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PloS One 2015Diagnosing obstructive sleep apnea (OSA) is clinically relevant because untreated OSA has been associated with increased morbidity and mortality. The STOP-Bang... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diagnosing obstructive sleep apnea (OSA) is clinically relevant because untreated OSA has been associated with increased morbidity and mortality. The STOP-Bang questionnaire is a validated screening tool for OSA. We conducted a systematic review and meta-analysis to determine the effectiveness of STOP-Bang for screening patients suspected of having OSA and to predict its accuracy in determining the severity of OSA in the different populations.
METHODS
A search of the literature databases was performed. Inclusion criteria were: 1) Studies that used STOP-Bang questionnaire as a screening tool for OSA in adult subjects (>18 years); 2) The accuracy of the STOP-Bang questionnaire was validated by polysomnography--the gold standard for diagnosing OSA; 3) OSA was clearly defined as apnea/hypopnea index (AHI) or respiratory disturbance index (RDI) ≥ 5; 4) Publications in the English language. The quality of the studies were explicitly described and coded according to the Cochrane Methods group on the screening and diagnostic tests.
RESULTS
Seventeen studies including 9,206 patients met criteria for the systematic review. In the sleep clinic population, the sensitivity was 90%, 94% and 96% to detect any OSA (AHI ≥ 5), moderate-to-severe OSA (AHI ≥15), and severe OSA (AHI ≥30) respectively. The corresponding NPV was 46%, 75% and 90%. A similar trend was found in the surgical population. In the sleep clinic population, the probability of severe OSA with a STOP-Bang score of 3 was 25%. With a stepwise increase of the STOP-Bang score to 4, 5, 6 and 7/8, the probability rose proportionally to 35%, 45%, 55% and 75%, respectively. In the surgical population, the probability of severe OSA with a STOP-Bang score of 3 was 15%. With a stepwise increase of the STOP-Bang score to 4, 5, 6 and 7/8, the probability increased to 25%, 35%, 45% and 65%, respectively.
CONCLUSION
This meta-analysis confirms the high performance of the STOP-Bang questionnaire in the sleep clinic and surgical population for screening of OSA. The higher the STOP-Bang score, the greater is the probability of moderate-to-severe OSA.
Topics: Humans; Mass Screening; Polysomnography; Reproducibility of Results; Severity of Illness Index; Sleep Apnea, Obstructive; Surveys and Questionnaires
PubMed: 26658438
DOI: 10.1371/journal.pone.0143697 -
Health Technology Assessment... Nov 2018Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early.
OBJECTIVES
To estimate the clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in high-risk populations.
DATA SOURCES
Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library.
METHODS
Clinical effectiveness - a systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programmes [such as chest X-ray (CXR)] was conducted. Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness - an independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were 12 different population eligibility criteria and four intervention frequencies [(1) single screen, (2) triple screen, (3) annual screening and (4) biennial screening] and a no-screening control arm.
RESULTS
Clinical effectiveness - 12 RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT, with ≤ 9.80 years of follow-up, was associated with a non-statistically significant decrease in lung cancer mortality (pooled relative risk 0.94, 95% confidence interval 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increase in all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis, including six RCTs, was performed to assess the relative clinical effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention and usual care was ranked second. Cost-effectiveness - screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/quality-adjusted life-year (QALY), but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60-75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in only a minority of analyses.
LIMITATIONS
Clinical effectiveness - the largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness - a representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included.
CONCLUSIONS
LDCT screening may be clinically effective in reducing lung cancer mortality, but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits.
FUTURE WORK
Clinical effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs [particularly the NEderlands Leuvens Longkanker Screenings ONderzoek (NELSON) screening trial].
STUDY REGISTRATION
This study is registered as PROSPERO CRD42016048530.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Cost-Benefit Analysis; Early Detection of Cancer; Humans; Lung Neoplasms; Mass Screening; Quality-Adjusted Life Years; Technology Assessment, Biomedical; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 30518460
DOI: 10.3310/hta22690 -
The Cochrane Database of Systematic... Mar 2021Venous thromboembolism (VTE), although rare, is a major cause of maternal mortality and morbidity. Some women are at increased risk of VTE during pregnancy and the early... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Venous thromboembolism (VTE), although rare, is a major cause of maternal mortality and morbidity. Some women are at increased risk of VTE during pregnancy and the early postnatal period (e.g. caesarean section, family history of VTE, or thrombophilia), and so prophylaxis may be considered. As some methods of prophylaxis carry risks of adverse effects, and risk of VTE is often low, benefits of thromboprophylaxis may be outweighed by harms.
