = 71%, GRADE: very low-quality evidence).\nSeven structured telephone support studies reported length of stay, with one reporting a significant reduction in length of stay in hospital. Nine telemonitoring studies reported length of stay outcome, with one study reporting a significant reduction in the length of stay with the intervention. One telemonitoring study reported a large difference in the total number of hospitalisations for more than three days, but this was not an analysis of length of stay per hospitalisation. Nine of 11 structured telephone support studies and five of 11 telemonitoring studies reported significant improvements in health-related quality of life. Nine structured telephone support studies and six telemonitoring studies reported costs of the intervention or cost effectiveness. Three structured telephone support studies and one telemonitoring study reported a decrease in costs and two telemonitoring studies reported increases in cost, due both to the cost of the intervention and to increased medical management. Adherence was rated between 55.1% and 98.5% for those structured telephone support and telemonitoring studies which reported this outcome. Participant acceptance of the intervention was reported in the range of 76% to 97% for studies which evaluated this outcome. Seven of nine studies that measured these outcomes reported significant improvements in heart failure knowledge and self-care behaviours.\nAuthors' conclusions\nFor people with heart failure, structured telephone support and non-invasive home telemonitoring reduce the risk of all-cause mortality and heart failure-related hospitalisations; these interventions also demonstrated improvements in health-related quality of life and heart failure knowledge and self-care behaviours. Studies also demonstrated participant satisfaction with the majority of the interventions which assessed this 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": "This review demonstrates that supporting people with heart failure at home using information technology can reduce the rates of death and heart failure-related hospitalisation. It can improve people's quality of life and knowledge about heart failure and self care. Most patients, even those who are elderly, learn to use the technology easily and are satisfied with these interventions." } ]

[ { "role": "user", "content": "Abstract: Background\nUnintentional injuries are the leading cause of death in children aged four to 18 years and are a major cause of ill health. The school setting offers the opportunity to deliver preventive interventions to a large number of children and has been used to address a range of public health problems. However, the effectiveness of the school setting for the prevention of different injury mechanisms in school-aged children is not well understood.\nObjectives\nTo assess the effects of school-based educational programmes for the prevention of injuries in children and evaluate their impact on improving children's safety skills, behaviour and practices, and knowledge, and assess their cost-effectiveness.\nSearch methods\nWe ran searches on the following electronic databases to 26 June 2015: PsycINFO, British Education Index (BEI), Education Resources Information Center (ERIC), Applied Social Sciences Index and Abstracts (ASSIA), International Bibliography of the Social Sciences (IBSS), Sociological Abstracts; Latin America and the Caribbean database (LILACS), together with several sources of grey literature. The Cochrane Injuries Information Specialist ran searches, to August 2013, on the Groups Specialised Register (SR-INJ), the Cochrane Central Register of Controlled Trials (CENTRAL) and other Cochrane Library databases, Ovid MEDLINE, Embase, CINAHL and the ISI Web of Science. In keeping with Cochrane standards, along with Cochrane Injuries' Information Specialist we ran an update search prior to publication (September and October 2016). We have screened the results and placed any relevant studies in the Characteristics of studies awaiting classification section of this review.These will be incorporated in the next version of this review, as appropriate.\nSelection criteria\nWe included randomised controlled trials (RCTs), non-randomised controlled trials (non-RCTs), and controlled before-and-after (CBA) studies that evaluated school-based educational programmes aimed at preventing a range of injury mechanisms. The primary outcome was self-reported or medically attended unintentional (or unspecified intent) injuries and secondary outcomes were observed safety skills, observed behaviour, self-reported behaviour and safety practices, safety knowledge, and health economic outcomes. The control groups received no intervention, a delayed injury-prevention intervention or alternative school-based curricular activities. We included studies that aimed interventions at primary or secondary prevention of injuries from more than one injury mechanism and were delivered, in part or in full, in schools catering for children aged four to 18 years.\nData collection and analysis\nWe used standard methodological procedures expected by Cochrane. Two review authors identified relevant trials from title and abstracts of studies identified in searches and two review authors extracted data from the included studies and assessed risk of bias. We grouped different types of interventions according to the outcome assessed and the injury mechanism targeted. Where data permitted, we performed random-effects meta-analyses to provide a summary of results across studies.\nMain results\nThe review included 27 studies reported in 30 articles. The studies had 73,557 participants with 12 studies from the US; four from China; two from each of Australia, Canada, the Netherlands and the UK; and one from each of Israel, Greece and Brazil. Thirteen studies were RCTs, six were non-RCTs and eight were CBAs. Of the included studies, 18 provided some element of the intervention in children aged four to 11 years, 17 studies included children aged 11 to 14 years and nine studies included children aged 14 to 18 years.\nThe overall quality of the results was poor, with the all studies assessed as being at high or unclear risks of bias across multiple domains, and varied interventions and data collection methods employed. Interventions comprised information-giving, peer education or were multi-component.\nSeven studies reported the primary outcome of injury occurrence and only three of these were similar enough to combine in a meta-analysis, with a pooled incidence rate ratio of 0.73 (95% confidence interval (CI) 0.49 to 1.08; 2073 children) and substantial statistical heterogeneity (I2 = 63%). However, this body of evidence was low certainty, due to concerns over this heterogeneity (inconsistency) and imprecision. This heterogeneity may be explained by the non-RCT study design of one of the studies, as a sensitivity analysis with this study removed found stronger evidence of an effect and no heterogeneity (I2 = 0%).\nTwo studies report an improvement in safety skills in the intervention group. Likewise, the four studies measuring observed safety behaviour reported an improvement in the intervention group relative to the control. Thirteen out of 19 studies describing self-reported behaviour and safety practices showed improvements, and of the 21 studies assessing changes in safety knowledge, 19 reported an improvement in at least one question domain in the intervention compared to the control group. However, we were unable to pool data for our secondary outcomes, so our conclusions were limited, as they were drawn from highly diverse single studies and the body of evidence was low (safety skills) or very low (behaviour, safety knowledge) certainty. Only one study reported intervention costs but did not undertake a full economic evaluation (very low certainty evidence).\nAuthors' conclusions\nThere is insufficient evidence to determine whether school-based educational programmes can prevent unintentional injuries. More high-quality studies are needed to evaluate the impact of educational programmes on injury occurrence. There is some weak evidence that such programmes improve safety skills, behaviour/practices and knowledge, although the evidence was of low or very low quality certainty. We found insufficient economic studies to assess cost-effectiveness.\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": "We wanted to discover whether teaching children in school education about injury prevention resulted in them having fewer injuries, improved their knowledge about injury prevention and improved their behaviours in relation to safety. We also wanted to assess whether this type of approach was good value for money." } ]

[ { "role": "user", "content": "Abstract: Background\nBetween 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children.\nObjectives\nTo determine the effectiveness of pharmacological interventions for RAP in children of school age.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies.\nSelection criteria\nRandomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life.\nData collection and analysis\nTwo review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results.\nMain results\nThis review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies.\nAuthors' conclusions\nThere is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.\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 scientific literature worldwide up to June 2016 for research studies of drug treatments for children with RAP. We found 16 studies that met our criteria, examining antidepressants, antibiotics, antihistamines, antispasmodics, a dopamine receptor antagonist, and a hormone treatment. Fourteen studies compared drug treatments to a placebo, and two to usual medical care. The trials were carried out in seven countries: seven in the USA, four in Iran, one in the UK, one in Switzerland, one in Turkey, one in Sri Lanka, and one in India. The studies included a total of 1024 children aged between five and 18 years. All children were recruited from outpatient clinics. Follow-up lasted between two weeks and four months." } ]

[ { "role": "user", "content": "Abstract: Background\nMicrobial cultures for diagnosis of neonatal sepsis have low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.\nObjectives\nTo assess the diagnostic accuracy of various molecular methods for the diagnosis of culture-positive bacterial and fungal sepsis in neonates and to explore heterogeneity among studies by analyzing subgroups classified by gestational age and type of sepsis onset and compare molecular tests with one another.\nSearch methods\nWe performed the systematic review as recommended by the Cochrane Diagnostic Test Accuracy Working Group. On 19 January 2016, we searched electronic bibliographic databases (the Cochrane Library, PubMed (from 1966), Embase (from 1982), and CINAHL (from 1982)), conference proceedings of the Pediatric Academic Societies annual conference (from 1990), clinical trial registries (ClinicalTrials.gov, International Standard Randomised Controlled Trial Number (ISRCTN) registry, and World Health Organization (WHO) International Clinical Trials Platform (ICTRP) Search portal), and Science Citation Index. We contacted experts in the field for studies.\nSelection criteria\nWe included studies that were prospective or retrospective, cohort or cross-sectional design, which evaluated molecular assays (index test) in neonates with suspected sepsis (participants) in comparison with microbial cultures (reference standard).\nData collection and analysis\nTwo review authors independently assessed the methodologic quality of the studies and extracted data. We performed meta-analyses using the bivariate and hierarchical summary receiver operating characteristic (HSROC) models and entered data into Review Manager 5.\nMain results\nThirty-five studies were eligible for inclusion and the summary estimate of sensitivity was 0.90 (95% confidence interval (CI) 0.82 to 0.95) and of specificity was 0.93 (95% CI 0.89 to 0.96) (moderate quality evidence). We explored heterogeneity by subgroup analyses of type of test, gestational age, type of sepsis onset, and prevalence of sepsis and we did not find sufficient explanations for the heterogeneity (moderate to very low quality evidence). Sensitivity analyses by including studies that analyzed blood samples and by good methodology revealed similar results (moderate quality evidence).\nAuthors' conclusions\nMolecular assays have the advantage of producing rapid results and may perform well as 'add-on' tests.\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": "Do molecular tests detect infection better than the standard culture methods for detecting infection in newborn babies?" } ]

[ { "role": "user", "content": "Abstract: Background\nAvascular necrosis of bone is a frequent and severe complication of sickle cell disease and its treatment is not standardised. This is an update of a previously published Cochrane Review.\nObjectives\nTo determine the impact of any surgical procedure compared with other surgical interventions or non-surgical procedures, on avascular necrosis of bone in people with sickle cell disease in terms of efficacy and safety.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Additional trials were sought from both ongoing trial registries and the reference lists of papers identified by the search strategy.\nDate of the most recent search of the Group's Haemoglobinopathies Trials Register: 17 September 2019.\nSelection criteria\nRandomized clinical trials comparing specific therapies for avascular necrosis of bone in people with sickle cell disease.\nData collection and analysis\nEach author independently extracted data and assessed trial quality. The quality of the evidence was assessed using GRADE. Given only one trial was identified, meta-analyses were not possible.\nMain results\nOne trial (46 participants) was eligible for inclusion. After randomization eight participants were withdrawn, mainly because they declined to participate in the trial. Data were analysed for 38 participants at the end of the trial. After a mean follow-up of three years, hip core decompression and physical therapy did not show clinical improvement when compared with physical therapy alone using the score from the original trial (an improvement of 18.1 points for those treated with intervention therapy versus an improvement of 15.7 points with control therapy). We are very uncertain whether there is any difference between groups regarding major complications (hip pain, risk ratio 0.95 (95% confidence interval 0.56 to 1.60; vaso-occlusive crises, risk ratio 1.14 (95% confidence interval 0.72 to 1.80; very low quality of evidence); and acute chest syndrome, risk ratio 1.06 (95% confidence interval 0.44 to 2.56; very low quality of evidence)). This trial did not report results on mortality or quality of life.\nAuthors' conclusions\nWe found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomized controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). The availability of participants to allow adequate trial power will be a key consideration for endpoint choice.\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: 17 September 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nAmbulatory or outpatient anaesthesia is performed in patients who are discharged on the same day as their surgery. Perioperative complications such as postoperative nausea and vomiting (PONV), postoperative behavioural disturbances and cardiorespiratory complications should be minimized in ambulatory anaesthesia. The choice of anaesthetic agents and techniques can influence the occurrence of these complications and thus delay in discharge.\nObjectives\nThe objective of this review was to evaluate the risk of complications (the risk of postoperative nausea and vomiting (PONV), admission or readmission to hospital, postoperative behavioural disturbances and perioperative respiratory and cardiovascular complications) and recovery times (time to discharge from recovery ward and time to discharge from hospital) comparing the use of intravenous to inhalational anaesthesia for paediatric outpatient surgery.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 8); MEDLINE (1948 to 1 October 2013); EMBASE (1974 to 1 October 2013); Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (1982 to 1 October 2013). We also handsearched relevant journals and searched the reference lists of the articles identified.\nSelection criteria\nWe included randomized controlled trials comparing paediatric outpatient surgery using intravenous versus inhalational anaesthesia.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted the data. When necessary, we requested additional information and clarification of published data from the authors of individual trials.\nMain results\nWe included 16 trials that involved 900 children in this review. Half of all the studies did not describe the generation of randomized sequence and most studies did not describe adequate allocation sequence concealment. The included studies showed variability in the types and combinations of drugs and the duration of anaesthesia, limiting the meta-analysis and interpretation of the results.\nFor the induction and maintenance of anaesthesia there was a significant difference favouring intravenous anaesthesia with propofol; the incidence of PONV was 32.6% for sevoflurane and 16.1% for propofol (odds ratio (OR) 2.96; 95% confidence interval (CI) 1.35 to 6.49, four studies, 176 children, low quality evidence). The risk of postoperative behavioural disturbances also favoured intravenous anaesthesiaas the incidence was 24.7% for sevoflurane and 11.5% for propofol (OR 2.67; 95% CI 1.14 to 6.23, four studies, 176 children, very low quality evidence). There were no differences between groups in the risk of intraoperative and postoperative respiratory and cardiovascular complications (OR 0.75; 95% CI 0.27 to 2.13, three studies,130 children, very low quality evidence) and there was no difference in the time to recovery from anaesthesia and discharge from hospital. These results should be interpreted with caution due to heterogeneity between studies in the type and duration of operations, types of reported complications and the high risk of bias in almost all studies. Two studies (105 participants) compared halothane to propofol and showed heterogeneity in duration of anaesthesia and in the type of ambulatory procedure. For the risk of PONV the results of the studies were conflicting, and for the risks of intraoperative and postoperative complications there were no significant differences between the groups.\nFor the maintenance of anaesthesia there was a significant difference favouring anaesthesia with propofol, with or without nitrous oxide (N2O), when compared to thiopentone and halothane + N2O (OR 3.23; 95% CI 1.49 to 7.02, four studies, 176 children, low quality evidence; and OR 7.44; 95% CI 2.60 to 21.26, two studies, 87 children, low quality evidence), respectively. For the time to discharge from the recovery room, there were no significant differences between groups. The studies were performed with different ambulatory surgeries and a high risk of bias.\nFour studies (250 participants) compared the induction of anaesthesia by the inhalational or intravenous route, with inhalational anaesthesia for maintenance, and found no significant differences between groups in all outcomes (the risk of PONV, behavioural disturbances, respiratory and cardiovascular complications and time to discharge from recovery room). Meta-analysis was not done in this comparison because of significant clinical heterogeneity.\nReadmission to hospital was not reported in any of the included studies. No other adverse effects were reported.\nAuthors' conclusions\nThere is insufficient evidence to determine whether intravenous anaesthesia with propofol for induction and maintenance of anaesthesia in paediatric outpatients undergoing surgery reduces the risk of postoperative nausea and vomiting and the risk of behavioural disturbances compared with inhaled anaesthesia. This evidence is of poor quality. More high-quality studies are needed to compare the different types of anaesthesia in different subsets of children undergoing ambulatory surgery.\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": "We wanted to find out whether intravenous or inhaled anaesthesia reduced the risk of outcomes such as postoperative nausea and sickness (vomiting) (PONV) and behavioural problems in children having day surgery. PONV is one of the most common problems for children having day surgery. PONV is a common reason for delay in a child's hospital discharge and for their unplanned admission to hospital. Postoperative pain can cause behavioural problems in children. These behavioural problems may present as moaning, being restless and confused, and physical movements such as thrashing about in the bed. Mental disturbances such as hallucinations, delusions and confusion can also be evident as a child emerges from GA." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople living with chronic kidney disease (CKD) experience a range of symptoms and often have complex comorbidities. Many pharmacological interventions for people with CKD have known risks of adverse events. Acupuncture is widely used for symptom management in patients with chronic diseases and in other palliative care settings. However, the safety and efficacy of acupuncture for people with CKD remains largely unknown.\nObjectives\nWe aimed to evaluate the benefits and harms of acupuncture, electro-acupuncture, acupressure, moxibustion and other acupuncture-related interventions (alone or combined with other acupuncture-related interventions) for symptoms of CKD. In particular, we planned to compare acupuncture and related interventions with conventional medicine, active non-pharmacological interventions, and routine care for symptoms of CKD.\nSearch methods\nWe searched the Cochrane Kidney and Transplant Specialised Register up to 28 January 2016 through contact with the Information Specialist using search terms relevant to this review. We also searched Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, the National Assembly Library) and Chinese databases (including the China Academic Journal).\nSelection criteria\nWe included randomised controlled trials (RCTs) and quasi-RCTs that investigated the effects of acupuncture and related point-stimulation interventions with or without needle penetration that involved six sessions or more in adults with CKD stage 3 to 5, regardless of the language and type of publication. We excluded studies that used herbal medicine or co-interventions administered unequally among the study groups.\nData collection and analysis\nTwo authors independently extracted data and assessed risk of bias. We calculated the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Primary outcomes were changes in pain and depression, and occurrence of serious of adverse events.\nMain results\nWe included 24 studies that involved a total of 1787 participants. Studies reported on various types of acupuncture and related interventions including manual acupuncture and acupressure, ear acupressure, transcutaneous electrical acupuncture point stimulation, far-infrared radiation on acupuncture points and indirect moxibustion. CKD stages included pre-dialysis stage 3 or 4 and end-stage kidney disease on either haemodialysis or peritoneal dialysis.\nNone of the included studies assessed pain outcomes, nor formally addressed occurrence of serious adverse events, although three studies reported three participant deaths and three hospitalisations as reasons for attrition. Three studies reported minor acupuncture-related harms; the remainder did not report if those events occurred.\nAll studies were assessed at high or unclear risk of bias in terms of allocation concealment. Seventeen studies reported outcomes measured for only two months.\nThere was very low quality of evidence that compared with routine care, manual acupressure reduced scores of the Beck Depression Inventory score (scale from 0 to 63) (3 studies, 128 participants: MD -4.29, 95% CI -7.48 to -1.11, I2 = 0%), the revised Piper Fatigue Scale (scale from 0 to 10) (3 studies, 128 participants: MD -1.19, 95% CI -1.77 to -0.60, I2 = 0%), and the Pittsburgh Sleep Quality Index (scale from 0 to 21) (4 studies, 180 participants: MD -2.46, 95% CI -4.23 to -0.69, I2 = 50%).\nWe were unable to perform further meta-analyses because of the paucity of data and problems with clinical heterogeneity, such as different interventions, comparisons and timing of outcome measurements.\nAuthors' conclusions\nThere was very low quality of evidence of the short-term effects of manual acupressure as an adjuvant intervention for fatigue, depression, sleep disturbance and uraemic pruritus in patients undergoing regular haemodialysis. The paucity of evidence indicates that there is little evidence of the effects of other types of acupuncture for other outcomes, including pain, in patients with other stages of CKD. Overall high or unclear risk of bias distorts the validity of the reported benefit of acupuncture and makes the estimated effects uncertain. The incomplete reporting of acupuncture-related harm does not permit us to assess the safety of acupuncture and related interventions. Future studies should investigate the effects and safety of acupuncture for pain and other common symptoms in patients with CKD and those undergoing dialysis.\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": "All studies were assessed at high or unclear risk of bias, especially in terms of selection of participants and selective outcome reporting, which made the validity of their results doubtful." } ]

[ { "role": "user", "content": "Abstract: Background\nBoth long-acting beta2-agonists (LABA) and inhaled corticosteroids (ICS) have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease (COPD). Their coadministration in a combination inhaler may facilitate adherence to medication regimens and improve efficacy.\nObjectives\nTo determine the efficacy and safety of combined ICS and LABA for stable COPD in comparison with placebo.\nSearch methods\nWe searched the Cochrane Airways Group Specialised Register of trials, reference lists of included studies and manufacturers' trial registries. The date of the most recent search was June 2013.\nSelection criteria\nWe included randomised and double-blind studies of at least four weeks' duration. Eligible studies compared combined ICS and LABA preparations with placebo.\nData collection and analysis\nTwo review authors independently assessed study risk of bias and extracted data. Dichotomous data were analysed as fixed-effect odds ratios (OR) or rate ratios (RR) with 95% confidence intervals (95% CI), and continuous data as mean differences with 95% confidence intervals.\nMain results\nNineteen studies met the inclusion criteria (with 10,400 participants randomly assigned, lasting between 4 and 156 weeks, mean 42 weeks). Studies used three different combined preparations (fluticasone/salmeterol, budesonide/formoterol or mometasone/formoterol). The studies were generally at low risk of bias for blinding but at unclear or high risk for attrition bias because of participant dropouts. Compared with placebo, both fluticasone/salmeterol and budesonide/formoterol reduced the rate of exacerbations. Mometasone/formoterol reduced the number of participants experiencing one or more exacerbation. Pooled analysis of the combined therapies indicated that exacerbations were less frequent when compared with placebo (Rate Ratio 0.73; 95% CI 0.69 to 0.78, 7 studies, 7495 participants); the quality of this evidence when GRADE criteria were applied was rated as moderate. Participants included in these trials had on average one or two exacerbations per year, which means that treatment with combined therapy would lead to a reduction of one exacerbation every two to four years in these individuals. An overall reduction in mortality was seen, but this outcome was dominated by the results of one study (TORCH) of fluticasone/salmeterol. Generally, deaths in the smaller, shorter studies were too few to contribute to the overall estimate. Further longer studies on budesonide/formoterol and mometasone/formoterol are required to clarify whether this is seen more widely. When a baseline risk of death of 15.2% from the placebo arm of TORCH was used, the three-year number needed to treat for an additional beneficial outcome (NNTB) with fluticasone/salmeterol to prevent one extra death was 42 (95% CI 24 to 775). All three combined treatments led to statistically significant improvement in health status measurements, although the mean differences observed are relatively small in relation to the minimum clinically important difference. Furthermore, symptoms and lung function assessments favoured combined treatments. An increase in the risk of pneumonia was noted with combined inhalers compared with placebo treatment (OR 1.62, 95% CI 1.36 to 1.94), and the quality of this evidence was rated as moderate, but no dose effect was seen. The three-year NNTH for one extra case of pneumonia was 17, based on a 12.3% risk of pneumonia in the placebo arm of TORCH. Fewer participants withdrew from the combined treatment arms for adverse events or lack of efficacy.\nAuthors' conclusions\nCombined inhaler therapy led to around a quarter fewer COPD exacerbations than were seen with placebo. A significant reduction in all-cause mortality was noted, but this outcome was dominated by one trial (TORCH), emphasising the need for further trials of longer duration. Furthermore, we note there has been some debate about the appropriateness of the analysis conducted in the TORCH trial (see Feeback). Increased risk of pneumonia is a concern; however, this did not translate into increased exacerbations, hospitalisations or deaths. Current evidence does not suggest any major differences between inhalers in terms of effects, but nor is the evidence strong enough to demonstrate that all are equivalent. Importantly, we cannot comment on the relative contribution of the individual components of combined therapy to the effects identified, as this review presents only the pair-wise comparison between combined therapy and placebo. To permit firmer conclusions about the effects of combined therapy, more data are needed, particularly in relation to the profile of adverse events and benefits in relation to different formulations and doses of inhaled ICS. Head-to-head comparisons are necessary to determine whether one combined inhaler is better than the others.\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 evidence presented in this review is generally considered to be of moderate quality. Most of the studies did not clearly explain how they decided which people would receive the combined inhaler and which would receive placebo, and this is an important part of a well-conducted study. Also, more people receiving placebo dropped out of the trials than those receiving a combined inhaler. This often happened because of exacerbations of COPD. This means that by the end of the trial, the groups might have been unbalanced, and this could affect the accuracy of the results." } ]

[ { "role": "user", "content": "Abstract: Background\nMeningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis.\nObjectives\nTo study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease.\nSearch methods\nWe searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017.\nSelection criteria\nRandomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach.\nMain results\nWe found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to 2.15; N = 477; 18 clinical failures; moderate-quality evidence), or neurological sequelae (RR 1.29, 95% CI 0.63 to 2.62; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae.\nAuthors' conclusions\nWe found no reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Moderate-quality evidence from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe, and economical in reducing serious outcomes. The choice between these antibiotics should be based on affordability, availability, and patterns of antibiotic resistance.\nFurther RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justified in people with less severe illness, and are needed to provide reliable evidence in different clinical settings.\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": "Meningococcal disease is a rapidly progressing, contagious bacterial infection that can cause epidemics of severe disease of the brain and blood. If not treated early many will die or have permanent disabilities. Antibiotics are very effective if given early. Waiting for confirmation of the diagnosis with laboratory tests can result in delays in starting antibiotics. Giving antibiotics early based on a clinical suspicion (empiric treatment) could prevent delays in treatment and consequent death and disability. However, doing so could also result in unnecessary treatment." } ]

[ { "role": "user", "content": "Abstract: Background\nPrimary sclerosing cholangitis is a chronic cholestatic liver disease that is associated with both hepatobiliary and colorectal malignancies, which can result in liver cirrhosis and its complications. The optimal pharmacological treatment for patients with primary sclerosing cholangitis remains controversial.\nObjectives\nTo assess the comparative benefits and harms of different pharmacological interventions in people with primary sclerosing cholangitis by performing a network meta-analysis, and to generate rankings of available pharmacological interventions according to their safety and efficacy. Given that it was not possible to assess whether potential effect modifiers were similar across comparisons, we did not perform the network meta-analysis but instead used standard Cochrane methods.\nWhen trials begin to provide an adequate description of potential effect modifiers, we will attempt to conduct network meta-analysis.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, Science Citation Index - Expanded, the WHO International Clinical Trials Registry Platform, and randomised controlled trials registers until February 2017 to identify randomised clinical trials (RCT) on pharmacological interventions for primary sclerosing cholangitis.\nSelection criteria\nWe included only RCTs, irrespective of language, blinding, or publication status, in which participants were given a diagnosis of primary sclerosing cholangitis. We excluded trials that included previously liver-transplanted participants. We considered any of various pharmacological interventions compared with one other or with placebo. We excluded trials that compared different doses of various pharmacological interventions or that reported different treatment durations, except for ursodeoxycholic acid (UDCA). As UDCA is the drug most commonly investigated for primary sclerosing cholangitis, we performed a second analysis in which we stratified the dose of UDCA.\nData collection and analysis\nWe calculated the odds ratio and the rate ratio with 95% confidence intervals (CIs) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE.\nMain results\nWe identified 22 RCTs in which 1211 participants were randomised to 13 different interventions. Most were placebo-controlled trials. Trials had few restrictions apart from an established diagnosis of primary sclerosing cholangitis, evidence of cholestasis, absence of decompensated liver disease, and absence of malignancy. However, some trials included symptomatic participants only, and others included both symptomatic and asymptomatic participants. A total of 11 RCTs (706 participants) provided data for one or more outcomes. The period of follow-up ranged from three months to three years in most trials. Only three trials reported follow-up longer than three years. Investigators found no evidence of differences in important clinical benefits such as reduction in mortality at maximal follow-up and improvement in health-related quality of life.\nPrimary outcomes \nMortality:Effect estimates: colchicine versus placebo: odds ratio 0.44, 95% CI 0.04 to 5.07, participants = 84, one trial; penicillamine versus placebo: odds ratio 1.18, 95% CI 0.39 to 3.58, participants = 70, one trial; steroids versus placebo: odds ratio 3.00, 95% CI 0.10 to 90.96, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.51, 95% CI 0.63 to 3.63, participants = 348, two trials, I2 = 0%; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial.\nSerious adverse events (proportion):Effect estimates: infliximab versus placebo: odds ratio not estimable (because of zero events in both arms), participants = 7, one trial; steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial.\nSerious adverse events (number):Effect estimates: infliximab versus placebo: rate ratio 0.80, 95% CI 0.02 to 40.44, participants = 7, one trial; penicillamine versus placebo: rate ratio 13.60, 95% CI 0.78 to 237.83, participants = 70, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial.\nAdverse events (proportion):Effect estimates: steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.22, 95% CI 0.68 to 2.17, participants = 198, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial.\nAdverse events (number):Effect estimates: cyclosporin versus placebo: rate ratio 2.64, 95% CI 0.99 to 7.03, participants = 26, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial; ursodeoxycholic acid plus metronidazole versus ursodeoxycholic acid: rate ratio 2.36, 95% CI 0.98 to 5.71, participants = 71, one trial.\nHealth-related quality of life: ursodeoxycholic acid versus placebo: mean difference 1.30, 95% CI -5.61 to 8.21, participants = 198, one trial (Short Form (SF)-36 General Health Scale).\nSecondary outcomes \nStudies provided no evidence of differences in clinical benefits such as a reduction in the requirement for liver transplantation or a reduction in the incidence proportion of cholangiocarcinoma. One small trial (29 participants) comparing vancomycin versus placebo reported no malignancies, no liver decompensation, and no liver transplantation in either group after a very short follow-up period of 12 weeks after treatment. None of the remaining trials clearly reported other clinical benefits such as decreased development of all malignancies, colorectal cancer, liver decompensation, time to liver decompensation, time to liver transplantation, or requirement for cholecystectomy to allow comparisons between different interventions.\nSource of funding: Fifteen trials reported the source of funding; three were funded by parties without vested interest in results of the trial, and 12 were funded in part or in full by drug companies.\nAuthors' conclusions\nEvidence is currently insufficient to show differences in effectiveness measures such as mortality, health-related quality of life, cirrhosis, or liver transplantation between any active pharmacological intervention and no intervention. However, trials were at high risk of bias and included small numbers of participants, had short follow-up periods, and reported few clinical outcomes. An urgent need exists to identify an effective medical treatment for primary sclerosing cholangitis through well-designed RCTs with adequate follow-up that aim to identify differences in outcomes important to people with primary sclerosing cholangitis.\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": "Differences in important clinical benefits such as reduction in mortality (deaths) at maximal follow-up, improvement in health-related quality of life, reduction in the requirement for liver transplantation, or reduction in development of cholangiocarcinoma were imprecise in all comparisons. Other important clinical benefits such as incidence proportion of all malignancies, colorectal cancer, liver decompensation, time to liver decompensation, and time to liver transplantation and requirement for cholecystectomy were not reported in any trial in a format that could be analysed to allow comparison between different treatments. No evidence currently suggests that any medical treatment for primary sclerosing cholangitis is effective. An urgent need exists to identify an effective medical treatment for patients with primary sclerosing cholangitis by performing additional well-designed randomised clinical trials." } ]

[ { "role": "user", "content": "Abstract: Background\nAn occlusion or stenosis of intracranial large arteries can be detected in the acute phase of ischaemic stroke in about 42% of patients. The approved therapies for acute ischaemic stroke are thrombolysis with intravenous recombinant tissue plasminogen activator (rt-PA), and mechanical thrombectomy; both aim to recanalise an occluded intracranial artery. The reference standard for the diagnosis of intracranial stenosis and occlusion is intra-arterial angiography (IA) and, recently, computed tomography angiography (CTA) and magnetic resonance angiography (MRA), or contrast-enhanced MRA. Transcranial Doppler (TCD) and transcranial colour Doppler (TCCD) are useful, rapid, noninvasive tools for the assessment of intracranial large arteries pathology. Due to the current lack of consensus regarding the use of TCD and TCCD in clinical practice, we systematically reviewed the literature for studies assessing the diagnostic accuracy of these techniques compared with intra-arterial IA, CTA, and MRA for the detection of intracranial stenosis and occlusion in people presenting with symptoms of ischaemic stroke.\nObjectives\nTo assess the diagnostic accuracy of TCD and TCCD for detecting stenosis and occlusion of intracranial large arteries in people with acute ischaemic stroke.\nSearch methods\nWe limited our searches from January 1982 onwards as the transcranial Doppler technique was only introduced into clinical practice in the 1980s. We searched MEDLINE (Ovid) (from 1982 to 2018); Embase (Ovid) (from 1982 to 2018); Database of Abstracts of Reviews of Effects (DARE); and Health Technology Assessment Database (HTA) (from 1982 to 2018). Moreover, we perused the reference lists of all retrieved articles and of previously published relevant review articles, handsearched relevant conference proceedings, searched relevant websites, and contacted experts in the field.\nSelection criteria\nWe included all studies comparing TCD or TCCD (index tests) with IA, CTA, MRA, or contrast-enhanced MRA (reference standards) in people with acute ischaemic stroke, where all participants underwent both the index test and the reference standard within 24 hours of symptom onset. We included prospective cohort studies and randomised studies of test comparisons. We also considered retrospective studies eligible for inclusion where the original population sample was recruited prospectively but the results were analysed retrospectively.\nData collection and analysis\nAt least two review authors independently screened the titles and abstracts identified by the search strategies, applied the inclusion criteria, extracted data, assessed methodological quality (using QUADAS-2), and investigated heterogeneity. We contacted study authors for missing data.\nMain results\nA comprehensive search of major relevant electronic databases (MEDLINE and Embase) from 1982 to 13 March 2018 yielded 13,534 articles, of which nine were deemed eligible for inclusion. The studies included a total of 493 participants. The mean age of included participants was 64.2 years (range 55.8 to 69.9 years). The proportion of men and women was similar across studies. Six studies recruited participants in Europe, one in south America, one in China, and one in Egypt. Risk of bias was high for participant selection but low for flow, timing, index and reference standard. The summary sensitivity and specificity estimates for TCD and TCCD were 95% (95% CI = 0.83 to 0.99) and 95% (95% CI = 0.90 to 0.98), respectively. Considering a prevalence of stenosis or occlusion of 42% (as reported in the literature), for every 1000 people who receive a TCD or TCCD test, stenosis or occlusion will be missed in 21 people (95% CI = 4 to 71) and 29 (95% CI = 12 to 58) will be wrongly diagnosed as harbouring an intracranial occlusion. However, there was substantial heterogeneity between studies, which was no longer evident when only occlusion of the MCA was considered, or when the analysis was limited to participants investigated within six hours. The performance of either TCD or TCCD in ruling in and ruling out a MCA occlusion was good. Limitations of this review were the small number of identified studies and the lack of data on the use of ultrasound contrast medium.\nAuthors' conclusions\nThis review provides evidence that TCD or TCCD, administered by professionals with adequate experience and skills, can provide useful diagnostic information for detecting stenosis or occlusion of intracranial vessels in people with acute ischaemic stroke, or guide the request for more invasive vascular neuroimaging, especially where CT or MR-based vascular imaging are not immediately available. More studies are needed to confirm or refute the results of this review in a larger sample of stroke patients, to verify the role of contrast medium and to evaluate the clinical advantage of the use of ultrasound.\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": "Ischaemic stroke is the third leading cause of death and the most common cause of long-term disability. It is usually caused by a blockage of the blood supply to one part of the brain. When stroke is caused by a blockage of a large artery due to a blood clot, the prognosis, without treatment, is often poor and can lead to severe disability. Curently, there are two effective treatment options that can be used to dissolve the blood clot: to administer a thrombolytic drug, or to physically extract the blood clot from the artery (mechanical thrombectomy). Both treatments work best within the first few hours of stroke onset. Ultrasound scans (TCD and TCCD) are a quick and simple way to detect the blockage of blood vessels in the brain. We reviewed the current literature for clinical studies assessing the accuracy of these diagnostic techniques compared with IA, CTA, and MRA for the detection of blocked blood vessels in the brain in people with symptoms of ischaemic stroke." } ]

[ { "role": "user", "content": "Abstract: Background\nStrontium ranelate is a new treatment for osteoporosis therefore, its benefits and harms need to be known.\nObjectives\nTo determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis.\nSearch methods\nWe searched MEDLINE (1996-March 2005), EMBASE (1996-week 9 2005), the Cochrane Library (1996-Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors.\nSelection criteria\nWe included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate to placebo and reporting fracture incidence, bone mineral density (BMD) or adverse events in postmenopausal women. Treatment population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T-score < -2.5 SD.\nData collection and analysis\nTwo reviewers independently determined study eligibility, assessed study validity, graded the evidence and extracted relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose and treatment duration. Where possible, meta-analysis was conducted using the random effects model.\nMain results\nFour trials met the inclusion criteria. Three had losses to follow-up > 20% and only one provided an adequate description of allocation concealment. Three included a treatment population (0.5 to 2 g/day of strontium ranelate) and one a prevention population (0.125, 0.5 and 1 g/day). A 37% reduction in vertebral fractures (RR 0.63, 95% CI 0.56, 0.71), and a 14% reduction in non-vertebral fractures with the upper boundary of the confidence interval approaching one (RR 0.86, 95% CI 0.75, 0.98), were demonstrated over three years with 2 g of strontium ranelate daily in a treatment population. An increase in BMD was shown at all sites after two to three years of treatment in both populations. Lower doses of strontium ranelate were superior to placebo and the highest dose demonstrated the greatest reduction in vertebral fractures and increase in BMD. An increased risk of diarrhea with 2 g of strontium ranelate daily was found; however, adverse events did not affect the risk of discontinuing treatment nor did it increase the risk of serious side effects, gastritis or death. Additional data suggests that the risk of vascular and nervous system side-effects is increased with taking 2 g of strontium ranelate daily over three to four years.\nAuthors' conclusions\nThere is silver level evidence (www.cochranemsk.org) to support the efficacy of strontium ranelate for the reduction of fractures (vertebral and to a lesser extent, non-vertebral) in postmenopausal osteoporotic women and an increase in BMD in postmenopausal women with/without osteoporosis. Diarrhea may occur, however, adverse events leading to study withdrawal were not significantly increased. Potential vascular and neurological side-effects need to be further explored.\n\nGiven the provided abstract, please respond to the following query: \"Harms of strontium ranelate\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In women after menopause who have osteoporosis:\n- strontium ranelate did not cause side effects that would make them stop taking it\n- strontium ranelate did not lead to serious side effects, stomach infections, back pain or death\n- strontium ranelate increased diarrhea\n6 out of 100 women had diarrhea taking strontium ranelate\n4 out of 100 women had diarrhea taking a placebo\nOther research shows that harms could include a chance of blood clots, and seizures, memory loss and consciousness. The cause of these vascular and neurological side effects are not known.\nThis review has several limitations which include difficulty interpreting the change in bone mineral density due to the unique aspects of strontium in bone as well, incomplete follow-up of some patients within the individual trials." } ]