OBJECTIVES
To assess the effects of thromboprophylaxis during pregnancy and the early postnatal period on the risk of venous thromboembolic disease and adverse effects in women at increased risk of VTE.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (18 October 2019). In addition, we searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for unpublished, planned and ongoing trial reports (18 October 2019).
SELECTION CRITERIA
Randomised trials comparing one method of thromboprophylaxis with placebo or no treatment, or two (or more) methods of thromboprophylaxis.
DATA COLLECTION AND ANALYSIS
At least two review authors assessed trial eligibility, extracted data, assessed risk of bias, and judged certainty of evidence for selected critical outcomes (using GRADE). We conducted fixed-effect meta-analysis and reported data (all dichotomous) as summary risk ratios (RRs) with 95% confidence intervals (CIs).
MAIN RESULTS
Twenty-nine trials (involving 3839 women), overall at moderate to high risk of bias were included. Trials were conducted across the antenatal, peripartum and postnatal periods, with most in high-income countries. Interventions included types and regimens of heparin (low molecular weight heparin (LMWH) and unfractionated heparin (UFH)), hydroxyethyl starch (HES), and compression stockings or devices. Data were limited due to a small number of trials in comparisons and/or few or no events reported. All critical outcomes (assessed for comparisons of heparin versus no treatment/placebo, and LMWH versus UFH) were considered to have very low-certainty evidence, downgraded mainly for study limitations and imprecise effect estimates. Maternal death was not reported in most studies. Antenatal (± postnatal) prophylaxis For the primary outcomes symptomatic thromboembolic events pulmonary embolism (PE) and/or deep vein thrombosis (DVT), and the critical outcome of adverse effects sufficient to stop treatment, the evidence was very uncertain. Symptomatic thromboembolic events: - heparin versus no treatment/placebo (RR 0.39; 95% CI 0.08 to 1.98; 4 trials, 476 women; very low-certainty evidence); - LMWH versus UFH (RR 0.47; 95% CI 0.09 to 2.49; 4 trials, 404 women; very low-certainty evidence); Symptomatic PE: - heparin versus no treatment/placebo (RR 0.33; 95% CI 0.02 to 7.14; 3 trials, 187 women; very low-certainty evidence); - LMWH versus UFH (no events; 3 trials, 287 women); Symptomatic DVT: - heparin versus no treatment/placebo (RR 0.33; 95% CI 0.04 to 3.10; 4 trials, 227 women; very low-certainty evidence); - LMWH versus UFH (no events; 3 trials, 287 women); Adverse effects sufficient to stop treatment: - heparin versus no treatment/placebo (RR 0.49; 95% CI 0.05 to 5.31; 1 trial, 139 women; very low-certainty evidence); - LMWH versus UFH (RR 0.07; 95% CI 0.01 to 0.54; 2 trials, 226 women; very low-certainty evidence). Peripartum/postnatal prophylaxis Vaginal or caesarean birth When UFH and no treatment were compared, the effects on symptomatic thromboembolic events (RR 0.16; 95% CI 0.02 to 1.36; 1 trial, 210 women; very low-certainty evidence), symptomatic PE (RR 0.16; 95% CI 0.01 to 3.34; 1 trial, 210 women; very low-certainty evidence), and symptomatic DVT (RR 0.27; 95% CI 0.03 to 2.55; 1 trial, 210 women; very low-certainty evidence) were very uncertain. Maternal death and adverse effects sufficient to stop treatment were not reported. Caesarean birth Symptomatic thromboembolic events: - heparin versus no treatment/placebo (RR 1.30; 95% CI 0.39 to 4.27; 4 trials, 840 women; very low-certainty evidence); - LMWH versus UFH (RR 0.33; 95% CI 0.01 to 7.99; 3 trials, 217 women; very low-certainty evidence); Symptomatic PE: - heparin versus no treatment/placebo (RR 1.10; 95% CI 0.25 to 4.87; 4 trials, 840 women; very low-certainty evidence); - LMWH versus UFH (no events; 3 trials, 217 women); Symptomatic DVT: - heparin versus no treatment/placebo (RR 1.30; 95% CI 0.24 to 6.94; 5 trials, 1140 women; very low-certainty evidence); LMWH versus UFH (RR 0.33; 95% CI 0.01 to 7.99; 3 trials, 217 women; very low-certainty evidence); Maternal death: - heparin versus placebo (no events, 1 trial, 300 women); Adverse effects sufficient to stop treatment: - heparin versus placebo (no events; 1 trial, 140 women). Postnatal prophylaxis No events were reported for LMWH versus no treatment/placebo for: symptomatic thromboembolic events, symptomatic PE and symptomatic DVT (all 2 trials, 58 women), or maternal death (1 trial, 24 women). Adverse effects sufficient to stop treatment were not reported. We were unable to conduct subgroup analyses due to lack of data. Sensitivity analysis including the nine studies at low risk of bias did not impact overall findings.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about benefits and harms of VTE thromboprophylaxis in women during pregnancy and the early postnatal period at increased risk of VTE. Further high-quality very large-scale randomised trials are needed to determine effects of currently used treatments in women with different VTE risk factors. As sufficiently large definitive trials are unlikely to be funded, secondary data analyses based on high-quality registry data are important.
Topics: Anticoagulants; Bias; Cesarean Section; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Randomized Controlled Trials as Topic; Venous Thrombosis
PubMed: 33779986
DOI: 10.1002/14651858.CD001689.pub4 -
The Cochrane Database of Systematic... Mar 2015Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Clot prevention with anticoagulants might improve outcomes if bleeding risks are low.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Clot prevention with anticoagulants might improve outcomes if bleeding risks are low. This is an update of a Cochrane review first published in 1995, with recent updates in 2004 and 2008.
OBJECTIVES
To assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) in people with acute presumed or confirmed ischaemic stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR), the Database of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA) (The Cochrane Library 2014 Issue 6), MEDLINE (2008 to June 2014) and EMBASE (2008 to June 2014). 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.
SELECTION CRITERIA
Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trial quality, and extracted the data.
MAIN RESULTS
We included 24 trials involving 23,748 participants. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence relates to the effects of anticoagulant therapy initiated within the first 48 hours of onset. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow-up. Similarly, based on eight trials (22,125 participants), there was no evidence that early anticoagulation reduced the odds of being dead or dependent at the end of follow-up (OR 0.99; 95% CI 0.93 to 1.04). Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99).
AUTHORS' CONCLUSIONS
Since the last version of the review, no new relevant studies have been published and so there is no additional information to change the conclusions. Early anticoagulant therapy is not associated with net short- or long-term benefit in people with acute ischaemic stroke. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any of the currently available anticoagulants in acute ischaemic stroke.
Topics: Anticoagulants; Brain Ischemia; Humans; Randomized Controlled Trials as Topic; Risk; Stroke
PubMed: 25764172
DOI: 10.1002/14651858.CD000024.pub4 -
Thrombosis and Haemostasis Jun 2017Data on paediatric pulmonary embolism (PE) are scarce. We sought to systematically review the current literature on childhood PE and conducted a search on paediatric PE... (Review)
Review
Data on paediatric pulmonary embolism (PE) are scarce. We sought to systematically review the current literature on childhood PE and conducted a search on paediatric PE via PubMed (1946-2013) and Embase (1980-2013). There was significant heterogeneity in reported data. Two patterns were noted: classic thromboembolic PE (TE-PE) and in situ pulmonary artery thrombosis (ISPAT). Mean age of presentation for TE-PE was 14.86 years, and 51 % of cases were males. The commonest method for diagnosis of TE-PE was contrast CT with angiography (74 % of patients). The diagnosis of TE-PE was often delayed. Although 85 % of children with TE-PE had an elevated D-dimer at presentation, it was non-discriminatory for the diagnosis. In paediatric TE-PE, the prevalence of central venous catheters was 23 %, immobilisation 38 %, systemic infection 31 % and obesity 13 %, elevated Factor VIII or von Willebrand factor levels 27 %, Protein C deficiency 17 %, Factor V Leiden 14 % and Protein S deficiency 7 %. In patients with TE-PE, pharmacologic thrombolysis was used in 29 %; unfractionated heparin was the most common initial anticoagulant treatment in 64 % and low-molecular-weight heparins the most common follow-up treatment in 83 %. Duration of anticoagulant therapy was variable and death was reported in 26 % of TE-PE patients. In contrast to TE-PE, patients with ISPAT were not investigated systematically for presence of thrombophilia, had more surgical interventions as the initial management and were often treated with anti-platelet medications. This review summarises important data and identifies gaps in the knowledge of paediatric PE, which may help to design future studies.