[ { "role": "user", "content": "Abstract: Background\nLate-onset sepsis is associated with increased rates of mortality and morbidity in newborn infants, in addition to poorer long-term developmental outcomes and increased length of stay and hospital costs. Central line-associated blood stream infection (CLABSI) is the most common cause of late-onset sepsis in hospitalised infants, and prevention of CLABSI is a key objective in neonatal care. Increased frequency of CLABSI around the time of removal of central venous catheters (CVCs) has been reported, and use of antibiotics at the time of removal may reduce the incidence and impact of late-onset sepsis in vulnerable newborn infants.\nObjectives\nTo determine the efficacy and safety of giving antibiotics at the time of removal of a central venous catheter (CVC) for reduction of morbidity and mortality in newborn infants, in particular effects on late-onset sepsis.\nSearch methods\nWe used the standard search strategy of the Cochrane Neonatal Review Group without language restriction to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 3), MEDLINE via PubMed (1966 to 6 April 2017), Embase (1980 to 6 April 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 6 April 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nRandomised, quasi-randomised, and cluster-randomised trials considering use of any antibiotic or combination of antibiotics at the time of CVC removal in newborn infants compared with placebo, no antibiotics, or another antibiotic or combination of antibiotics.\nData collection and analysis\nWe extracted data using standard methods of the Cochrane Neonatal Review Group. Two review authors independently selected, assessed the quality of, and extracted data from the included study.\nMain results\nOnly one randomised controlled trial was eligible for inclusion in this analysis. Forty-four of a total of 88 infants received two doses of cephazolin at the time of removal of CVC compared with no antibiotics at the time of removal of CVC in the control group. No infant in the intervention group developed late-onset sepsis after CVC removal compared with five of 44 (11%) in the control group (risk ratio (RR) 0.09, 95% confidence interval (CI) 0.01 to 1.60). Cephazolin given at the time of removal of CVC did not statistically significantly alter late-onset sepsis rates and led to no significant differences in any of the prespecified outcomes. Review authors judged the study to be of low quality because of high risk of bias and imprecision.\nAuthors' conclusions\nRandomised controlled trials have provided inadequate evidence for assessment of the efficacy or safety of antibiotics given at the time of CVC removal. The single identified trial was underpowered to address this question. Future research should be directed towards targeting use of antibiotics upon removal of CVC for those at greatest risk of complications from CVC removal-related CLABSI. Researchers should include safety data such as impact upon antibiotic use and resistance patterns. This investigation would best occur as part of a bundle of quality improvement care interventions provided by neonatal networks.\n\nGiven the provided abstract, please respond to the following query: \"Conclusion\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "At present, review authors have not found enough evidence to recommend giving antibiotics at the time of removal of a central line to prevent complications in newborn babies." } ]

[ { "role": "user", "content": "Abstract: Background\nPhysical restraints, such as bedrails, belts in chairs or beds, and fixed tables, are commonly used for older people in general hospital settings. Reasons given for using physical restraints are to prevent falls and fall-related injuries, to control challenging behavior (such as agitation or wandering), and to ensure the delivery of medical treatments. Clear evidence of their effectiveness is lacking, and potential harms are recognised, including injuries associated with the use of physical restraints and a negative impact on people's well-being. There are widespread recommendations that their use should be reduced or eliminated.\nObjectives\nTo assess the best evidence for the effects and safety of interventions aimed at preventing and reducing the use of physical restraint of older people in general hospital settings.\nTo describe the content, components and processes of these interventions.\nSearch methods\nWe searched the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register the International Clinical Trials Registry Portal on 20 April 2022.\nSelection criteria\nWe included randomised controlled trials and controlled clinical trials that investigated the effects of interventions that aimed to prevent or reduce the use of physical restraints in general hospital settings. Eligible settings were acute care and rehabilitation wards. We excluded emergency departments, intensive care and psychiatric units, as well as the use of restrictive measures for penal reasons (e.g. prisoners in general medical wards). We included studies with a mean age of study participants of at least 65 years. Control groups received usual care or active control interventions that were ineligible for inclusion as experimental interventions.\nData collection and analysis\nTwo review authors independently selected the articles for inclusion, extracted data, and assessed the risk of bias of all included studies. Data were unsuitable for meta-analysis, and we reported results narratively. We used GRADE methods to describe our certainty in the results.\nMain results\nWe included four studies: two randomised controlled trials (one individually-randomised, parallel-group trial and one clustered, stepped-wedge trial) and two controlled clinical trials (both with a clustered design). One study was conducted in general medical wards in Canada and three studies were conducted in rehabilitation hospitals in Hong Kong. A total of 1709 participants were included in three studies; in the fourth study the number of participants was not reported. The mean age ranged from 67 years to 84 years. The duration of follow-up covered the period of patients' hospitalisation in one study (21 days average length of stay) and ranged from 4 to 11 months in the other studies. The definition of physical restraints differed slightly, and one study did not include bedrails.\nThree studies investigated organisational interventions aimed at implementing a least-restraint policy to reduce physical restraints. The theoretical approach of the interventions and the content of the educational components was comparable across studies. The fourth study investigated the use of pressure sensors for participants with an increased falls risk, which gave an alarm if the participant left the bed or chair. Control groups in all studies received usual care.\nThree studies were at high risk of selection bias and risk of detection bias was unclear in all studies.\nBecause of very low-certainty evidence, we are uncertain about the effect of organisational interventions aimed at implementing a least-restraint policy on our primary efficacy outcome: the use of physical restraints in general hospital settings. One study found an increase in the number of participants with at least one physical restraint in the intervention and control groups, one study found a small reduction in both groups, and in the third study (the stepped-wedge study), the number of participants with at least one physical restraint decreased in all clusters after implementation of the intervention but no detailed information was reported. For the use of bed or chair pressure sensor alarms for people with an increased fall risk, we found moderate-certainty evidence of little to no effect of the intervention on the number of participants with at least one physical restraint compared with usual care. None of the studies systematically assessed adverse events related to use of physical restraint use, e.g. direct injuries, or reported such events.\nWe are uncertain about the effect of organisational interventions aimed at implementing a least-restraint policy on the number of participants with at least one fall (very low-certainty evidence), and there was no evidence that organisational interventions or the use of bed or chair pressure sensor alarms for people with an increased fall risk reduce the number of falls (low-certainty evidence from one study each). None of the studies reported fall-related injuries. We found low-certainty evidence that organisational interventions may result in little to no difference in functioning (including mobility), and moderate-certainty evidence that the use of bed or chair pressure sensor alarms has little to no effect on mobility. We are uncertain about the effect of organisational interventions on the use of psychotropic medication; one study found no difference in the prescription of psychotropic medication. We are uncertain about the effect of organisational interventions on nurses' attitudes and knowledge about the use of physical restraints (very low-certainty evidence).\nAuthors' conclusions\nWe are uncertain whether organisational interventions aimed at implementing a least-restraint policy can reduce physical restraints in general hospital settings. The use of pressure sensor alarms in beds or chairs for people with an increased fall risk has probably little to no effect on the use of physical restraints. Because of the small number of studies and the study limitations, the results should be interpreted with caution. Further research on effective strategies to implement a least-restraint policy and to overcome barriers to physical restraint reduction in general hospital settings is needed.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for trials that investigated interventions intended to reduce or prevent the use of physical restraint of older people in hospital. The trials had to include a comparison group of people who did not get the intervention (a control group). We included four studies. One study was conducted in general medical wards in a hospital in Canada and three studies were conducted in rehabilitation hospitals in Hong Kong. The average age of the people in the studies was between 67 and 84 years. In all the studies, the intervention being tested was compared with treatment as usual.\nThree studies tested organisational interventions intended to change policy and practice so that fewer physical restraints were used. This was done by offering education and training for nursing staff, and other strategies to support staff in avoiding physical restraints. One study tested the use of pressure sensor alarms in the beds or chairs of people at high risk of falling, which sounded an alarm if the person got up." } ]

[ { "role": "user", "content": "Abstract: Background\nGuidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence.\nObjectives\nOur primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects.\nSearch methods\nWe searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature.\nSelection criteria\nWe included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients.\nData collection and analysis\nWe examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes.\nMain results\nWe included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients.\nNo trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence).\nNo trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence).\nAuthors' conclusions\nThere were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.\n\nGiven the provided abstract, please respond to the following query: \"Key findings\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found no evidence to support or refute the suggestion that antipsychotics shorten the course of delirium in hospitalised patients. Based on the available studies, antipsychotics do not reduce the severity of delirium or resolve symptoms compared to nonantipsychotic drugs or placebo or lower the risk of dying. We found no evidence to support or refute the suggestion that antipsychotics shorten hospital length of stay or improve health-related quality of life. Side effects were rarely reported in the studies." } ]

[ { "role": "user", "content": "Abstract: Background\nPotential benefits and harms of different lighting in neonatal units have not been quantified.\nObjectives\n• To determine effectiveness and safety of cycled light (CL) (approximately 12 hours of light on and 12 hours of light off) for growth in preterm infants at three and six months' corrected age (CA).\n• In separate analyses, to compare effects of CL with those of irregularly dimmed light (DL) or near darkness (ND), and effects of CL with those of continuous bright light (CBL), on growth in preterm infants at three and six months' CA.\n• To assess, in subgroup analyses, the effectiveness and safety of CL (vs control interventions (DL, ND and CBL)) introduced at different postmenstrual ages (PMAs) - before 32 weeks', at 32 weeks' and from 36 weeks' PMA - and to compare effectiveness and safety of CL for small for gestational age (GA) infants versus appropriately grown infants.\nSearch methods\nWe used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE via PubMed (1966 to January 2016), Embase (1980 to January 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 2016). We searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nRandomised or quasi-randomised trials of CL versus ND or CBL in preterm and low birth weight infants.\nData collection and analysis\nWe performed data collection and analyses according to the methods of the Cochrane Neonatal Review Group. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.\nMain results\nWe identified one additional study enrolling 38 participants for inclusion in this update, for a total of nine studies reporting on 544 infants. In general, the quality of the studies was low, mainly owing to lack of blinding and small sample sizes.\nSix studies enrolling 424 infants compared CL versus ND. No study reported on weight at three or six months. One study (n = 40) found no statistically significant difference in weight at four months between CL and ND groups. In another study (n = 62), the ratio of day-night activity before discharge favoured the CL group (mean difference (MD) 0.18, 95% confidence interval (CI) 0.17 to 0.19), indicating 18% more activity during the day than during the night in the CL group compared with the ND group. Two studies (n = 189) reported on retinopathy of prematurity (stage ≥ 3) and reported no statistically significant differences between CL and ND groups (typical risk ratio (RR) 0.53, 95% CI 0.25 to 1.11, I2 = 0%; typical risk difference (RD) -0.09, 95% CI -0.19 to 0.01, I2 = 0%). Two studies (n = 77) reported length of hospital stay (days) and noted a significant reduction in length of stay between CL and ND groups favouring the CL group (weighted mean difference (WMD) -13 days, 95% CI -23 to -2, I2 = 0%; no heterogeneity). The quality of the evidence according to GRADE was low for this outcome. One study (n = 37) reported less crying at 11 weeks' corrected age (CA) in the CL group compared with the ND group (MD -0.57 hours/24 h, 95% CI -1.09 to -0.05). Tests for heterogeneity were not applicable.\nThree studies enrolling 120 infants compared CL versus CBL. Two studies (n = 79) reported significantly shorter length of stay in the CL group compared with the CBL group (WMD -16.5 days, 95% CI -26.2 to -6.8, I2 = 0%; no heterogeneity). The quality of the evidence according to GRADE was low for this outcome. One study (n = 41) reported higher mean weight at three months' CA among infants cared for in the CL nursery (P value < 0.02) and a lower mean number of hours spent awake in 24 hours at three months of age (P value < 0.005). Data could not be entered into RevMan or GRADE. One study (n = 41) reported shorter time on the ventilator in the CL compared with the CBL group (MD -18.2 days, 95% CI -31.40 to -5.0). One study (n = 41) reported a shorter time to first oral feeding in the CL group (MD -6.8 days, 95% CI -13.29 to -0.31). We identified no safety issues.\nAuthors' conclusions\nTrials assessing the effects of CL have enrolled 544 infants. No study reported on our primary outcome of weight at three or six months. Results from one additional study strengthen our findings that CL versus CBL shortens length of stay, as does CL versus ND. The quality of the evidence on both comparisons for this outcome according to GRADE was low. Future research should focus on comparing CL versus ND.\n\nGiven the provided abstract, please respond to the following query: \"Study funding resources\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "To our knowledge, no studies included in this review were funded by industry." } ]

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

[ { "role": "user", "content": "Abstract: Background\nVitamin A deficiency is a major public health problem in low and middle income countries. Vitamin A supplementation in children six months of age and older has been found to be beneficial, but no effect of supplementation has been noted for children between one and five months of age. Supplementation during the neonatal period has been suggested to have an impact by increasing body stores in early infancy.\nObjectives\nTo evaluate the role of vitamin A supplementation for term neonates in low and middle income countries with respect to prevention of mortality and morbidity.\nSearch methods\nWe used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE via PubMed (1966 to 13 March 2016), Embase (1980 to 13 March 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 13 March 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nRandomised and quasi-randomised controlled trials. Also trials with a factorial design.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted study data. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.\nMain results\nWe included 12 trials (168,460 neonates) in this review, with only a few trials reporting disaggregated data for term infants. Therefore, we analysed data and presented estimates for term infants (when specified) and for all infants.\nData for term neonates from three studies did not show a statistically significant effect on the risk of infant mortality at six months in the vitamin A group compared with the control group (typical risk ratio (RR) 0.80; 95% confidence interval (CI) 0.54 to 1.18; I2 = 63%). Analysis of data for all infants from 11 studies revealed no evidence of a significant reduction in the risk of infant mortality at six months among neonates supplemented with vitamin A compared with control neonates (typical RR 0.98, 95% CI 0.89 to 1.07; I2 = 47%). We observed similar results for infant mortality at 12 months of age with no significant effect of vitamin A compared with control (typical RR 1.04, 95% CI 0.94 to 1.15; I2 = 47%). Limited data were available for the outcomes of cause-specific mortality and morbidity, vitamin A deficiency, anaemia and adverse events.\nAuthors' conclusions\nGiven the high burden of death among children younger than five years of age in low and middle income countries, and the fact that mortality in infancy is a major contributory cause, it is critical to obtain sound scientific evidence of the effect of vitamin A supplementation during the neonatal period on infant mortality and morbidity. Evidence provided in this review does not indicate a potential beneficial effect of vitamin A supplementation among neonates at birth in reducing mortality during the first six months or 12 months of life. Given this finding and the absence of a clear indication of the biological mechanism through which vitamin A could affect mortality, along with substantial conflicting findings from individual studies conducted in settings with potentially varying levels of maternal vitamin A deficiency and infant mortality, absence of follow-up studies assessing any long-term impact of a bulging fontanelle after supplementation and the finding of a potentially harmful effect among female infants, additional research is warranted before a decision can be reached regarding policy recommendations for this intervention.\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 vitamin A supplementation among term neonates in low and middle income countries prevent mortality and morbidity?" } ]

[ { "role": "user", "content": "Abstract: Background\nSuccessful treatments for gestational diabetes mellitus (GDM) have the potential to improve health outcomes for women with GDM and their babies.\nObjectives\nTo provide a comprehensive synthesis of evidence from Cochrane systematic reviews of the benefits and harms associated with interventions for treating GDM on women and their babies.\nMethods\nWe searched the Cochrane Database of Systematic Reviews (5 January 2018) for reviews of treatment/management for women with GDM. Reviews of pregnant women with pre-existing diabetes were excluded.\nTwo overview authors independently assessed reviews for inclusion, quality (AMSTAR; ROBIS), quality of evidence (GRADE), and extracted data.\nMain results\nWe included 14 reviews. Of these, 10 provided relevant high-quality and low-risk of bias data (AMSTAR and ROBIS) from 128 randomised controlled trials (RCTs), 27 comparisons, 17,984 women, 16,305 babies, and 1441 children. Evidence ranged from high- to very low-quality (GRADE). Only one effective intervention was found for treating women with GDM.\nEffective\nLifestyle versus usual care\nLifestyle intervention versus usual care probably reduces large-for-gestational age (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.50 to 0.71; 6 RCTs, N = 2994; GRADE moderate-quality).\nPromising\nNo evidence for any outcome for any comparison could be classified to this category.\nIneffective or possibly harmful\nLifestyle versus usual care\nLifestyle intervention versus usual care probably increases the risk of induction of labour (IOL) suggesting possible harm (average RR 1.20, 95% CI 0.99 to 1.46; 4 RCTs, N = 2699; GRADE moderate-quality).\nExercise versus control\nExercise intervention versus control for return to pre-pregnancy weight suggested ineffectiveness (body mass index, BMI) MD 0.11 kg/m², 95% CI -1.04 to 1.26; 3 RCTs, N = 254; GRADE moderate-quality).\nInsulin versus oral therapy\nInsulin intervention versus oral therapy probably increases the risk of IOL suggesting possible harm (RR 1.3, 95% CI 0.96 to 1.75; 3 RCTs, N = 348; GRADE moderate-quality).\nProbably ineffective or harmful interventions\nInsulin versus oral therapy\nFor insulin compared to oral therapy there is probably an increased risk of the hypertensive disorders of pregnancy (RR 1.89, 95% CI 1.14 to 3.12; 4 RCTs, N = 1214; GRADE moderate-quality).\nInconclusive\nLifestyle versus usual care\nThe evidence for childhood adiposity kg/m² (RR 0.91, 95% CI 0.75 to 1.11; 3 RCTs, N = 767; GRADE moderate-quality) and hypoglycaemia was inconclusive (average RR 0.99, 95% CI 0.65 to 1.52; 6 RCTs, N = 3000; GRADE moderate-quality).\nExercise versus control\nThe evidence for caesarean section (RR 0.86, 95% CI 0.63 to 1.16; 5 RCTs, N = 316; GRADE moderate quality) and perinatal death or serious morbidity composite was inconclusive (RR 0.56, 95% CI 0.12 to 2.61; 2 RCTs, N = 169; GRADE moderate-quality).\nInsulin versus oral therapy\nThe evidence for the following outcomes was inconclusive: pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 RCTs, N = 2060), caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 RCTs, N = 1988), large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 RCTs, N = 2352), and perinatal death or serious morbidity composite (RR 1.03; 95% CI 0.84 to 1.26; 2 RCTs, N = 760). GRADE assessment was moderate-quality for these outcomes.\nInsulin versus diet\nThe evidence for perinatal mortality was inconclusive (RR 0.74, 95% CI 0.41 to 1.33; 4 RCTs, N = 1137; GRADE moderate-quality).\nInsulin versus insulin\nThe evidence for insulin aspart versus lispro for risk of caesarean section was inconclusive (RR 1.00, 95% CI 0.91 to 1.09; 3 RCTs, N = 410; GRADE moderate quality).\nNo conclusions possible\nNo conclusions were possible for: lifestyle versus usual care (perineal trauma, postnatal depression, neonatal adiposity, number of antenatal visits/admissions); diet versus control (pre-eclampsia, caesarean section); myo-inositol versus placebo (hypoglycaemia); metformin versus glibenclamide (hypertensive disorders of pregnancy, pregnancy-induced hypertension, death or serious morbidity composite, insulin versus oral therapy (development of type 2 diabetes); intensive management versus routine care (IOL, large-for-gestational age); post- versus pre-prandial glucose monitoring (large-for-gestational age). The evidence ranged from moderate-, low- and very low-quality.\nAuthors' conclusions\nCurrently there is insufficient high-quality evidence about the effects on health outcomes of relevance for women with GDM and their babies for many of the comparisons in this overview comparing treatment interventions for women with GDM. Lifestyle changes (including as a minimum healthy eating, physical activity and self-monitoring of blood sugar levels) was the only intervention that showed possible health improvements for women and their babies. Lifestyle interventions may result in fewer babies being large. Conversely, in terms of harms, lifestyle interventions may also increase the number of inductions. Taking insulin was also associated with an increase in hypertensive disorders, when compared to oral therapy. There was very limited information on long-term health and health services costs. Further high-quality research is needed.\n\nGiven the provided abstract, please respond to the following query: \"Supplements\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Supplements(myo-inositol given as a water-soluble powder or capsule).\nWe found there was not enough data to be able to say if myo-inositol was helpful or not." } ]

[ { "role": "user", "content": "Abstract: Background\nDirect laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta-analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects.\nObjectives\nTo assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers (www.clinicaltrials.gov and www.controlledtrials) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions.\nSelection criteria\nWe included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes.\nData collection and analysis\nWe used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias.\nMain results\nWe included 12 studies (803 children) in this review and meta-analysis. We identified three studies that are awaiting classification and two ongoing studies.\nTrial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I2 = 90%; very low-quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I2 = 67%; low-quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I2 = 0%; low-quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low-quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group.\nTwo studies (n = 100) reported other haemodynamic responses to intubation (very low-quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low-quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group.\nUse of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I2 = 59%).\nAuthors' conclusions\nEvidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low-quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome.\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 found considerable variation in results from included studies in terms of assessment of intubation time, number of attempts at intubation, number of unsuccessful intubations, adverse effects, and assessments of how well the vocal cords were seen. None of the included studies was funded by a laryngoscope manufacturer, hence minimizing the risk of other bias. The quality of the studies varied, and only a few were of highest quality. For these reasons, we graded the overall quality of evidence as very low." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of a previous Cochrane Review published in 2012, Issue 9.\nSurgery for endometrial cancer (hysterectomy with removal of both fallopian tubes and ovaries) is performed through laparotomy. It has been suggested that the laparoscopic approach is associated with a reduction in operative morbidity. Over the last two decades there has been a steady increase of the use of laparoscopy for endometrial cancer. This review investigated the evidence of benefits and harms of laparoscopic surgery compared with laparotomy for presumed early stage endometrial cancer.\nObjectives\nTo compare overall survival (OS) and disease free survival (DFS) for laparoscopic surgery versus laparotomy in women with presumed early stage endometrial cancer.\nSearch methods\nFor this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5) in the Cochrane Library, MEDLINE via Ovid (April 2012 to June 2018) and Embase via Ovid (April 2012 to June 2018). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. The trial registers included NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta-Register and Physician Data Query Protocol.\nSelection criteria\nRandomised controlled trials (RCTs) comparing laparoscopy and laparotomy for early stage endometrial cancer.\nData collection and analysis\nWe independently abstracted data and assessed risk of bias. We used hazard ratios (HRs) for OS and recurrence free survival (RFS), risk ratios (RR) for severe adverse events and mean differences (MD) for continuous outcomes in women who received laparoscopy or laparotomy with 9% confidence intervals (CI). These were pooled in random-effects meta-analyses.\nMain results\nWe identified one new study in this update of the review. The review contains nine RCTs comparing laparoscopy with laparotomy for the surgical management of early stage endometrial cancer.\nAll nine studies met the inclusion criteria and assessed 4389 women at the end of the studies. Six studies assessing 3993 participants with early stage endometrial cancer found no significant difference in the risk of death between women who underwent laparoscopy and women who underwent laparotomy (HR 1.04, 95% 0.86 to 1.25; moderate-certainty evidence) and five studies assessing 3710 participants found no significant difference in the risk of recurrence between the laparoscopy and laparotomy groups (HR 1.14, 95% CI 0.90 to 1.43; moderate-certainty evidence). There was no significant difference in the rate of perioperative death; women requiring a blood transfusion; and bladder, ureteric, bowel and vascular injury. However, one meta-analysis of three studies found that women in the laparoscopy group lost significantly less blood than women in the laparotomy group (MD –106.82 mL, 95% CI –141.59 to –72.06; low-certainty evidence). A further meta-analysis of two studies, which assessed 3344 women and included one very large trial of over 2500 participants, found that there was no clinical difference in the risk of severe postoperative complications in women in the laparoscopy and laparotomy groups (RR 0.78, 95% CI 0.44 to 1.38). Most studies were at moderate risk of bias. All nine studies reported hospital stay and results showed that on average, laparoscopy was associated with a significantly shorter hospital stay.\nAuthors' conclusions\nThis review found low to moderate-certainty evidence to support the role of laparoscopy for the management of early endometrial cancer. For presumed early stage primary endometrioid adenocarcinoma of the endometrium, laparoscopy is associated with similar OS and DFS. Furthermore, laparoscopy is associated with reduced operative morbidity and hospital stay. There is no significant difference in severe postoperative morbidity between the two modalities.\nThe certainty of evidence for OS and RFS was moderate and was downgraded for unclear risk of bias profiles and imprecision in effect estimates. However, most studies used adequate methods of sequence generation and concealment of allocation so studies were not prone to selection bias. Adverse event outcomes were downgraded for the same reasons and additionally for low event rates and low power thus these outcomes provided low-certainty evidence.\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": "Results from six trials where women were randomly put into one of two treatment groups showed no difference in the risk of death between women who had laparoscopy and women who had laparotomy. In addition, results from five randomised trials confirmed no difference in the risk of cancer recurrence between women who had laparoscopy and women who had laparotomy. Notably, laparoscopy was associated with less blood loss and earlier discharge from hospital." } ]

[ { "role": "user", "content": "Abstract: Background\nDental implants offer one way to replace missing teeth. Patients who have undergone radiotherapy and those who have also undergone surgery for cancer in the head and neck region may particularly benefit from reconstruction with implants. Hyperbaric oxygen therapy (HBO) has been advocated to improve the success of implant treatment in patients who have undergone radiotherapy but this remains a controversial issue.\nObjectives\nTo compare the success, morbidity, patient satisfaction and cost effectiveness of dental implant treatment carried out with and without HBO in irradiated patients.\nSearch methods\nThe following electronic databases were searched: Cochrane Oral Health's Trials Register (to 17 June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 5), MEDLINE via OVID (1946 to 17 June 2013) and EMBASE via OVID (1980 to 17 June 2013). No restrictions were placed on the language or date of publication when searching the electronic databases. We checked the bibliographies of relevant clinical trials and review articles for studies outside the searched journals. We wrote to authors of the identified randomised controlled trials (RCTs) and to more than 55 oral implant manufacturers; we used personal contacts and we made a request on an internet discussion group in an attempt to identify unpublished or ongoing RCTs.\nSelection criteria\nRandomised controlled trials (RCTs) of HBO therapy for irradiated patients requiring dental implants.\nData collection and analysis\nScreening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Results were analysed using random-effects models to determine mean differences for continuous outcomes and risk ratios for dichotomous outcomes, with 95% confidence intervals.\nMain results\nOnly one RCT, providing very low-quality evidence, was identified and included. Thirteen patients received HBO therapy while another 13 did not. Two to six implants were placed in people with fully edentulous mandibles to be rehabilitated with bar-retained overdentures. One year after implant loading, four patients had died from each group. One patient, treated with HBO, developed an osteoradionecrosis and lost all implants so the prosthesis could not be provided. Five patients in the HBO group had at least one implant failure versus two in the control group. There were no statistically significant differences for prosthesis and implant failures, postoperative complications and patient satisfaction between the two groups.\nAuthors' conclusions\nDespite the limited amount of clinical research available, it appears that HBO therapy in irradiated patients requiring dental implants may not offer any appreciable clinical benefits. There is a definite need for more RCTs to ascertain the effectiveness of HBO in irradiated patients requiring dental implants. These trials ought to be of a high quality and reported as recommended by the CONSORT statement (www.consort-statement.org/). Each clinical centre may have limited numbers of patients and it is likely that trials will need to be multicentred.\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 was very low as it was based on one small trial at high risk of bias." } ]

[ { "role": "user", "content": "Abstract: Background\nAs preterm infants do not experience the nutrient accretion and rapid growth phase of the third trimester of pregnancy, they are vulnerable to postnatal nutritional deficits, including of fat. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Human milk fat provides the major energy needs of the preterm infant and also contributes to several metabolic and physiological functions. Although human milk has many benefits for this population, its fat content is highly variable and may be inadequate for their optimum growth and development. This is a 2020 update of a Cochrane Review last published in 2000.\nObjectives\nTo determine whether supplementation of human milk with fat compared with unsupplemented human milk fed to preterm infants improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes without significant adverse effects.\nSearch methods\nWe used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 8) in the Cochrane Library and MEDLINE via PubMed on 23 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.\nSelection criteria\nPublished and unpublished randomised controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants fed human milk in hospital to supplementation or no supplementation with additional fat.\nData collection and analysis\nNo new randomised controlled trials matching the selection criteria were found but we extracted data from the previously included trial due to changes in review outcomes from when the protocol was first published. Two reviewers independently abstracted data, assessed trial quality, and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We planned to perform meta-analyses using risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses.\nMain results\nOne randomised trial involving 14 preterm infants was included. This risk of bias was unclear for all methodological domains. Very low-quality evidence means that there is uncertainty about the effect of fat supplemention on in-hospital rates of growth in weight (MD 0.6 g/kg/day, 95% CI −2.4 to 3.6; 1 RCT, n = 14 infants,), length (MD 0.1 cm/week, 95% CI −0.08 to 0.3; 1 RCT, n = 14 infants) and head circumference (MD 0.2 cm/week, 95% CI −0.07 to 0.4; 1 RCT n = 14 infants), and on the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants). No data were available regarding the effects of fat supplementation on the risk of necrotising enterocolitis or neurodevelopmental outcomes.\nAuthors' conclusions\nThe one included trial suggests no evidence of an effect of fat supplementation of human milk on short-term growth and feeding intolerance in preterm infants. However, the very low-quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long-term outcomes were reported. Further high-quality research should evaluate the effect on growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers.\n\nGiven the provided abstract, please respond to the following query: \"Conclusions\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "There was insufficient high-quality evidence on the benefits and harms of the addition of extra fat to human milk in preterm infants, and no long-term outcomes have been reported. Since addition of extra fat to human milk is currently done as part of multi-nutrient fortification, future trials should evaluate the effect of the fat component on short- and long-term growth, body fat, obesity, high blood sugar, or brain development. The right amount and composition of extra fat needed, side effects, and delivery practices should also be evaluated." } ]

[ { "role": "user", "content": "Abstract: Background\nThere is increasing evidence that propofol is efficacious and safe for procedural sedation (PS) in the emergency department (ED) setting. However, propofol has a narrow therapeutic window and lacks of a reversal agent. The aim of this review was to cohere the evidence base regarding the efficacy and safety profile of propofol when used in the ED setting for PS.\nObjectives\nTo identify and evaluate all randomized controlled trials (RCTs) comparing propofol with alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE (1950 to September week 2 2013) and EMBASE (1980 to week 2 2013). We searched the Current Controlled Trials metaRegister of Clinical Trials (compiled by Current Science) (September 2013). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction. We re-ran the search in February 2015. We will deal with the one study awaiting classification when we update the review.\nSelection criteria\nRCTs comparing propofol to alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS in participants of all ages.\nData collection and analysis\nTwo authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using The Cochrane Collaboration tool for assessing risk of bias.\nMain results\nTen studies (813 participants) met the inclusion criteria. Two studies only included participants 18 years and younger; six studies only included participants 18 years and older; one study included participants between 16 and 65 years of age and one study included only adults but did not specify the age range. Eight of the included studies had a high risk of bias. The included studies were clinically heterogeneous. We undertook no meta-analysis.\nThe primary outcome measures of this review were: adverse effects (as defined by the study authors) and participant satisfaction (as defined by the study authors). In one study comparing propofol/fentanyl with ketamine/midazolam, delayed adverse reactions (nightmares and behavioural change) were noted in 10% of the ketamine/midazolam group and none in the propofol/fentanyl group. Seven individual studies reported no evidence of a difference in adverse effects between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions. Three individual studies reported no evidence of a difference in pain at the injection site between intravenous propofol and alternative interventions. Four individual studies reported no evidence of a difference in participant satisfaction between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions (ketamine, etomidate, midazolam). All the studies employed propofol without the use of an adjunctive analgesic and all, except one, were small (fewer than 100 participants) studies. The quality of evidence for the adverse effects and participant satisfaction outcomes was very low.\nNine included studies (eight comparisons) reported all the secondary outcome measures of the review except mortality. It was not possible to pool the results of the included studies for any of the secondary outcome measures because the comparator interventions were different and the measures were reported in different ways. Seven individual studies reported no evidence of difference in incidence of hypoxia between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions.\nAuthors' conclusions\nNo firm conclusions can be drawn concerning the comparative effects of administering intravenous propofol, with or without an adjunctive analgesic agent, with alternative interventions in participants undergoing PS in the ED setting on adverse effects (including pain at the injection site) and participant satisfaction. The review was limited because no two included studies employed the same comparator interventions, and because the number of participants in eight of the included studies were small (fewer than 100 participants).\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 obtained is current to September 2013. We re-ran the search in February 2015 and we will deal with the study awaiting classification when we update the review. We included 10 studies involving 813 participants. The included studies compared propofol with five other alternative drugs used to sedate people in the ED. We could not pool the results of the 10 studies because no two studies compared the same drug options." } ]

[ { "role": "user", "content": "Abstract: Background\nOvarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.\nObjectives\nTo assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment.\nSearch methods\nWe searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature.\nSelection criteria\nWe considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events.\nData collection and analysis\nTwo review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence.\nMain results\nThe search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine.\nDopamine agonists versus placebo or no intervention\nDopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence).\nDopamine agonists plus co-intervention versus co-intervention\nDopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence).\nDopamine agonists versus other active interventions\nWe are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported.\nAuthors' conclusions\nDopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.\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": "Dopamine agonists versus placebo/no treatment\nDopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS compared with placebo (a pretend treatment) or no treatment. This suggests that of every 100 women having IVF or ICSI, 27 women taking placebo or no treatment will have moderate or severe OHSS, compared to eight to 14 women taking dopamine agonists. Dopamine agonists may improve pregnancy outcomes, but we remain uncertain if it might increase mild side effects, such as stomach upsets, feeling sick, or dizziness. We are uncertain of the effect of dopamine agonists on pregnancy outcomes, as, pregnancy data were scarcely reported.\nDopamine agonist plus another treatment versus another treatment\nTaking dopamine agonists combined with another active treatment may reduce the risk of moderate or severe OHSS compared to women taking another active treatment alone. This means that of 100 women having treatment with another active treatment alone for OHSS, 11 women will have moderate or severe OHSS compared to three to nine women using dopamine agonists plus another active treatment. We remain uncertain if dopamine combined with another treatment improves pregnancy outcomes and side effects.\nDopamine agonist versus another treatment\nWe are uncertain whether the dopamine agonist cabergoline decreases OHSS rates compared to other active treatments (e.g. hydroxyethyl starch, prednisolone, calcium infusion or coasting). We are uncertain whether cabergoline improves pregnancy outcomes compared with other interventions. There were no side effects in the only study for this comparison." } ]

[ { "role": "user", "content": "Abstract: Background\nIncurable cancer, which often constitutes an enormous challenge for patients, their families, and medical professionals, profoundly affects the patient's physical and psychosocial well-being. In standard cancer care, palliative measures generally are initiated when it is evident that disease-modifying treatments have been unsuccessful, no treatments can be offered, or death is anticipated. In contrast, early palliative care is initiated much earlier in the disease trajectory and closer to the diagnosis of incurable cancer.\nObjectives\nTo compare effects of early palliative care interventions versus treatment as usual/standard cancer care on health-related quality of life, depression, symptom intensity, and survival among adults with a diagnosis of advanced cancer.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, OpenGrey (a database for grey literature), and three clinical trial registers to October 2016. We checked reference lists, searched citations, and contacted study authors to identify additional studies.\nSelection criteria\nRandomised controlled trials (RCTs) and cluster-randomised controlled trials (cRCTs) on professional palliative care services that provided or co-ordinated comprehensive care for adults at early advanced stages of cancer.\nData collection and analysis\nWe used standard methodological procedures as expected by Cochrane. We assessed risk of bias, extracted data, and collected information on adverse events. For quantitative synthesis, we combined respective results on our primary outcomes of health-related quality of life, survival (death hazard ratio), depression, and symptom intensity across studies in meta-analyses using an inverse variance random-effects model. We expressed pooled effects as standardised mean differences (SMDs, or Hedges' adjusted g). We assessed certainty of evidence at the outcome level using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) and created a 'Summary of findings' table.\nMain results\nWe included seven randomised and cluster-randomised controlled trials that together recruited 1614 participants. Four studies evaluated interventions delivered by specialised palliative care teams, and the remaining studies assessed models of co-ordinated care. Overall, risk of bias at the study level was mostly low, apart from possible selection bias in three studies and attrition bias in one study, along with insufficient information on blinding of participants and outcome assessment in six studies.\nCompared with usual/standard cancer care alone, early palliative care significantly improved health-related quality of life at a small effect size (SMD 0.27, 95% confidence interval (CI) 0.15 to 0.38; participants analysed at post treatment = 1028; evidence of low certainty). As re-expressed in natural units (absolute change in Functional Assessment of Cancer Therapy-General (FACT-G) score), health-related quality of life scores increased on average by 4.59 (95% CI 2.55 to 6.46) points more among participants given early palliative care than among control participants. Data on survival, available from four studies enrolling a total of 800 participants, did not indicate differences in efficacy (death hazard ratio 0.85, 95% CI 0.56 to 1.28; evidence of very low certainty). Levels of depressive symptoms among those receiving early palliative care did not differ significantly from levels among those receiving usual/standard cancer care (five studies; SMD -0.11, 95% CI -0.26 to 0.03; participants analysed at post treatment = 762; evidence of very low certainty). Results from seven studies that analysed 1054 participants post treatment suggest a small effect for significantly lower symptom intensity in early palliative care compared with the control condition (SMD -0.23, 95% CI -0.35 to -0.10; evidence of low certainty). The type of model used to provide early palliative care did not affect study results. One RCT reported potential adverse events of early palliative care, such as a higher percentage of participants with severe scores for pain and poor appetite; the remaining six studies did not report adverse events in study publications. For these six studies, principal investigators stated upon request that they had not observed any adverse events.\nAuthors' conclusions\nThis systematic review of a small number of trials indicates that early palliative care interventions may have more beneficial effects on quality of life and symptom intensity among patients with advanced cancer than among those given usual/standard cancer care alone. Although we found only small effect sizes, these may be clinically relevant at an advanced disease stage with limited prognosis, at which time further decline in quality of life is very common. At this point, effects on mortality and depression are uncertain. We have to interpret current results with caution owing to very low to low certainty of current evidence and between-study differences regarding participant populations, interventions, and methods. Additional research now under way will present a clearer picture of the effect and specific indication of early palliative care. Upcoming results from several ongoing studies (N = 20) and studies awaiting assessment (N = 10) may increase the certainty of study results and may lead to improved decision making. In perspective, early palliative care is a newly emerging field, and well-conducted studies are needed to explicitly describe the components of early palliative care and control treatments, after blinding of participants and outcome assessors, and to report on possible adverse events.\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": "When evaluated together in a meta-analysis, studies showed that in patients with advanced cancer, early palliative care may slightly increase quality of life. It may also decrease symptom intensity to a small degree. Effects on survival and depression are uncertain. A single study reported side effects (adverse events), for example, more pain and reduced appetite. For the remaining six studies, information about side effects was not published, but trial authors told us they had not observed any." } ]