Topics: Adolescent; Angiography; Anticoagulants; Comorbidity; Female; Heparin; Humans; Male; Pneumoradiography; Prevalence; Pulmonary Artery; Pulmonary Embolism; Survival Analysis; Thromboembolism; Thrombosis
PubMed: 28331932
DOI: 10.1160/TH16-07-0529 -
Annals of Cardiothoracic Surgery Mar 2018Secondary tracheal tumors arise from mural invasion by primary tumors in adjacent organs, metastatic lymph nodes or blood-born metastasis from distant sites. This... (Review)
Review
BACKGROUND
Secondary tracheal tumors arise from mural invasion by primary tumors in adjacent organs, metastatic lymph nodes or blood-born metastasis from distant sites. This systematic review aims to assess the presentation, management options, and clinical outcomes of these uncommon non-tracheal malignancies.
METHODS
Electronic searches of the MEDLINE database were performed to identify case series and individual case reports of tracheal invasion by primary non-tracheal tumors or metastatic disease. All English-language studies with available abstracts or articles containing primary data were included.
RESULTS
From 1978 to 2017, a total of 160 case reports or case series identified 2,242 patients with invasion of the trachea by tumors of adjacent organs (n=1,853) or by metastatic lymph nodes or hematogenous spread (n=389). Common primary sites of origin were thyroid, esophagus, and lung, and the most common presentation was metachronous (range of interval: 0 to 564 months) with dyspnea, neck mass, voice change and/or hemoptysis. A majority of patients in case reports (77.9%) and case series (66.0%) underwent resection and the most common reported operation was segmental tracheal resection. Fewer patients underwent bronchoscopic intervention (21.7%) and radiation was used in 32.2% of patients. Complications after bronchoscopic treatment included bleeding, granulation tissue, and retained secretions, while anastomotic leak, unplanned tracheostomy, and new recurrent laryngeal nerve paralysis were observed after surgical resection. The rate of 30-day mortality was low (0.01-1.80%). Median survival was higher in patients with thyroid malignancy and in patients who underwent surgical management. Follow-up time ranged from 0.03 to 183 months.
CONCLUSIONS
Patients with tracheal invasion by metastatic or primary non-tracheal malignancies should be assessed for symptoms, tumor grade, tumor recurrence and concurrent metastases to decide on optimal surgical, bronchoscopic or noninterventional therapy. Clinical experience suggests that palliative endoscopic intervention for tracheal obstruction by metastasis-bearing lymph nodes is underreported.
PubMed: 29707496
DOI: 10.21037/acs.2018.02.01 -
International Journal of Environmental... Feb 2022Lung cancer (LC) represents the main cause of cancer-related deaths worldwide, especially because the majority of patients present with an advanced stage of the disease... (Review)
Review
Lung cancer (LC) represents the main cause of cancer-related deaths worldwide, especially because the majority of patients present with an advanced stage of the disease at the time of diagnosis. This systematic review describes the evidence behind screening results and the current guidelines available to manage lung nodules. This review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The following electronic databases were searched: PubMed, EMBASE, and the Web of Science. Five studies were included in the systematic review. The study cohort included 46,364 patients, and, in this case series, LC was detected in 9028 patients. Among the patients with detected LC, 1261 died of lung cancer, 3153 died of other types of cancers and 4614 died of other causes. This systematic review validates the use of CT in LC screening follow-ups, and bids for future integration and implementation of nodule management protocols to improve LC screening, avoid missed cancers and to reduce the number of unnecessary investigations.