[ { "role": "user", "content": "Abstract: Background\nStudies report that up to 80% of individuals with chronic obstructive pulmonary disease (COPD) may struggle with symptoms of depression. However, this major comorbidity in COPD is rarely managed effectively. A number of recent studies indicate that left untreated, COPD-related depression is associated with worse quality of life, worse compliance with COPD treatment plan, increased exacerbations, hospital admissions, and healthcare costs when compared to individuals with COPD without depression. Regrettably, COPD practice guidelines do not provide conclusive treatment recommendations for the use of antidepressants in patients with COPD, and base their guidelines on findings from trials in the general population. This may be problematic, as there is an elevated risk of respiratory issues associated with antidepressant treatment and COPD. Evaluating effectiveness and safety of pharmacological interventions specifically for patients with COPD and depression was therefore paramount.\nObjectives\nTo assess the effectiveness and safety of pharmacological interventions for the treatment of depression in patients with COPD.\nSearch methods\nThe last search was performed on 26 November 2018. We initially searched the following databases via the Specialised Trials Registers of the Cochrane Airways and Common Mental Disorders Groups (to June 2016): MEDLINE, Embase, PsycINFO, CINAHL, AMED, and the Cochrane Library trials register (CENTRAL). Searches from June 2016 to November 2018 were performed directly on Ovid MEDLINE, Embase, PsycINFO and the Cochrane Library (Issue 11, 2018). We searched ClinicalTrials.gov, the ISRCTN registry, and the World Health Organization International Clinical Trials Registry Platform to 26 November 2018. We searched the grey literature databases to identify studies not indexed in major databases and the reference lists of studies initially identified for full-text screening.\nSelection criteria\nAll published and unpublished randomised controlled trials (RCTs) comparing the efficacy of pharmacological interventions with no intervention, placebo or co-intervention in adults with diagnosed COPD and depression were eligible for inclusion.\nData collection and analysis\nTwo review authors independently assessed articles identified by the search for eligibility. Our primary outcomes were change in depressive symptoms and adverse events. The secondary outcomes were: change in quality of life, change in dyspnoea, change in forced expiratory volume in one second (FEV1), change in exercise tolerance, change in hospital utilisation (length of stay and readmission rates), and cost-effectiveness. For continuous outcomes, we calculated the pooled mean difference (MD) or standardised mean difference (SMD) with 95% confidence interval (CI) as appropriate. For dichotomous outcomes, we calculated the pooled odds ratio (OR) and corresponding 95% CI using a random-effects model. We assessed the quality of evidence using the GRADE framework.\nMain results\nOf the 1125 records screened for eligibility, four RCTs (N = 201 participants), and one on-going study, met the inclusion criteria. Two classes of antidepressants were investigated in two separate comparisons with placebo: a tricyclic antidepressant (TCA) and selective serotonin reuptake inhibitors (SSRIs).\nTCA versus placebo\nOnly one RCT (N = 30 participants) provided results for this comparison.\nPrimary outcomes\nThe TCA (nortriptyline) reduced depressive symptoms post-treatment compared to placebo (MD -10.20, 95% CI -16.75 to -3.65; P = 0.007; very low-quality evidence), as measured by the Hamilton Depression Rating Scale (HAM-D). Three participants withdrew from the trial due to adverse events related to the tested antidepressant (dry mouth, sedation, orthostatic hypotension).\nSecondary outcomes\nThe overall results post-treatment indicated that nortriptyline was not effective in improving the quality of life of individuals with COPD, as measured by the Sickness Impact Profile (MD -2.80, 95% CI -11.02 to 5.42; P = 0.50; very low-quality evidence).\nThe results for the change in dyspnoea for the domains examined (e.g. dyspnoea scores for 'most day-to-day activities') post-treatment showed no improvement in the intervention group (MD 9.80, 95% CI -6.20 to 25.80; P = 0.23; very low-quality evidence).\nNo data were reported for change in FEV1, change in exercise tolerance, change in hospital utilisation, or cost-effectiveness. The TCA study provided short-term results, with the last follow-up data collection at 12 weeks.\nThe quality of the evidence for all the outcomes evaluated was very low due to a small sample size, imprecision, attrition, and selection and reporting bias.\nSSRIs versus placebo\nThree RCTs (N = 171 participants) provided results for this comparison.\nPrimary outcomes\nThe pooled results for two studies showed no difference for the change in depressive symptoms post-intervention (SMD 0.75, 95% CI -1.14 to 2.64; 148 participants; 2 studies; P = 0.44; very low-quality evidence). High heterogeneity was observed (I² = 95%), limiting the reliability of these findings.\nWhile it was not possible to meta-analyse the total adverse events rates across the studies, it was possible to combine the results for two medication-specific adverse effects: nausea and dizziness. There were no significant post-treatment group differences for nausea (OR 2.32, 95% CI 0.66 to 8.12; 171 participants; 3 studies; P = 0.19; very low-quality evidence) or dizziness (OR 0.61, 95% CI 0.09 to 4.06; 143 participants; 2 studies; P = 0.61; very low-quality evidence).\nSecondary outcomes\nThe pooled analysis of two trials reporting data for the change in quality of life did not show improvement post-treatment in the intervention group compared to placebo (SMD 1.17, 95% CI -0.80 to 3.15; 148 participants; 2 studies; P = 0.25; very low-quality evidence).\nThere was no difference between groups in change in FEV1 post-treatment (MD 0.01, 95% CI -0.03 to 0.05; 148 participants; 2 studies; P = 0.60; low-quality evidence). However, two trials reported improvement in exercise tolerance in the SSRI group versus the placebo group (MD 13.88, 95% CI 11.73 to 16.03; 148 participants; 2 studies; P < 0.001; very low-quality evidence).\nThe trials included in this comparison did not report data related to the change in dyspnoea, hospital utilisation rates, or cost-effectiveness.\nAuthors' conclusions\nThere is insufficient evidence to make definitive statements about the efficacy or safety of antidepressants for treating COPD-related depression. New RCTs are needed; with better methodological quality and more accurate reporting of the methods used. Moreover, longer-term follow-up data collection is needed, including outcomes such as adverse events, hospital utilisation and cost-effectiveness.\n\nGiven the provided abstract, please respond to the following query: \"Which studies were included in the review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review included experimental studies called randomised controlled trials (studies in which participants are assigned to a treatment group based on a random method) that compared the effectiveness of pharmacological interventions (antidepressants) to placebo (inactive treatment in the same form as the active treatment, e.g. a pill). Study participants were adults diagnosed with COPD and depression." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with cystic fibrosis (CF) experience chronic airway infections as a result of mucus buildup within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review.\nObjectives\nTo compare the clinical effectiveness of ACBT with other airway clearance therapies in CF.\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 clinical trials registries and the reference lists of relevant articles and reviews.\nDate of last search: 29 March 2021.\nSelection criteria\nWe included randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing ACBT with other airway clearance therapies in CF.\nData collection and analysis\nTwo review authors independently screened each article, abstracted data and assessed the risk of bias of each study. We used GRADE to assess our confidence in the evidence assessing quality of life, participant preference, adverse events, forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, sputum weight, and number of pulmonary exacerbations.\nMain results\nOur search identified 99 studies, of which 22 (559 participants) met the inclusion criteria. Eight randomised controlled studies (259 participants) were included in the analysis; five were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 18.7 years). In 13 studies follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis.\nIncluded studies compared ACBT with autogenic drainage, airway oscillating devices (AOD), high-frequency chest compression devices, conventional chest physiotherapy (CCPT), positive expiratory pressure (PEP), and exercise. We found no difference in quality of life between ACBT and PEP mask therapy, AOD, other breathing techniques, or exercise (very low-certainty evidence). There was no difference in individual preference between ACBT and other breathing techniques (very low-certainty evidence). One study comparing ACBT with ACBT plus postural exercise reported no deaths and no adverse events (very low-certainty evidence). We found no differences in lung function (forced expiratory volume in one second (FEV1) % predicted and forced vital capacity (FVC) % predicted), oxygen saturation or expectorated sputum between ACBT and any other technique (very low-certainty evidence). There were no differences in the number of pulmonary exacerbations between people using ACBT and people using CCPT (low-certainty evidence) or ACBT with exercise (very low-certainty evidence), the only comparisons to report this outcome.\nAuthors' conclusions\nThere is little evidence to support or reject the use of the ACBT over any other airway clearance therapy and ACBT is comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of ACBT on outcomes important for people with cystic fibrosis such as quality of life and preference.\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": "What are the effects of active cycle of breathing technique (ACBT) compared with other methods of airway clearance in people with cystic fibrosis?" } ]

[ { "role": "user", "content": "Abstract: Background\nInvasive urodynamic tests are used to investigate men with lower urinary tract symptoms (LUTS) and voiding dysfunction to determine a definitive objective diagnosis. The aim is to help clinicians select the treatment that is most likely to be successful. These investigations are invasive and time-consuming.\nObjectives\nTo determine whether performing invasive urodynamic investigation, as opposed to other methods of diagnosis such as non-invasive urodynamics or clinical history and examination alone, reduces the number of men with continuing symptoms of voiding dysfunction. This goal will be achieved by critically appraising and summarising current evidence from randomised controlled trials related to clinical outcomes and cost-effectiveness. This review is not intended to consider whether urodynamic tests are reliable for making clinical diagnoses, nor whether one type of urodynamic test is better than another for this purpose.\nThe following comparisons were made.\n• Urodynamics versus clinical management.\n• One type of urodynamics versus another.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, issue 10), MEDLINE (1 January 1946 to Week 4 October 2014), MEDLINE In-Process and other non-indexed citations (covering 27 November 2014; all searched on 28 November 2014), EMBASE Classic and EMBASE (1 January 2010 to Week 47 2014, searched on 28 November 2014), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (searched on 1 December 2014 and 3 December 2014, respectively), as well as the reference lists of relevant articles.\nSelection criteria\nRandomised and quasi-randomised trials comparing clinical outcomes in men who were and were not investigated with the use of invasive urodynamics, or comparing one type of urodynamics against another, were included. Trials were excluded if they did not report clinical outcomes.\nData collection and analysis\nThree review authors independently assessed trial quality and extracted data.\nMain results\nWe included two trials, but data were available for only 339 men in one trial, of whom 188 underwent invasive urodynamic studies. We found evidence of risk of bias, such as lack of outcome information for 24 men in one arm of the trial.\nStatistically significant evidence suggests that the tests did change clinical decision making. Men in the invasive urodynamics arm were more likely to have their management changed than men in the control arm (proportion with change in management 24/188 (13%) vs 0/151 (0%), risk ratio (RR) 39.41, 95% confidence interval (CI) 2.42 to 642.74). However, the quality of the evidence was low.\nLow-quality evidence indicates that men in the invasive urodynamics group were less likely to undergo surgery as treatment for voiding LUTS (164/188 (87%) vs 151/151 (100%), RR 0.87, 95% CI 0.83 to 0.92).\nInvestigators observed no difference in urine flow rates before and after surgery for LUTS (mean percentage increase in urine flow rate, 140% in invasive urodynamic group vs 149% in immediate surgery group, P value = 0.13). Similarly, they found no differences between groups with regards to International Prostate Symptom Score (IPSS) (mean percentage decrease in IPSS score, 58% in invasive urodynamics group vs 59% in immediate surgery group, P value = 0.22).\nNo evidence was available to demonstrate whether differences in management equated to improved health outcomes, such as relief of symptoms of voiding dysfunction or improved quality of life.\nNo evidence from randomised trials revealed the adverse effects associated with invasive urodynamic studies.\nAuthors' conclusions\nAlthough invasive urodynamic testing did change clinical decision making, we found no evidence to demonstrate whether this led to reduced symptoms of voiding dysfunction after treatment. Larger definitive trials of better quality are needed, in which men are randomly allocated to management based on invasive urodynamic findings or to management based on findings obtained by other diagnostic means. This research will show whether performance of invasive urodynamics results in reduced symptoms of voiding dysfunction after treatment.\n\nGiven the provided abstract, please respond to the following query: \"Adverse effects\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "No information obtained from the included trials reveals how common side effects were in those undergoing invasive urodynamic testing." } ]

[ { "role": "user", "content": "Abstract: Background\nPeople with cystic fibrosis (CF) and pancreatic insufficiency are at risk of a deficiency in fat-soluble vitamins, including vitamin A. Vitamin A deficiency predominantly causes eye and skin problems, while excessive levels of vitamin A can harm the respiratory and skeletal systems in children and interfere with the metabolism of other fat-soluble vitamins. Most CF centres administer vitamin A as supplements to reduce the frequency of vitamin A deficiency in people with CF and to improve clinical outcomes such as growth, although the recommended dose varies between different guidelines. Thus, a systematic review on vitamin A and vitamin A-like supplementation (carotenes or other retinoids) in people with CF would help guide clinical practice. This is an update of an earlier Cochrane Review.\nObjectives\nTo determine if supplementation with vitamin A, carotenes or other retinoid supplements in children and adults with CF reduces the frequency of vitamin A deficiency disorders, improves general and respiratory health and affects the frequency of vitamin A toxicity.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. Additionally we searched several ongoing trials registries, including ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and the International Standard Randomised Controlled Trial Number Registry.\nMost recent database searches: 01 June 2018.\nSelection criteria\nAll randomised or quasi-randomised controlled studies comparing all preparations of oral vitamin A, carotenes or retinoids (or in combination), used as a supplement compared to placebo at any dose, for at least three months, in people with CF (diagnosed by sweat tests or genetic testing) with and without pancreatic insufficiency.\nData collection and analysis\nTwo authors individually assessed study quality and extracted data on outcome measures. The authors assessed the quality of the evidence using the GRADE system. Investigators were contacted to retrieve missing quantitative data.\nMain results\nNo studies of vitamin A or other retinoid supplementation were eligible for inclusion. However, one randomised study of beta (β)-carotene supplementation involving 24 people with CF who were receiving pancreatic enzyme substitution was included. The study compared successive β-carotene supplementation periods (high dose followed by low dose) compared to placebo. The results for the low-dose supplementation period should be interpreted with caution, due to the lack of a wash-out period after the high-dose supplementation.\nThe included study did not report on two of the review's primary outcomes (vitamin A deficiency disorders and mortality); results for our third primary outcome of growth and nutritional status (reported as z score for height) showed no difference between supplementation and placebo, mean difference (MD) -0.23 (95% confidence interval (CI) -0.89 to 0.43) (low-quality evidence). With regards to secondary outcomes, supplementation with high-dose β-carotene for three months led to significantly fewer days of systemic antibiotics required to treat pulmonary exacerbations, compared to controls, MD -15 days (95% CI -27.60 to -2.40); however, this was not maintained in the second three-month section of the study when the level of β-carotene supplementation was reduced, MD -8 days (95% CI -18.80 to 2.80) (low-quality evidence). There were no statistically significant effects between groups in lung function (low-quality evidence) and no adverse events were observed (low-quality evidence). Supplementation affected levels of β-carotene in plasma, but not vitamin A levels. The study did not report on quality of life or toxicity.\nAuthors' conclusions\nSince no randomised or quasi-randomised controlled studies on retinoid supplementation were identified, no conclusion on the supplementation of vitamin A in people with CF can be drawn. Additionally, due to methodological limitations in the included study, also reflected in the low-quality evidence judged following the specific evidence grading system (GRADE), no clear conclusions on β-carotene supplementation can be drawn. Until further data are available, country- or region-specific guidelines regarding these practices should be followed.\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: 01 June 2018." } ]

[ { "role": "user", "content": "Abstract: Background\nTinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy (TRT), cognitive behavioural therapy (CBT), sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as insomnia, anxiety or depression.\nObjectives\nTo assess the effects of Ginkgo biloba for tinnitus in adults and children.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2022, Issue 6); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 June 2022.\nSelection criteria\nRandomised controlled trials (RCTs) recruiting adults and children with acute or chronic subjective tinnitus. We included studies where the intervention involved Ginkgo biloba and this was compared to placebo, no intervention, or education and information. Concurrent use of other medication or other treatment was acceptable if used equally in each group. Where an additional intervention was used equally in both groups, we analysed this as a separate comparison. The review included all courses of Ginkgo biloba, regardless of dose regimens or formulations, and for any duration of treatment.\nData collection and analysis\nWe used standard Cochrane methods. Our primary outcomes were tinnitus symptom severity measured as a global score on a multi-item tinnitus questionnaire and serious adverse effects (bleeding, seizures). Our secondary outcomes were tinnitus loudness (change in subjective perception), tinnitus intrusiveness, generalised depression, generalised anxiety, health-related quality of life and other adverse effects (gastrointestinal upset, headache, allergic reaction). We used GRADE to assess the certainty of the evidence for each outcome.\nMain results\nThis review included 12 studies (with a total of  1915 participants). Eleven studies compared the effects of Ginkgo biloba with placebo and one study compared the effects of Ginkgo biloba with hearing aids to hearing aids alone. All included studies were parallel-group RCTs. In general, risk of bias was high or unclear due to selection bias and poor reporting of allocation concealment and blinding of participants, personnel and outcome assessments. Due to heterogeneity in the outcomes measured and measurement methods used, only limited data pooling was possible.\nGinkgo biloba versus placebo\nWhen we pooled data from two studies for the primary outcome tinnitus symptom severity, we found that Ginkgo biloba may have little to no effect (Tinnitus Handicap Inventory scores) at three to six months compared to placebo, but the evidence is very uncertain (mean difference (MD) -1.35 (scale 0 to 100), 95% confidence interval (CI) -8.26 to 5.55; 2 studies; 85 participants) (very low-certainty). Ginkgo biloba may result in little to no difference in the risk of bleeding or seizures, with no serious adverse effects reported in either group (4 studies; 1154 participants; low-certainty).\nFor the secondary outcomes, one study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on tinnitus loudness measured with audiometric loudness matching at 12 weeks, but the evidence is very uncertain (MD -4.00 (scale -10 to 140 dB), 95% CI -13.33 to 5.33; 1 study; 73 participants) (very low-certainty). One study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on health-related quality of life measured with the Glasgow Health Status Inventory at three months (MD -0.58 (scale 0 to 100), 95% CI -4.67 to 3.51; 1 study; 60 participants) (low-certainty). Ginkgo biloba may not increase the frequency of other adverse effects (gastrointestinal upset, headache, allergic reaction) at three months compared to placebo (risk ratio 0.91, 95% CI 0.52 to 1.60; 4 studies; 1175 participants) (low-certainty). None of the studies reported the other secondary outcomes of tinnitus intrusiveness or changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety.\nGingko biloba with concurrent intervention versus concurrent intervention only\nOne study compared Ginkgo biloba with hearing aids to hearing aids only. It assessed the mean difference in the change in Tinnitus Handicap Inventory scores and tinnitus loudness using a 10-point visual analogue scale (VAS) at three months. The study did not report adverse effects, tinnitus intrusiveness, changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health-related quality of life. This was a single, very small study (22 participants) and for all outcomes the certainty of the evidence was very low. We were unable to draw meaningful conclusions from the numerical results.\nAuthors' conclusions\nThere is uncertainty about the benefits and harms of Ginkgo biloba for the treatment of tinnitus when compared to placebo. We were unable to draw meaningful conclusions regarding the benefits and harms of Ginkgo biloba when used with concurrent intervention (hearing aids). The certainty of the evidence for the reported outcomes, assessed using GRADE, ranged from low to very low. Future research into the effectiveness of Ginkgo biloba in patients with tinnitus should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the use of validated, patient-centred outcome measures for research in the field of tinnitus.\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 June 2022." } ]

[ { "role": "user", "content": "Abstract: Background\nTransitional care provides for the continuity of care as patients move between different stages and settings of care. Medication discrepancies arising at care transitions have been reported as prevalent and are linked with adverse drug events (ADEs) (e.g. rehospitalisation).\nMedication reconciliation is a process to prevent medication errors at transitions. Reconciliation involves building a complete list of a person's medications, checking them for accuracy, reconciling and documenting any changes. Despite reconciliation being recognised as a key aspect of patient safety, there remains a lack of consensus and evidence about the most effective methods of implementing reconciliation and calls have been made to strengthen the evidence base prior to widespread adoption.\nObjectives\nTo assess the effect of medication reconciliation on medication discrepancies, patient-related outcomes and healthcare utilisation in people receiving this intervention during care transitions compared to people not receiving medication reconciliation.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, seven other databases and two trials registers on 18 January 2018 together with reference checking, citation searching, grey literature searches and contact with study authors to identify additional studies.\nSelection criteria\nWe included only randomised trials. Eligible studies described interventions fulfilling the Institute for Healthcare Improvement definition of medication reconciliation aimed at all patients experiencing a transition of care as compared to standard care in that institution. Included studies had to report on medication discrepancies as an outcome.\nData collection and analysis\nTwo review authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. Study-specific estimates were pooled, using a random-effects model to yield summary estimates of effect and 95% confidence intervals (CI). We used the GRADE approach to assess the overall certainty of evidence for each pooled outcome.\nMain results\nWe identified 25 randomised trials involving 6995 participants. All studies were conducted in hospital or immediately related settings in eight countries. Twenty-three studies were provider orientated (pharmacist mediated) and two were structural (an electronic reconciliation tool and medical record changes). A pooled result of 20 studies comparing medication reconciliation interventions to standard care of participants with at least one medication discrepancy showed a risk ratio (RR) of 0.53 (95% CI 0.42 to 0.67; 4629 participants). The certainty of the evidence on this outcome was very low and therefore the effect of medication reconciliation to reduce discrepancies was uncertain. Similarly, reconciliation's effect on the number of reported discrepancies per participant was also uncertain (mean difference (MD) –1.18, 95% CI –2.58 to 0.23; 4 studies; 1963 participants), as well as its effect on the number of medication discrepancies per participant medication (RR 0.13, 95% CI 0.01 to 1.29; 2 studies; 3595 participants) as the certainty of the evidence for both outcomes was very low.\nReconciliation may also have had little or no effect on preventable adverse drug events (PADEs) due to the very low certainty of the available evidence (RR 0.37. 95% CI 0.09 to 1.57; 3 studies; 1253 participants), with again uncertainty on its effect on ADE (RR 1.09, 95% CI 0.91 to 1.30; 4 studies; 1363 participants; low-certainty evidence). Evidence of the effect of the interventions on healthcare utilisation was conflicting; it probably made little or no difference on unplanned rehospitalisation when reported alone (RR 0.72, 95% CI 0.44 to 1.18; 5 studies; 1206 participants; moderate-certainty evidence), and had an uncertain effect on a composite measure of hospital utilisation (emergency department, rehospitalisation RR 0.78, 95% CI 0.50 to 1.22; 4 studies; 597 participants; very low-certainty evidence).\nAuthors' conclusions\nThe impact of medication reconciliation interventions, in particular pharmacist-mediated interventions, on medication discrepancies is uncertain due to the certainty of the evidence being very low. There was also no certainty of the effect of the interventions on the secondary clinical outcomes of ADEs, PADEs and healthcare utilisation.\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 included studies that used a randomised design where people were randomly put into one of two or more treatment groups. The main outcome of interest was whether the possibility of any discrepancies in a patient's medication list was reduced following the intervention. Other outcomes that were assessed in the review were the intervention's impact on the number of medication discrepancies, medication side effects, preventable medication side effects, hospital usage (e.g. emergency department visits and readmission to hospital), negative/adverse impacts of the intervention and resource usage." } ]

[ { "role": "user", "content": "Abstract: Background\nOlder people taking multiple medications represent a large and growing proportion of the population. Managing multiple medications can be challenging, and this is especially the case for older people, who have higher rates of comorbidity and physical and cognitive impairment than younger adults. Good medication-taking ability and medication adherence are necessary to ensure safe and effective use of medications.\nObjectives\nTo evaluate the effectiveness of interventions designed to improve medication-taking ability and/or medication adherence in older community-dwelling adults prescribed multiple long-term medications.\nSearch methods\nWe searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL Plus, and International Pharmaceutical Abstracts from inception until June 2019. We also searched grey literature, online trial registries, and reference lists of included studies.\nSelection criteria\nWe included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs. Eligible studies tested interventions aimed at improving medication-taking ability and/or medication adherence among people aged ≥ 65 years (or of mean/median age > 65 years), living in the community or being discharged from hospital back into the community, and taking four or more regular prescription medications (or with group mean/median of more than four medications). Interventions targeting carers of older people who met these criteria were also included.\nData collection and analysis\nTwo review authors independently reviewed abstracts and full texts of eligible studies, extracted data, and assessed risk of bias of included studies. We conducted meta-analyses when possible and used a random-effects model to yield summary estimates of effect, risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, along with 95% confidence intervals (CIs). Narrative synthesis was performed when meta-analysis was not possible. We assessed overall certainty of evidence for each outcome using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Primary outcomes were medication-taking ability and medication adherence. Secondary outcomes included health-related quality of life (HRQoL), emergency department (ED)/hospital admissions, and mortality.\nMain results\nWe identified 50 studies (14,269 participants) comprising 40 RCTs, six cluster-RCTs, and four quasi-RCTs. All included studies evaluated interventions versus usual care; six studies also reported a comparison between two interventions as part of a three-arm RCT design.\nInterventions were grouped on the basis of their educational and/or behavioural components: 14 involved educational components only, 7 used behavioural strategies only, and 29 provided mixed educational and behavioural interventions. Overall, our confidence in results regarding the effectiveness of interventions was low to very low due to a high degree of heterogeneity of included studies and high or unclear risk of bias across multiple domains in most studies.\nFive studies evaluated interventions for improving medication-taking ability, and 48 evaluated interventions for improving medication adherence (three studies evaluated both outcomes).\nNo studies involved educational or behavioural interventions alone for improving medication-taking ability. Low-quality evidence from five studies, each using a different measure of medication-taking ability, meant that we were unable to determine the effects of mixed interventions on medication-taking ability.\nLow-quality evidence suggests that behavioural only interventions (RR 1.22, 95% CI 1.07 to 1.38; 4 studies) and mixed interventions (RR 1.22, 95% CI 1.08 to 1.37; 12 studies) may increase the proportions of people who are adherent compared with usual care. We could not include in the meta-analysis results from two studies involving mixed interventions: one had a positive effect on adherence, and the other had little or no effect. Very low-quality evidence means that we are uncertain of the effects of educational only interventions (5 studies) on the proportions of people who are adherent.\nLow-quality evidence suggests that educational only interventions (SMD 0.16, 95% CI -0.12 to 0.43; 5 studies) and mixed interventions (SMD 0.47, 95% CI -0.08 to 1.02; 7 studies) may have little or no impact on medication adherence assessed through continuous measures of adherence. We excluded 10 studies (4 educational only and 6 mixed interventions) from the meta-analysis including four studies with unclear or no available results. Very low-quality evidence means that we are uncertain of the effects of behavioural only interventions (3 studies) on medication adherence when assessed through continuous outcomes.\nLow-quality evidence suggests that mixed interventions may reduce the number of ED/hospital admissions (RR 0.67, 95% CI 0.50 to 0.90; 11 studies) compared with usual care, although results from six further studies that we were unable to include in meta-analyses indicate that the intervention may have a smaller, or even no, effect on these outcomes. Similarly, low-quality evidence suggests that mixed interventions may lead to little or no change in HRQoL (7 studies), and very low-quality evidence means that we are uncertain of the effects on mortality (RR 0.93, 95% CI 0.67 to 1.30; 7 studies).\nModerate-quality evidence shows that educational interventions alone probably have little or no effect on HRQoL (6 studies) or on ED/hospital admissions (4 studies) when compared with usual care. Very low-quality evidence means that we are uncertain of the effects of behavioural interventions on HRQoL (1 study) or on ED/hospital admissions (2 studies). We identified no studies evaluating effects of educational or behavioural interventions alone on mortality.\nSix studies reported a comparison between two interventions; however due to the limited number of studies assessing the same types of interventions and comparisons, we are unable to draw firm conclusions for any outcomes.\nAuthors' conclusions\nBehavioural only or mixed educational and behavioural interventions may improve the proportion of people who satisfactorily adhere to their prescribed medications, but we are uncertain of the effects of educational only interventions. No type of intervention was found to improve adherence when it was measured as a continuous variable, with educational only and mixed interventions having little or no impact and evidence of insufficient quality to determine the effects of behavioural only interventions. We were unable to determine the impact of interventions on medication-taking ability. The quality of evidence for these findings is low due to heterogeneity and methodological limitations of studies included in the review. Further well-designed RCTs are needed to investigate the effects of interventions for improving medication-taking ability and medication adherence in older adults prescribed multiple medications.\n\nGiven the provided abstract, please respond to the following query: \"Search strategy\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "To find relevant studies, we searched seven online databases, trial registries, and the reference lists of previous reviews, retrieving studies published until June 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nA small minority of people with coronavirus disease 2019 (COVID-19) develop a severe illness, characterised by inflammation, microvascular damage and coagulopathy, potentially leading to myocardial injury, venous thromboembolism (VTE) and arterial occlusive events. People with risk factors for or pre-existing cardiovascular disease may be at greater risk.\nObjectives\nTo assess the prevalence of pre-existing cardiovascular comorbidities associated with suspected or confirmed cases of COVID-19 in a variety of settings, including the community, care homes and hospitals. We also assessed the nature and rate of subsequent cardiovascular complications and clinical events in people with suspected or confirmed COVID-19.\nSearch methods\nWe conducted an electronic search from December 2019 to 24 July 2020 in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, covid-19.cochrane.org, ClinicalTrials.gov and EU Clinical Trial Register.\nSelection criteria\nWe included prospective and retrospective cohort studies, controlled before-and-after, case-control and cross-sectional studies, and randomised controlled trials (RCTs). We analysed controlled trials as cohorts, disregarding treatment allocation. We only included peer-reviewed studies with 100 or more participants, and excluded articles not written in English or only published in pre-print servers.\nData collection and analysis\nTwo review authors independently screened the search results and extracted data. Given substantial variation in study designs, reported outcomes and outcome metrics, we undertook a narrative synthesis of data, without conducting a meta-analysis. We critically appraised all included studies using the Joanna Briggs Institute (JBI) checklist for prevalence studies and the JBI checklist for case series.\nMain results\nWe included 220 studies. Most of the studies originated from China (47.7%) or the USA (20.9%); 9.5% were from Italy. A large proportion of the studies were retrospective (89.5%), but three (1.4%) were RCTs and 20 (9.1%) were prospective.\nUsing JBI’s critical appraisal checklist tool for prevalence studies, 75 studies attained a full score of 9, 57 studies a score of 8, 31 studies a score of 7, 5 studies a score of 6, three studies a score of 5 and one a score of 3; using JBI’s checklist tool for case series, 30 studies received a full score of 10, six studies a score of 9, 11 studies a score of 8, and one study a score of 5\nWe found that hypertension (189 studies, n = 174,414, weighted mean prevalence (WMP): 36.1%), diabetes (197 studies, n = 569,188, WMP: 22.1%) and ischaemic heart disease (94 studies, n = 100,765, WMP: 10.5%)  are highly prevalent in people hospitalised with COVID-19, and are associated with an increased risk of death. In those admitted to hospital, biomarkers of cardiac stress or injury are often abnormal, and the incidence of a wide range of cardiovascular complications is substantial, particularly arrhythmias (22 studies, n = 13,115, weighted mean incidence (WMI) 9.3%), heart failure (20 studies, n = 29,317, WMI: 6.8%) and thrombotic complications (VTE: 16 studies, n = 7700, WMI: 7.4%).\nAuthors' conclusions\nThis systematic literature review indicates that cardiometabolic comorbidities are common in people who are hospitalised with a COVID-19 infection, and cardiovascular complications are frequent. We plan to update this review and to conduct a formal meta-analysis of outcomes based on a more homogeneous selected subsample of high-certainty studies.\n\nGiven the provided abstract, please respond to the following query: \"What we did\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for published studies that reported heart and blood vessel problems in people with possible or confirmed COVID-19. Studies could be of any design and could take place anywhere, but they had to have been checked by other researchers (be peer-reviewed), be written in English, and include at least 100 cases.\nThe evidence is current until July 2020." } ]

[ { "role": "user", "content": "Abstract: Background\nThis review is one of a suite of six Cochrane reviews looking at the primary medical management options for patients with chronic rhinosinusitis.\nChronic rhinosinusitis is a common condition involving inflammation of the lining of the nose and paranasal sinuses. It is characterised by nasal blockage and nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Oral corticosteroids are used to control the inflammatory response and improve symptoms.\nObjectives\nTo assess the effects of a short course of oral corticosteroids as an adjunct ('add-on') therapy in people with chronic rhinosinusitis who are already on standard treatments.\nSearch methods\nThe Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.\nSelection criteria\nRandomised controlled trials (RCTs) comparing a short course (up to 21 days) of oral corticosteroids to placebo or no treatment, where all patients were also receiving pharmacological treatment for chronic rhinosinusitis.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity, and the adverse event of mood or behavioural disturbances. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score, and the adverse events of insomnia, gastrointestinal disturbances and osteoporosis. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.\nMain results\nTwo trials with a total of 78 participants met the inclusion criteria. Both the populations and the 'standard' treatments differed in the two studies.\nOral steroids as an adjunct to intranasal corticosteroids\nOne trial in adults with nasal polyps included 30 participants. All participants used intranasal corticosteroids and were randomised to either short-course oral steroids (oral methylprednisolone, 1 mg/kg and reduced progressively over a 21-day treatment course) or no additional treatment. None of the primary outcome measures of interest in this review were reported by the study. There may have been an important reduction in the size of the polyps (measured by the nasal polyps score, a secondary outcome measure) in patients receiving oral steroids and intranasal corticosteroids, compared to intranasal corticosteroids alone (mean difference (MD) -0.46, 95% confidence interval (CI) -0.87 to -0.05; 30 participants; scale 1 to 4) at the end of treatment (21 days). This corresponds to a large effect size, but we are very uncertain about this estimate as we judged the study to be at high risk of bias. Moreover, longer-term data were not available and the other outcomes of interest were not reported.\nOral steroids as an adjunct to antibiotics\nOne trial in children (mean age of eight years) without nasal polyps included 48 participants. The trial compared oral corticosteroids (oral methylprednisolone, 1 mg/kg and reduced progressively over a 15-day treatment course) with placebo in participants who also received a 30-day course of antibiotics. This study addressed one of the primary outcome measures (disease severity) and one secondary outcome (CT score). For disease severity the four key symptoms used to define chronic rhinosinusitis in children (nasal blockage, nasal discharge, facial pressure, cough) were combined into one score. There was a greater improvement in symptom severity 30 days after the start of treatment in patients who received oral steroids and antibiotics compared with placebo and antibiotics (MD -7.10, 95% CI -9.59 to -4.61; 45 participants; scale 0 to 40). The observed mean difference corresponds to a large effect size. At the same time point there was a difference in CT scan score (MD -2.90, 95% CI -4.91 to -0.89; 45 participants; scale 0 to 24). We assessed the quality of the evidence to be low.\nThere were no data available for the longer term (three months).\nAuthors' conclusions\nThere might be an improvement in symptom severity, polyps size and condition of the sinuses when assessed using CT scans in patients taking oral corticosteroids when these are used as an adjunct therapy to antibiotics or intranasal corticosteroids, but the quality of the evidence supporting this is low orvery low (we are uncertain about the effect estimate; the true effect may be substantially different from the estimate of the effect). It is unclear whether the benefits of oral corticosteroids as an adjunct therapy are sustained beyond the short follow-up period reported (up to 30 days), as no longer-term data were available.\nThere were no data in this review about the adverse effects associated with short courses of oral corticosteroids as an adjunct therapy.\nMore research in this area, particularly research evaluating longer-term outcomes and adverse effects, is required.\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": "At the end of a three-week treatment course, people who took both intranasal corticosteroids and oral steroids may have had smaller nasal polyps than people who just received intranasal corticosteroids. The trial did not follow up people to determine whether the polyp size increased after the end of the trial. The trial did not provide information on adverse events or other outcomes important to patients, such as symptom severity or quality of life.\nChildren who received both antibiotics and oral corticosteroids seemed to have a lower total symptom score and better computerised tomography (CT) scan score after treatment compared with children who received antibiotics and control treatment. The reporting of adverse effects in this trial was not very clear and so is difficult to tell if any participant experienced gastrointestinal disturbances, mood changes or difficulty in sleeping." } ]

[ { "role": "user", "content": "Abstract: Background\nStroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be improved if they are offered anticoagulants that reduce their risk of developing new blood clots and do not increase the risk of bleeding. This is an update of a Cochrane Review first published in 1995, with updates in 2004, 2008, and 2015.\nObjectives\nTo assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) for people with acute presumed or confirmed ischaemic stroke.\nOur hypotheses were that, compared with a policy of avoiding their use, early anticoagulation would be associated with:\n• reduced risk of death or dependence in activities of daily living a few months after stroke onset;\n• reduced risk of early recurrent ischaemic stroke;\n• increased risk of symptomatic intracranial and extracranial haemorrhage; and\n• reduced risk of deep vein thrombosis and pulmonary embolism.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (August 2021); the Cochrane Database of Systematic Reviews (CDSR); the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 7), in the Cochrane Library (searched 5 August 2021); MEDLINE (2014 to 5 August 2021); and Embase (2014 to 5 August 2021). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies.\nSelection criteria\nRandomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke.\nData collection and analysis\nTwo review authors independently selected trials for inclusion, assessed trial quality, and extracted data. We assessed the overall certainty of the evidence for each outcome using RoB1 and GRADE methods.\nMain results\nWe included 28 trials involving 24,025 participants. Quality of the trials varied considerably. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition, or reporting bias. Anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence is related to effects of anticoagulant therapy initiated within the first 48 hours of onset. No evidence suggests that early anticoagulation reduced the odds of death or dependence at the end of follow-up (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 12 RCTs, 22,428 participants; high-certainty evidence). Similarly, we found no evidence suggesting that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (OR 0.99, 95% CI 0.90 to 1.09; 22 RCTs, 22,602 participants; low-certainty evidence) during the treatment period. Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.75, 95% CI 0.65 to 0.88; 12 RCTs, 21,665 participants; moderate-certainty evidence), it was also associated with an increase in symptomatic intracranial haemorrhage (OR 2.47; 95% CI 1.90 to 3.21; 20 RCTs, 23,221 participants; moderate-certainty evidence). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60, 95% CI 0.44 to 0.81; 14 RCTs, 22,544 participants; high-certainty evidence), but this benefit was offset by an increase in extracranial haemorrhage (OR 2.99, 95% CI 2.24 to 3.99; 18 RCTs, 22,255 participants; moderate-certainty evidence).\nAuthors' conclusions\nSince the last version of this review, four new relevant studies have been published, and conclusions remain consistent. People who have early anticoagulant therapy after acute ischaemic stroke do not demonstrate any net short- or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis, and pulmonary embolism but increased bleeding risk. Data do not support the routine use of any of the currently available anticoagulants for acute ischaemic stroke.\n\nGiven the provided abstract, please respond to the following query: \"Conclusion\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "This review did not provide any evidence to suggest that early use of anticoagulants is beneficial overall for people with stroke caused by blood clots. More research is needed to find out if there are ways to select people with stroke who will benefit most from anticoagulants without suffering the bleeding complications." } ]

[ { "role": "user", "content": "Abstract: Background\nTreadmill training, with or without body weight support using a harness, is used in rehabilitation and might help to improve walking after stroke. This is an update of the Cochrane review first published in 2003 and updated in 2005 and 2014.\nObjectives\nTo determine if treadmill training and body weight support, individually or in combination, improve walking ability, quality of life, activities of daily living, dependency or death, and institutionalisation or death, compared with other physiotherapy gait-training interventions after stroke. The secondary objective was to determine the safety and acceptability of this method of gait training.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (last searched 14 February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Reviews of Effects (DARE) (the Cochrane Library 2017, Issue 2), MEDLINE (1966 to 14 February 2017), Embase (1980 to 14 February 2017), CINAHL (1982 to 14 February 2017), AMED (1985 to 14 February 2017) and SPORTDiscus (1949 to 14 February 2017). We also handsearched relevant conference proceedings and ongoing trials and research registers, screened reference lists, and contacted trialists to identify further trials.\nSelection criteria\nRandomised or quasi-randomised controlled and cross-over trials of treadmill training and body weight support, individually or in combination, for the treatment of walking after stroke.\nData collection and analysis\nTwo review authors independently selected trials, extracted data, and assessed risk of bias and methodological quality. The primary outcomes investigated were walking speed, endurance, and dependency.\nMain results\nWe included 56 trials with 3105 participants in this updated review. The average age of the participants was 60 years, and the studies were carried out in both inpatient and outpatient settings. All participants had at least some walking difficulties and many could not walk without assistance. Overall, the use of treadmill training did not increase the chances of walking independently compared with other physiotherapy interventions (risk difference (RD) -0.00, 95% confidence interval (CI) -0.02 to 0.02; 18 trials, 1210 participants; P = 0.94; I² = 0%; low-quality evidence). Overall, the use of treadmill training in walking rehabilitation for people after stroke increased the walking velocity and walking endurance significantly. The pooled mean difference (MD) (random-effects model) for walking velocity was 0.06 m/s (95% CI 0.03 to 0.09; 47 trials, 2323 participants; P < 0.0001; I² = 44%; moderate-quality evidence) and the pooled MD for walking endurance was 14.19 metres (95% CI 2.92 to 25.46; 28 trials, 1680 participants; P = 0.01; I² = 27%; moderate-quality evidence). Overall, the use of treadmill training with body weight support in walking rehabilitation for people after stroke did not increase the walking velocity and walking endurance at the end of scheduled follow-up. The pooled MD (random-effects model) for walking velocity was 0.03 m/s (95% CI -0.05 to 0.10; 12 trials, 954 participants; P = 0.50; I² = 55%; low-quality evidence) and the pooled MD for walking endurance was 21.64 metres (95% CI -4.70 to 47.98; 10 trials, 882 participants; P = 0.11; I² = 47%; low-quality evidence). In 38 studies with a total of 1571 participants who were independent in walking at study onset, the use of treadmill training increased the walking velocity significantly. The pooled MD (random-effects model) for walking velocity was 0.08 m/s (95% CI 0.05 to 0.12; P < 0.00001; I2 = 49%). There were insufficient data to comment on any effects on quality of life or activities of daily living. Adverse events and dropouts did not occur more frequently in people receiving treadmill training and these were not judged to be clinically serious events.\nAuthors' conclusions\nOverall, people after stroke who receive treadmill training, with or without body weight support, are not more likely to improve their ability to walk independently compared with people after stroke not receiving treadmill training, but walking speed and walking endurance may improve slightly in the short term. Specifically, people with stroke who are able to walk (but not people who are dependent in walking at start of treatment) appear to benefit most from this type of intervention with regard to walking speed and walking endurance. This review did not find, however, that improvements in walking speed and endurance may have persisting beneficial effects. Further research should specifically investigate the effects of different frequencies, durations, or intensities (in terms of speed increments and inclination) of treadmill training, as well as the use of handrails, in ambulatory participants, but not in dependent walkers.\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 treadmill training for walking after stroke was low to moderate. It was moderate for walking speed and walking endurance at the end of treatment and low for improving the ability to walk independently." } ]

[ { "role": "user", "content": "Abstract: Background\nPancreatic and periampullary adenocarcinomas account for some of the most aggressive malignancies, and the leading causes of cancer-related mortalities. Partial pancreaticoduodenectomy (PD) with negative resection margins is the only potentially curative therapy. The high prevalence of lymph node metastases has led to the hypothesis that wider excision with the removal of more lymphatic tissue could result in an improvement of survival, and higher rates of negative resection margins.\nObjectives\nTo compare overall survival following standard (SLA) versus extended lymph lymphadenectomy (ELA) for pancreatic head and periampullary adenocarcinoma. We also compared secondary outcomes, such as morbidity, mortality, and tumour involvement of the resection margins between the two procedures.\nSearch methods\nWe searched CENTRAL, MEDLINE, PubMed, and Embase from 1973 to September 2020; we applied no language restrictions.\nSelection criteria\nRandomised controlled trials (RCT) comparing PD with SLA versus PD with ELA, including participants with pancreatic head and periampullary adenocarcinoma.\nData collection and analysis\nTwo review authors independently screened references and extracted data from study reports. We calculated pooled risk ratios (RR) for most binary outcomes except for postoperative mortality, for which we estimated a Peto odds ratio (Peto OR), and mean differences (MD) for continuous outcomes. We used a fixed-effect model in the absence of substantial heterogeneity (I² < 25%), and a random-effects model in cases of substantial heterogeneity (I² > 25%). Two review authors independently assessed risk of bias, and we used GRADE to assess the quality of the evidence for important outcomes.\nMain results\nWe included seven studies with 843 participants (421 ELA and 422 SLA).\nAll seven studies included Kaplan-Meier curves for overall survival. There was little or no difference in survival between groups (log hazard ratio (log HR) 0.12, 95% confidence interval (CI) -3.06 to 3.31; P = 0.94; seven studies, 843 participants; very low-quality evidence).\nThere was little or no difference in postoperative mortality between the groups (Peto odds ratio (OR) 1.20, 95% CI 0.51 to 2.80; seven studies, 843 participants; low-quality evidence).\nOperating time was probably longer for ELA (mean difference (MD) 50.13 minutes, 95% CI 19.19 to 81.06 minutes; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 88%; P < 0.00001).\nThere may have been more blood loss during ELA (MD 137.43 mL, 95% CI 11.55 to 263.30 mL; two studies, 463 participants; very low-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P = 0.02).\nThere may have been more lymph nodes retrieved during ELA (MD 11.09 nodes, 95% CI 7.16 to 15.02; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P < 0.00001).\nThere was little or no difference in the incidence of positive resection margins between groups (RR 0.81, 95% CI 0.58 to 1.13; six studies, 783 participants; very low-quality evidence).\nAuthors' conclusions\nThere is no evidence of an impact on survival with extended versus standard lymph node resection. However, the operating time may have been longer and blood loss greater in the extended resection group. In conclusion, current evidence neither supports nor refutes the effect of extended lymph lymphadenectomy in people with adenocarcinoma of the head of the pancreas.\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 attempted to find out whether more extensive surgical removal of lymph nodes had a positive effect on survival, recurrence, and eventual complications, and how their removal may affect the person’s quality of life." } ]

[ { "role": "user", "content": "Abstract: Background\nStaphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. This is an update of a previously published review.\nObjectives\nTo assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested the following hypotheses to investigate whether prophylaxis:\n1. improves clinical status, lung function and survival;\n2. leads to fewer isolates of Staphylococcus aureus;\n3. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis);\n4. leads to fewer isolates of other common pathogens from respiratory secretions;\n5. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa.\nSearch methods\nWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted.\nMost recent search of the Group's Register: 27 February 2020.\nOnline trials registries were also searched. Most recent search of online trials registries: 15 September 2020.\nSelection criteria\nRandomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity.\nData collection and analysis\nThe authors assessed studies for eligibility and methodological quality and extracted data. The quality of the evidence was assessed using the GRADE criteria. The review's primary outcomes of interest were lung function by spirometry (forced expiratory volume in one second (FEV1)) and the number of people with one or more isolates of Staphylococcus aureus (sensitive strains).\nMain results\nWe included four studies, with a total of 401 randomised participants aged zero to seven years on enrolment; one study is ongoing. The two older included studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results. Evidence quality was judged to be low for all outcomes assessed after being downgraded based on GRADE assessments. Downgrading decisions were due to limitations in study design (all outcomes), for imprecision and for inconsistency .\nProphylactic anti-staphylococcal antibiotics probably make little or no difference to lung function measured as FEV1 % predicted after six years (mean difference (MD) -2.30, 95% confidence interval (CI) -13.59 to 8.99, one study, n = 119, low-quality evidence); but may reduce the number of children having one or more isolates of Staphylococcus aureus at two years (odds ratio (OR) 0.21, 95% CI 0.13 to 0.35, three studies, n = 315, low-quality evidence). At the same time point, there may be little or no effect on nutrition as reported using weight z score (MD 0.06, 95% CI -0.33 to 0.45, two studies, n = 140, low-quality evidence), additional courses of antibiotics (OR 0.18, 95% CI 0.01 to 3.60, one study, n = 119, low-quality evidence) or adverse effects (low-quality evidence). There was no difference in the number of isolates of Pseudomonas aeruginosa between groups at two years (OR 0.74, 95% CI 0.45 to 1.23, three studies, n = 312, low-quality evidence), though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis.\nAuthors' conclusions\nAnti-staphylococcal antibiotic prophylaxis may lead to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.\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 review found some low-quality evidence that giving regular antibiotics to young children (continued up to six years of age) may lead to fewer infections with Staphylococcus aureus. For other outcomes in the review (weight, need for additional antibiotics, side effects or the number of infections with Pseudomonas aeruginosa) there was no difference between giving regular antibiotics or not. Since none of the studies lasted longer than six years, we can't draw any conclusions about long-term use. Also, since all studies were in children, we can not comment on the use of these drugs in adults. Future research should seek more fully to address whether this treatment reduces, increases or has no effect on subsequent rates of infection with Pseudomonas aeruginosa and look at patterns of antibiotic resistance and survival. A large ongoing study called CF-START aims to address these uncertainties." } ]

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

[ { "role": "user", "content": "Abstract: Background\nTotal hip arthroplasty (THA) is one of the most common orthopaedic operations performed worldwide. Painful osteoarthritis of the hip is the primary indication for THA. Following THA, people have conventionally been provided with equipment, such as raised toilet seats and chairs, and educated to avoid activities that could cause the hip joint to be in a position of flexion over 90 degrees, or adduction or rotation past the midline. These aspects of occupational therapy have been advocated to reduce the risks of prosthesis dislocation. However, the appropriateness of these recommendations has been questioned.\nObjectives\nTo assess the effects of provision of assistive devices, education on hip precautions, environmental modifications and training in activities of daily living (ADL) and extended ADL (EADL) for people undergoing THA.\nSearch methods\nWe searched MEDLINE (1946 to April 2016), EMBASE (1947 to April 2016), the Cochrane Library including CENTRAL (Issue 4 of 12, 2016), Database of Reviews of Effects (DARE), Health Technology Assessment (HTA), Economic Evaluations Database (EED), CINAHL, PEDro and CIRRIE from inception to April 2016. In addition we checked Controlled Clinical Trials, Clinicaltrials.gov, the National Institutes of Health Trial Registry, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the OpenGrey database from inception to April 2016.\nSelection criteria\nWe included randomised controlled trials (RCTs), quasi-RCTs and cluster-RCTs that evaluated the effectiveness of the provision of assistive devices, education on hip precautions, environmental modifications, or training in ADL and EADL for people undergoing THA. The main outcomes of interest were pain, function, health-related quality of life (HRQOL), global assessment of treatment success, reoperation rate, hip dislocation and adverse events.\nData collection and analysis\nWe used standard methodological procedures recognised by Cochrane. We conducted a systematic literature search using several databases and contacted corresponding authors, appraised the evidence using the Cochrane risk of bias tool, analysed the data using a narrative analysis approach (as it was not possible to conduct a meta-analysis due to heterogeneity in interventions), and interpreted all outcomes using the GRADE approach.\nMain results\nWe included three trials with a total of 492 participants who had received 530 THA. The evidence presented with a high risk of performance, detection and reporting bias.\nOne study (81 participants) compared outcomes for participants randomised to the provision of hip precautions, equipment and functional restrictions versus no provision of hip precautions, equipment or functional restrictions. Due to the quality of evidence being very low, we are uncertain if the provision of hip precautions, equipment and functional restrictions improved function measured using the Harris Hip Score at 12 month follow-up, or health-related quality of life (HRQOL) measured by the Short Form-12 at four week follow-up, compared to not providing this. There were no incidences of hip dislocation or adverse events in either group during the initial 12 postoperative months. The study did not measure pain score, global assessment of treatment success or total adverse events.\nOne study (265 participants; 303 THAs) evaluated the provision of hip precautions with versus without the prescription of postoperative equipment and restrictions to functional activities. Due to the quality of evidence being very low, we are uncertain if perceived satisfaction in the rate of recovery differed in people who were not prescribed postoperative equipment and restrictions (135/151 satisfied) compared to those prescribed equipment and restrictions (113/152) (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.93; 265 participants, one trial; number needed to treat for an additional beneficial outcome (NNTB) = 7). Due to the low quality evidence, we are uncertain if the incidence of hip dislocation differed between participants provided with hip precautions with (1/152) compared to without providing equipment or restrictions post-THA (0/151) (RR 2.98, 95% CI 0.12 to 72.59). The study did not measure pain, function, HRQOL, re-operation rates or total adverse events.\nOne study (146 participants) investigated the provision of an enhanced postoperative education and rehabilitation service on hospital discharge to promote functional ADL versus a conventional rehabilitation intervention in the community. This study was of very low quality evidence. We were uncertain if the provision of enhanced postoperative education and rehabilitation improved function at six months follow-up, when assessed using the Objective and Subjective Functional Capability Index (146 participants, one trial; P > 0.05; no numerical results provided) compared to conventional rehabilitation. The study did not measure pain score, HRQOL, global assessment of treatment success, hip dislocation, re-operation rate or total adverse events.\nAuthors' conclusions\nVery low quality evidence is available from single trials, thus we are uncertain if hip precautions with or without the addition of equipment and functional restrictions are effective in preventing dislocation and improving outcomes after THA. There is also insufficient evidence to support or refute the adoption of a postoperative community rehabilitation programme consisting of functional reintegration and education compared to conventional rehabilitation strategies based on functional outcomes.\nFurther high-quality trials are warranted to assess the outcomes of different occupational therapy interventions both in the short and longer-term for those who undergo THA. An assessment of the impact of such interventions on pain and restriction on personal ADL, EADL and instrumental ADL is needed, and also of functional integration-type interventions rather than just hip precautions, equipment and restrictions.\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": "One study compared outcomes for participants randomised to the provision of hip precautions, equipment and functional restrictions versus no provision of hip precautions or equipment or functional restrictions. This is the main comparator in the review.\nHealth-related quality of life (lower scores mean better quality of life)\nWe cannot tell from our results whether the intervention has an important effect on health-related quality of life (no numerical results provided) because the sample size was small and the study design flawed.\nFunction\nWe cannot tell from our results whether the intervention has an important effect on functional outcomes (no numerical results provided) because the sample size was small and the study design flawed.\nComplications and adverse events\nThere were no dislocations or adverse events.\nOutcomes of interest not measured\nPain, treatment success and re-operation rate were not measured." } ]

[ { "role": "user", "content": "Abstract: Background\nApproximately half of people with heart failure have chronic kidney disease (CKD). Pharmacological interventions for heart failure in people with CKD have the potential to reduce death (any cause) or hospitalisations for decompensated heart failure. However, these interventions are of uncertain benefit and may increase the risk of harm, such as hypotension and electrolyte abnormalities, in those with CKD.\nObjectives\nThis review aims to look at the benefits and harms of pharmacological interventions for HF (i.e., antihypertensive agents, inotropes, and agents that may improve the heart performance indirectly) in people with HF and CKD.\nSearch methods\nWe searched the Cochrane Kidney and Transplant Register of Studies through 12 September 2019 in consultation with an Information Specialist and using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.\nSelection criteria\nWe included randomised controlled trials of any pharmacological intervention for acute or chronic heart failure, among people of any age with chronic kidney disease of at least three months duration.\nData collection and analysis\nTwo authors independently screened the records to identify eligible studies and extracted data on the following dichotomous outcomes: death, hospitalisations, worsening heart failure, worsening kidney function, hyperkalaemia, and hypotension. We used random effects meta-analysis to estimate treatment effects, which we expressed as a risk ratio (RR) with 95% confidence intervals (CI). We assessed the risk of bias using the Cochrane tool. We applied the GRADE methodology to rate the certainty of evidence.\nMain results\nOne hundred and twelve studies met our selection criteria: 15 were studies of adults with CKD; 16 studies were conducted in the general population but provided subgroup data for people with CKD; and 81 studies included individuals with CKD, however, data for this subgroup were not provided. The risk of bias in all 112 studies was frequently high or unclear. Of the 31 studies (23,762 participants) with data on CKD patients, follow-up ranged from three months to five years, and study size ranged from 16 to 2916 participants. In total, 26 studies (19,612 participants) reported disaggregated and extractable data on at least one outcome of interest for our review and were included in our meta-analyses.\nIn acute heart failure, the effects of adenosine A1-receptor antagonists, dopamine, nesiritide, or serelaxin on death, hospitalisations, worsening heart failure or kidney function, hyperkalaemia, hypotension or quality of life were uncertain due to sparse data or were not reported.\nIn chronic heart failure, the effects of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (4 studies, 5003 participants: RR 0.85, 95% CI 0.70 to 1.02; I2 = 78%; low certainty evidence), aldosterone antagonists (2 studies, 34 participants: RR 0.61 95% CI 0.06 to 6.59; very low certainty evidence), and vasopressin receptor antagonists (RR 1.26, 95% CI 0.55 to 2.89; 2 studies, 1840 participants; low certainty evidence) on death (any cause) were uncertain. Treatment with beta-blockers may reduce the risk of death (any cause) (4 studies, 3136 participants: RR 0.69, 95% CI 0.60 to 0.79; I2 = 0%; moderate certainty evidence).\nTreatment with ACEi or ARB (2 studies, 1368 participants: RR 0.90, 95% CI 0.43 to 1.90; I2 = 97%; very low certainty evidence) had uncertain effects on hospitalisation for heart failure, as treatment estimates were consistent with either benefit or harm. Treatment with beta-blockers may decrease hospitalisation for heart failure (3 studies, 2287 participants: RR 0.67, 95% CI 0.43 to 1.05; I2 = 87%; low certainty evidence).\nAldosterone antagonists may increase the risk of hyperkalaemia compared to placebo or no treatment (3 studies, 826 participants: RR 2.91, 95% CI 2.03 to 4.17; I2 = 0%; low certainty evidence). Renin inhibitors had uncertain risks of hyperkalaemia (2 studies, 142 participants: RR 0.86, 95% CI 0.49 to 1.49; I2 = 0%; very low certainty). We were unable to estimate whether treatment with sinus node inhibitors affects the risk of hyperkalaemia, as there were few studies and meta-analysis was not possible. Hyperkalaemia was not reported for the CKD subgroup in studies investigating other therapies.\nThe effects of ACEi or ARB, or aldosterone antagonists on worsening heart failure or kidney function, hypotension, or quality of life were uncertain due to sparse data or were not reported.\nEffects of anti-arrhythmic agents, digoxin, phosphodiesterase inhibitors, renin inhibitors, sinus node inhibitors, vasodilators, and vasopressin receptor antagonists were very uncertain due to the paucity of studies.\nAuthors' conclusions\nThe effects of pharmacological interventions for heart failure in people with CKD are uncertain and there is insufficient evidence to inform clinical practice. Study data for treatment outcomes in patients with heart failure and CKD are sparse despite the potential impact of kidney impairment on the benefits and harms of treatment. Future research aimed at analysing existing data in general population HF studies to explore the effect in subgroups of patients with CKD, considering stage of disease, may yield valuable insights for the management of people with HF and CKD.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for all research studies that assessed the different treatments for heart failure up to September 2019. We evaluated whether medicines prevent death or hospital admissions, or increase risk of harm, for people with kidney disease. We also measured how certain we could be about the effects of these medicines on the body using a system called \"GRADE\"." } ]

[ { "role": "user", "content": "Abstract: Background\nBlood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed.\nObjectives\nTo examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders.\nSearch methods\nWe searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2017, issue 3) in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion Evidence Library (from 1980), and ongoing trial databases (all searches to 3 April 2017).\nSelection criteria\nWe included randomised controlled trials comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid, aprotinin) before, during, or immediately after surgery or after invasive procedures in adults or children.\nData collection and analysis\nWe used the standard methodological procedures expected by Cochrane.\nMain results\nWe identified 65 completed trials (3874 participants) and four ongoing trials. Of the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on vascular surgery; seven studies were conducted in surgery for other conditions. These trials were conducted between 1986 and 2016, and 11 were funded by pharmaceutical companies or by a party with a commercial interest in the outcome of the trial.\nThe GRADE quality of evidence was very low to moderate across all outcomes. No trial reported quality of life.\nDDAVP versus placebo or no treatment\nTrial results showed considerable heterogeneity between surgical settings for total volume of red cells transfused (low-quality evidence) and for total blood loss (very low-quality evidence) due to large differences in baseline blood loss. Consequently, these outcomes were not pooled and were reported in subgroups.\nCompared with placebo, DDAVP may slightly decrease the total volume of red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units, 95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants), but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI -0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95% CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD -0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants).\nDDAVP probably leads to little or no difference in the total number of participants transfused with blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants) (moderate-quality evidence).\nWhether DDAVP decreases total blood loss in adult cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358 participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53 mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI -1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the quality of evidence is very low.\nDDAVP probably leads to little or no difference in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22 trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to 2.16; 29 trials, 1984 participants) (both low-quality evidence).\nDDAVP versus placebo or no treatment for people with platelet dysfunction\nCompared with placebo, DDAVP may lead to a reduction in the total volume of red cells transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388 participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95% CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality evidence).\nDDAVP probably leads to little or no difference in the total number of participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5 trials, 258 participants) (moderate-quality evidence).\nWhether DDAVP leads to a difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422 participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials, 422 participants) is uncertain because the quality of evidence is very low.\nDDAVP versus tranexamic acid\nCompared with tranexamic acid, DDAVP may increase the volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40 participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2 trials, 115 participants) (both low-quality evidence).\nWhether DDAVP increases or decreases the total number of participants transfused with blood is uncertain because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3 trials, 135 participants).\nNo trial reported all-cause mortality.\nWhether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115 participants).\nDDAVP versus aprotinin\nCompared with aprotinin, DDAVP probably increases the total number of participants transfused with blood (RR 2.41, 95% CI 1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence).\nNo trials reported volume of blood transfused or total blood loss and the single trial that included mortality as an outcome reported no deaths.\nWhether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants).\nAuthors' conclusions\nMost of the evidence derived by comparing DDAVP versus placebo was obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary bypass. In adults undergoing cardiac surgery, the reduction in volume of red cells transfused and total blood loss was small and was unlikely to be clinically important. It is less clear whether DDAVP may be of benefit for children and for those undergoing non-cardiac surgery. A key area for researchers is examining the effects of DDAVP for people with platelet dysfunction. Few trials have compared DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the relative efficacy of these interventions.\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": "Compared with placebo (an inactive substance that looks the same as the substance being tested, i.e. DDAVP) or no treatment, DDAVP may slightly reduce the amount of blood transfused in adult heart surgery. DDAVP may lead to little or no difference in the amount of blood transfused in heart surgery for children, bone and joint surgery, surgery on major blood vessels, or liver surgery. DDAVP probably leads to little or no difference in the total number of people who receive a blood transfusion. Whether DDAVP increases or reduces total blood loss is uncertain because the quality of evidence is very low. DDAVP may lead to little or no difference in the risk of death, heart attack, or stroke.\nFor people who are more vulnerable to bleeding because they are taking an antiplatelet medicine that stops their blood from clotting normally, DDAVP may lead to a reduction in the total volume of red cells transfused and in total blood loss. It probably leads to little or no difference in the number of people receiving a red cell transfusion. Whether DDAVP increases or reduces the risk of death, heart attack, or stroke is uncertain because the quality of evidence is very low.\nCompared with tranexamic acid (a medication used to treat or prevent excessive blood loss) DDAVP may be less effective in reducing the volume of blood transfused and total blood loss. Whether DDAVP increases or reduces the number of people who receive a blood transfusion, or risk of death, heart attack, or stroke is uncertain because the quality of evidence is very low.\nCompared with aprotinin (another medication used to reduce bleeding) DDAVP probably increases the number of people who receive a blood transfusion. Whether it increases or decreases the risk of a heart attack or stroke is uncertain because the quality of evidence is very low. No trials comparing DDAVP against aprotinin reported the volume of blood transfused, total blood loss, or risk of death.\nNone of the 65 trials assessed quality of life." } ]

[ { "role": "user", "content": "Abstract: Background\nResearch suggests that measurable change in cerebrospinal fluid (CSF) biomarkers occurs years in advance of the onset of clinical symptoms (Beckett 2010). In this review, we aimed to assess the ability of CSF tau biomarkers (t-tau and p-tau) and the CSF tau (t-tau or p-tau)/ABeta ratio to enable the detection of Alzheimer’s disease pathology in patients with mild cognitive impairment (MCI). These biomarkers have been proposed as important in new criteria for Alzheimer's disease dementia that incorporate biomarker abnormalities.\nObjectives\nTo determine the diagnostic accuracy of 1) CSF t-tau, 2) CSF p-tau, 3) the CSF t-tau/ABeta ratio and 4) the CSF p-tau/ABeta ratio index tests for detecting people with MCI at baseline who would clinically convert to Alzheimer’s disease dementia or other forms of dementia at follow-up.\nSearch methods\nThe most recent search for this review was performed in January 2013. We searched MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection, including Conference Proceedings Citation Index (Thomson Reuters Web of Science), PsycINFO (OvidSP), and LILACS (BIREME). We searched specialized sources of diagnostic test accuracy studies and reviews. We checked reference lists of relevant studies and reviews for additional studies. We contacted researchers for possible relevant but unpublished data. We did not apply any language or data restriction to the electronic searches. We did not use any methodological filters as a method to restrict the search overall.\nSelection criteria\nWe selected those studies that had prospectively well-defined cohorts with any accepted definition of MCI and with CSF t-tau or p-tau and CSF tau (t-tau or p-tau)/ABeta ratio values, documented at or around the time the MCI diagnosis was made. We also included studies which looked at data from those cohorts retrospectively, and which contained sufficient data to construct two by two tables expressing those biomarker results by disease status. Moreover, studies were only selected if they applied a reference standard for Alzheimer's disease dementia diagnosis, for example, the NINCDS-ADRDA or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.\nData collection and analysis\nWe screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies, and the full papers for eligibility. Two independent assessors performed data extraction and quality assessment. Where data allowed, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic (ROC) curve.\nMain results\nIn total, 1282 participants with MCI at baseline were identified in the 15 included studies of which 1172 had analysable data; 430 participants converted to Alzheimer’s disease dementia and 130 participants to other forms of dementia. Follow-up ranged from less than one year to over four years for some participants, but in the majority of studies was in the range one to three years.\nConversion to Alzheimer’s disease dementia\nThe accuracy of the CSF t-tau was evaluated in seven studies (291 cases and 418 non-cases).The sensitivity values ranged from 51% to 90% while the specificity values ranged from 48% to 88%. At the median specificity of 72%, the estimated sensitivity was 75% (95% CI 67 to 85), the positive likelihood ratio was 2.72 (95% CI 2.43 to 3.04), and the negative likelihood ratio was 0.32 (95% CI 0.22 to 0.47).\nSix studies (164 cases and 328 non-cases) evaluated the accuracy of the CSF p-tau. The sensitivities were between 40% and 100% while the specificities were between 22% and 86%. At the median specificity of 47.5%, the estimated sensitivity was 81% (95% CI: 64 to 91), the positive likelihood ratio was 1.55 (CI 1.31 to 1.84), and the negative likelihood ratio was 0.39 (CI: 0.19 to 0.82).\nFive studies (140 cases and 293 non-cases) evaluated the accuracy of the CSF p-tau/ABeta ratio. The sensitivities were between 80% and 96% while the specificities were between 33% and 95%. We did not conduct a meta-analysis because the studies were few and small. Only one study reported the accuracy of CSF t-tau/ABeta ratio.\nOur findings are based on studies with poor reporting. A significant number of studies had unclear risk of bias for the reference standard, participant selection and flow and timing domains. According to the assessment of index test domain, eight of 15 studies were of poor methodological quality.\nThe accuracy of these CSF biomarkers for ‘other dementias’ had not been investigated in the included primary studies.\nInvestigation of heterogeneity\nThe main sources of heterogeneity were thought likely to be reference standards used for the target disorders, sources of recruitment, participant sampling, index test methodology and aspects of study quality (particularly, inadequate blinding).\nWe were not able to formally assess the effect of each potential source of heterogeneity as planned, due to the small number of studies available to be included.\nAuthors' conclusions\nThe insufficiency and heterogeneity of research to date primarily leads to a state of uncertainty regarding the value of CSF testing of t-tau, p-tau or p-tau/ABeta ratio for the diagnosis of Alzheimer's disease in current clinical practice. Particular attention should be paid to the risk of misdiagnosis and overdiagnosis of dementia (and therefore over-treatment) in clinical practice. These tests, like other biomarker tests which have been subject to Cochrane DTA reviews, appear to have better sensitivity than specificity and therefore might have greater utility in ruling out Alzheimer's disease as the aetiology to the individual's evident cognitive impairment, as opposed to ruling it in. The heterogeneity observed in the few studies awaiting classification suggests our initial summary will remain valid. However, these tests may have limited clinical value until uncertainties have been addressed. Future studies with more uniformed approaches to thresholds, analysis and study conduct may provide a more homogenous estimate than the one that has been available from the included studies we have identified.\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": "Our findings are based on studies with poor reporting, with a majority of studies at unclear risk of bias due to insufficient details given on how participants were selected and how the clinical diagnosis of dementia was established. According to the assessment of how the CSF tests were conducted and analysed, eight of 15 studies were of poor methodological quality." } ]

[ { "role": "user", "content": "Abstract: Background\nPulmonary rehabilitation is a proven, effective intervention for people with chronic respiratory diseases including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and bronchiectasis. However, relatively few people attend or complete a program, due to factors including a lack of programs, issues associated with travel and transport, and other health issues. Traditionally, pulmonary rehabilitation is delivered in-person on an outpatient basis at a hospital or other healthcare facility (referred to as centre-based pulmonary rehabilitation). Newer, alternative modes of pulmonary rehabilitation delivery include home-based models and the use of telehealth.\nTelerehabilitation is the delivery of rehabilitation services at a distance, using information and communication technology. To date, there has not been a comprehensive assessment of the clinical efficacy or safety of telerehabilitation, or its ability to improve uptake and access to rehabilitation services, for people with chronic respiratory disease.\nObjectives\nTo determine the effectiveness and safety of telerehabilitation for people with chronic respiratory disease.\nSearch methods\nWe searched the Cochrane Airways Trials Register, and the Cochrane Central Register of Controlled Trials; six databases including MEDLINE and Embase; and three trials registries, up to 30 November 2020. We checked reference lists of all included studies for additional references, and handsearched relevant respiratory journals and meeting abstracts.\nSelection criteria\nAll randomised controlled trials and controlled clinical trials of telerehabilitation for the delivery of pulmonary rehabilitation were eligible for inclusion. The telerehabilitation intervention was required to include exercise training, with at least 50% of the rehabilitation intervention being delivered by telerehabilitation.\nData collection and analysis\nWe used standard methods recommended by Cochrane. We assessed the risk of bias for all studies, and used the ROBINS-I tool to assess bias in non-randomised controlled clinical trials. We assessed the certainty of evidence with GRADE. Comparisons were telerehabilitation compared to traditional in-person (centre-based) pulmonary rehabilitation, and telerehabilitation compared to no rehabilitation. We analysed studies of telerehabilitation for maintenance rehabilitation separately from trials of telerehabilitation for initial primary pulmonary rehabilitation.\nMain results\nWe included a total of 15 studies (32 reports) with 1904 participants, using five different models of telerehabilitation. Almost all (99%) participants had chronic obstructive pulmonary disease (COPD). Three studies were controlled clinical trials. For primary pulmonary rehabilitation, there was probably little or no difference between telerehabilitation and in-person pulmonary rehabilitation for exercise capacity measured as 6-Minute Walking Distance (6MWD) (mean difference (MD) 0.06 metres (m), 95% confidence interval (CI) -10.82 m to 10.94 m; 556 participants; four studies; moderate-certainty evidence). There may also be little or no difference for quality of life measured with the St George's Respiratory Questionnaire (SGRQ) total score (MD -1.26, 95% CI -3.97 to 1.45; 274 participants; two studies; low-certainty evidence), or for breathlessness on the Chronic Respiratory Questionnaire (CRQ) dyspnoea domain score (MD 0.13, 95% CI -0.13 to 0.40; 426 participants; three studies; low-certainty evidence). Participants were more likely to complete a program of telerehabilitation, with a 93% completion rate (95% CI 90% to 96%), compared to a 70% completion rate for in-person rehabilitation. When compared to no rehabilitation control, trials of primary telerehabilitation may increase exercise capacity on 6MWD (MD 22.17 m, 95% CI -38.89 m to 83.23 m; 94 participants; two studies; low-certainty evidence) and may also increase 6MWD when delivered as maintenance rehabilitation (MD 78.1 m, 95% CI 49.6 m to 106.6 m; 209 participants; two studies; low-certainty evidence). No adverse effects of telerehabilitation were noted over and above any reported for in-person rehabilitation or no rehabilitation.\nAuthors' conclusions\nThis review suggests that primary pulmonary rehabilitation, or maintenance rehabilitation, delivered via telerehabilitation for people with chronic respiratory disease achieves outcomes similar to those of traditional centre-based pulmonary rehabilitation, with no safety issues identified. However, the certainty of the evidence provided by this review is limited by the small number of studies, of varying telerehabilitation models, with relatively few participants. Future research should consider the clinical effect of telerehabilitation for individuals with chronic respiratory diseases other than COPD, the duration of benefit of telerehabilitation beyond the period of the intervention, and the economic cost of telerehabilitation.\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": "For people with chronic lung conditions, pulmonary rehabilitation is proven to improve physical functioning and general well-being, and to reduce symptoms, particularly breathlessness. Pulmonary rehabilitation is a program of exercise training and education that is traditionally offered as an in-person program at a healthcare facility such as a hospital, where people attend program appointments but are not hospitalised overnight. To make it easier for more people to access pulmonary rehabilitation, new ways of delivering programs using technology have been investigated. Pulmonary rehabilitation delivered using technology is known as telerehabilitation. Telerehabilitation models can include (but are not limited to) talking with a health professional and/or other patients on the telephone, using a website or mobile application, or via video-conferencing. In some circumstances, undertaking telerehabilitation may require patients to have access to their own device (e.g. telephone, smart phone, tablet or computer) in order to participate." } ]

[ { "role": "user", "content": "Abstract: Background\nVenous thromboembolism (VTE) is a collective term for two conditions: deep vein thrombosis (DVT) and pulmonary embolism (PE). A proportion of people with VTE have no underlying or immediately predisposing risk factors and the VTE is referred to as unprovoked. Unprovoked VTE can often be the first clinical manifestation of an underlying malignancy. This has raised the question of whether people with an unprovoked VTE should be investigated for an underlying cancer. Treatment for VTE is different in cancer and non-cancer patients and a correct diagnosis would ensure that people received the optimal treatment for VTE to prevent recurrence and further morbidity. Furthermore, an appropriate cancer diagnosis at an earlier stage could avoid the risk of cancer progression and lead to improvements in cancer-related mortality and morbidity. This is the third update of the review first published in 2015.\nObjectives\nTo determine whether testing for undiagnosed cancer in people with a first episode of unprovoked VTE (DVT of the lower limb or PE) is effective in reducing cancer- or VTE-related mortality and morbidity and to determine which tests for cancer are best at identifying treatable cancers early.\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 5 May 2021. We also undertook reference checking to identify additional studies.\nSelection criteria\nRandomised and quasi-randomised trials in which people with an unprovoked VTE were allocated to receive specific tests for identifying cancer or clinically indicated tests only were eligible for inclusion.\nData collection and analysis\nTwo review authors independently selected studies, assessed risk of bias and extracted data. We assessed the certainty of the evidence using GRADE criteria. We resolved any disagreements by discussion. The main outcomes of interest were all-cause mortality, cancer-related mortality and VTE-related mortality.\nMain results\nNo new studies were identified for this 2021 update. In total, four studies with 1644 participants are included. Two studies assessed the effect of extensive tests including computed tomography (CT) scanning versus tests at the physician's discretion, while the other two studies assessed the effect of standard testing plus positron emission tomography (PET)/CT scanning versus standard testing alone. For extensive tests including CT versus tests at the physician's discretion, the certainty of the evidence, as assessed according to GRADE, was low due to risk of bias (early termination of the studies). When comparing standard testing plus PET/CT scanning versus standard testing alone, the certainty of evidence was moderate due to a risk of detection bias. The certainty of the evidence was downgraded further as detection bias was present in one study with a low number of events.\nWhen comparing extensive tests including CT versus tests at the physician's discretion, pooled analysis on two studies showed that testing for cancer was consistent with either benefit or no benefit on cancer-related mortality (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.15 to 1.67; 396 participants; 2 studies; low-certainty evidence). One study (201 participants) showed that, overall, malignancies were less advanced at diagnosis in extensively tested participants than in participants in the control group. In total, 9/13 participants diagnosed with cancer in the extensively tested group had a T1 or T2 stage malignancy compared to 2/10 participants diagnosed with cancer in the control group (OR 5.00, 95% CI 1.05 to 23.76; low-certainty evidence). There was no clear difference in detection of advanced stages between extensive tests versus tests at the physician's discretion: one participant in the extensively tested group had stage T3 compared with four participants in the control group (OR 0.25, 95% CI 0.03 to 2.28; low-certainty evidence). In addition, extensively tested participants were diagnosed earlier than control group (mean: 1 month with extensive tests versus 11.6 months with tests at physician's discretion to cancer diagnosis from the time of diagnosis of VTE). Extensive testing did not increase the frequency of an underlying cancer diagnosis (OR 1.32, 95% CI 0.59 to 2.93; 396 participants; 2 studies; low-certainty evidence). Neither study measured all-cause mortality, VTE-related morbidity and mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life.\nWhen comparing standard testing plus PET/CT screening versus standard testing alone, standard testing plus PET/CT screening was consistent with either benefit or no benefit on all-cause mortality (OR 1.22, 95% CI 0.49 to 3.04; 1248 participants; 2 studies; moderate-certainty evidence), cancer-related mortality (OR 0.55, 95% CI 0.20 to 1.52; 1248 participants; 2 studies; moderate-certainty evidence) or VTE-related morbidity (OR 1.02, 95% CI 0.48 to 2.17; 854 participants; 1 study; moderate-certainty evidence). Regarding stage of cancer, there was no clear difference for detection of early (OR 1.78, 95% 0.51 to 6.17; 394 participants; 1 study; low-certainty evidence) or advanced (OR 1.00, 95% CI 0.14 to 7.17; 394 participants; 1 study; low-certainty evidence) stages of cancer. There was also no clear difference in the frequency of an underlying cancer diagnosis (OR 1.71, 95% CI 0.91 to 3.20; 1248 participants; 2 studies; moderate-certainty evidence). Time to cancer diagnosis was 4.2 months in the standard testing group and 4.0 months in the standard testing plus PET/CT group (P = 0.88). Neither study measured VTE-related mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life.\nAuthors' conclusions\nSpecific testing for cancer in people with unprovoked VTE may lead to earlier diagnosis of cancer at an earlier stage of the disease. However, there is currently insufficient evidence to draw definitive conclusions concerning the effectiveness of testing for undiagnosed cancer in people with a first episode of unprovoked VTE (DVT or PE) in reducing cancer- or VTE-related morbidity and mortality. The results could be consistent with either benefit or no benefit. Further good-quality large-scale randomised controlled trials are required before firm conclusions can be made.\n\nGiven the provided abstract, please respond to the following query: \"What did we do?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We searched for randomised controlled studies that assessed whether testing for undiagnosed cancer in people with a first unprovoked VTE (DVT or PE) was effective in reducing cancer and VTE-related illness and death. In randomised controlled studies the treatments or tests people receive are decided at random and these usually give the most reliable evidence about treatment effects." } ]