Topics: Early Detection of Cancer; Humans; Lung; Lung Neoplasms; Mass Screening; Research
PubMed: 35206646
DOI: 10.3390/ijerph19042460 -
Journal of Orthopaedics and... Jan 2024Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached. The present investigation compared enoxaparin, fondaparinux, aspirin and non-vitamin K antagonist oral anticoagulants (NOACs) commonly used as prophylaxis following total hip arthroplasty (THA). A Bayesian network meta-analysis was performed, setting as outcomes of interest the rate of deep venous thrombosis (DVT), pulmonary embolism (PE) and major and minor haemorrhages.
METHODS
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions. All randomised controlled trials (RCTs) comparing two or more drugs used for the prophylaxis of VTE following THA were accessed. PubMed, Web of Science and Google Scholar databases were accessed in March 2023 with no time constraint.
RESULTS
Data from 31,705 patients were extracted. Of these, 62% (19,824) were women, with age, sex ratio, and body mass index (BMI) being comparable at baseline. Apixaban 5 mg, fondaparinux, and rivaroxaban 60 mg were the most effective in reducing the rate of DVT. Dabigatran 220 mg, apixaban 5 mg, and aspirin 100 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, ximelagatran 2 mg and aspirin 100 mg were associated with the lowest rate of major haemorrhages, while rivaroxaban 2.5 mg, apixaban 5 mg and enoxaparin 40 mg were associated with the lowest rate of minor haemorrhages.
CONCLUSION
Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following THA. Level of evidence Level I, network meta-analysis of RCTs.
Topics: Female; Humans; Male; Arthroplasty, Replacement, Hip; Aspirin; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism
PubMed: 38194191
DOI: 10.1186/s10195-023-00742-2 -
Journal of Internal Medicine Mar 2017Obesity is a risk factor for a plethora of severe morbidities and premature death. Most supporting evidence comes from observational studies that are prone to chance,... (Review)
Review
Obesity is a risk factor for a plethora of severe morbidities and premature death. Most supporting evidence comes from observational studies that are prone to chance, bias and confounding. Even data on the protective effects of weight loss from randomized controlled trials will be susceptible to confounding and bias if treatment assignment cannot be masked, which is usually the case with lifestyle and surgical interventions. Thus, whilst obesity is widely considered the major modifiable risk factor for many chronic diseases, its causes and consequences are often difficult to determine. Addressing this is important, as the prevention and treatment of any disease requires that interventions focus on causal risk factors. Disease prediction, although not dependent on knowing the causes, is nevertheless enhanced by such knowledge. Here, we provide an overview of some of the barriers to causal inference in obesity research and discuss analytical approaches, such as Mendelian randomization, that can help to overcome these obstacles. In a systematic review of the literature in this field, we found: (i) probable causal relationships between adiposity and bone health/disease, cancers (colorectal, lung and kidney cancers), cardiometabolic traits (blood pressure, fasting insulin, inflammatory markers and lipids), uric acid concentrations, coronary heart disease and venous thrombosis (in the presence of pulmonary embolism), (ii) possible causal relationships between adiposity and gray matter volume, depression and common mental disorders, oesophageal cancer, macroalbuminuria, end-stage renal disease, diabetic kidney disease, nuclear cataract and gall stone disease, and (iii) no evidence for causal relationships between adiposity and Alzheimer's disease, pancreatic cancer, venous thrombosis (in the absence of pulmonary embolism), liver function and periodontitis.
Topics: Biomedical Research; Comorbidity; Humans; Mendelian Randomization Analysis; Obesity; Risk Factors
PubMed: 27933671
DOI: 10.1111/joim.12577 -
The Cochrane Database of Systematic... Oct 2023Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain, which has potential neuroprotective properties. It is widely used... (Review)
Review
BACKGROUND
Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain, which has potential neuroprotective properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. This is an update of a review first published in 2010 and last updated in 2020.