[ { "role": "user", "content": "Abstract: Background\nHealth services have traditionally been developed to focus on specific diseases or medical specialties. Involving consumers as partners in planning, delivering and evaluating health services may lead to services that are person-centred and so better able to meet the needs of and provide care for individuals. Globally, governments recommend consumer involvement in healthcare decision-making at the systems level, as a strategy for promoting person-centred health services. However, the effects of this 'working in partnership' approach to healthcare decision-making are unclear. Working in partnership is defined here as collaborative relationships between at least one consumer and health provider, meeting jointly and regularly in formal group formats, to equally contribute to and collaborate on health service-related decision-making in real time. In this review, the terms 'consumer' and 'health provider' refer to partnership participants, and 'health service user' and 'health service provider' refer to trial participants.\nThis review of effects of partnership interventions was undertaken concurrently with a Cochrane Qualitative Evidence Synthesis (QES) entitled Consumers and health providers working in partnership for the promotion of person-centred health services: a co-produced qualitative evidence synthesis.\nObjectives\nTo assess the effects of consumers and health providers working in partnership, as an intervention to promote person-centred health services.\nSearch methods\nWe searched the CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL databases from 2000 to April 2019; PROQUEST Dissertations and Theses Global from 2016 to April 2019; and grey literature and online trial registries from 2000 until September 2019.\nSelection criteria\nWe included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs of ‘working in partnership’ interventions meeting these three criteria: both consumer and provider participants meet; they meet jointly and regularly in formal group formats; and they make actual decisions that relate to the person-centredness of health service(s).\nData collection and analysis\nTwo review authors independently screened most titles and abstracts. One review author screened a subset of titles and abstracts (i.e. those identified through clinical trials registries searches, those classified by the Cochrane RCT Classifier as unlikely to be an RCT, and those identified through other sources). Two review authors independently screened all full texts of potentially eligible articles for inclusion. In case of disagreement, they consulted a third review author to reach consensus. One review author extracted data and assessed risk of bias for all included studies and a second review author independently cross-checked all data and assessments. Any discrepancies were resolved by discussion, or by consulting a third review author to reach consensus. Meta-analysis was not possible due to the small number of included trials and their heterogeneity; we synthesised results descriptively by comparison and outcome. We reported the following outcomes in GRADE ‘Summary of findings’ tables: health service alterations; the degree to which changed service reflects health service user priorities; health service users' ratings of health service performance; health service users' health service utilisation patterns; resources associated with the decision-making process; resources associated with implementing decisions; and adverse events.\nMain results\nWe included five trials (one RCT and four cluster-RCTs), with 16,257 health service users and more than 469 health service providers as trial participants. For two trials, the aims of the partnerships were to directly improve the person-centredness of health services (via health service planning, and discharge co-ordination). In the remaining trials, the aims were indirect (training first-year medical doctors on patient safety) or broader in focus (which could include person-centredness of health services that targeted the public/community, households or health service delivery to improve maternal and neonatal mortality). Three trials were conducted in high income-countries, one was in a middle-income country and one was in a low-income country. Two studies evaluated working in partnership interventions, compared to usual practice without partnership (Comparison 1); and three studies evaluated working in partnership as part of a multi-component intervention, compared to the same intervention without partnership (Comparison 2). No studies evaluated one form of working in partnership compared to another (Comparison 3).\nThe effects of consumers and health providers working in partnership compared to usual practice without partnership are uncertain: only one of the two studies that assessed this comparison measured health service alteration outcomes, and data were not usable, as only intervention group data were reported. Additionally, none of the included studies evaluating this comparison measured the other primary or secondary outcomes we sought for the 'Summary of findings' table.\nWe are also unsure about the effects of consumers and health providers working in partnership as part of a multi-component intervention compared to the same intervention without partnership. Very low-certainty evidence indicated there may be little or no difference on health service alterations or health service user health service performance ratings (two studies); or on health service user health service utilisation patterns and adverse events (one study each). No studies evaluating this comparison reported the degree to which health service alterations reflect health service user priorities, or resource use.\nOverall, our confidence in the findings about the effects of working in partnership interventions was very low due to indirectness, imprecision and publication bias, and serious concerns about risk of selection bias; performance bias, detection bias and reporting bias in most studies.\nAuthors' conclusions\nThe effects of consumers and providers working in partnership as an intervention, or as part of a multi-component intervention, are uncertain, due to a lack of high-quality evidence and/or due to a lack of studies. Further well-designed RCTs with a clear focus on assessing outcomes directly related to partnerships for patient-centred health services are needed in this area, which may also benefit from mixed-methods and qualitative research to build the evidence base.\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 five studies that involved a total of 16,257 health service users and more than 469 health service providers. Three studies took place in high income-countries and one each in middle- and low-income countries.\nThe studies compared:\n- working in partnership against usual practice without partnership working (2 studies); and\n- working in partnership as part of a wider strategy to promote person-centred health services, against the same wider strategy without partnership working (3 studies).\nNo studies evaluated one form of working in partnership compared to another." } ]

[ { "role": "user", "content": "Abstract: Background\nTiotropium and ipratropium bromide are both recognised treatments in the management of people with stable chronic obstructive pulmonary disease (COPD). There are new studies which have compared tiotropium with ipratropium bromide, making an update necessary.\nObjectives\nTo compare the relative effects of tiotropium to ipratropium bromide on markers of quality of life, exacerbations, symptoms, lung function and serious adverse events in patients with COPD using available randomised controlled trial (RCT) data.\nSearch methods\nWe identified RCTs from the Cochrane Airways Group Specialised Register of trials (CAGR) and ClinicalTrials.gov up to August 2015.\nSelection criteria\nWe included parallel group RCTs of 12 weeks duration or longer comparing treatment with tiotropium with ipratropium bromide for patients with stable COPD.\nData collection and analysis\nTwo review authors independently assessed studies for inclusion and then extracted data on study quality and outcome results. We contacted trial sponsors for additional information. We analysed the data using Cochrane Review Manager.\nMain results\nThis review included two studies of good methodological quality that enrolled 1073 participants with COPD. The studies used a similar design and inclusion criteria and were of at least 12 weeks duration; the participants had a mean forced expiratory volume in one second (FEV1) of 40% predicted value at baseline. One study used tiotropium via the HandiHaler (18 µg) for 12 months and the other via the Respimat device (5 µg and 10 µg) for 12 weeks. In general, the treatment groups were well matched at baseline but not all outcomes were reported for both studies. Overall the risk of bias across the included RCTs was low.\nFor primary outcomes this review found that at the three months trough (the lowest level measured before treatment) FEV1 significantly increased with tiotropium compared to ipratropium bromide (mean difference (MD) 109 mL; 95% confidence interval (CI) 81 to 137, moderate quality evidence, I2 = 62%). There were fewer people experiencing one or more non-fatal serious adverse events on tiotropium compared to ipratropium (odds ratio (OR) 0.5; 95% CI 0.34 to 0.73, high quality evidence). This represents an absolute reduction in risk from 176 to 97 per 1000 people over three to 12 months. Concerning disease specific adverse events, the tiotropium group were also less likely to experience a COPD-related serious adverse event when compared to ipratropium bromide (OR 0.59; 95% CI 0.41 to 0.85, moderate quality evidence).\nFor secondary outcomes, both studies reported fewer hospital admissions in the tiotropium group (OR 0.34; 95% CI 0.15 to 0.70, moderate quality evidence); as well as fewer patients experiencing one or more exacerbations leading to hospitalisation in the people on tiotropium in both studies (OR 0.56; 95% CI 0.31 to 0.99, moderate quality evidence). There was no significant difference in mortality between the treatments (OR 1.39; 95% CI 0.44 to 4.39, moderate quality evidence). One study measured quality of life using the St George's Respiratory Questionnaire (SGRQ); the mean SGRQ score at 52 weeks was lower in the tiotropium group than the ipratropium group (lower on the scale is favourable) (MD -3.30; 95% CI -5.63 to -0.97, moderate quality evidence). There were fewer participants suffering one of more exacerbations in the tiotropium arm (OR 0.71; 95% CI 0.52 to 0.95, high quality evidence) and there was also a reported difference in the mean number of exacerbations per person per year which reached statistical significance (MD -0.23; 95% CI -0.39 to -0.07, P = 0.006, moderate quality evidence). From the 1073 participants there were significantly fewer withdrawals from the tiotropium group (OR 0.58; 95% CI 0.41 to 0.83, high quality evidence).\nAuthors' conclusions\nThis review shows that tiotropium treatment, when compared with ipratropium bromide, was associated with improved lung function, fewer hospital admissions (including those for exacerbations of COPD), fewer exacerbations of COPD and improved quality of life. There were both fewer serious adverse events and disease specific events in the tiotropium group, but no significant difference in deaths with ipratropium bromide when compared to tiotropium. Thus, tiotropium appears to be a reasonable choice (instead of ipratropium bromide) for patients with stable COPD, as proposed in guidelines. A recent large double-blind trial of the two delivery devices found no substantial difference in mortality using 2.5 µg or 5 µg of tiotropium via Respimat in comparison to 18 µg via Handihaler.\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 evidence was of moderate to high quality. Tiotrpium is available in two different inhalers, Respimat and Handihaler. A recent large double-blind trial of the two delivery devices found no substantial difference in mortality using 2.5 µg or 5 µg of tiotropium via Respimat in comparison to 18 µg via Handihaler." } ]

[ { "role": "user", "content": "Abstract: Background\nThe common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study.\nObjectives\nTo compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults.\nSearch methods\nWe searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015).\nSelection criteria\nRandomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management.\nData collection and analysis\nTwo review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence.\nMain results\nWe included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data.\nAuthors' conclusions\nCurrent evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.\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": "Common colds are experienced by over half a billion patients annually in the USA alone and result in significant loss of productivity. Although there are a number of medications used to help improve the symptoms of the common cold, none have good evidence of benefit. Steroids (corticosteroids) have been shown to help relieve symptoms in other types of upper respiratory tract infections by reducing the inflammation of the lining of the nose and throat, which means they might also improve the symptoms of the common cold." } ]

[ { "role": "user", "content": "Abstract: Background\nAttention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric conditions affecting children and adolescents. Amphetamines are among the most commonly prescribed medications to manage ADHD. There are three main classes of amphetamines: dexamphetamine, lisdexamphetamine and mixed amphetamine salts, which can be further broken down into short- and long-acting formulations. A systematic review assessing their efficacy and safety in this population has never been conducted.\nObjectives\nTo assess the efficacy and safety of amphetamines for ADHD in children and adolescents.\nSearch methods\nIn August 2015 we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, ProQuest Dissertation and Theses, and the Networked Digital Library of Theses and Dissertations. We also searched ClinicalTrials.gov, and checked the reference lists of relevant studies and reviews identified by the searches. No language or date restrictions were applied.\nSelection criteria\nParallel-group and cross-over randomized controlled trials (RCTs) comparing amphetamine derivatives against placebo in a pediatric population (< 18 years) with ADHD.\nData collection and analysis\nTwo authors independently extracted data on participants, settings, interventions, methodology, and outcomes for each included study. For continuous outcomes, we calculated the standardized mean difference (SMD) and for dichotomous outcomes we calculated the risk ratio (RR). Where possible, we conducted meta-analyses using a random-effects model. We also performed a meta-analysis of the most commonly reported adverse events in the primary studies.\nMain results\nWe included 23 trials (8 parallel-group and 15 cross-over trials), with 2675 children aged three years to 17 years. All studies compared amphetamines to placebo. Study durations ranged from 14 days to 365 days, with the majority lasting less than six months. Most studies were conducted in the United States; three studies were conducted across Europe. We judged 11 included studies to be at a high risk of bias due to insufficient blinding methods, failing to account for dropouts and exclusions from the analysis, and failing to report on all outcomes defined a priori. We judged the remaining 12 studies to be at unclear risk of bias due to inadequate reporting.\nAmphetamines improved total ADHD core symptom severity according to parent ratings (SMD -0.57; 95% confidence interval (CI) -0.86 to -0.27; 7 studies; 1247 children/adolescents; very low quality evidence), teacher ratings (SMD -0.55; 95% CI -0.83 to -0.27; 5 studies; 745 children/adolescents; low quality evidence), and clinician ratings (SMD -0.84; 95% CI -1.32 to -0.36; 3 studies; 813 children/adolescents; very low quality evidence). In addition, the proportion of responders as rated by the Clinical Global Impression - Improvement (CGI-I) scale was higher when children were taking amphetamines (RR 3.36; 95% CI 2.48 to 4.55; 9 studies; 2207 children/adolescents; very low quality evidence).\nThe most commonly reported adverse events included decreased appetite, insomnia/trouble sleeping, abdominal pain, nausea/vomiting, headaches, and anxiety. Amphetamines were associated with a higher proportion of participants experiencing decreased appetite (RR 6.31; 95% CI 2.58 to 15.46; 11 studies; 2467 children/adolescents), insomnia (RR 3.80; 95% CI 2.12 to 6.83; 10 studies; 2429 children/adolescents), and abdominal pain (RR 1.44; 95% CI 1.03 to 2.00; 10 studies; 2155 children/adolescents). In addition, the proportion of children who experienced at least one adverse event was higher in the amphetamine group (RR 1.30; 95% CI 1.18 to 1.44; 6 studies; 1742 children/adolescents; low quality evidence).\nWe performed subgroup analyses for amphetamine preparation (dexamphetamine, lisdexamphetamine, mixed amphetamine salts), amphetamine release formulation (long acting versus short acting), and funding source (industry versus non industry). Between-group differences were observed for proportion of participants experiencing decreased appetite in both the amphetamine preparation (P < 0.00001) and amphetamine release formulation (P value = 0.008) subgroups, as well as for retention in the amphetamine release formulation subgroup (P value = 0.03).\nAuthors' conclusions\nMost of the included studies were at high risk of bias and the overall quality of the evidence ranged from low to very low on most outcomes. Although amphetamines seem efficacious at reducing the core symptoms of ADHD in the short term, they were associated with a number of adverse events. This review found no evidence that supports any one amphetamine derivative over another, and does not reveal any differences between long-acting and short-acting amphetamine preparations. Future trials should be longer in duration (i.e. more than 12 months), include more psychosocial outcomes (e.g. quality of life and parent stress), and be transparently reported.\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": "Do children and adolescents (under 18 years of age) diagnosed with ADHD benefit from treatment with amphetamines to reduce the core symptoms of ADHD, compared to other children and adolescents who receive no drug or a fake drug (placebo)?" } ]

[ { "role": "user", "content": "Abstract: Background\nSince the introduction of the Swedish back school in 1969, back schools have frequently been used for treating people with low-back pain (LBP). However, the content of back schools has changed and appears to vary widely today. In this review we defined back school as a therapeutic programme given to groups of people, which includes both education and exercise. This is an update of a Cochrane review first published in 1999, and updated in 2004. For this review update, we split the review into two distinct reviews which separated acute from chronic LBP.\nObjectives\nTo assess the effectiveness of back schools on pain and disability for people with acute or subacute non-specific LBP. We also examined the effect on work status and adverse events.\nSearch methods\nWe searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, PubMed and two clinical trials registers up to 4 August 2015. We also checked the reference lists of articles and contacted experts in the field of research on LBP.\nSelection criteria\nWe included randomised controlled trials (RCTs) or quasi-RCTs that reported on back school for acute or subacute non-specific LBP. The primary outcomes were pain and disability. The secondary outcomes were work status and adverse events. Back school had to be compared with another treatment, a placebo (or sham or attention control) or no treatment.\nData collection and analysis\nWe used the 2009 updated method guidelines for this Cochrane review. Two review authors independently screened the references, assessed the quality of the trials and extracted the data. We set the threshold for low risk of bias, a priori, as six or more of 13 internal validity criteria and no serious flaws (e.g. large drop-out rate). We classified the quality of the evidence into one of four levels (high, moderate, low or very low) using the adapted Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We contacted study authors for additional information. We collected adverse effects information from the trials.\nMain results\nThe search update identified 273 new references, of which none fulfilled our inclusion criteria. We included four studies (643 participants) in this updated review, which were all included in the previous (2004) update. The quality of the evidence was very low for all outcomes. As data were too clinically heterogeneous to be pooled, we described individual trial results. The results indicate that there is very low quality evidence that back schools are no more effective than a placebo (or sham or attention control) or another treatment (physical therapies, myofascial therapy, joint manipulations, advice) on pain, disability, work status and adverse events at short-term, intermediate-term and long-term follow-up. There is very low quality evidence that shows a statistically significant difference between back schools and a placebo (or sham or attention control) for return to work at short-term follow-up in favour of back school. Very low quality evidence suggests that back school added to a back care programme is more effective than a back care programme alone for disability at short-term follow-up. Very low quality evidence also indicates that there is no difference in terms of adverse events between back school and myofascial therapy, joint manipulation and combined myofascial therapy and joint manipulation.\nAuthors' conclusions\nIt is uncertain if back schools are effective for acute and subacute non-specific LBP as there is only very low quality evidence available. While large well-conducted studies will likely provide more conclusive findings, back schools are not widely used interventions for acute and subacute LBP and further research into this area may not be a priority.\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 very low for all the outcomes according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. This was due to poor study designs and imprecision in the results." } ]

[ { "role": "user", "content": "Abstract: Background\nInhaled anticholinergics given in addition to β2-agonists are effective in reducing hospital admissions in children presenting to the emergency department with a moderate to severe asthma exacerbation. It seems logical to assume a similar beneficial effect in children hospitalised for an acute asthma exacerbation.\nObjectives\nTo assess the efficacy and safety of anticholinergics added to β2-agonists as inhaled or nebulised therapy in children hospitalised for an acute asthma exacerbation. To investigate the characteristics of patients or therapy, if any, that would influence the magnitude of response attributable to the addition of anticholinergics.\nSearch methods\nWe identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED and PsycINFO and through handsearching of respiratory journals and meeting abstracts. The search is current to November 2013.\nSelection criteria\nRandomised trials comparing the combination of inhaled or nebulised anticholinergics and short-acting β2-agonists versus short-acting β2-agonists alone in children one to 18 years of age hospitalised for an acute asthma exacerbation were eligible.\nData collection and analysis\nTwo review authors independently assessed the methodological quality of trials and extracted data; disagreement was resolved by consensus or with the input of a third review author, when needed. Primary outcomes were duration of hospital stay and serious adverse events. Secondary outcomes included admission and duration of stay in the intensive care unit (ICU), ventilation assistance, time to short-acting β2-agonists spaced at four hours or longer, supplemental asthma therapy, duration of supplemental oxygen, change from baseline in asthma severity, relapse after discharge, adverse health effects and withdrawals.\nMain results\nSeven randomised trials were included, four of which reported usable data on 472 children with asthma one to 18 years of age who were admitted to paediatric wards. No trials included patients admitted to the ICU. The anticholinergic used, ipratropium bromide 250 μg, was given every one to eight hours over a period from four hours to the entire length of the hospital stay. Two of four trials (50%) contributing data were deemed of high methodological quality. The addition of anticholinergics to β2-agonists showed no evidence of effect on the duration of hospital admission (mean difference (MD) -0.28 hours, 95% confidence interval (CI) -5.07 to 4.52, 3 studies, 327 participants, moderate quality evidence) and no serious or non-serious adverse events were reported in any included trials. As a result of the similarity of trials, we could not explore the influence of age, admission site, intensity of anticholinergic treatment and co-interventions on primary outcomes. No statistically significant group difference was noted in other secondary outcomes, including the need for supplemental asthma therapy, time to short-acting β2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason.\nAuthors' conclusions\nIn children hospitalised for an acute asthma exacerbation, no evidence of benefit for length of hospital stay and other markers of response to therapy was noted when nebulised anticholinergics were added to short-acting β2-agonists. No adverse health effects were reported, yet the small number of trials combined with inadequate reporting prevent firm reassurance regarding the safety of anticholinergics. In the absence of trials conducted in ICUs, no conclusion can be drawn regarding children with impending respiratory failure. These findings support current national and international recommendations indicating that healthcare practitioners should refrain from using anticholinergics in children hospitalised for acute asthma.\n\nGiven the provided abstract, please respond to the following query: \"Results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "No additional benefit was noted by adding anticholinergics to β2-agonists in terms of duration of hospital stay in patients compared to those who received beta2-agonists alone. Two of four trials (50%) contributing data were deemed of high methodological quality. No trial reported information on serious adverse events. No statistically significant group difference was noted in other markers of response to therapy, that is, the need for supplemental asthma therapy, time to short-acting beta2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason." } ]

[ { "role": "user", "content": "Abstract: Background\nMost people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of quitting. Interventions to prevent weight gain could improve health outcomes, but there is a concern that they may undermine quitting.\nObjectives\nTo systematically review the effects of: (1) interventions targeting post-cessation weight gain on weight change and smoking cessation (referred to as 'Part 1') and (2) interventions designed to aid smoking cessation that plausibly affect post-cessation weight gain (referred to as 'Part 2').\nSearch methods\nPart 1 - We searched the Cochrane Tobacco Addiction Group's Specialized Register and CENTRAL; latest search 16 October 2020.\nPart 2 - We searched included studies in the following 'parent' Cochrane reviews: nicotine replacement therapy (NRT), antidepressants, nicotine receptor partial agonists, e-cigarettes, and exercise interventions for smoking cessation published in Issue 10, 2020 of the Cochrane Library. We updated register searches for the review of nicotine receptor partial agonists.\nSelection criteria\nPart 1 - trials of interventions that targeted post-cessation weight gain and had measured weight at any follow-up point or smoking cessation, or both, six or more months after quit day.\nPart 2 - trials included in the selected parent Cochrane reviews reporting weight change at any time point.\nData collection and analysis\nScreening and data extraction followed standard Cochrane methods. Change in weight was expressed as difference in weight change from baseline to follow-up between trial arms and was reported only in people abstinent from smoking. Abstinence from smoking was expressed as a risk ratio (RR). Where appropriate, we performed meta-analysis using the inverse variance method for weight, and Mantel-Haenszel method for smoking.\nMain results\nPart 1: We include 37 completed studies; 21 are new to this update. We judged five studies to be at low risk of bias, 17 to be at unclear risk and the remainder at high risk.\nAn intermittent very low calorie diet (VLCD) comprising full meal replacement provided free of charge and accompanied by intensive dietitian support significantly reduced weight gain at end of treatment compared with education on how to avoid weight gain (mean difference (MD) −3.70 kg, 95% confidence interval (CI) −4.82 to −2.58; 1 study, 121 participants), but there was no evidence of benefit at 12 months (MD −1.30 kg, 95% CI −3.49 to 0.89; 1 study, 62 participants). The VLCD increased the chances of abstinence at 12 months (RR 1.73, 95% CI 1.10 to 2.73; 1 study, 287 participants). However, a second study  found that no-one completed the VLCD intervention or achieved abstinence.\nInterventions aimed at increasing acceptance of weight gain reported mixed effects at end of treatment, 6 months and 12 months with confidence intervals including both increases and decreases in weight gain compared with no advice or health education. Due to high heterogeneity, we did not combine the data. These interventions increased quit rates at 6 months (RR 1.42, 95% CI 1.03 to 1.96; 4 studies, 619 participants; I2 = 21%), but there was no evidence at 12 months (RR 1.25, 95% CI 0.76 to 2.06; 2 studies, 496 participants; I2 = 26%).\nSome pharmacological interventions tested for limiting post-cessation weight gain (PCWG) reduced weight gain at the end of treatment (dexfenfluramine, phenylpropanolamine, naltrexone). The effects of ephedrine and caffeine combined, lorcaserin, and chromium were too imprecise to give useful estimates of treatment effects. There was very low-certainty evidence that personalized weight management support reduced weight gain at end of treatment (MD −1.11 kg, 95% CI −1.93 to −0.29; 3 studies, 121 participants; I2 = 0%), but no evidence in the longer-term 12 months (MD −0.44 kg, 95% CI −2.34 to 1.46; 4 studies, 530 participants; I2 = 41%). There was low to very low-certainty evidence that detailed weight management education without personalized assessment, planning and feedback did not reduce weight gain and may have reduced smoking cessation rates (12 months: MD −0.21 kg, 95% CI −2.28 to 1.86; 2 studies, 61 participants; I2 = 0%; RR for smoking cessation 0.66, 95% CI 0.48 to 0.90; 2 studies, 522 participants; I2 = 0%).\nPart 2: We include 83 completed studies, 27 of which are new to this update.\nThere was low certainty that exercise interventions led to minimal or no weight reduction compared with standard care at end of treatment (MD −0.25 kg, 95% CI −0.78 to 0.29; 4 studies, 404 participants; I2 = 0%). However, weight was reduced at 12 months (MD −2.07 kg, 95% CI −3.78 to −0.36; 3 studies, 182 participants; I2 = 0%).\nBoth bupropion and fluoxetine limited weight gain at end of treatment (bupropion MD −1.01 kg, 95% CI −1.35 to −0.67; 10 studies, 1098 participants; I2 = 3%); (fluoxetine MD −1.01 kg, 95% CI −1.49 to −0.53; 2 studies, 144 participants; I2 = 38%; low- and very low-certainty evidence, respectively). There was no evidence of benefit at 12 months for bupropion, but estimates were imprecise (bupropion MD −0.26 kg, 95% CI −1.31 to 0.78; 7 studies, 471 participants; I2 = 0%). No studies of fluoxetine provided data at 12 months.\nThere was moderate-certainty that NRT reduced weight at end of treatment (MD −0.52 kg, 95% CI −0.99 to −0.05; 21 studies, 2784 participants; I2 = 81%) and moderate-certainty that the effect may be similar at 12 months (MD −0.37 kg, 95% CI −0.86 to 0.11; 17 studies, 1463 participants; I2 = 0%), although the estimates are too imprecise to assess long-term benefit.\nThere was mixed evidence of the effect of varenicline on weight, with high-certainty evidence that weight change was very modestly lower at the end of treatment (MD −0.23 kg, 95% CI −0.53 to 0.06; 14 studies, 2566 participants; I2 = 32%); a low-certainty estimate gave an imprecise estimate of higher weight at 12 months (MD 1.05 kg, 95% CI −0.58 to 2.69; 3 studies, 237 participants; I2 = 0%).\nAuthors' conclusions\nOverall, there is no intervention for which there is moderate certainty of a clinically useful effect on long-term weight gain. There is also no moderate- or high-certainty evidence that interventions designed to limit weight gain reduce the chances of people achieving abstinence from smoking.\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 are not certain which programmes or treatments work best to help people avoid gaining weight in the long term (up to 12 months) when stopping smoking, or how they affect success in stopping smoking. This is because the evidence shows varied and unclear effects on weight gain. Further studies should continue to look at how to limit weight gain in people who are stopping smoking. Future studies of new medicines to help people stop smoking should also measure changes in their weight." } ]

[ { "role": "user", "content": "Abstract: Background\nThe timing of surgery for recently symptomatic carotid artery stenosis remains controversial. Early cerebral revascularization may prevent a disabling or fatal ischemic recurrence, but it may also increase the risk of hemorrhagic transformation, or of dislodging a thrombus. This review examined the randomized controlled evidence that addressed whether the increased risk of recurrent events outweighed the increased benefit of an earlier intervention.\nObjectives\nTo assess the risks and benefits of performing very early cerebral revascularization (within two days) compared with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis.\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register in January 2016, the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (1948 to 26 January 2016), EMBASE (1974 to 26 January 2016), LILACS (1982 to 26 January 2016), and trial registers (from inception to 26 January 2016). We also handsearched conference proceedings and journals, and searched reference lists. There were no language restrictions. We contacted colleagues and pharmaceutical companies to identify further studies and unpublished trials.\nSelection criteria\nAll completed, truly randomized trials (RCT) that compared very early cerebral revascularization (within two days) with delayed treatment (after two days) for people with recently symptomatic carotid artery stenosis.\nData collection and analysis\nWe independently selected trials for inclusion according to the above criteria, assessed risk of bias for each trial, and performed data extraction. We utilized an intention-to-treat analysis strategy.\nMain results\nWe identified one RCT that involved 40 participants, and addressed the timing of surgery for people with recently symptomatic carotid artery stenosis. It compared very early surgery with surgery performed after 14 days of the last symptomatic event. The overall quality of the evidence was very low, due to the small number of participants from only one trial, and missing outcome data. We found no statistically significant difference between the effects of very early or delayed surgery in reducing the combined risk of stroke and death within 30 days of surgery (risk ratio (RR) 3.32; confidence interval (CI) 0.38 to 29.23; very low-quality evidence), or the combined risk of perioperative death and stroke (RR 0.47; CI 0.14 to 1.58; very low-quality evidence). To date, no results are available to confirm the optimal timing for surgery.\nAuthors' conclusions\nThere is currently no high-quality evidence available to support either very early or delayed cerebral revascularization after a recent ischemic stroke. Hence, further randomized trials to identify which patients should undergo very urgent revascularization are needed. Future studies should stratify participants by age group, sex, grade of ischemia, and degree of stenosis. Currently, there is one ongoing RCT that is examining the timing of cerebral revascularization.\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": "From the limited evidence available, we cannot tell if the timing of surgery is an important factor in determining the outcome for individuals with recent symptoms from carotid artery narrowing." } ]

[ { "role": "user", "content": "Abstract: Background\nIn an effort to improve outcomes of in vitro fertilisation (IVF) cycles, the use of growth hormone (GH) has been considered as adjuvant treatment in ovarian stimulation. Improving the outcomes of IVF is especially important for women with infertility who are considered 'poor responders'. We have compared the outcomes of IVF with adjuvant GH versus no adjuvant treatment in routine use, and specifically in poor responders.\nObjectives\nTo assess the effectiveness and safety of growth hormone as an adjunct to IVF compared to standard IVF for women with infertility\nSearch methods\nWe searched the following databases (to November 2020): Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL, MEDLINE, Embase, CINAHL, Epistemonikos database and trial registers together with reference checking and contact with study authors and experts in the field to identify additional trials.\nSelection criteria\nWe included all randomised controlled trials (RCTs) of adjuvant GH treatment in IVF compared with no adjuvant treatment for women with infertility. We excluded trials where additional adjuvant treatments were used with GH. We also excluded trials comparing different IVF protocols.\nData collection and analysis\nWe used standard methodological procedures recommended by Cochrane. Two review authors independently performed assessment of trial risk of bias and extraction of relevant data. The primary review outcome was live birth rate. The secondary outcomes were clinical pregnancy rate, oocytes retrieved, embryo transfer, units of gonadotropin used and adverse events, i.e. ectopic pregnancy, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), congenital anomalies, oedema.\nMain results\nWe included 16 RCTs (1352 women). Two RCTs (80 women) studied GH in routine use, and 14 RCTs (1272 women) studied GH in poor responders. The evidence was low to very low certainty, the main limitations being risk of bias, imprecision and heterogeneity.\nAdjuvant growth hormone compared to no adjuvant: routine use for in vitro fertilisation (IVF)\nThe evidence is very uncertain about the effect of GH on live birth rate per woman randomised for routine use in IVF (odds ratio (OR) 1.32, 95% confidence interval (CI) 0.40 to 4.43; I2 = 0%; 2 trials, 80 participants; very low-certainty evidence). If the chance of live birth without adjuvant GH is assumed to be 15%, the chance of live birth with GH would be between 6% and 43%.\nThere was insufficient evidence to reach a conclusion regarding clinical pregnancy rates per woman randomised, number of women with at least one oocyte retrieved per woman randomised and embryo transfer achieved per woman randomised; reported data were unsuitable for analysis.\nThe evidence is very uncertain about the effect of GH on mean number of oocytes retrieved in normal responders (mean difference (MD) -0.02, 95% CI -0.79 to 0.74; I2 = 0%; 2 trials, 80 participants; very low-certainty evidence).\nThe evidence is very uncertain about the effect of GH on mean units of gonadotropin used in normal responders (MD 13.57, 95% CI -112.88 to 140.01; I2 = 0%; 2 trials, 80 participants; very low-certainty evidence).\nWe are uncertain of the effect of GH on adverse events in normal responders.\nAdjuvant growth hormone compared to no adjuvant: use in poor responders for in vitro fertilisation (IVF)\nThe evidence is very uncertain about the effect of GH on live birth rate per woman randomised for poor responders (OR 1.77, 95% CI 1.17 to 2.70; I2 = 0%; 8 trials, 737 participants; very low-certainty evidence). If the chance of live birth without adjuvant GH is assumed to be 11%, the chance of live birth with GH would be between 13% and 25%. Adjuvant GH results in a slight increase in pregnancy rates in poor responders (OR 1.85, 95% CI 1.35 to 2.53; I2 = 15%; 11 trials, 1033 participants; low-certainty evidence). The results suggest, if the pregnancy rate without adjuvant GH is assumed to be 15%, with GH the pregnancy rate in poor responders would be between 19% and 31%. The evidence suggests that GH results in little to no difference in number of women with at least one oocyte retrieved (OR 5.67, 95% CI 1.54 to 20.83; I2 = 0%; 2 trials, 148 participants; low-certainty evidence). If the chance of retrieving at least one oocyte in poor responders was 81%, with GH the chance is between 87% and 99%. There is a slight increase in mean number of oocytes retrieved with the use of GH for poor responders (MD 1.40, 95% CI 1.16 to 1.64; I2 = 87%; 12 trials, 1153 participants; low-certainty evidence). The evidence is very uncertain about the effect of GH on embryo transfer achieved (OR 2.32, 95% CI 1.08 to 4.96; I2 = 25%; 4 trials, 214 participants; very low-certainty evidence). If the chance of achieving embryo transfer is assumed to be 77%, the chance with GH will be 78% to 94%. Use of GH results in reduction of mean units of gonadotropins used for stimulation in poor responders (MD -1088.19, 95% CI -1203.20 to -973.18; I2 = 91%; 8 trials, 685 participants; low-certainty evidence).\nHigh heterogeneity in the analyses for mean number of oocytes retrieved and units of GH used suggests quite different effects according to differences including in trial protocols (populations, GH dose and schedule), so these results should be interpreted with caution.\nWe are uncertain of the effect of GH on adverse events in poor responders as six of the 14 included trials failed to report this outcome.\nAuthors' conclusions\nThe use of adjuvant GH in IVF treatment protocols has uncertain effect on live birth rates and mean number of oocytes retrieved in normal responders. However, it slightly increases the number of oocytes retrieved and pregnancy rates in poor responders, while there is an uncertain effect on live birth rates in this group. The results however, need to be interpreted with caution, as the included trials were small and few in number, with significant bias and imprecision. Also, the dose and regimen of GH used in trials was variable. Therefore, further research is necessary to fully define the role of GH as adjuvant therapy in IVF.\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": "During an IVF cycle, women need to be given gonadotrophin therapy to stimulate ovaries to produce eggs. Theoretically, the use of growth hormone as an added treatment may enhance the response of gonadotrophin therapy. We assessed the benefits and risks of using growth hormone compared with no growth hormone treatment in women undergoing IVF. 'Poor responders' in IVF treatment are usually older women with low ovarian reserve or women who had previous IVF treatment with less than five eggs collected despite a maximum dose of stimulation medication. Younger women with good ovarian reserve and good ovarian response (> 5 eggs collected) after ovarian stimulation are considered normal responders." } ]

[ { "role": "user", "content": "Abstract: Background\nEvidence suggests that many perimenopausal and early postmenopausal women will experience menopausal symptoms; hot flushes are the most common. Symptoms caused by fluctuating levels of oestrogen may be alleviated by hormone therapy (HT), but a marked global decline in its use has resulted from concerns about the risks and benefits of HT. Consequently, many women are seeking alternatives. As large numbers of women are choosing not to take HT, it is increasingly important to identify evidence-based lifestyle modifications that have the potential to reduce vasomotor menopausal symptoms.\nObjectives\nTo examine the effectiveness of any type of exercise intervention in the management of vasomotor symptoms in symptomatic perimenopausal and postmenopausal women.\nSearch methods\nSearches of the following electronic bibliographic databases were performed to identify randomised controlled trials (RCTs): Cochrane Menstrual Disorders and Subfertility Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Wiley Internet interface), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), the Science Citation Index and the Social Science Citation Index (Web of Science), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (Ovid) and SPORTDiscus. Searches include findings up to 3 March 2014.\nSelection criteria\nRCTs in which any type of exercise intervention was compared with no treatment/control or other treatments in the management of menopausal vasomotor symptoms in symptomatic perimenopausal/postmenopausal women.\nData collection and analysis\nFive studies were deemed eligible for inclusion. Two review authors independently selected the studies, and three review authors independently extracted the data. The primary review outcome was vasomotor symptoms, defined as hot flushes and/or night sweats. We combined data to calculate standardised mean differences (SMDs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I2 statistic. We assessed the overall quality of the evidence for main comparisons using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods.\nMain results\nWe included five RCTs (733 women) comparing exercise with no active treatment, exercise with yoga and exercise with HT. The evidence was of low quality: Limitations in study design were noted, along with inconsistency and imprecision. In the comparison of exercise versus no active treatment (three studies, n = 454 women), no evidence was found of a difference between groups in frequency or intensity of vasomotor symptoms (SMD -0.10, 95% CI -0.33 to 0.13, three RCTs, 454 women, I2 = 30%, low-quality evidence). Nor was any evidence found of a difference between groups in the frequency or intensity of vasomotor symptoms when exercise was compared with yoga (SMD -0.03, 95% CI -0.45 to 0.38, two studies, n = 279 women, I2 = 61%, low-quality evidence). It was not possible to include one of the trials in the meta-analyses; this trial compared three groups: exercise plus soy milk, soy milk only and control; results favoured exercise relative to the comparators, but study numbers were small. One trial compared exercise with HT, and the HT group reported significantly fewer flushes in 24 hours than the exercise group (mean difference 5.8, 95% CI 3.17 to 8.43, 14 participants). None of the trials found evidence of a difference between groups with respect to adverse effects, but data were very scanty.\nAuthors' conclusions\nEvidence was insufficient to show whether exercise is an effective treatment for vasomotor menopausal symptoms. One small study suggested that HT is more effective than exercise. Evidence was insufficient to show the relative effectiveness of exercise when compared with HT or yoga.\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 methodological quality of the studies was variable. We assessed the evidence as of low quality: The main limitations were poor reporting of study methods, inconsistent results and lack of precision." } ]

[ { "role": "user", "content": "Abstract: Background\nInfants born preterm are at increased risk of early hypernatraemia (above-normal blood sodium levels) and late hyponatraemia (below-normal blood sodium levels). There are concerns that imbalances of sodium intake may impact neonatal morbidities, growth and developmental outcomes.\nObjectives\nTo determine the effects of higher versus lower sodium supplementation in preterm infants.\nSearch methods\nWe searched CENTRAL in February 2023; and MEDLINE, Embase and trials registries in March and April 2022. We checked reference lists of included studies and systematic reviews where subject matter related to the intervention or population examined in this review. We compared early (< 7 days following birth), late (≥ 7 days following birth), and early and late sodium supplementation, separately.\nSelection criteria\nWe included randomised, quasi-randomised or cluster-randomised controlled trials that compared nutritional supplementation that included higher versus lower sodium supplementation in parenteral or enteral intake, or both. Eligible participants were preterm infants born before 37 weeks' gestational age or with a birth weight less than 2500 grams, or both. We excluded studies that had prespecified differential water intakes between groups.\nData collection and analysis\nTwo review authors independently assessed eligibility and risk of bias, and extracted data. We used the GRADE approach to assess the certainty of evidence.\nMain results\nWe included nine studies in total. However, we were unable to extract data from one study (20 infants); some studies contributed to more than one comparison. Eight studies (241 infants) were available for quantitative meta-analysis. Four studies (103 infants) compared early higher versus lower sodium intake, and four studies (138 infants) compared late higher versus lower sodium intake. Two studies (103 infants) compared intermediate sodium supplementation (≥ 3 mmol/kg/day to < 5 mmol/kg/day) versus no supplementation, and two studies (52 infants) compared higher sodium supplementation (≥ 5 mmol/kg/day) versus no supplementation. We assessed only two studies (63 infants) as low risk of bias.\nEarly (less than seven days following birth) higher versus lower sodium intake\nEarly higher versus lower sodium intake may not affect mortality (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.38 to 2.72; I2 = 0%; 3 studies, 83 infants; low-certainty evidence). Neurodevelopmental follow-up was not reported. Early higher versus lower sodium intake may lead to a similar incidence of hyponatraemia < 130 mmol/L (RR 0.68, 95% CI 0.40 to 1.13; I2 = 0%; 3 studies, 83 infants; low-certainty evidence) but an increased incidence of hypernatraemia ≥ 150 mmol/L (RR 1.62, 95% CI 1.00 to 2.65; I2 = 0%; 4 studies, 103 infants; risk difference (RD) 0.17, 95% CI 0.01 to 0.34; number needed to treat for an additional harmful outcome 6, 95% CI 3 to 100; low-certainty evidence). Postnatal growth failure was not reported. The evidence is uncertain for an effect on necrotising enterocolitis (RR 4.60, 95% CI 0.23 to 90.84; 1 study, 46 infants; very low-certainty evidence). Chronic lung disease at 36 weeks was not reported.\nLate (seven days or more following birth) higher versus lower sodium intake\nLate higher versus lower sodium intake may not affect mortality (RR 0.13, 95% CI 0.01 to 2.20; 1 study, 49 infants; very low-certainty evidence). Neurodevelopmental follow-up was not reported. Late higher versus lower sodium intake may reduce the incidence of hyponatraemia < 130 mmol/L (RR 0.13, 95% CI 0.03 to 0.50; I2 = 0%; 2 studies, 69 infants; RD −0.42, 95% CI −0.59 to −0.24; number needed to treat for an additional beneficial outcome 2, 95% CI 2 to 4; low-certainty evidence). The evidence is uncertain for an effect on hypernatraemia ≥ 150 mmol/L (RR 7.88, 95% CI 0.43 to 144.81; I2 = 0%; 2 studies, 69 infants; very low-certainty evidence). A single small study reported that later higher versus lower sodium intake may reduce the incidence of postnatal growth failure (RR 0.25, 95% CI 0.09 to 0.69; 1 study; 29 infants; low-certainty evidence). The evidence is uncertain for an effect on necrotising enterocolitis (RR 0.07, 95% CI 0.00 to 1.25; 1 study, 49 infants; very low-certainty evidence) and chronic lung disease (RR 2.03, 95% CI 0.80 to 5.20; 1 study, 49 infants; very low-certainty evidence).\nEarly and late (day 1 to 28 after birth) higher versus lower sodium intake for preterm infants\nEarly and late higher versus lower sodium intake may not have an effect on hypernatraemia ≥ 150 mmol/L (RR 2.50, 95% CI 0.63 to 10.00; 1 study, 20 infants; very low-certainty evidence). No other outcomes were reported.\nAuthors' conclusions\nEarly (< 7 days following birth) higher sodium supplementation may result in an increased incidence of hypernatraemia and may result in a similar incidence of hyponatraemia compared to lower supplementation. We are uncertain if there are any effects on mortality or neonatal morbidity. Growth and longer-term development outcomes were largely unreported in trials of early sodium supplementation.\nLate (≥ 7 days following birth) higher sodium supplementation may reduce the incidence of hyponatraemia. We are uncertain if late higher intake affects the incidence of hypernatraemia compared to lower supplementation. Late higher sodium intake may reduce postnatal growth failure. We are uncertain if late higher sodium intake affects mortality, other neonatal morbidities or longer-term development.\nWe are uncertain if early and late higher versus lower sodium supplementation affects outcomes.\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": "Early (before 7 days after birth) higher sodium intake may result in more infants with high sodium levels but similar numbers of infants with low sodium levels in preterm infants. However, we are uncertain if there are any effects on infant death or other effects on infant health whilst in hospital. Few studies reported growth and longer-term infant development after discharge from hospital.\nLate (7 or more days after birth) higher sodium intake may reduce the incidence of low sodium levels. We are uncertain if late higher intake affects the incidence of high sodium levels. Late higher sodium intake may reduce postnatal growth failure. We are uncertain if late higher sodium intake affects infant death or has other effects on health whilst in hospital, or longer-term infant development after discharge from hospital.\nWe don't know if early and late higher versus lower sodium intake affects blood sodium, growth, infant death, newborn health in hospital, and long-term outcomes." } ]

[ { "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: \"What did we find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We included 13 studies involving a total of 823 babies. The largest study was in 150 babies, and the smallest in 12 babies. All studies were performed in a hospital. Four studies were conducted in India, two each in Italy and the UK, one each in Canada, Finland, Iran, and the USA, and one was an international study conducted in France and the USA.\nSeven studies compared opioids to placebo; two studies compared opioids to oral sweet solution or other treatments such as touching the baby's body; and five studies compared opioids to another drug.\nCompared to placebo, opioids probably result in a reduction in pain score assessed with certain scales during the procedure, but in little or no difference between groups with other scales 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 breathing stops requiring resuscitation. Opioids may increase episodes of breathing stops. No studies reported parent satisfaction with medical care.\nThe evidence is very uncertain about the effect of opioids on any outcome when compared to other treatments, such as touching the baby's body or giving other drugs." } ]

[ { "role": "user", "content": "Abstract: Background\nThe success of epidural anaesthesia depends on correct identification of the epidural space. For several decades, the decision of whether to use air or physiological saline during the loss of resistance technique for identification of the epidural space has been governed by the personal experience of the anaesthesiologist. Epidural block remains one of the main regional anaesthesia techniques. It is used for surgical anaesthesia, obstetrical analgesia, postoperative analgesia and treatment of chronic pain and as a complement to general anaesthesia. The sensation felt by the anaesthesiologist from the syringe plunger with loss of resistance is different when air is compared with saline (fluid). Frequently fluid allows a rapid change from resistance to non-resistance and increased movement of the plunger. However, the ideal technique for identification of the epidural space remains unclear.\nObjectives\n• To evaluate the efficacy and safety of both air and saline in the loss of resistance technique for identification of the epidural space.\n• To evaluate complications related to the air or saline injected.\nSearch methods\nWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE, EMBASE and the Latin American and Caribbean Health Science Information Database (LILACS) (from inception to September 2013). We applied no language restrictions. The date of the most recent search was 7 September 2013.\nSelection criteria\nWe included randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) on air and saline in the loss of resistance technique for identification of the epidural space.\nData collection and analysis\nTwo review authors independently assessed trial quality and extracted data.\nMain results\nWe included in the review seven studies with a total of 852 participants. The methodological quality of the included studies was generally ranked as showing low risk of bias in most domains, with the exception of one study, which did not mask participants. We were able to include data from 838 participants in the meta-analysis. We found no statistically significant differences between participants receiving air and those given saline in any of the outcomes evaluated: inability to locate the epidural space (three trials, 619 participants) (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.33 to 2.31, low-quality evidence); accidental intravascular catheter placement (two trials, 223 participants) (RR 0.90, 95% CI 0.33 to 2.45, low-quality evidence); accidental subarachnoid catheter placement (four trials, 682 participants) (RR 2.95, 95% CI 0.12 to 71.90, low-quality evidence); combined spinal epidural failure (two trials, 400 participants) (RR 0.98, 95% CI 0.44 to 2.18, low-quality evidence); unblocked segments (five studies, 423 participants) (RR 1.66, 95% CI 0.72 to 3.85); and pain measured by VAS (two studies, 395 participants) (mean difference (MD) -0.09, 95% CI -0.37 to 0.18). With regard to adverse effects, we found no statistically significant differences between participants receiving air and those given saline in the occurrence of paraesthesias (three trials, 572 participants) (RR 0.89, 95% CI 0.69 to 1.15); difficulty in advancing the catheter (two trials, 227 participants) (RR 0.91, 95% CI 0.32 to 2.56); catheter replacement (two trials, 501 participants) (RR 0.69, 95% CI 0.26 to 1.83); and postdural puncture headache (one trial, 110 participants) (RR 0.83, 95% CI 0.12 to 5.71).\nAuthors' conclusions\nLow-quality evidence shows that results do not differ between air and saline in terms of the loss of resistance technique for identification of the epidural space and reduction of complications. Applicability might be compromised, as most of the results described in this review were obtained from parturient patients. This review underlines the need to conduct well-designed trials in this field.\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": "Because conducted studies were only reasonably well conducted (results very similar across studies; minor issues with study design; and not enough data), we ranked the overall quality of the evidence as low. The applicability of findings might be compromised, as most of the results described in this review were obtained from parturient patients." } ]

[ { "role": "user", "content": "Abstract: Background\nWe performed a systematic review, a standard meta-analysis and network meta-analysis (NMA), which updates the 2009 Cochrane Overview, 'Biologics for rheumatoid arthritis (RA)'. This review is focused on biologic monotherapy in people with RA in whom treatment with traditional disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) had failed (MTX/other DMARD-experienced).\nObjectives\nTo assess the benefits and harms of biologic monotherapy (includes anti-tumor necrosis factor (TNF) (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) or non-TNF (abatacept, anakinra, rituximab, tocilizumab)) or tofacitinib monotherapy (oral small molecule) versus comparator (placebo or MTX/other DMARDs) in adults with RA who were MTX/other DMARD-experienced.\nMethods\nWe searched for randomized controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2015, Issue 6, June), MEDLINE (via OVID 1946 to June 2015), and Embase (via OVID 1947 to June 2015). Article selection, data extraction and risk of bias and GRADE assessments were done in duplicate. We calculated direct estimates with 95% confidence intervals (CI) using standard meta-analysis. We used a Bayesian mixed treatment comparisons (MTC) approach for NMA estimates with 95% credible intervals (CrI). We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We calculated absolute measures as risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB).\nMain results\nThis update includes 40 new RCTs for a total of 46 RCTs, of which 41 studies with 14,049 participants provided data. The comparator was placebo in 16 RCTs (4,532 patients), MTX or other DMARD in 13 RCTs (5,602 patients), and another biologic in 12 RCTs (3,915 patients).\nMonotherapy versus placebo\nBased on moderate-quality direct evidence, biologic monotherapy (without concurrent MTX/other DMARDs) was associated with a clinically meaningful and statistically significant improvement in American College of Rheumatology score (ACR50) and physical function, as measured by the Health Assessment Questionnaire (HAQ) versus placebo. RR was 4.68 for ACR50 (95% CI, 2.93 to 7.48); absolute benefit RD 23% (95% CI, 18% to 29%); and NNTB = 5 (95% CI, 3 to 8). The mean difference (MD) was -0.32 for HAQ (95% CI, -0.42 to -0.23; a negative sign represents greater HAQ improvement); absolute benefit of -10.7% (95% CI, -14% to -7.7%); and NNTB = 4 (95% CI, 3 to 5). Direct and NMA estimates for TNF biologic, non-TNF biologic or tofacitinib monotherapy showed similar results for ACR50 , downgraded to moderate-quality evidence. Direct and NMA estimates for TNF biologic, anakinra or tofacitinib monotherapy showed a similar results for HAQ versus placebo with mostly moderate quality evidence.\nBased on moderate-quality direct evidence, biologic monotherapy was associated with a clinically meaningful and statistically significant greater proportion of disease remission versus placebo with RR 1.12 (95% CI 1.03 to 1.22); absolute benefit 10% (95% CI, 3% to 17%; NNTB = 10 (95% CI, 8 to 21)).\nBased on low-quality direct evidence, results for biologic monotherapy for withdrawals due to adverse events and serious adverse events were inconclusive, with wide confidence intervals encompassing the null effect and evidence of an important increase. The direct estimate for TNF monotherapy for withdrawals due to adverse events showed a clinically meaningful and statistically significant result with RR 2.02 (95% CI, 1.08 to 3.78), absolute benefit RD 3% (95% CI,1% to 4%), based on moderate-quality evidence. The NMA estimates for TNF biologic, non-TNF biologic, anakinra, or tofacitinib monotherapy for withdrawals due to adverse events and for serious adverse events were all inconclusive and downgraded to low-quality evidence.\nMonotherapy versus active comparator (MTX/other DMARDs)\nBased on direct evidence of moderate quality, biologic monotherapy (without concurrent MTX/other DMARDs) was associated with a clinically meaningful and statistically significant improvement in ACR50 and HAQ scores versus MTX/other DMARDs with a RR of 1.54 (95% CI, 1.14 to 2.08); absolute benefit 13% (95% CI, 2% to 23%), NNTB = 7 (95% CI, 4 to 26) and a mean difference in HAQ of -0.27 (95% CI, -0.40 to -0.14); absolute benefit of -9% (95% CI, -13.3% to -4.7%), NNTB = 2 (95% CI, 2 to 4). Direct and NMA estimates for TNF monotherapy and NMA estimate for non-TNF biologic monotherapy for ACR50 showed similar results, based on moderate-quality evidence. Direct and NMA estimates for non-TNF biologic monotherapy, but not TNF monotherapy, showed similar HAQ improvements , based on mostly moderate-quality evidence.\nThere were no statistically significant or clinically meaningful differences for direct estimates of biologic monotherapy versus active comparator for RA disease remission. NMA estimates showed a statistically significant and clinically meaningful difference versus active comparator for TNF monotherapy (absolute improvement 7% (95% CI, 2% to 14%)) and non-TNF monotherapy (absolute improvement 19% (95% CrI, 7% to 36%)), both downgraded to moderate quality.\nBased on moderate-quality direct evidence from a single study, radiographic progression (scale 0 to 448) was statistically significantly reduced in those on biologic monotherapy versus active comparator, MD -4.34 (95% CI, -7.56 to -1.12), though the absolute reduction was small, -0.97% (95% CI, -1.69% to -0.25%). We are not sure of the clinical relevance of this reduction.\nDirect and NMA evidence (downgraded to low quality), showed inconclusive results for withdrawals due to adverse events, serious adverse events and cancer, with wide confidence intervals encompassing the null effect and evidence of an important increase.\nAuthors' conclusions\nBased mostly on RCTs of six to 12-month duration in people with RA who had previously experienced and failed treatment with MTX/other DMARDs, biologic monotherapy improved ACR50, function and RA remission rates compared to placebo or MTX/other DMARDs.\nRadiographic progression was reduced versus active comparator, although the clinical significance was unclear.\nResults were inconclusive for whether biologic monotherapy was associated with an increased risk of withdrawals due to adverse events, serious adverse events or cancer, versus placebo (no data on cancer) or MTX/other DMARDs.\n\nGiven the provided abstract, please respond to the following query: \"The review shows that in people with RA\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "compared to salt water (placebo) or traditional drugs such as MTX/other DMARDs, biologic monotherapy (without MTX/other DMARDs) improves or probably improves signs and symptoms of RA (tender or swollen joints), function and chances of RA remission (disappearance of symptoms). Compared to salt water (placebo) or MTX/other DMARDs, biologic monotherapy may increase slightly or make no difference to the number of serious adverse events and withdrawals due to adverse events. In the short-term evidence summarised here, biologic monotherapy does not increase the risk of cancer compared to MTX/other DMARDs." } ]

[ { "role": "user", "content": "Abstract: Background\nRespiratory distress syndrome (RDS) is considered one of the major contributors to severe pulmonary dysfunction and consequent death in preterm infants. Despite widespread improvements in care, including increased utilization of antenatal steroids, use of surfactant replacement therapy, and advances in conventional mechanical ventilation (CMV), chronic lung disease (CLD) occurs in 42% of surviving preterm infants born at less than 28 weeks gestational age (GA). High frequency ventilation (HFV) aims to optimize lung expansion while minimizing tidal volume (Vt) to decrease lung injury. Two methods of HFV - high frequency oscillatory ventilation (HFOV) and high frequency jet ventilation (HFJV) - are widely used, but neither has demonstrated clear superiority in elective or rescue mode.\nObjectives\nTo compare the benefits and side effects of HFJV versus HFOV for mortality and morbidity in preterm infants born at less than 37 weeks GA with pulmonary dysfunction in both elective and rescue modes.\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 11), MEDLINE via PubMed (1966 to November 30, 2015), EMBASE (1980 to November 30, 2015), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to November 30, 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. We imposed no date, language, or publication restrictions.\nSelection criteria\nWe planned to include randomized, cluster-randomized, and quasi-randomized controlled trials if study authors stated explicitly that groups compared in the trial were established by a random or systematic method of allocation. We planned to exclude cross-over studies, as they would not allow assessment of the outcomes of interest.\nData collection and analysis\nWe used the standard methods of the Neonatal Cochrane Review Group, including independent trial assessment and data extraction. We intended to analyze the data by using risk ratios (RRs) and risk differences (RDs) and 1/RD. We planned to calculate the number needed to treat for an additional beneficial outcome (NNTB) or the number needed to treat for an additional harmful outcome (NNTH).\nMain results\nWe found no studies that met our inclusion criteria.\nAuthors' conclusions\nWe found no evidence to support the superiority of HFJV or HFOV as elective or rescue therapy. Until such evidence is available, comparison of potential side effects or presumed benefits of either mode is not feasible.\n\nGiven the provided abstract, please respond to the following query: \"Our review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "In preterm infants (born before term) at risk for or having RDS, we planned to compare the risks and benefits of two modes of breathing machines: HFJV and HFOV." } ]

[ { "role": "user", "content": "Abstract: Background\nBoth paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United Kingdom, this drug has shown promising results to date and we have chosen to also compare the combined drug with the single drugs using this model. In this review we investigated the optimal doses of both paracetamol and ibuprofen via comparison of both and via comparison with the novel combined drug. We have taken into account the side effect profile of the study drugs. This review will help oral surgeons to decide on which analgesic to prescribe following wisdom tooth removal.\nObjectives\nTo compare the beneficial and harmful effects of paracetamol, ibuprofen and the novel combination of both in a single tablet for pain relief following the surgical removal of lower wisdom teeth, at different doses and administered postoperatively.\nSearch methods\nWe searched the Cochrane Oral Health Group'sTrials Register (to 20 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4); MEDLINE via OVID (1946 to 20 May 2013); EMBASE via OVID (1980 to 20 May 2013) and the metaRegister of Controlled Trials (to 20 May 2013). We checked the bibliographies of relevant clinical trials and review articles for further studies. We wrote to authors of the identified randomised controlled trials (RCTs), and searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied to the searches of the electronic databases.\nSelection criteria\nOnly randomised controlled double-blinded clinical trials were included. Cross-over studies were included provided there was a wash out period of at least 14 days. There had to be a direct comparison in the trial of two or more of the trial drugs at any dosage. All trials used the third molar pain model.\nData collection and analysis\nAll trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief (based on total pain relief (TOTPAR) and summed pain intensity difference (SPID) data) was calculated for all three drugs at both two and six hours postdosing and meta-analysed for comparison. The proportion of participants using rescue medication over both six and eight hours was also collated and compared. The number of patients experiencing adverse events or the total number of adverse events reported or both were analysed for comparison.\nMain results\nSeven studies were included, they were all parallel-group studies, two studies were assessed as at low risk of bias and three at high risk of bias; two were considered to have unclear bias in their methodology. A total of 2241 participants were enrolled in these trials.\nIbuprofen was found to be a superior analgesic to paracetamol at several doses with high quality evidence suggesting that ibuprofen 400 mg is superior to 1000 mg paracetamol based on pain relief (estimated from TOTPAR data) and the use of rescue medication meta-analyses. The risk ratio for at least 50% pain relief (based on TOTPAR) at six hours was 1.47 (95% confidence interval (CI) 1.28 to 1.69; five trials) favouring 400 mg ibuprofen over 1000 mg paracetamol, and the risk ratio for not using rescue medication (also favouring ibuprofen) was 1.50 (95% CI 1.25 to 1.79; four trials).\nThe combined drug showed promising results, with a risk ratio for at least 50% of the maximum pain relief over six hours of 1.77 (95% CI 1.32 to 2.39) (paracetamol 1000 mg and ibuprofen 400 mg) (one trial; moderate quality evidence), and risk ratio not using rescue medication 1.60 (95% CI 1.36 to 1.88) (two trials; moderate quality evidence).\nThe information available regarding adverse events from the studies (including nausea, vomiting, headaches and dizziness) indicated that they were comparable between the treatment groups. However, we could not formally analyse the data as it was not possible to work out how many adverse events there were in total.\nAuthors' conclusions\nThere is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and 600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively. The majority of this evidence (five out of six trials) compared ibuprofen 400 mg with paracetamol 1000 mg, these are the most frequently prescribed doses in clinical practice. The novel combination drug is showing encouraging results based on the outcomes from two trials when compared to the single drugs.\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": "All of the results (outcomes) comparing ibuprofen to paracetamol are of high quality. This means that further research is very unlikely to change our confidence in the estimates of the effect.\nWhen comparing combined versus single drugs, the body of evidence for the proportion of patients with > 50% maximum pain relief (TOTPAR) over two and six hours, was assessed as of moderate quality due to imprecise estimates based on single studies. This means that further research is likely to have an important impact on our confidence in the estimate of the effect. The body of evidence for the use of rescue medication was assessed as being of high quality." } ]

[ { "role": "user", "content": "Abstract: Background\nUsual-type vulval intraepithelial neoplasia (uVIN) is a pre-cancerous condition of the vulval skin. Also known as high-grade VIN, VIN 2/3 or high-grade vulval squamous intraepithelial lesion (HSIL), uVIN is associated with high-risk subtype human papilloma virus (HPV) infection. The condition causes distressing vulval symptoms in the majority of affected women and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of uVIN. High morbidity and recurrence rates associated with surgical treatments make less invasive treatments highly desirable.\nObjectives\nTo determine which interventions are the most effective, safe and tolerable for treating women with uVIN.\nSearch methods\nWe searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 8 2015, MEDLINE and EMBASE (up to 1 September 2015). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.\nSelection criteria\nRandomised controlled trials (RCTs) that assessed medical and surgical interventions in women with uVIN. If no RCTs were available, we included non-randomised studies (NRSs) with concurrent comparison groups that controlled for baseline case mix in multivariate analysis.\nData collection and analysis\nWe used Cochrane methodology with two review authors independently extracting data and assessing risk of bias. Where possible, we synthesised data in meta-analyses using random-effects methods. Network meta-analysis was not possible due to insufficient data.\nMain results\nWe included six RCTs involving 327 women and five NRSs involving 648 women. The condition was variously named by investigators as uVIN, VIN2/3 or high-grade VIN. Five RCTs evaluated medical treatments (imiquimod, cidofovir, indole-3 carbinol), and six studies (one RCT and five NRSs) evaluated surgical treatments or photodynamic therapy. We judged two RCTs and four NRSs to be at a high or unclear risk of bias; we considered the others at relatively low risk of bias. Types of outcome measures reported in NRSs varied and we were unable to pool NRS data.\nMedical interventions: Topical imiquimod was more effective than placebo in achieving a response (complete or partial) to treatment at five to six months post-randomisation (three RCTs, 104 women; risk ratio (RR) 11.95, 95% confidence interval (CI) 3.21 to 44.51; high-quality evidence). At five to six months, a complete response occurred in 36/62 (58%) and 0/42 (0%) women in the imiquimod and placebo groups, respectively (RR 14.40, 95% CI 2.97 to 69.80). Moderate-quality evidence suggested that the complete response was sustained at one year (one RCT, nine complete responses out of 52 women (38%)) and beyond, particularly in women with smaller VIN lesions. Histologically confirmed complete response rates with imiquimod versus cidofovir at six months were 45% (41/91) and 46% (41/89), respectively (one RCT, 180 women; RR 1.00, 95% CI 0.73 to 1.37; moderate-quality evidence). Twelve-month data from this trial are awaited; however, interim findings suggested that complete responses were sustained at 12 months. Only one trial reported vulval cancer at one year (1/24 and 2/23 in imiquimod and placebo groups, respectively). Adverse events were more common with imiquimod than placebo and dose reductions occurred more frequently in the imiquimod group than in the placebo group (two RCTs, 83 women; RR 7.77, 95% CI 1.61 to 37.36; high-quality evidence). Headache, fatigue and discontinuation were slightly more common with imiquimod than cidofovir (moderate-quality evidence). Quality of life scores reported in one trial (52 women) were not significantly different for imiquimod and placebo. The evidence of effectiveness of topical treatments in immunosuppressed women was scant. There was insufficient evidence on other medical interventions.\nSurgical and other interventions: Low-quality evidence from the best included NRS indicated, when data were adjusted for confounders, that there was little difference in the risk of VIN recurrence between surgical excision and laser vaporisation. Recurrence occurred in 51% (37/70) of women overall, at a median of 14 months, and was more common in multifocal than unifocal lesions (66% versus 34%). Vulval cancer occurred in 11 women (15.1%) overall at a median of 71.5 months (9 to 259 months). The risk of vulval cancer did not differ significantly between excision and laser vaporisation in any of the NRSs; however, events were too few for robust findings. Alternative surgical procedures that might be as effective include Cavitron ultrasonic surgical aspiration (CUSA) and loop electrosurgical excision (LEEP) procedures, based on low- to very low-quality evidence, respectively. Very low-quality evidence also suggested that photodynamic therapy may be a useful treatment option.\nWe found one ongoing RCT of medical treatment (imiquimod) compared with surgical treatment.\nAuthors' conclusions\nTopical treatment (imiquimod or cidofovir) may effectively treat about half of uVIN cases after a 16-week course of treatment, but the evidence on whether this effect is sustained is limited. Factors predicting response to treatment are not clear, but small lesions may be more likely to respond. The relative risk of progression to vulval cancer is uncertain. However, imiquimod and cidofovir appear to be relatively well tolerated and may be favoured by some women over primary surgical treatment.\nThere is currently no evidence on how medical treatment compares with surgical treatment. Women who undergo surgical treatment for uVIN have about a 50% chance of the condition recurring one year later, irrespective of whether treatment is by surgical excision or laser vaporisation. Multifocal uVIN lesions are at a higher risk of recurrence and progression, and pose greater therapeutic dilemmas than unifocal lesions. If occult cancer is suspected despite a biopsy diagnosis of uVIN, surgical excision remains the treatment of choice. If occult cancer is not a concern, treatment needs to be individualised to take into account the site and extent of disease, and a woman's preferences. Combined modalities may hold the key to optimal treatment of this complex disease.\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": "Usual-type vulval intraepithelial neoplasia (uVIN) is a pre-malignant condition affecting the vulval skin, which has the potential for progression to vulval cancer. Most patients have distressing symptoms that include itching, burning and soreness of the vulva, and painful intercourse. There may be white, brown, or red colour changes of the skin, breaks in the skin, or skin thickening. Usual-type VIN is associated with infection with a virus called human papilloma virus (HPV or wart virus). Treatments are aimed at relieving distressing symptoms and ensuring that the condition does not become cancerous. The most common treatment option has been surgery to remove the affected skin areas. Surgery, however, does not guarantee a cure, can be disfiguring, and may result in physical and psychological problems. Alternatives include the use of laser technology to destroy the layer of affected skin, which may give better cosmetic results, but usually does not yield a specimen to exclude cancer. It may also be ineffective in treating uVIN that extends into hair follicles. Non-surgical treatment alternatives include topical creams and gels, and HPV vaccines. This review aimed to assess the effectiveness and safety of these treatments." } ]

[ { "role": "user", "content": "Abstract: Background\nAcquired brain injury (ABI) can result in impairments in motor function, language, cognition, and sensory processing, and in emotional disturbances, which can severely reduce a survivor's quality of life. Music interventions have been used in rehabilitation to stimulate brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. An update of the systematic review published in 2010 was needed to gauge the efficacy of music interventions in rehabilitation for people with ABI.\nObjectives\nTo assess the effects of music interventions for functional outcomes in people with ABI. We expanded the criteria of our existing review to: 1) examine the efficacy of music interventions in addressing recovery in people with ABI including gait, upper extremity function, communication, mood and emotions, cognitive functioning, social skills, pain, behavioural outcomes, activities of daily living, and adverse events; 2) compare the efficacy of music interventions and standard care with a) standard care alone, b) standard care and placebo treatments, or c) standard care and other therapies; 3) compare the efficacy of different types of music interventions (music therapy delivered by trained music therapists versus music interventions delivered by other professionals).\nSearch methods\nWe searched the Cochrane Stroke Group Trials Register (January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to June 2015), Embase (1980 to June 2015), CINAHL (1982 to June 2015), PsycINFO (1806 to June 2015), LILACS (1982 to January 2016), and AMED (1985 to June 2015). We handsearched music therapy journals and conference proceedings, searched dissertation and specialist music databases, trials and research registers, reference lists, and contacted relevant experts and music therapy associations to identify unpublished research. We imposed no language restriction. We performed the original search in 2009.\nSelection criteria\nWe included all randomised controlled trials and controlled clinical trials that compared music interventions and standard care with standard care alone or combined with other therapies. We examined studies that included people older than 16 years of age who had ABI of a non-degenerative nature and were participating in treatment programmes offered in hospital, outpatient, or community settings. We included studies in any language, published and unpublished.\nData collection and analysis\nTwo review authors independently extracted data and assessed the risk of bias of the included studies. We contacted trial researchers to obtain missing data or for additional information when necessary. Where possible, we presented results for continuous outcomes in meta-analyses using mean differences (MDs) and standardised mean differences (SMDs). We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted a sensitivity analysis to assess the impact of the randomisation method.\nMain results\nWe identified 22 new studies for this update. The evidence for this update is based on 29 trials involving 775 participants. A music intervention known as rhythmic auditory stimulation may be beneficial for improving the following gait parameters after stroke. We found a reported increase in gait velocity of 11.34 metres per minute (95% confidence interval (CI) 8.40 to 14.28; 9 trials; 268 participants; P < 0.00001; moderate-quality evidence). Stride length of the affected side may also benefit, with a reported average of 0.12 metres more (95% CI 0.04 to 0.20; 5 trials; 129 participants; P = 0.003; moderate-quality evidence). We found a reported average improvement for general gait of 7.67 units on the Dynamic Gait Index (95% CI 5.67 to 9.67; 2 trials; 48 participants; P < 0.00001). There may also be an improvement in gait cadence, with a reported average increase of 10.77 steps per minute (95% CI 4.36 to 17.18; 7 trials; 223 participants; P = 0.001; low-quality evidence).\nMusic interventions may be beneficial for improving the timing of upper extremity function after stroke as scored by a reduction of 1.08 seconds on the Wolf Motor Function Test (95% CI -1.69 to -0.47; 2 trials; 122 participants; very low-quality evidence).\nMusic interventions may be beneficial for communication outcomes in people with aphasia following stroke. Overall, communication improved by 0.75 standard deviations in the intervention group, a moderate effect (95% CI 0.11 to 1.39; 3 trials; 67 participants; P = 0.02; very low-quality evidence). Naming was reported as improving by 9.79 units on the Aachen Aphasia Test (95% CI 1.37 to 18.21; 2 trials; 35 participants; P = 0.02). Music interventions may have a beneficial effect on speech repetition, reported as an average increase of 8.90 score on the Aachen Aphasia Test (95% CI 3.25 to 14.55; 2 trials; 35 participants; P = 0.002).\nThere may be an improvement in quality of life following stroke using rhythmic auditory stimulation, reported at 0.89 standard deviations improvement on the Stroke Specific Quality of Life Scale, which is considered to be a large effect (95% CI 0.32 to 1.46; 2 trials; 53 participants; P = 0.002; low-quality evidence). We found no strong evidence for effects on memory and attention. Data were insufficient to examine the effect of music interventions on other outcomes.\nThe majority of studies included in this review update presented a high risk of bias, therefore the quality of the evidence is low.\nAuthors' conclusions\nMusic interventions may be beneficial for gait, the timing of upper extremity function, communication outcomes, and quality of life after stroke. These results are encouraging, but more high-quality randomised controlled trials are needed on all outcomes before recommendations can be made for clinical practice.\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 research was generally low. We found only one study that we considered as having a low risk of bias. The quality of the evidence for walking speed and stride length was moderate. The quality of the evidence for other aspects of walking was low. The quality of the evidence for the speed of repetitive arm movements was very low, as was the quality of the evidence for overall communication. The quality of the evidence for quality of life was low. Further clinical trials are needed." } ]

[ { "role": "user", "content": "Abstract: Background\nPatients with medically unexplained or functional somatic symptoms are common in primary care. Previous reviews have reported benefit from specialised interventions such as cognitive behavioural therapy and consultation letters, but there is a need for treatment models which can be applied within the primary care setting. Primary care studies of enhanced care, which includes techniques of reattribution or cognitive behavioural therapy, or both, have shown changes in healthcare professionals' attitudes and behaviour. However, studies of patient outcome have shown variable results and the value of enhanced care on patient outcome remains unclear.\nObjectives\nWe aimed to assess the clinical effectiveness of enhanced care interventions for adults with functional somatic symptoms in primary care. The intervention should be delivered by professionals providing first contact care and be compared to treatment as usual. The review focused on patient outcomes only.\nSearch methods\nWe searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR-Studies and CCDANCTR-References) (all years to August 2012), together with Ovid searches (to September 2012) on MEDLINE (1950 - ), EMBASE (1980 - ) and PsycINFO (1806 - ). Earlier searches of the Database of Abstracts of Reviews of Effectiveness (DARE), CINAHL, PSYNDEX, SIGLE, and LILACS were conducted in April 2010, and the Cochrane Central Register of Controlled Trials (CENTRAL) in October 2009. No language restrictions were applied. Electronic searches were supplemented by handsearches of relevant conference proceedings (2004 to 2012), reference lists (2011) and contact with authors of included studies and experts in the field (2011).\nSelection criteria\nWe limited our literature search to randomised controlled trials (RCTs), primary care, and adults with functional somatic symptoms. Subsequently we selected studies including all of the following: 1) a trial arm with treatment as usual; 2) an intervention using a structured treatment model which draws on explanations for symptoms in broad bio-psycho-social terms or encourages patients to develop additional strategies for dealing with their physical symptoms, or both; 3) delivery of the intervention by primary care professionals providing first contact care; and 4) assessment of patient outcome.\nData collection and analysis\nTwo authors independently screened identified study abstracts. Disagreements about trial selections were resolved by a third review author. Data from selected publications were independently extracted and risk of bias assessed by two of three authors, avoiding investigators reviewing their own studies. We contacted authors from included studies to obtain missing information. We used continuous outcomes converted to standardised mean differences (SMDs) and based analyses on changes from baseline to follow-up, adjusted for clustering.\nMain results\nWe included seven studies from the literature search, but only six provided sufficient data for analyses. Included studies were European, cluster RCTs with adult participants seeing their usual doctor (in total 233 general practitioners and 1787 participants). Methodological quality was only moderate as studies had no blinding of healthcare professionals and several studies had a risk of recruitment and attrition bias. Studies were heterogeneous with regard to selection of patient populations and intensity of interventions. Outcomes relating to physical or general health (physical symptoms, quality of life) showed substantial heterogeneity between studies (I2 > 70%) and post hoc analysis suggested that benefit was confined to more intensive interventions; thus we did not calculate a pooled effect. Outcomes relating to mental health showed less heterogeneity and we conducted meta-analyses, which found non-significant overall effect sizes with SMDs for changes at 6 to 24 months follow-up: mental health (3 studies) SMD -0.04 (95% CI -0.18 to 0.10), illness worry (3 studies) SMD 0.09 (95% CI -0.04 to 0.22), depression (4 studies) SMD 0.07 (95% CI -0.05 to 0.20) and anxiety (2 studies) SMD -0.07 (95% CI -0.38 to 0.25). Effects on sick leave could not be estimated. Three studies of patient satisfaction with care all showed positive but non-significant effects, and measures were too heterogeneous to allow meta-analysis. Results on healthcare utilisation were inconclusive. We analysed study discontinuation and found that both short term and long term discontinuation occurred more often in patients allocated to the intervention group, RR of 1.25 (95% CI 1.08 to 1.46) at 12 to 24 months.\nAuthors' conclusions\nCurrent evidence does not answer the question whether enhanced care delivered by front line primary care professionals has an effect or not on the outcome of patients with functional somatic symptoms. Enhanced care may have an effect when delivered per protocol to well-defined groups of patients with functional disorders, but this needs further investigation. Attention should be paid to difficulties including limited consultation time, lack of skills, the need for a degree of diagnostic openness, and patient resistance towards psychosomatic attributions. There is some indication from this and other reviews that more intensive interventions are more successful in changing patient outcomes.\n\nGiven the provided abstract, please respond to the following query: \"Who may be interested in this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "People affected by a range of unexplained physical symptoms or syndromes, and their carers\nGPs and practice nurses\nGP commissioning groups\nMedical schools\nHealth economists" } ]

[ { "role": "user", "content": "Abstract: Background\nObservational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing intrauterine adhesions (IUAs).\nObjectives\nTo assess the effectiveness of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy, following operative hysteroscopy for treatment of female subfertility.\nSearch methods\nWe searched the following databases from inception to June 2017: the Cochrane Gynaecology and Fertility Group Specialised Register; the Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; CINAHL and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched the Journal of Minimally Invasive Gynecology, and we contacted experts in the field. We also searched reference lists of appropriate papers.\nSelection criteria\nRandomised controlled trials (RCTs) of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second-look hysteroscopy, along with mean adhesion scores and severity of IUAs.\nData collection and analysis\nTwo review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of evidence using the GRADE method.\nMain results\nThe overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown.\nNo study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy).\nAnti-adhesion therapy versus placebo or no treatment following operative hysteroscopy.\nThere was insufficient evidence to determine whether there was a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I² = 0%; very-low-quality evidence).\nThere were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I² = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17).\nComparisons of different anti-adhesion therapies following operative hysteroscopy\nIt was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I² = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I² = 0%; low-quality evidence).\nAuthors' conclusions\nImplications for clinical practice\nThe quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain.\nImplications for research\nMore research is needed to assess the comparative safety and (cost-)effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women.\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": "To assess the effects of treatments for prevention of scar tissue (called adhesions) anti-adhesion treatment) inside the womb after surgical treatment in women having difficulty becoming pregnant." } ]