OBJECTIVES
To assess the benefits and harms of Cerebrolysin or Cerebrolysin-like agents for treating acute ischaemic stroke.
SEARCH METHODS
We searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, and LILACS in May 2022 and a number of Russian databases in June 2022. We also searched reference lists, ongoing trials registers, and conference proceedings.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing Cerebrolysin or Cerebrolysin-like agents started within 48 hours of stroke onset and continued for any length of time, with placebo or no treatment in people with acute ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Three review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, extracted data, and applied GRADE criteria to the evidence.
MAIN RESULTS
Seven RCTs (1773 participants) met the inclusion criteria of the review. In this update we added one RCT of Cerebrolysin-like agent Cortexin, which contributed 272 participants. We used the same approach for risk of bias assessment that was re-evaluated for the previous update: we added consideration of the public availability of study protocols and reported outcomes to the selective outcome reporting judgement, through identification, examination, and evaluation of study protocols. For the Cerebrolysin studies, we judged the risk of bias for selective outcome reporting to be unclear across all studies; for blinding of participants and personnel to be low in three studies and unclear in the remaining four; and for blinding of outcome assessors to be low in three studies and unclear in four studies. We judged the risk of bias for generation of allocation sequence to be low in one study and unclear in the remaining six studies; for allocation concealment to be low in one study and unclear in six studies; and for incomplete outcome data to be low in three studies and high in the remaining four studies. The manufacturer of Cerebrolysin supported three multicentre studies, either totally, or by providing Cerebrolysin and placebo, randomisation codes, research grants, or statisticians. We judged two studies to be at high risk of other bias and the remaining five studies to be at unclear risk of other bias. We judged the study of Cortexin to be at low risk of bias for incomplete outcome data and at unclear risk of bias for all other domains. All-cause death: Cerebrolysin or Cortexin probably result in little to no difference in all-cause death (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.41; 6 trials, 1689 participants; moderate-certainty evidence). None of the included studies reported on poor functional outcome, defined as death or dependence at the end of the follow-up period, early death (within two weeks of stroke onset), quality of life, or time to restoration of capacity for work. Only one study clearly reported on the cause of death: cerebral infarct (four in the Cerebrolysin and two in the placebo group), heart failure (two in the Cerebrolysin and one in the placebo group), pulmonary embolism (two in the placebo group), and pneumonia (one in the placebo group). Non-death attrition (secondary outcome): Cerebrolysin or similar peptide mixtures may result in little to no difference in non-death attrition, but the evidence is very uncertain, with a considerable level of heterogeneity (RR 0.72, 95% CI 0.38 to 1.39; 6 trials, 1689 participants; very low-certainty evidence). Serious adverse events (SAEs): Cerebrolysin probably results in little to no difference in the total number of people with SAEs (RR 1.16, 95% CI 0.81 to 1.66; 3 trials, 1335 participants; moderate-certainty evidence). This comprised fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38; 3 trials, 1335 participants; moderate-certainty evidence) and an increase in the total number of people with non-fatal SAEs (RR 2.39, 95% CI 1.10 to 5.23; 3 trials, 1335 participants; moderate-certainty evidence). In the subgroup of dosing schedule 30 mL for 10 days (cumulative dose 300 mL), the increase was more prominent (RR 2.87, 95% CI 1.24 to 6.69; 2 trials, 1189 participants). Total number of people with adverse events: Cerebrolysin or similar peptide mixtures may result in little to no difference in the total number of people with adverse events (RR 1.03, 95% CI 0.92 to 1.14; 4 trials, 1607 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Moderate-certainty evidence indicates that Cerebrolysin or Cerebrolysin-like peptide mixtures derived from cattle brain probably have no beneficial effect on preventing all-cause death in acute ischaemic stroke. Moderate-certainty evidence suggests that Cerebrolysin probably has no beneficial effect on the total number of people with serious adverse events. Moderate-certainty evidence also indicates a potential increase in non-fatal serious adverse events with Cerebrolysin use.
Topics: Humans; Animals; Swine; Stroke; Ischemic Stroke; Amino Acids; Peptides
PubMed: 37818733
DOI: 10.1002/14651858.CD007026.pub7