[ { "role": "user", "content": "Abstract: Background\nNewborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive.\nObjectives\n1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately.\n2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately.\n3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates.\nSearch methods\nWe searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials.\nSelection criteria\nWe included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone.\nData collection and analysis\nTwo review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence.\nMain results\nWe included 18 trials (1342 infants) in this review.\nPhenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial)\nPhenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months.\nPhenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial)\nWe are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months.\nMaintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials)\nWe are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence).\nTreatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates (two trials)\nTreatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation (MD -1871.16, 95% CI -4525.05 to 782.73; 68 participants; low-certainty evidence), mortality before discharge (RR 0.59, 95% CI 0.28 to 1.27; 68 participants; low-certainty evidence) and epilepsy post-discharge (RR 0.75, 95% CI 0.12 to 4.73; 35 participants; low-certainty evidence). The trials did not report on mortality or neurodevelopmental disability at 18 to 24 months.\nWe report data from the most important comparisons here; readers are directed to Results and Summary of Findings tables for all comparisons.\nAuthors' conclusions\nPhenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes.\nIn neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence).\nIn neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence).\nAll findings of this review apply only to term and late preterm neonates.\nWe need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.\n\nGiven the provided abstract, please respond to the following query: \"What did we want to find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We looked for evidence from studies that assessed one medication versus another to treat seizures in newborns, studies that evaluated whether maintenance doses of anti-seizure medication should be continued or not, and studies that assessed whether to treat seizures that were identified only on EEG." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an update of the Cochrane Review first published in 2010; it includes one additional study.\nPrimary generalised tonic-clonic seizures are a type of generalised seizure. Other types of seizures include: absence, myoclonic, and atonic seizures. Effective control of tonic-clonic seizures reduces the risk of injury and death, and improves quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not, and require a combination of antiepileptic drugs.\nObjectives\nTo assess the effectiveness and tolerability of add-on lamotrigine for drug-resistant primary generalised tonic-clonic seizures.\nSearch methods\nFor the latest update, we searched these databases on 19 March 2019: Cochrane Register of Studies (CRS) Web, MEDLINE Ovid, and the WHO International Clinical Trials Registry Platform (ICTRP). The CRS includes records from the Cochrane Epilepsy Group Specialized Register, CENTRAL, Embase, and ClinicalTrials.gov. We imposed no language restrictions. We also contacted GlaxoSmithKline, manufacturers of lamotrigine.\nSelection criteria\nRandomised controlled parallel or cross-over trials of add-on lamotrigine for people of any age with drug-resistant primary generalised tonic-clonic seizures.\nData collection and analysis\nWe followed standard Cochrane methodology; two review authors independently assessed trials for inclusion, evaluated risk of bias, extracted relevant data, and GRADE-assessed evidence. We investigated these outcomes: (1) 50% or greater reduction in primary generalised tonic-clonic seizure frequency; (2) seizure freedom; (3) treatment withdrawal; (4) adverse effects; (5) cognitive effects; and (6) quality of life. We used an intention-to-treat (ITT) population for all analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs); for adverse effects, we used 99% CIs to compensate for multiple hypothesis testing.\nMain results\nWe included three studies (total 300 participants): two parallel-group studies and one cross-over study. We assessed varied risks of bias across studies; most limitations arose from the poor reporting of methodological details. We meta-analysed data extracted from the two parallel-group studies, and conducted a narrative synthesis for data from the cross-over study.\nBoth parallel-group studies (270 participants) reported all dichotomous outcomes. Participants taking lamotrigine were almost twice as likely to attain a 50% or greater reduction in primary generalised tonic-clonic seizure frequency than those taking a placebo (RR 1.88, 95% CI 1.43 to 2.45; low-certainty evidence). The results between groups were inconclusive for the likelihood of seizure freedom (RR 1.55, 95% CI 0.89 to 2.72; very low-certainty evidence); treatment withdrawal (RR 1.20, 95% CI 0.72 to 1.99; very low-certainty evidence); and individual adverse effects: ataxia (RR 3.05, 99% CI 0.05 to 199.36); dizziness (RR 0.91, 99% CI 0.29 to 2.86; very low-certainty evidence); fatigue (RR 1.02, 99% CI 0.13 to 8.14; very low-certainty evidence); nausea (RR 1.60, 99% CI 0.48 to 5.32; very low-certainty evidence); and somnolence (RR 3.73, 99% CI 0.36 to 38.90; low-certainty evidence).\nThe cross-over trial (26 participants) reported that 7/14 participants with generalised tonic-clonic seizures experienced a 50% or greater reduction in seizure frequency with add-on lamotrigine compared to placebo. The authors reported four treatment withdrawals, but did not specify during which treatment allocation they occurred. Rash (seven lamotrigine participants; zero placebo participants) and fatigue (five lamotrigine participants; zero placebo participants) were the most frequently reported adverse effects.\nNone of the included studies measured cognition. One parallel-group study (N = 153) evaluated quality of life. They reported inconclusive results for the overall quality of life score between groups (P = 0.74).\nAuthors' conclusions\nThis review provides insufficient information to inform clinical practice.\nLow-certainty evidence suggests that lamotrigine reduces the rate of generalised tonic-clonic seizures by 50% or more. Very low-certainty evidence found inconclusive results between groups for all other outcomes. Therefore, we are uncertain to very uncertain that the results reported are accurate, and suggest that the true effect could be grossly different.\nMore trials, recruiting larger populations, over longer periods, are necessary to determine lamotrigine's clinical use.\n\nGiven the provided abstract, please respond to the following query: \"Results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found three trials, involving 300 people, that investigated lamotrigine for people with drug-resistant generalised tonic-clonic seizures. People who received add-on lamotrigine were almost twice as likely to have a 50% or greater reduction in the number of generalised tonic-clonic seizures than people who received add-on placebo (an inactive, dummy drug). Lamotrigine did not significantly affect: the number of people who were completely free of seizures, the number of people who withdrew from treatment, or the number of people who experienced common adverse effects.\nHowever, we are very uncertain whether these findings are accurate. This is because there were not many people involved in the studies, and we are unclear about the methods some of the studies used. For this reason, we cannot comment on the use of lamotrigine.\nMore trials, which include more people, and are carried out over longer time periods are needed to properly guide the use of lamotrigine for people with drug-resistant generalised tonic-clonic seizures.\nThe evidence is current to March 2019." } ]

[ { "role": "user", "content": "Abstract: Background\nEarly accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and cutaneous squamous cell carcinoma (cSCC) are high-risk skin cancers which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Computer-assisted diagnosis (CAD) systems use artificial intelligence to analyse lesion data and arrive at a diagnosis of skin cancer. When used in unreferred settings ('primary care'), CAD may assist general practitioners (GPs) or other clinicians to more appropriately triage high-risk lesions to secondary care. Used alongside clinical and dermoscopic suspicion of malignancy, CAD may reduce unnecessary excisions without missing melanoma cases.\nObjectives\nTo determine the accuracy of CAD systems for diagnosing cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC in adults, and to compare its accuracy with that of dermoscopy.\nSearch methods\nWe undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles.\nSelection criteria\nStudies of any design that evaluated CAD alone, or in comparison with dermoscopy, in adults with lesions suspicious for melanoma or BCC or cSCC, and compared with a reference standard of either histological confirmation or clinical follow-up.\nData collection and analysis\nTwo review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities separately by type of CAD system, using the bivariate hierarchical model. We compared CAD with dermoscopy using (a) all available CAD data (indirect comparisons), and (b) studies providing paired data for both tests (direct comparisons). We tested the contribution of human decision-making to the accuracy of CAD diagnoses in a sensitivity analysis by removing studies that gave CAD results to clinicians to guide diagnostic decision-making.\nMain results\nWe included 42 studies, 24 evaluating digital dermoscopy-based CAD systems (Derm–CAD) in 23 study cohorts with 9602 lesions (1220 melanomas, at least 83 BCCs, 9 cSCCs), providing 32 datasets for Derm–CAD and seven for dermoscopy. Eighteen studies evaluated spectroscopy-based CAD (Spectro–CAD) in 16 study cohorts with 6336 lesions (934 melanomas, 163 BCC, 49 cSCCs), providing 32 datasets for Spectro–CAD and six for dermoscopy. These consisted of 15 studies using multispectral imaging (MSI), two studies using electrical impedance spectroscopy (EIS) and one study using diffuse-reflectance spectroscopy. Studies were incompletely reported and at unclear to high risk of bias across all domains. Included studies inadequately address the review question, due to an abundance of low-quality studies, poor reporting, and recruitment of highly selected groups of participants.\nAcross all CAD systems, we found considerable variation in the hardware and software technologies used, the types of classification algorithm employed, methods used to train the algorithms, and which lesion morphological features were extracted and analysed across all CAD systems, and even between studies evaluating CAD systems. Meta–analysis found CAD systems had high sensitivity for correct identification of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in highly selected populations, but with low and very variable specificity, particularly for Spectro–CAD systems. Pooled data from 22 studies estimated the sensitivity of Derm–CAD for the detection of melanoma as 90.1% (95% confidence interval (CI) 84.0% to 94.0%) and specificity as 74.3% (95% CI 63.6% to 82.7%). Pooled data from eight studies estimated the sensitivity of multispectral imaging CAD (MSI–CAD) as 92.9% (95% CI 83.7% to 97.1%) and specificity as 43.6% (95% CI 24.8% to 64.5%). When applied to a hypothetical population of 1000 lesions at the mean observed melanoma prevalence of 20%, Derm–CAD would miss 20 melanomas and would lead to 206 false-positive results for melanoma. MSI–CAD would miss 14 melanomas and would lead to 451 false diagnoses for melanoma. Preliminary findings suggest CAD systems are at least as sensitive as assessment of dermoscopic images for the diagnosis of invasive melanoma and atypical intraepidermal melanocytic variants. We are unable to make summary statements about the use of CAD in unreferred populations, or its accuracy in detecting keratinocyte cancers, or its use in any setting as a diagnostic aid, because of the paucity of studies.\nAuthors' conclusions\nIn highly selected patient populations all CAD types demonstrate high sensitivity, and could prove useful as a back-up for specialist diagnosis to assist in minimising the risk of missing melanomas. However, the evidence base is currently too poor to understand whether CAD system outputs translate to different clinical decision–making in practice. Insufficient data are available on the use of CAD in community settings, or for the detection of keratinocyte cancers. The evidence base for individual systems is too limited to draw conclusions on which might be preferred for practice. Prospective comparative studies are required that evaluate the use of already evaluated CAD systems as diagnostic aids, by comparison to face–to–face dermoscopy, and in participant populations that are representative of those in which the test would be used in practice.\n\nGiven the provided abstract, please respond to the following query: \"How reliable are the results of the studies of this review?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Incomplete reporting of studies made it difficult for us to judge how reliable they were. Many studies had important limitations. Some studies only included particular types of skin lesions or excluded lesions that were considered difficult to diagnose. Importantly, most of the studies only included skin lesions with a biopsy result, which means that only a sample of lesions that would be seen by a doctor in practice were included. These characteristics may result in CAD systems appearing more or less accurate than they actually are." } ]

[ { "role": "user", "content": "Abstract: Background\nDrinking is influenced by youth perceptions of how their peers drink. These perceptions are often incorrect, overestimating peer drinking norms. If inaccurate perceptions can be corrected, young people may drink less.\nObjectives\nTo determine whether social norms interventions reduce alcohol-related negative consequences, alcohol misuse or alcohol consumption when compared with a control (ranging from assessment only/no intervention to other educational or psychosocial interventions) among university and college students.\nSearch methods\nThe following electronic databases were searched up to July 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO. The Cumulative Index to Nursing and Allied Health Literature (CINAHL) only to March 2008. Reference lists of included studies and review articles were manually searched. No restriction based on language or date was applied.\nSelection criteria\nRandomised controlled trials or cluster-randomised controlled trials that compared a social normative intervention versus no intervention, alcohol education leaflet or other 'non-normative feedback' alcohol intervention and reported on alcohol consumption or alcohol-related problems in university or college students.\nData collection and analysis\nWe used standard methodological procedures as expected by Cochrane. Each outcome was analysed by mode of delivery: mailed normative feedback (MF); web/computer normative feedback (WF); individual face-to-face normative feedback (IFF); group face-to-face normative feedback (GFF); and normative marketing campaign (MC).\nMain results\nA total of 70 studies (44,958 participants) were included in the review, and 63 studies (42,784 participants) in the meta-analyses. Overall, the risk of bias assessment showed that these studies provided moderate or low quality evidence.\nOutcomes at four or more months post-intervention were of particular interest to assess when effects were sustained beyond the immediate short term. We have reported pooled effects across delivery modes only for those analyses for which heterogeneity across delivery modes is not substantial (I2 < 50%).\nAlcohol-related problems at four or more months: IFF standardised mean difference (SMD) -0.14, 95% confidence interval (CI) -0.24 to -0.04 (participants = 2327; studies = 11; moderate quality evidence), equivalent to a decrease of 1.28 points in the 69-point alcohol problems scale score. No effects were found for WF or MF.\nBinge drinking at four or more months: results pooled across delivery modes: SMD -0.06, 95% CI -0.11 to -0.02 (participants = 11,292; studies = 16; moderate quality evidence), equivalent to 2.7% fewer binge drinkers if 30-day prevalence is 43.9%.\nDrinking quantity at four or more months: results pooled across delivery modes: SMD -0.08, 95% CI -0.12 to -0.04 (participants = 21,169; studies = 32; moderate quality evidence), equivalent to a reduction of 0.9 drinks consumed each week, from a baseline of 13.7 drinks per week.\nDrinking frequency at four or more months: WF SMD -0.11, 95% CI -0.17 to -0.04 (participants = 9929; studies = 10; moderate quality evidence), equivalent to a decrease of 0.17 drinking days/wk, from a baseline of 2.74 days/wk; IFF SMD -0.21, 95% CI -0.31 to -0.10 (participants = 1464; studies = 8; moderate quality evidence), equivalent to a decrease of 0.32 drinking days/wk, from a baseline of 2.74 days/wk. No effects were found for GFF or MC.\nEstimated blood alcohol concentration (BAC) at four or more months: peak BAC results pooled across delivery modes: SMD -0.08, 95% CI -0.17 to 0.00 (participants = 7198; studies = 11; low quality evidence), equivalent to a reduction in peak BAC from an average of 0.144% to 0.135%. No effects were found for typical BAC with IFF.\nAuthors' conclusions\nThe results of this review indicate that no substantive meaningful benefits are associated with social norms interventions for prevention of alcohol misuse among college/university students. Although some significant effects were found, we interpret the effect sizes as too small, given the measurement scales used in the studies included in this review, to be of relevance for policy or practice. Moreover, the significant effects are not consistent for all misuse measures, heterogeneity was a problem in some analyses and bias cannot be discounted as a potential cause of these findings.\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": "Drinking is influenced by youth perceptions of how their peers drink. These perceptions are often incorrect, overestimating peer drinking norms. If inaccurate perceptions can be corrected, with social norms information or feedback, young people may drink less." } ]

[ { "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 characteristics\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We found 34 randomised controlled trials (RCTs) involving 3244 women that compared traditional slings with drugs or other types of surgery (colposuspension, mid-urethral slings, bladder neck needle suspension, single-incision slings (mini-slings); one type of traditional sling with another; and traditional slings with injectables. All trials included women with SUI, but some also involved women with UUI, who are said to have MUI.\nWe did not find any studies comparing suburethral slings with no treatment or sham treatment, conservative management such as pelvic floor exercises, anterior repair, or laparoscopic colposuspension." } ]

[ { "role": "user", "content": "Abstract: Background\nThe estimated likelihood of lower limb amputation is 10 to 30 times higher amongst people with diabetes compared to those without diabetes. Of all non-traumatic amputations in people with diabetes, 85% are preceded by a foot ulcer. Foot ulceration associated with diabetes (diabetic foot ulcers) is caused by the interplay of several factors, most notably diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD) and changes in foot structure. These factors have been linked to chronic hyperglycaemia (high levels of glucose in the blood) and the altered metabolic state of diabetes. Control of hyperglycaemia may be important in the healing of ulcers.\nObjectives\nTo assess the effects of intensive glycaemic control compared to conventional control on the outcome of foot ulcers in people with type 1 and type 2 diabetes.\nSearch methods\nIn December 2015 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; EBSCO CINAHL; Elsevier SCOPUS; ISI Web of Knowledge Web of Science; BioMed Central and LILACS. We also searched clinical trial databases, pharmaceutical trial databases and current international and national clinical guidelines on diabetes foot management for relevant published, non-published, ongoing and terminated clinical trials. There were no restrictions based on language or date of publication or study setting.\nSelection criteria\nPublished, unpublished and ongoing randomised controlled trials (RCTs) were considered for inclusion where they investigated the effects of intensive glycaemic control on the outcome of active foot ulcers in people with diabetes. Non randomised and quasi-randomised trials were excluded. In order to be included the trial had to have: 1) attempted to maintain or control blood glucose levels and measured changes in markers of glycaemic control (HbA1c or fasting, random, mean, home capillary or urine glucose), and 2) documented the effect of these interventions on active foot ulcer outcomes. Glycaemic interventions included subcutaneous insulin administration, continuous insulin infusion, oral anti-diabetes agents, lifestyle interventions or a combination of these interventions. The definition of the interventional (intensive) group was that it should have a lower glycaemic target than the comparison (conventional) group.\nData collection and analysis\nAll review authors independently evaluated the papers identified by the search strategy against the inclusion criteria. Two review authors then independently reviewed all potential full-text articles and trials registry results for inclusion.\nMain results\nWe only identified one trial that met the inclusion criteria but this trial did not have any results so we could not perform the planned subgroup and sensitivity analyses in the absence of data. Two ongoing trials were identified which may provide data for analyses in a later version of this review. The completion date of these trials is currently unknown.\nAuthors' conclusions\nThe current review failed to find any completed randomised clinical trials with results. Therefore we are unable to conclude whether intensive glycaemic control when compared to conventional glycaemic control has a positive or detrimental effect on the treatment of foot ulcers in people with diabetes. Previous evidence has however highlighted a reduction in risk of limb amputation (from various causes) in people with type 2 diabetes with intensive glycaemic control. Whether this applies to people with foot ulcers in particular is unknown. The exact role that intensive glycaemic control has in treating foot ulcers in multidisciplinary care (alongside other interventions targeted at treating foot ulcers) requires further investigation.\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": "This Cochrane review aimed to answer the question; how does controlling blood glucose more intensively compared to conventional blood glucose control influence foot ulcer healing in people with diabetes?" } ]

[ { "role": "user", "content": "Abstract: Background\nBiologic disease-modifying anti-rheumatic drugs (DMARDs: referred to as biologics) are effective in treating rheumatoid arthritis (RA), however there are few head-to-head comparison studies. Our systematic review, standard meta-analysis and network meta-analysis (NMA) updates the 2009 Cochrane overview, 'Biologics for rheumatoid arthritis (RA)' and adds new data. This review is focused on biologic or tofacitinib therapy in people with RA who had previously been treated unsuccessfully with biologics.\nObjectives\nTo compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (placebo or methotrexate (MTX)/other DMARDs) in people with RA, previously unsuccessfully treated with biologics.\nMethods\nOn 22 June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, and Embase; and trials registries (WHO trials register, Clinicaltrials.gov). We carried out article selection, data extraction, and risk of bias and GRADE assessments in duplicate. We calculated direct estimates with 95% confidence intervals (CI) using standard meta-analysis. We used a Bayesian mixed treatment comparison (MTC) approach for NMA estimates with 95% credible intervals (CrI). We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We have also presented results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB). Outcomes measured included four benefits (ACR50, function measured by Health Assessment Questionnaire (HAQ) score, remission defined as DAS < 1.6 or DAS28 < 2.6, slowing of radiographic progression) and three harms (withdrawals due to adverse events, serious adverse events, and cancer).\nMain results\nThis update includes nine new RCTs for a total of 12 RCTs that included 3364 participants. The comparator was placebo only in three RCTs (548 participants), MTX or other traditional DMARD in six RCTs (2468 participants), and another biologic in three RCTs (348 participants). Data were available for four tumor necrosis factor (TNF)-biologics: (certolizumab pegol (1 study; 37 participants), etanercept (3 studies; 348 participants), golimumab (1 study; 461 participants), infliximab (1 study; 27 participants)), three non-TNF biologics (abatacept (3 studies; 632 participants), rituximab (2 studies; 1019 participants), and tocilizumab (2 studies; 589 participants)); there was only one study for tofacitinib (399 participants). The majority of the trials (10/12) lasted less than 12 months.\nWe judged 33% of the studies at low risk of bias for allocation sequence generation, allocation concealment and blinding, 25% had low risk of bias for attrition, 92% were at unclear risk for selective reporting; and 92% had low risk of bias for major baseline imbalance. We downgraded the quality of the evidence for most outcomes to moderate or low due to study limitations, heterogeneity, or rarity of direct comparator trials.\nBiologic monotherapy versus placebo\nCompared to placebo, biologics were associated with clinically meaningful and statistically significant improvement in RA as demonstrated by higher ACR50 and RA remission rates. RR was 4.10 for ACR50 (95% CI 1.97 to 8.55; moderate-quality evidence); absolute benefit RD 14% (95% CI 6% to 21%); and NNTB = 8 (95% CI 4 to 23). RR for RA remission was 13.51 (95% CI 1.85 to 98.45, one study available; moderate-quality evidence); absolute benefit RD 9% (95% CI 5% to 13%); and NNTB = 11 (95% CI 3 to 136). Results for withdrawals due to adverse events and serious adverse events did not show any statistically significant or clinically meaningful differences. There were no studies available for analysis for function measured by HAQ, radiographic progression, or cancer outcomes. There were not enough data for any of the outcomes to look at subgroups.\nBiologic + MTX versus active comparator (MTX/other traditional DMARDs)\nCompared to MTX/other traditional DMARDs, biologic + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50, function measured by HAQ, and RA remission rates in direct comparisons. RR for ACR50 was 4.07 (95% CI 2.76 to 5.99; high-quality evidence); absolute benefit RD 16% (10% to 21%); NNTB = 7 (95% CI 5 to 11). HAQ scores showed an improvement with a mean difference (MD) of 0.29 (95% CI 0.21 to 0.36; high-quality evidence); absolute benefit RD 9.7% improvement (95% CI 7% to 12%); and NNTB = 5 (95% CI 4 to 7). Remission rates showed an improved RR of 20.73 (95% CI 4.13 to 104.16; moderate-quality evidence); absolute benefit RD 10% (95% CI 8% to 13%); and NNTB = 17 (95% CI 4 to 96), among the biologic + MTX group compared to MTX/other DMARDs. There were no studies for radiographic progression. Results were not clinically meaningful or statistically significantly different for withdrawals due to adverse events or serious adverse events, and were inconclusive for cancer.\nTofacitinib monotherapy versus placebo\nThere were no published data.\nTofacitinib + MTX versus active comparator (MTX)\nIn one study, compared to MTX, tofacitinib + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50 (RR 3.24; 95% CI 1.78 to 5.89; absolute benefit RD 19% (95% CI 12% to 26%); NNTB = 6 (95% CI 3 to 14); moderate-quality evidence), and function measured by HAQ, MD 0.27 improvement (95% CI 0.14 to 0.39); absolute benefit RD 9% (95% CI 4.7% to 13%), NNTB = 5 (95% CI 4 to 10); high-quality evidence). RA remission rates were not statistically significantly different but the observed difference may be clinically meaningful (RR 15.44 (95% CI 0.93 to 256.1; high-quality evidence); absolute benefit RD 6% (95% CI 3% to 9%); NNTB could not be calculated. There were no studies for radiographic progression. There were no statistically significant or clinically meaningful differences for withdrawals due to adverse events and serious adverse events, and results were inconclusive for cancer.\nAuthors' conclusions\nBiologic (with or without MTX) or tofacitinib (with MTX) use was associated with clinically meaningful and statistically significant benefits (ACR50, HAQ, remission) compared to placebo or an active comparator (MTX/other traditional DMARDs) among people with RA previously unsuccessfully treated with biologics.\nNo studies examined radiographic progression. Results were not clinically meaningful or statistically significant for withdrawals due to adverse events and serious adverse events, and were inconclusive for cancer.\n\nGiven the provided abstract, please respond to the following query: \"Cancer\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "" } ]

[ { "role": "user", "content": "Abstract: Background\nEndodontic treatment involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root-filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite, directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth, and may influence durability and cost. The decision to use a post and core in addition to the crown is clinician driven. The comparative clinical performance of crowns or conventional fillings used to restore root-filled teeth is unknown. This review updates the original, which was published in 2012.\nObjectives\nTo assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials.\nSearch methods\nWe searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME. We also searched the reference lists of articles and ongoing trials registries.There were no restrictions regarding language or date of publication. The search is up-to-date as of 26 March 2015.\nSelection criteria\nRandomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth that have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration or indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any.\nData collection and analysis\nTwo review authors independently extracted data from the included trial and assessed its risk of bias. We carried out data analysis using the 'treatment as allocated' patient population, expressing estimates of intervention effect for dichotomous data as risk ratios, with 95% confidence intervals (CI).\nMain results\nWe included one trial, which was judged to be at high risk of performance, detection and attrition bias. The 117 participants with a root-filled, premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. None experienced a catastrophic failure (i.e. when the restoration cannot be repaired), although only 104 teeth were included in the final, three-year assessment. There was no clear difference between the crown and composite group and the composite only group for non-catastrophic failures of the restoration (1/54 versus 3/53; RR 0.33; 95% CI 0.04 to 3.05) or failures of the post (2/54 versus 1/53; RR 1.96; 95% CI 0.18 to 21.01) at three years. The quality of the evidence for these outcomes is very low. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of caries, periodontal health status, and costs.\nAuthors' conclusions\nThere is insufficient evidence to assess the effects of crowns compared to conventional fillings for the restoration of root-filled teeth. Until more evidence becomes available, clinicians should continue to base decisions about how to restore root-filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.\n\nGiven the provided abstract, please respond to the following query: \"Key results\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The evidence produced from one study concluded that none of the 117 root-filled premolars experienced a catastrophic failure (i.e. one that cannot be repaired) after three years, although only 104 teeth were included in the final, three-year assessment. The study concluded there was no difference between treatments for the risk of non-catastrophic failure. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of decay, periodontal health status, and costs." } ]

[ { "role": "user", "content": "Abstract: Background\nThis is an updated version of the original Cochrane Review published in the Cochrane Library in 2013 (Issue 8) on the risk of ovarian cancer in women using infertility drugs when compared to the general population or to infertile women not treated. The link between fertility drugs and ovarian cancer remains controversial.\nObjectives\nTo evaluate the risk of invasive ovarian cancer and borderline ovarian tumours in women treated with ovarian stimulating drugs for subfertility.\nSearch methods\nThe original review included published and unpublished observational studies from 1990 to February 2013. For this update, we extended the searches from February 2013 to November 2018; we evaluated the quality of the included studies and judged the certainty of evidence by using the GRADE approach. We have reported the results in a Summary of findings table to present effect sizes across all outcome types.\nSelection criteria\nIn the original review and in this update, we searched for randomised controlled trials (RCTs) and non-randomised studies and case series including more than 30 participants.\nData collection and analysis\nAt least two review authors independently conducted eligibility and 'Risk of bias' assessments and extracted data. We grouped studies based on the fertility drug used for two outcomes: borderline ovarian tumours and invasive ovarian cancer. We conducted no meta-analyses due to expected methodological and clinical heterogeneity.\nMain results\nWe included 13 case-control and 24 cohort studies (an additional nine new cohort and two case-control studies), which included a total of 4,684,724 women.\nTwo cohort studies reported an increased incidence of invasive ovarian cancer in exposed subfertile women compared with unexposed women. One reported a standardised incidence ratio (SIR) of 1.19 (95% confidence interval (CI) 0.54 to 2.25) based on 17 cancer cases. The other cohort study reported a hazard ratio (HR) of 1.93 (95% CI 1.18 to 3.18), and this risk was increased in women remaining nulligravid after using clomiphene citrate (HR 2.49, 95% CI 1.30 to 4.78) versus multiparous women (HR 1.52, 95% CI 0.67 to 3.42) (very low-certainty evidence). The slight increase in ovarian cancer risk among women having between one and three cycles of in vitro fertilisation (IVF) was reported, but this was not clinically significant (P = 0.18). There was no increase in risk of invasive ovarian cancer after use of infertility drugs in women with the BRCA mutation according to one cohort and one case-control study. The certainty of evidence as assessed using GRADE was very low.\nFor borderline ovarian tumours, one cohort study reported increased risk in exposed women with an SIR of 3.61 (95% CI 1.45 to 7.44), and this risk was greater after treatment with clomiphene citrate (SIR 7.47, 95% CI 1.54 to 21.83) based on 12 cases. In another cohort study, the risk of a borderline ovarian tumour was increased, with an HR of 4.23 (95% CI 1.25 to 14.33), for subfertile women treated with IVF compared with a non-IVF-treated group with more than one year of follow-up. A large cohort reported increased risk of borderline ovarian tumours, with HR of 2.46 (95% CI 1.20 to 5.04), and this was based on 17 cases. A significant increase in serous borderline ovarian tumours was reported in one cohort study after the use of progesterone for more than four cycles (risk ratio (RR) 2.63, 95% CI 1.04 to 6.64). A case-control study reported increased risk after clomiphene citrate was taken, with an SIR of 2.5 (95% CI 1.3 to 4.5) based on 11 cases, and another reported an increase especially after human menopausal gonadotrophin was taken (odds ratio (OR) 9.38, 95% CI 1.66 to 52.08). Another study estimated an increased risk of borderline ovarian tumour, but this estimation was based on four cases with no control reporting use of fertility drugs. The certainty of evidence as assessed using GRADE was very low.\nHowever, although some studies suggested a slight increase in risks of ovarian cancer and borderline ovarian tumour, none provided moderate- or high-certainty evidence, as summarised in the GRADE tables.\nAuthors' conclusions\nSince the last version of this review, only a few new relevant studies have provided additional findings with supporting evidence to suggest that infertility drugs may increase the risk of ovarian cancer slightly in subfertile women treated with infertility drugs when compared to the general population or to subfertile women not treated. The risk is slightly higher in nulliparous than in multiparous women treated with infertility drugs, and for borderline ovarian tumours. However, few studies have been conducted, the number of cancers is very small, and information on the dose or type of fertility drugs used is insufficient.\n\nGiven the provided abstract, please respond to the following query: \"What are the main findings?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Overall, based on 37 studies, which included a total of 4,684,724 women, we did not find enough strong evidence suggesting a potentially higher risk of ovarian cancer in women treated with fertility drugs.\nA cumulative analysis of 12 case-control studies from the USA revealed increased risk of ovarian cancer in women using fertility drugs, and this risk was higher in nulliparous women (women who have not given birth) when compared to multiparous women (women who have given birth to more than one child). One of the 37 included studies reported a two-fold increase in development of serous borderline ovarian tumour in women after more than four cycles of progesterone; however the number of cases included in this group was very small. One cohort study also suggested an increased risk of borderline ovarian tumour in infertile women treated with clomiphene citrate when compared to infertile women who did not undergo treatment to conceive." } ]

[ { "role": "user", "content": "Abstract: Background\nThere is growing interest in paying for performance (P4P) as a means to align the incentives of healthcare providers with public health goals. Rigorous evidence on the effectiveness of these strategies in improving health care and health in low- and middle-income countries (LMICs) is lacking; this is an update of the 2012 review on this topic.\nObjectives\nTo assess the effects of paying for performance on the provision of health care and health outcomes in low- and middle-income countries.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase, and 10 other databases between April and June 2018. We also searched two trial registries, websites, online resources of international agencies, organizations and universities, and contacted experts in the field. Studies identified from rerunning searches in 2020 are under 'Studies awaiting classification.'\nSelection criteria\nWe included randomized or non-randomized trials, controlled before-after studies, or interrupted time series studies conducted in LMICs (as defined by the World Bank in 2018). P4P refers to the transfer of money or material goods conditional on taking a measurable action or achieving a predetermined performance target. To be included, a study had to report at least one of the following outcomes: patient health outcomes, changes in targeted measures of provider performance (such as the delivery of healthcare services), unintended effects, or changes in resource use.\nData collection and analysis\nWe extracted data as per original review protocol and narratively synthesised findings. We used standard methodological procedures expected by Cochrane. Given diversity and variability in intervention types, patient populations, analyses and outcome reporting, we deemed meta-analysis inappropriate. We noted the range of effects associated with P4P against each outcome of interest. Based on intervention descriptions provided in documents, we classified design schemes and explored variation in effect by scheme design.\nMain results\nWe included 59 studies: controlled before-after studies (19), non-randomized (16) or cluster randomized trials (14);  and interrupted time-series studies (9). One study included both an interrupted time series and a controlled before-after study.\nStudies focused on a wide range of P4P interventions, including target payments and payment for outputs as modified by quality (or quality and equity assessments). Only one study assessed results-based aid. Many schemes were funded by national governments (23 studies) with the World Bank funding most externally funded schemes (11 studies). Targeted services varied; however, most interventions focused on reproductive, maternal and child health indicators. Participants were predominantly located in public or in a mix of public, non-governmental and faith-based facilities (54 studies). P4P was assessed predominantly at health facility level, though districts and other levels were also involved.\nMost studies assessed the effects of P4P against a status quo control (49 studies); however, some studies assessed effects against comparator interventions (predominantly enhanced financing intended to match P4P funds (17 studies)). Four studies reported intervention effects against both comparator and status quo.\nControlled before-after studies were at higher risk of bias than other study designs. However, some randomised trials were also downgraded due to risk of bias. The interrupted time-series studies provided insufficient information on other concurrent changes in the study context.\nP4P compared to a status quo control\nFor health services that are specifically targeted, P4P may slightly improve health outcomes (low certainty evidence), but few studies assessed this. P4P may also improve service quality overall (low certainty evidence); and probably increases the availability of health workers, medicines and well-functioning infrastructure and equipment (moderate certainty evidence). P4P may have mixed effects on the delivery and use of services (low certainty evidence) and may have few or no distorting unintended effects on outcomes that were not targeted (low-certainty evidence), but few studies assessed these. For secondary outcomes, P4P may make little or no difference to provider absenteeism, motivation or satisfaction (low certainty evidence); but may improve patient satisfaction and acceptability (low certainty evidence); and may positively affect facility managerial autonomy (low certainty evidence). P4P probably makes little to no difference to management quality or facility governance (low certainty evidence). Impacts on equity were mixed (low certainty evidence).\nFor health services that are untargeted, P4P probably improves some health outcomes (moderate certainty evidence); may improve the delivery, use and quality of some health services but may make little or no difference to others (low certainty evidence); and may have few or no distorting unintended effects (low certainty evidence). The effects of P4P on the availability of medicines and other resources are uncertain (very low certainty evidence).\nP4P compared to other strategies\nFor health outcomes and services that are specifically targeted, P4P may make little or no difference to health outcomes (low certainty evidence), but few studies assessed this. P4P may improve service quality (low certainty evidence); and may have mixed effects on the delivery and use of health services and on the availability of equipment and medicines (low certainty evidence).\nFor health outcomes and services that are untargeted, P4P may make little or no difference to health outcomes and to the delivery and use of health services (low certainty evidence). The effects of P4P on service quality, resource availability and unintended effects are uncertain (very low certainty evidence).\nFindings of subgroup analyses\nResults-based aid, and schemes using payment per output adjusted for service quality, appeared to yield the greatest positive effects on outcomes. However, only one study evaluated results-based aid, so the effects may be spurious. Overall, schemes adjusting both for quality of service and rewarding equitable delivery of services appeared to perform best in relation to service utilization outcomes.\nAuthors' conclusions\nThe evidence base on the impacts of P4P schemes has grown considerably, with study quality gradually increasing. P4P schemes may have mixed effects on outcomes of interest, and there is high heterogeneity in the types of schemes implemented and evaluations conducted. P4P is not a uniform intervention, but rather a range of approaches. Its effects depend on the interaction of several variables, including the design of the intervention (e.g., who receives payments ), the amount of additional funding,  ancillary components (such as technical support) and contextual factors (including organizational context).\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 studies included in this review looked at pay for performance approaches that varied in their design, setting and implementation. The review shows that pay for performance may have both positive and negative effects on the health services it targets. It may also have positive effects on other health services that are not directly targeted and may have no unintended negative effects on these services. However, most of this evidence is of low certainty and we need more, well-conducted studies on this topic." } ]

[ { "role": "user", "content": "Abstract: Background\nRoutine monitoring of gastric residuals in preterm infants on tube feeds is a common practice in neonatal intensive care units used to guide initiation and advancement of enteral feeding. There is a paucity of consensus on whether to re-feed or discard the aspirated gastric residuals. While re-feeding gastric residuals may aid in digestion and promote gastrointestinal motility and maturation by replacing partially digested milk, gastrointestinal enzymes, hormones, and trophic substances, abnormal residuals may result in vomiting, necrotising enterocolitis, or sepsis.\nObjectives\nTo assess the efficacy and safety of re-feeding when compared to discarding gastric residuals in preterm infants.\nSearch methods\nSearches were conducted in February 2022 in Cochrane CENTRAL via CRS, Ovid MEDLINE and Embase, and CINAHL. We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.\nSelection criteria\nWe selected RCTs that compared re-feeding versus discarding gastric residuals in preterm infants.\nData collection and analysis\nReview authors assessed trial eligibility and risk of bias and extracted data, in duplicate. We analysed treatment effects in individual trials and reported the risk ratio (RR) for dichotomous data and the mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence.\nMain results\nWe found one eligible trial that included 72 preterm infants. The trial was unmasked but was otherwise of good methodological quality.\nRe-feeding gastric residual may have little or no effect on time to regain birth weight (MD 0.40 days, 95% CI −2.89 to 3.69; 59 infants; low-certainty evidence), risk of necrotising enterocolitis stage ≥ 2 or spontaneous intestinal perforation (RR 0.71, 95% CI 0.25 to 2.04; 72 infants; low-certainty evidence), all-cause mortality before hospital discharge (RR 0.50, 95% CI 0.14 to 1.85; 72 infants; low-certainty evidence), time to establish enteral feeds ≥ 120 mL/kg/d (MD −1.30 days, 95% CI −2.93 to 0.33; 59 infants; low-certainty evidence), number of total parenteral nutrition days (MD −0.30 days, 95% CI −2.07 to 1.47; 59 infants; low-certainty evidence), and risk of extrauterine growth restriction at discharge (RR 1.29, 95% CI 0.38 to 4.34; 59 infants; low-certainty evidence). We are uncertain as to the effect of re-feeding gastric residual on number of episodes of feed interruption lasting for ≥ 12 hours (RR 0.80, 95% CI 0.42 to 1.52; 59 infants; very low-certainty evidence).\nAuthors' conclusions\nWe found only limited data from one small unmasked trial on the efficacy and safety of re-feeding gastric residuals in preterm infants. Low-certainty evidence suggests re-feeding gastric residual may have little or no effect on important clinical outcomes such as necrotising enterocolitis, all-cause mortality before hospital discharge, time to establish enteral feeds, number of total parenteral nutrition days, and in-hospital weight gain. A large RCT is needed to assess the efficacy and safety of re-feeding of gastric residuals in preterm infants with adequate certainty of evidence to inform policy and practice.\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 search is up-to-date as of February 2022." } ]

[ { "role": "user", "content": "Abstract: Background\nThe unanticipated difficult airway is a potentially life-threatening event during anaesthesia or acute conditions. An unsuccessfully managed upper airway is associated with serious morbidity and mortality. Several bedside screening tests are used in clinical practice to identify those at high risk of difficult airway. Their accuracy and benefit however, remains unclear.\nObjectives\nThe objective of this review was to characterize and compare the diagnostic accuracy of the Mallampati classification and other commonly used airway examination tests for assessing the physical status of the airway in adult patients with no apparent anatomical airway abnormalities. We performed this individually for each of the four descriptors of the difficult airway: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation.\nSearch methods\nWe searched major electronic databases including CENTRAL, MEDLINE, Embase, ISI Web of Science, CINAHL, as well as regional, subject specific, and dissertation and theses databases from inception to 16 December 2016, without language restrictions. In addition, we searched the Science Citation Index and checked the references of all the relevant studies. We also handsearched selected journals, conference proceedings, and relevant guidelines. We updated this search in March 2018, but we have not yet incorporated these results.\nSelection criteria\nWe considered full-text diagnostic test accuracy studies of any individual index test, or a combination of tests, against a reference standard. Participants were adults without obvious airway abnormalities, who were having laryngoscopy performed with a standard laryngoscope and the trachea intubated with a standard tracheal tube. Index tests included the Mallampati test, modified Mallampati test, Wilson risk score, thyromental distance, sternomental distance, mouth opening test, upper lip bite test, or any combination of these. The target condition was difficult airway, with one of the following reference standards: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation.\nData collection and analysis\nWe performed screening and selection of the studies, data extraction and assessment of methodological quality (using QUADAS-2) independently and in duplicate. We designed a Microsoft Access database for data collection and used Review Manager 5 and R for data analysis. For each index test and each reference standard, we assessed sensitivity and specificity. We produced forest plots and summary receiver operating characteristic (ROC) plots to summarize the data. Where possible, we performed meta-analyses to calculate pooled estimates and compare test accuracy indirectly using bivariate models. We investigated heterogeneity and performed sensitivity analyses.\nMain results\nWe included 133 (127 cohort type and 6 case-control) studies involving 844,206 participants. We evaluated a total of seven different prespecified index tests in the 133 studies, as well as 69 non-prespecified, and 32 combinations. For the prespecified index tests, we found six studies for the Mallampati test, 105 for the modified Mallampati test, six for the Wilson risk score, 52 for thyromental distance, 18 for sternomental distance, 34 for the mouth opening test, and 30 for the upper lip bite test. Difficult face mask ventilation was the reference standard in seven studies, difficult laryngoscopy in 92 studies, difficult tracheal intubation in 50 studies, and failed intubation in two studies. Across all studies, we judged the risk of bias to be variable for the different domains; we mostly observed low risk of bias for patient selection, flow and timing, and unclear risk of bias for reference standard and index test. Applicability concerns were generally low for all domains. For difficult laryngoscopy, the summary sensitivity ranged from 0.22 (95% confidence interval (CI) 0.13 to 0.33; mouth opening test) to 0.67 (95% CI 0.45 to 0.83; upper lip bite test) and the summary specificity ranged from 0.80 (95% CI 0.74 to 0.85; modified Mallampati test) to 0.95 (95% CI 0.88 to 0.98; Wilson risk score). The upper lip bite test for diagnosing difficult laryngoscopy provided the highest sensitivity compared to the other tests (P < 0.001). For difficult tracheal intubation, summary sensitivity ranged from 0.24 (95% CI 0.12 to 0.43; thyromental distance) to 0.51 (95% CI 0.40 to 0.61; modified Mallampati test) and the summary specificity ranged from 0.87 (95% CI 0.82 to 0.91; modified Mallampati test) to 0.93 (0.87 to 0.96; mouth opening test). The modified Mallampati test had the highest sensitivity for diagnosing difficult tracheal intubation compared to the other tests (P < 0.001). For difficult face mask ventilation, we could only estimate summary sensitivity (0.17, 95% CI 0.06 to 0.39) and specificity (0.90, 95% CI 0.81 to 0.95) for the modified Mallampati test.\nAuthors' conclusions\nBedside airway examination tests, for assessing the physical status of the airway in adults with no apparent anatomical airway abnormalities, are designed as screening tests. Screening tests are expected to have high sensitivities. We found that all investigated index tests had relatively low sensitivities with high variability. In contrast, specificities were consistently and markedly higher than sensitivities across all tests. The standard bedside airway examination tests should be interpreted with caution, as they do not appear to be good screening tests. Among the tests we examined, the upper lip bite test showed the most favourable diagnostic test accuracy properties. Given the paucity of available data, future research is needed to develop tests with high sensitivities to make them useful, and to consider their use for screening difficult face mask ventilation and failed intubation. The 27 studies in 'Studies awaiting classification' may alter the conclusions of the review, once we have assessed them.\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": "For difficult laryngoscopy, the average sensitivity (percentage of correctly identified difficult airways) ranged from 22% (mouth opening test) to 63% (upper lip bite test). The average specificity (percentage of correctly classified patients without difficult airways) ranged from 80% (modified Mallampati test) to 95% (Wilson risk score). The upper lip bite test had the highest sensitivity of all tests considered.\nFor difficult tube insertion, the average sensitivity ranged from 24% (thyromental distance) to 51% (modified Mallampati test) and the average specificity ranged from 87% (modified Mallampati test) to 93% (mouth opening test). The modified Mallampati test had the highest sensitivity of all tests considered.\nFor difficult face mask ventilation (another indication of a difficult airway), there were only enough data to calculate average sensitivity of 17% and specificity 90% for the modified Mallampati test." } ]

[ { "role": "user", "content": "Abstract: Background\nCystic fibrosis (CF) a life-limiting inherited disease affecting a number of organs, but classically associated with chronic lung infection and progressive loss of lung function. Chronic infection by Burkholderia cepacia complex (BCC) is associated with increased morbidity and mortality and therefore represents a significant challenge to clinicians treating people with CF. This review examines the current evidence for long-term antibiotic therapy in people with CF and chronic BCC infection.\nObjectives\nThe objective of this review is to assess the effects of long-term oral and inhaled antibiotic therapy targeted against chronic BCC lung infections in people with CF. The primary objective is to assess the efficacy of treatments in terms of improvements in lung function and reductions in exacerbation rate. Secondary objectives include quantifying adverse events, mortality and changes in quality of life associated with treatment.\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 online trial registries and the reference lists of relevant articles and reviews.\nDate of last search: 12 April 2021.\nSelection criteria\nRandomised controlled trials (RCTs) of long-term antibiotic therapy in people with CF and chronic BCC infection.\nData collection and analysis\nTwo authors independently extracted data, assessed risk of bias and assessed the quality of the evidence using GRADE.\nMain results\nWe included one RCT (100 participants) which lasted 52 weeks comparing continuous inhaled aztreonam lysine (AZLI) and placebo in a double-blind RCT for 24 weeks, followed by a 24-week open-label extension and a four-week follow-up period. The average participant age was 26.3 years, 61% were male and average lung function was 56.5% predicted.\nTreatment with AZLI for 24 weeks was not associated with improvement in forced expiratory volume in one second (FEV1), mean difference 0.91% (95% confidence interval (CI) -3.15 to 4.97) (moderate-quality evidence). The median time to the next exacerbation was 75 days in the AZLI group compared to 51 days in the placebo group, but the difference was not significant (P = 0.27) (moderate-quality evidence). Similarly, the number of participants hospitalised for respiratory exacerbations showed no difference between groups, risk ratio (RR) 0.88 (95% CI 0.53 to 1.45) (moderate-quality evidence). Overall adverse events were similar between groups, RR 1.08 (95% CI 0.98 to 1.19) (moderate-quality evidence). There were no significant differences between treatment groups in relation to mortality (moderate-quality evidence), quality of life or sputum density.\nIn relation to methodological quality, the overall risk of bias in the study was assessed to be unclear to low risk.\nAuthors' conclusions\nWe found insufficient evidence from the literature to determine an effective strategy for antibiotic therapy for treating chronic BCC infection.\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": "This review included one study of 100 people aged between 6 and 57 years old. The study compared an inhaled antibiotic called aztreonam to placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly (by chance). The study lasted 52 weeks." } ]

[ { "role": "user", "content": "Abstract: Background\nIt is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors influencing placebo rates may lead to more informed clinical trial design.\nObjectives\nA systematic review and meta-analysis was conducted to evaluate placebo response and remission rates in RCTs evaluating UC treatments in adult patients.\nSearch methods\nElectronic databases (i.e. MEDLINE, EMBASE, and CENTRAL) were searched from inception to 1 March 2017 with no language restrictions applied. Reference lists and conference proceedings of major gastroenterology meetings were also handsearched to identify additional studies.\nSelection criteria\nPlacebo-controlled RCTs of adult patients with UC treated with corticosteroids, aminosalicylates, immunosuppressives or biologics were eligible, provided enrolment and outcome assessment was conducted using the Ulcerative Colitis Disease Activity Index (UCDAI) or the Mayo Clinic Score. The minimum trial duration was two weeks for induction trials and four months maintenance trials.\nData collection and analysis\nPairs of authors independently determined study eligibility and extracted data with any disagreements resolved through consensus. Outcomes of interest included the proportion of patients with clinical response and remission. Trial characteristics such as the design, participant demographics and disease history, interventions, and enrolment and assessment criteria were also recorded. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tool. Pooled placebo response and remission rates and 95% confidence intervals (95% CI) were calculated using a binomial normal model for proportions. Induction of remission and maintenance studies were pooled separately. The impact of study-level characteristics on placebo response and remission rates was investigated using mixed-effects meta-regression analyses with logits of event rates as the outcome variables. An assessment of pooled placebo rates over time was conducted using a cumulative meta-analysis based on date of publication. Publication bias was examined using funnel plots.\nMain results\nThe screening process identified 61 included studies which encompass 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). For induction trials, the pooled estimate of placebo response was 33% (95% CI 30% to 36%) while the pooled estimate of placebo remission was 12% (95% CI 9% to 15%). For maintenance trials, the pooled estimate of placebo response was 23% (95% CI 19% to 28%) while the pooled estimate of placebo remission was 17% (95% CI 10% to 27%).\nStudies enrolling patients with more active disease confirmed objectively by endoscopy were associated with significantly lower placebo remission and response rates than trials enrolling patients with less active disease (27% versus 4%, OR 2.60, 95% CI 1.25 to 5.42, P = 0.01 for UCDAI endoscopy sub score ≥1 versus ≥ 2 for remission; and 27% versus 4%, OR 1.70, 95% CI 1.02 to 2.82, P = 0.02 for UCDAI endoscopy sub score greater than or equal to one versus greater than or equal to two for response). With respect to drug class, the lowest placebo response and remission rates were observed in trials evaluating corticosteroids (23%; 95% CI 19 to 29%, and 5%; 95% CI 2 to 11%, respectively). Trials of biologics had the highest placebo response rate (35%; 95% CI 30 to 41%), while trials evaluating aminosalicylates had the highest placebo remission rate (18%; 95% CI 12 to 24%). Disease duration of greater than five years prior to enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years (29% versus 47%, respectively; OR 0.54, 95% CI 0.32 to 0.92, P = 0.02). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility (37% versus 32%, respectively; OR 1.70, 95% CI 1.02 to 2.82, P = 0.02). Finally, the time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with a 6% increase in the placebo remission rate (OR 1.06, 95% CI 1.02 to 1.10, P = 0.01).\nCumulative meta-analysis indicated a consistent increase in the placebo response rate from 1987 to 2007 (from 13% to 33%), although rates have remained constant from 2008 to 2015 (32% to 34%). Similarly, placebo remission rates increased from 1987 to 2007 (5% to 14%) but have remained constant from 2008 to 2015 (12 to 14%). On meta-regression, there were no statistically significant differences between the 1987-2007 and 2008-2015 point estimates for both response (P = 0.81) and remission (P = 0.32).\nAuthors' conclusions\nPlacebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, class of agent, disease duration, and the time point at which the primary outcome was measured. These observations have important implications for the design and conduct of future clinical trials in UC and will help researchers design trials, determine required sample sizes and also provide useful information about trial design features which should be considered when planning new trials.\n\nGiven the provided abstract, please respond to the following query: \"What did the researchers investigate?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "The researchers reviewed published randomised placebo-controlled trials in UC of several classes of drugs to quantify what the placebo response rates were overall, and how these response rates have evolved over time. They also investigated how factors related to the study design, participants, treatments or outcomes influenced the placebo rates in UC trials. The medical literature was searched and analysed up to 1 March 2017." } ]

[ { "role": "user", "content": "Abstract: Background\nSerum procalcitonin (PCT) evaluation has been proposed for early diagnosis and accurate staging and to guide decisions regarding patients with sepsis, severe sepsis and septic shock, with possible reduction in mortality.\nObjectives\nTo assess the effectiveness and safety of serum PCT evaluation for reducing mortality and duration of antimicrobial therapy in adults with sepsis, severe sepsis or septic shock.\nSearch methods\nWe searched the Central Register of Controlled Trials (CENTRAL; 2015, Issue 7); MEDLINE (1950 to July 2015); Embase (Ovid SP, 1980 to July 2015); Latin American Caribbean Health Sciences Literature (LILACS via BIREME, 1982 to July 2015); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCO host, 1982 to July 2015), and trial registers (ISRCTN registry, ClinicalTrials.gov and CenterWatch, to July 2015). We reran the search in October 2016. We added three studies of interest to a list of ‘Studies awaiting classification' and will incorporate these into formal review findings during the review update.\nSelection criteria\nWe included only randomized controlled trials (RCTs) testing PCT-guided decisions in at least one of the comparison arms for adults (≥ 18 years old) with sepsis, severe sepsis or septic shock, according to international definitions and irrespective of the setting.\nData collection and analysis\nTwo review authors extracted study data and assessed the methodological quality of included studies. We conducted meta-analysis with random-effects models for the following primary outcomes: mortality and time spent receiving antimicrobial therapy in hospital and in the intensive care unit (ICU), as well as time spent on mechanical ventilation and change in antimicrobial regimen from a broad to a narrower spectrum.\nMain results\nWe included 10 trials with 1215 participants. Low-quality evidence showed no significant differences in mortality at longest follow-up (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.01; I2 = 10%; 10 trials; N = 1156), at 28 days (RR 0.89, 95% CI 0.61 to 1.31; I2 = 0%; four trials; N = 316), at ICU discharge (RR 1.03, 95% CI 0.50 to 2.11; I2 = 49%; three trials; N = 506) and at hospital discharge (RR 0.98, 95% CI 0.75 to 1.27; I2 = 0%; seven trials; N = 805; moderate-quality evidence). However, mean time receiving antimicrobial therapy in the intervention groups was -1.28 days (95% CI to -1.95 to -0.61; I2 = 86%; four trials; N = 313; very low-quality evidence). No primary study has analysed the change in antimicrobial regimen from a broad to a narrower spectrum.\nAuthors' conclusions\nUp-to-date evidence of very low to moderate quality, with insufficient sample power per outcome, does not clearly support the use of procalcitonin-guided antimicrobial therapy to minimize mortality, mechanical ventilation, clinical severity, reinfection or duration of antimicrobial therapy of patients with septic conditions.\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 considered the body of available evidence as having very low to moderate quality owing to absence of methods to prevent errors during studies or absence of information about such methods, as well as possibly insufficient numbers of studies and patients per outcome. Additionally, the authors of most studies worked as consultants and/or received payments from companies involved in the procalcitonin analysis." } ]

[ { "role": "user", "content": "Abstract: Background\nFrostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue. Depending on the degree of tissue damage, thrombosis, ischaemia, necrosis (tissue death), gangrene and ultimately amputation may occur. Several interventions for frostbite injuries have been proposed, such as hyperbaric oxygen therapy, sympathectomy (nerve block), thrombolytic (blood-thinning) therapy and vasodilating agents such as iloprost, reserpine, pentoxifylline and buflomedil, but the benefits and harms of these interventions are unclear.\nObjectives\nTo assess the benefits and harms of the different management options for frostbite injuries.\nSearch methods\nOn 25 February 2020, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S), as well as trials registers. Shortly before publication, we searched Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, OpenGrey and GreyLit (9 November 2020) again. We investigated references from relevant articles, and corresponded with a trial author.\nSelection criteria\nWe included randomised controlled trials (RCTs) that compared any medical intervention, e.g. pharmacological therapy, topical treatments or rewarming techniques, for frostbite injuries to another treatment, placebo or no treatment.\nData collection and analysis\nTwo authors independently extracted data. We used Review Manager 5 for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CIs). We used the Cochrane 'Risk of bias' tool to assess bias in the included trial. We assessed incidence of amputations, rates of serious and non-serious adverse events, acute pain, chronic pain, ability to perform activities of daily living, quality of life, withdrawal rate from medical therapy due to adverse events, occupational effects and mortality. We used GRADE to assess the quality of the evidence.\nMain results\nWe included one, open-label randomised trial involving 47 participants with severe frostbite injuries. We judged this trial to be at high risk of bias for performance bias, and uncertain risk for attrition bias; all other risk of bias domains we judged as low.\nAll participants underwent rapid rewarming, received 250 mg of aspirin and 400 mg intravascular (IV) buflomedil (since withdrawn from practice), and were then randomised to one of three treatment groups for the following eight days. Group 1 received additional IV buflomedil 400 mg for one hour per day. Group 2 received the prostacyclin, iloprost, 0.5 ng to 2 ng/kg/min IV for six hours per day. Group 3 received IV iloprost 2 ng/kg/min for six hours per day plus fibrinolysis with 100 mg recombinant tissue plasminogen activator (rtPA) for the first day only.\nThe results suggest that iloprost and iloprost plus rtPA may reduce the rate of amputations in people with severe frostbite compared to buflomedil alone, RR 0.05 (95% CI 0.00 to 0.78; P = 0.03; very low-quality evidence) and RR 0.31 (95% CI 0.10 to 0.94; P = 0.04; very low-quality evidence), respectively. Iloprost may be as effective as iloprost plus rtPA at reducing the amputation rate, RR 0.14 (95% CI 0.01 to 2.56; P = 0.19; very low-quality evidence). There were no reported deaths or withdrawals due to adverse events in any of the groups; we assessed evidence for both outcomes as being of very low quality. Adverse events (including flushing, nausea, palpitations and vomiting) were common, but not reported separately by comparator arm (very low-quality evidence). The included study did not measure the outcomes of acute pain, chronic pain, ability to perform activities of daily living, quality of life or occupational effects.\nAuthors' conclusions\nThere is a paucity of evidence regarding interventions for frostbite injuries. Very low-quality evidence from a single small trial indicates that iloprost, and iloprost plus rtPA, in combination with buflomedil may reduce the need for amputation in people with severe frostbite compared to buflomedil alone. However, buflomedil has been withdrawn from use. High quality randomised trials are needed to establish firm evidence for the treatment of frostbite injuries.\n\nGiven the provided abstract, please respond to the following query: \"What is frostbite?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Frostbite is an injury to skin and the tissues beneath that is caused by exposure of the skin to freezing temperatures. Freezing temperatures cause ice crystals to form in the tissue, this reduces the blood supply to the tissue and damages it. The parts of the body most commonly affected are the fingers, toes, nose, ears and cheeks. Symptoms include a loss of feeling in the affected areas, combined with a pale waxy discolouration of the skin, followed eventually by blisters and swelling. If the affected areas are not warmed up, and the exposure to the cold continues, deeper layers of tissue may become affected, which may ultimately result in loss of the tissue, that is, removal of fingers or toes (amputations).\nWarming up (rewarming) of frostbitten areas may cause severe pain. At present, treatment involves:\n- rapid rewarming of the affected area in a 37 °C to 39 °C whirlpool bath;\n- giving the patient pain-killing medication in the form of aspirin and ibuprofen; and\n- if the affected area does not return to normal after rewarming, transferring the patient to hospital for further treatment.\nSeveral different specialised treatments can be given in hospitals, including a medication called 'iloprost', which may increase blood flow to frostbitten areas. It is hoped that iloprost may reverse the damage to frostbitten tissue." } ]

[ { "role": "user", "content": "Abstract: Background\nPerioperative hypertension requires careful management. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) have shown efficacy in treating hypertension associated with surgery. However, there is lack of consensus about whether they can prevent mortality and morbidity.\nObjectives\nTo systematically assess the benefits and harms of administration of ACEIs or ARBs perioperatively for the prevention of mortality and morbidity in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia.\nSearch methods\nWe searched the current issue of the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 12), Ovid MEDLINE (1966 to 8 December 2014), EMBASE (1980 to 8 December 2014), and references of the retrieved randomized trials, meta-analyses, and systematic reviews. We reran the search on February 3, 2017. Three potential new studies of interest were added to a list of 'Studies awaiting Classification' and will be incorporated into the formal review findings during the review update.\nSelection criteria\nWe included randomized controlled trials (RCTs) comparing perioperative administration of ACEIs or ARBs with placebo in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia. We excluded studies in which participants underwent procedures that required local anaesthesia only, or participants who had already been on ACEIs or ARBs.\nData collection and analysis\nTwo review authors independently performed study selection, assessed the risk of bias, and extracted data. We used standard methodological procedures expected by Cochrane.\nMain results\nWe included seven RCTs with a total of 571 participants in the review. Two of the seven trials involved 36 participants undergoing non-cardiac vascular surgery (infrarenal aortic surgery), and five involved 535 participants undergoing cardiac surgery, including valvular surgery, coronary artery bypass surgery, and cardiopulmonary bypass surgery. The intervention was started from 11 days to 25 minutes before surgery in six trials and during surgery in one trial. We considered all seven RCTs to carry a high risk of bias. The effects of ACEIs or ARBs on perioperative mortality and acute myocardial infarction were uncertain because the quality of the evidence was very low. The risk of death was 2.7% in the ACEIs or ARBs group and 1.6% in the placebo group (risk ratio (RR) 1.61; 95% confidence interval (CI) 0.44 to 5.85). The risk of acute myocardial infarction was 1.7% in the ACEIs or ARBs group and 3.0% in the placebo group (RR 0.55; 95% CI 0.14 to 2.26). ACEIs or ARBs may improve congestive heart failure (cardiac index) perioperatively (mean difference (MD) -0.60; 95% CI -0.70 to -0.50, very low-quality evidence). In terms of rate of complications, there was no difference in perioperative cerebrovascular complications (RR 0.48; 95% CI 0.18 to 1.28, very low-quality evidence) and hypotension (RR 1.95; 95% CI 0.86 to 4.41, very low-quality evidence). Cardiac surgery-related renal failure was not reported. ACEIs or ARBs were associated with shortened length of hospital stay (MD -0.54; 95% CI -0.93 to -0.16, P value = 0.005, very low-quality evidence). These findings should be interpreted cautiously due to likely confounding by the clinical backgrounds of the participants. ACEIs or ARBs may shorten the length of hospital stay, (MD -0.54; 95% CI -0.93 to -0.16, very low-quality evidence) Two studies reported adverse events, and there was no evidence of a difference between the ACEIs or ARBs and control groups.\nAuthors' conclusions\nOverall, this review did not find evidence to support that perioperative ACEIs or ARBs can prevent mortality, morbidity, and complications (hypotension, perioperative cerebrovascular complications, and cardiac surgery-related renal failure). We found no evidence showing that the use of these drugs may reduce the rate of acute myocardial infarction. However, ACEIs or ARBs may increase cardiac output perioperatively. Due to the low and very low methodology quality, high risk of bias, and lack of power of the included studies, the true effect may be substantially different from the observed estimates. Perioperative (mainly elective cardiac surgery, according to included studies) initiation of ACEIs or ARBs therapy should be individualized.\n\nGiven the provided abstract, please respond to the following query: \"Review question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "We reviewed the evidence on two drugs that are used to lower blood pressure (angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs)) around the time of surgery for reducing the risk of death and serious illness in adults undergoing surgery using a general anaesthetic." } ]

[ { "role": "user", "content": "Abstract: Background\nBreast cancer is the most common type of cancer amongst women worldwide, and one distressing complication of breast cancer treatment is breast and upper-limb lymphoedema. There is uncertainty regarding the effectiveness of surgical interventions in both the prevention and management of lymphoedema affecting the arm after breast cancer treatment.\nObjectives\n1. To assess and compare the efficacy of surgical interventions for the prevention of the development of lymphoedema (LE) in the arm after breast cancer treatment.\n2. To assess and compare the efficacy of surgical interventions for the treatment of established LE in the arm after breast cancer treatment.\nSearch methods\nWe searched the Cochrane Breast Cancer Group’s Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for all prospectively registered and ongoing trials on 2 November 2017. Reference lists of included studies were also handsearched by three review authors for additional eligible trials.\nSelection criteria\nAll randomised controlled trials (RCTs) comparing a surgical intervention for the prevention or treatment of lymphoedema of the arm after breast cancer treatment to either standard intervention, placebo intervention, or another surgical intervention were included. Patients of both sexes and all ages who have had treatment for their breast cancer were considered. No limits were applied to language or study location. Three authors independently determined the eligibility of each study.\nData collection and analysis\nThree authors independently extracted data for each included study using a pre-designed data extraction pro forma and used Cochrane's 'risk of bias' tool for assessing risk of bias. Dichotomous variables were analysed using the Mantel-Haenszel method to estimate risk ratios (RRs). Differences in continuous variables were expressed as mean differences (MDs). GRADE was used to assess the certainty of the evidence provided by the included studies.\nMain results\nTwo studies involving 95 participants examined surgical interventions for preventing breast cancer-related lymphoedema. Both studies evaluated the efficacy of the lymphaticovenular anastomosis technique as part of a preventative management protocol. Both studies were deemed to be at unclear risk of bias overall. Statistical variation between the studies was low, which increases the reliability of the evidence. However, the two studies were conducted in the same centre. Lymphaticovenular anastomosis appears to result in a reduction in the incidence of lymphoedema compared to nonoperative management with a risk ratio of 0.20 (95% CI 0.06 to 0.63, P = 0.006; 95 participants; low-certainty evidence). The RCTs did not evaluate any of the secondary outcomes.\nOne study involving 36 participants evaluated the effectiveness of vascularised lymph node transfer for treating breast cancer-related lymphoedema. The trial was deemed to be at unclear risk of bias. For participants suffering from stage 2 lymphoedema, the evidence suggested reductions in limb volume (MD -39.00%, 95% CI -47.37% to -30.63%, very low-certainty evidence), pain scores (MD -4.16, 95% CI -5.17 to -3.15, very low-certainty evidence), heaviness sensation (MD -4.27, 95% CI -5.74 to -2.80, very low-certainty evidence), mean number of infections/year (MD -1.22, 95% CI -2.00 to -0.44, very low-certainty evidence), and an improvement in overall function scores (MD -3.77, 95% CI -4.89 to -2.65, very low-certainty evidence) for those who had undergone vascularised lymph node transfer compared to those who had undergone no treatment.\nAuthors' conclusions\nThere is low-certainty evidence that lymphaticovenular anastomosis is effective in preventing the development of lymphoedema after breast cancer treatment based on the findings from two studies. One study providing very low-certainty evidence found that vascularised lymph node transfer is an efficacious option in the treatment of established stage 2 lymphoedema related to breast cancer. Important secondary outcomes in this review were rarely reported in the included studies. More high-quality RCTs are required to further elucidate the effectiveness of surgical interventions in the prevention and treatment of lymphoedema after breast cancer treatment. At the time of this review, no ongoing trials on this topic were identified.\n\nGiven the provided abstract, please respond to the following query: \"Study question\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Health care professionals have examined alternative ways to manage lymphoedema after breast cancer treatment. This report reviews the effectiveness of surgical techniques that have been developed to either prevent or treat this condition." } ]

[ { "role": "user", "content": "Abstract: Background\nIntimate partner violence (IPV) includes any violence (physical, sexual or psychological/emotional) by a current or former partner. This review reflects the current understanding of IPV as a profoundly gendered issue, perpetrated most often by men against women. IPV may result in substantial physical and mental health impacts for survivors. Women affected by IPV are more likely to have contact with healthcare providers (HCPs) (e.g. nurses, doctors, midwives), even though women often do not disclose the violence. Training HCPs on IPV, including how to respond to survivors of IPV, is an important intervention to improve HCPs' knowledge, attitudes and practice, and subsequently the care and health outcomes for IPV survivors.\nObjectives\nTo assess the effectiveness of training programmes that seek to improve HCPs' identification of and response to IPV against women, compared to no intervention, wait-list, placebo or training as usual.\nSearch methods\nWe searched CENTRAL, MEDLINE, Embase and seven other databases up to June 2020. We also searched two clinical trials registries and relevant websites. In addition, we contacted primary authors of included studies to ask if they knew of any relevant studies not identified in the search. We evaluated the reference lists of all included studies and systematic reviews for inclusion. We applied no restrictions by search dates or language.\nSelection criteria\nAll randomised and quasi-randomised controlled trials comparing IPV training or educational programmes for HCPs compared with no training, wait-list, training as usual, placebo, or a sub-component of the intervention.\nData collection and analysis\nWe used standard methodological procedures outlined by Cochrane. Two review authors independently assessed studies for eligibility, undertook data extraction and assessed risks of bias. Where possible, we synthesised the effects of IPV training in a meta-analysis. Other analyses were synthesised in a narrative manner. We assessed evidence certainty using the GRADE approach.\nMain results\nWe included 19 trials involving 1662 participants. Three-quarters of all studies were conducted in the USA, with single studies from Australia, Iran, Mexico, Turkey and the Netherlands. Twelve trials compared IPV training versus no training, and seven trials compared the effects of IPV training to training as usual or a sub-component of the intervention in the comparison group, or both.\nStudy participants included 618 medical staff/students, 460 nurses/students, 348 dentists/students, 161 counsellors or psychologists/students, 70 midwives and 5 social workers. Studies were heterogeneous and varied across training content delivered, pedagogy and time to follow-up (immediately post training to 24 months). The risk of bias assessment highlighted unclear reporting across many areas of bias. The GRADE assessment of the studies found that the certainty of the evidence for the primary outcomes was low to very low, with studies often reporting on perceived or self-reported outcomes rather than actual HCPs' practices or outcomes for women. Eleven of the 19 included studies received some form of research grant funding to complete the research.\nWithin 12 months post-intervention, the evidence suggests that compared to no intervention, wait-list or placebo, IPV training:\n· may improve HCPs' attitudes towards IPV survivors (standardised mean difference (SMD) 0.71, 95% CI 0.39 to 1.03; 8 studies, 641 participants; low-certainty evidence);\n· may have a large effect on HCPs' self-perceived readiness to respond to IPV survivors, although the evidence was uncertain (SMD 2.44, 95% CI 1.51 to 3.37; 6 studies, 487 participants; very low-certainty evidence);\n· may have a large effect on HCPs' knowledge of IPV, although the evidence was uncertain (SMD 6.56, 95% CI 2.49 to 10.63; 3 studies, 239 participants; very low-certainty evidence);\n· may make little to no difference to HCPs' referral practices of women to support agencies, although this is based on only one study (with 49 clinics) assessed to be very low certainty;\n· has an uncertain effect on HCPs' response behaviours (based on two studies of very low certainty), with one trial (with 27 participants) reporting that trained HCPs were more likely to successfully provide advice on safety planning during their interactions with standardised patients, and the other study (with 49 clinics) reporting no clear impact on safety planning practices;\n· may improve identification of IPV at six months post-training (RR 4.54, 95% CI 2.5 to 8.09) as in one study (with 54 participants), although three studies (with 48 participants) reported little to no effects of training on identification or documentation of IPV, or both.\nNo studies assessed the impact of training HCPs on the mental health of women survivors of IPV compared to no intervention, wait-list or placebo.\nWhen IPV training was compared to training as usual or a sub-component of the intervention, or both, no clear effects were seen on HCPs' attitudes/beliefs, safety planning, and referral to services or mental health outcomes for women. Inconsistent results were seen for HCPs' readiness to respond (improvements in two out of three studies) and HCPs' IPV knowledge (improved in two out of four studies). One study found that IPV training improved HCPs' validation responses.\nNo adverse IPV-related events were reported in any of the studies identified in this review.\nAuthors' conclusions\nOverall, IPV training for HCPs may be effective for outcomes that are precursors to behaviour change. There is some, albeit weak evidence that IPV training may improve HCPs' attitudes towards IPV. Training may also improve IPV knowledge and HCPs' self-perceived readiness to respond to those affected by IPV, although we are not certain about this evidence. Although supportive evidence is weak and inconsistent, training may improve HCPs' actual responses, including the use of safety planning, identification and documentation of IPV in women's case histories. The sustained effect of training on these outcomes beyond 12 months is undetermined. Our confidence in these findings is reduced by the substantial level of heterogeneity across studies and the unclear risk of bias around randomisation and blinding of participants, as well as high risk of bias from attrition in many studies. Further research is needed that overcomes these limitations, as well as assesses the impacts of IPV training on HCPs' behavioral outcomes and the well-being of women survivors of IPV.\n\nGiven the provided abstract, please respond to the following query: \"Key results with an assessment of the certainty of the evidence\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Compared to no training, placebo or wait-list, IPV training may have positive effects on HCPs' attitudes towards survivors of IPV. Training may improve their knowledge around, and readiness to respond to survivors of IPV, but the evidence is very uncertain. There is limited evidence that some types of IPV training can lead to improvements in identification, safety planning and documentation of IPV, but the findings are inconsistent, and most studies report little to no impact of training on these outcomes. Training may make little to no difference to referral practices. No studies with no training, placebo or wait-list in the comparison group, assessed IPV survivors' mental health outcomes. No adverse effects of IPV training were reported in any of these studies.\nThe studies that compared training of HCPs to training as usual or a sub-component of the training typically found no difference in HCPs' attitudes, safety planning, and referral to services or mental health outcomes for women. The evidence was inconsistent about provider readiness to respond, their actual response and changes in IPV knowledge.\nOverall, the certainty of the evidence for the effectiveness of training HCPs in how to respond to IPV is low to very low. Future research should include higher-quality trials, with greater clarity of methods that objectively measure outcomes (actual rather than perceived), with an emphasis on behaviour change in HCPs, and the well-being of women survivors of IPV." } ]

[ { "role": "user", "content": "Abstract: Background\nPatients with longstanding ulcerative colitis and colonic Crohn's disease have an increased risk of colorectal cancer (CRC) compared with the general population. This review assessed the evidence that endoscopic surveillance may prolong life by allowing earlier detection of CRC or its pre-cursor lesion, dysplasia, in patients with inflammatory bowel disease (IBD).\nObjectives\nTo assess the effectiveness of cancer surveillance programs for diagnosis of IBD-associated colorectal cancer and in reducing the mortality rate from colorectal cancer in patients with IBD.\nSearch methods\nWe searched MEDLINE, EMBASE, CENTRAL and clinical clinicaltrials.gov from inception to 19 September 2016. We also searched conference abstracts and reference lists to identify additional studies.\nSelection criteria\nPotentially relevant articles were reviewed independently and unblinded by two authors to determine eligibility. Randomised controlled trials (RCTs) or observational studies (cohort or case control) assessing any form of endoscopic surveillance aimed at early detection of CRC were considered for inclusion. Studies had to have a no surveillance comparison group to be eligible for inclusion.\nData collection and analysis\nEligible studies were reviewed in duplicate and the results of the primary research trials were independently extracted by two authors. The primary outcome was detection of CRC. Secondary outcomes included death from CRC, time to cancer detection, time to death and adverse events. Deaths from CRC were derived from life tables, survival curves or where possible, by calculating life tables from the data provided. The presence of significant heterogeneity among studies was tested by the chi-square test. Because this is a relatively insensitive test, a P value of less than 0.1 was considered statistically significant. Provided statistical heterogeneity was not present, the fixed effects model was used for the pooling of data. The 2x2 tables were combined into a summary test statistic using the pooled odds ratio (OR) and 95% confidence intervals as described by Cochrane and Mantel and Haenszel. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale for non-randomised studies The overall quality of the evidence supporting the primary and selected secondary outcomes was assessed using the GRADE criteria.\nMain results\nNo RCTs were identified. Five observational studies (N = 7199) met the inclusion criteria. The studies scored well on the Newcastle-Ottawa scale, but due to the nature of observational studies, a high risk of bias was assigned to all the studies. Three studies were pooled to assess the rate of cancer detected in the surveillance group compared to the non-surveillance group. The studies found a significantly higher rate of cancer detection in the non surveillance group compared to the surveillance group. CRC was detected in 1.83% (53/2895) of patients in the surveillance group compared to 3.17% (135/4256) of patients in the non-surveillance group (OR 0.58, 95% CI 0.42 to 0.80; P = 0.0009). Four studies were pooled to assess the death rate associated with CRC in patients who underwent surveillance compared to patients who did not undergo surveillance. There was a significantly lower death rate associated with CRC in the surveillance group compared to the non-surveillance group. Eight per cent (15/176) of patients in the surveillance group died from CRC compared to 22% (79/354) of patients in the non-surveillance group (OR 0.36, 95% CI 0.19 to 0.69, P=0.002). Data were pooled from two studies to examine the rate of early stage versus late stage colorectal cancer (Duke stages A & B compared to Duke stages C & D) in patients who underwent surveillance compared to patients who do not undergo surveillance. A significantly higher rate of early stage CRC (Duke A & B) was detected in the surveillance group compared to the non-surveillance group. Sixteen per cent (17/110) of patients in the surveillance group had early stage CRC compared to 8% (9/117) of patients in the non-surveillance group (OR 5.40, 95% CI 1.51 to 19.30; P = 0.009). A higher rate of late stage CRC (Duke C & D) was observed in the non-surveillance group compared to the surveillance group. Nine per cent (10/110) of patients in the surveillance group had late stage CRC compared to 16% (19/117) of patients in the non-surveillance group (OR 0.46, 95% CI 0.08 to 2.51; P = 0.37). A GRADE analysis indicated that the quality of the data was very low for all of these outcomes. The included studies did not report on the other pre-specified outcomes including time to cancer detection, time to death and adverse events.\nAuthors' conclusions\nThe current data suggest that colonoscopic surveillance in IBD may reduce the development of both CRC and the rate of CRC-associated death through early detection, although the quality of the evidence is very low. The detection of earlier stage CRC in the surveillance group may explain some of the survival benefit observed. RCTs assessing the efficacy of endoscopic surveillance in people with IBD are unlikely to be undertaken due to ethical considerations.\n\nGiven the provided abstract, please respond to the following query: \"What did the researchers find?\". Use language that can be easily comprehended by individuals without domain knowledge:\n" }, { "role": "assistant", "content": "Five observational studies with 7199 patients were used to compare endoscopic surveillance to non-surveillance. The key findings of the review were that a higher rate of cancer occurred in the non-surveillance group compared to the surveillance group, and that a lower rate of colon cancer-associated death was demonstrated in the surveillance group compared to the non-surveillance group. In patients undergoing surveillance, the odds of colon cancer development were reduced by 42% and the odds of death associated with colon cancer was reduced by 64%. Surveillance resulted in detection of a higher rate of early stage colorectal cancer in the surveillance group compared to the non surveillance group which may explain the improved survival seen with surveillance. The overall quality of the evidence is very low due to the nature of observation studies and the low number of events. Nonetheless, these results suggest that endoscopic surveillance in people with IBD may reduce the development of colon cancer through early detection and may also reduce the chances of dying from colon cancer." } ]