Effectiveness of smoking cessation interventions among adults: an overview of systematic reviews.

BACKGROUND: This overview of reviews aims to identify evidence on the benefits (i.e. tobacco use abstinence and reduction in smoking frequency) and harms (i.e. possible adverse events/outcomes) of smoking cessation interventions among adults aged 18 years and older. METHODS: We searched Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the CADTH Health Technology Assessment Database and several other websites for grey literature. Searches were conducted on November 12, 2018, updated on September 24, 2020, with publication years 2008 to 2020. Two reviewers independently performed title-abstract and full-text screening considering pre-determined inclusion criteria. Data extraction and quality assessments were initially completed by two reviewers independently (i.e. 73% of included studies (n = 22)) using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR 2), and the remainder done by one reviewer and verified by another due to resources and feasibility. The application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was performed by one independent reviewer and verified by another. RESULTS: A total of 22 Cochrane systematic reviews evaluating the impact of smoking cessation interventions on outcomes such as tobacco use abstinence, reduction in smoking frequency, quality of life and possible adverse events were included. Pharmaceutical (i.e. varenicline, cytisine, nicotine replacement therapy (NRT), bupropion) and behavioural interventions (i.e. physician advice, non-tailored print-based self-help materials, stage-based individual counselling, etc.) showed to have increased smoking cessation; whereas, data for mobile phone-based interventions including text messaging, hypnotherapy, acupuncture, continuous auricular stimulation, laser therapy, electrostimulation, acupressure, St John's wort, S-adenosyl-L-methionine (SAMe), interactive voice response systems and other combination treatments were unclear. Considering harms related to smoking cessation interventions, small/mild harms (i.e. increased palpitations, chest pain, nausea, insomnia, headache) were observed following NRT, varenicline and cytisine use. There were no data on harms related to behavioural therapies (i.e. individual or group counselling self-help materials, internet interventions), combination therapies or other therapies (i.e. laser therapy, electrostimulation, acupressure, St John's wort, SAMe). CONCLUSION: Results suggest that pharmacological and behavioural interventions may help the general smoking population quit smoking with observed small/mild harms following NRT or varenicline. Consequently, evidence regarding ideal intervention strategies and the long-term impact of these interventions for preventing smoking was unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099691.

Predictors of Adverse Pregnancy Outcomes in Pregnant Women Living with Obesity: A Systematic Review.

Obesity is a well-recognized risk factor for pregnancy complications. Most studies to date are in large cohorts, with results presented in a way that assumes all women living with obesity are at equal risk. This study investigates which women living with obesity are at higher risk of specific pregnancy complications. A systematic search of MEDLINE and Embase identified 7894 prospective or retrospective cohort studies exploring predictors of adverse outcomes among pregnant women living with obesity. Following screening, 61 studies were deemed eligible. Studies were selected if the effects of exposure to any predictor amongst pregnant women living with obesity could be collected. Maternal characteristics assessed for association with adverse outcomes included maternal age, race/ethnicity, maternal height, mode of conception, complement activation factors, and history of various comorbidities/procedures. Gestational diabetes mellitus was the most studied outcome (n = 32), followed by preterm birth (n = 29), preeclampsia (n = 27), low birthweight infants (n = 20), small for gestational age newborns (n = 12), and stillbirth (n = 7). This review identified important characteristics that should be considered during the screening and follow-up sessions of pregnant women living with obesity, including pre-existing type 1 diabetes, maternal age < 20 years or ≥35 years, non-White ethnicity, abdominal adiposity obesity, and history of bariatric surgery.

Optimising weight-loss interventions in cancer patients-A systematic review and network meta-analysis.

BACKGROUND: Excess weight has been associated with increased morbidity and a worse prognosis in adult patients with early-stage cancer. The optimal lifestyle interventions to optimize anthropometric measures amongst cancer patients and survivors remain inconsistent. OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the effects of exercise and dietary interventions alone or in combination on anthropometric measures of adult cancer patients and survivors. METHODS: A systematic search of Medline, Embase and the Cochrane Trials Registry was performed. Outcomes of interest included changes in weight, body mass index (BMI), and waist circumference. Screening and data collection were performed by two reviewers. Bayesian NMAs were performed. RESULTS: Overall, 98 RCTs were included; 75 were incorporated in NMAs (n = 12,199). Groups of intervention strategies included: 3 exercise interventions, 8 dietary interventions, 7 combination interventions of diet and exercise and standard care. Median intervention duration was 26 weeks. NMA suggested that diet alone (mean difference [MD] -2.25kg, 95% CrI -3.43 to -0.91kg) and combination strategies (MD -2.52kg, 95% CrI -3.54 to -1.62kg) were associated with more weight loss compared to standard care. All dietary interventions achieved a similar magnitude of weight loss (MD range from -2.03kg to -2.52kg). Both diet alone and combination strategies demonstrated greater BMI reductions versus standard care, and each of diet alone, exercise alone and combination strategies demonstrated greater reductions in waist circumference than standard care. CONCLUSION: Diet and exercise alone or in combination are effective lifestyle interventions to improve anthropometric measures in cancer patients and survivors. All reputable diets appear to be similarly effective to achieve weight loss.

Combination Tests in the Diagnosis of Chronic Periprosthetic Joint Infection: Systematic Review and Development of a Stepwise Clinical Decision-Making Tool.

BACKGROUND: Our objective was to identify combination tests used to diagnose chronic periprosthetic joint infection (PJI) and develop a stepwise decision-making tool to facilitate diagnosis. METHODS: We conducted a systematic review of existing combinations of serum, synovial, and tissue-based tests for diagnosing chronic PJI after hip or knee replacement. This work is an extension of our systematic review of single tests, from which we chose eligible studies that also described the diagnostic performance of combination tests. RESULTS: Thirty-seven eligible articles described the performance of 56 combination tests, of which 8 combinations had at least 2 studies informing both sensitivity and specificity. We also identified 5 types of combination tests: (1) a type-I Boolean combination, which uses Boolean logic (AND, OR) and usually increases specificity at the cost of sensitivity; (2) a type-II Boolean combination, which usually increases sensitivity at the cost of specificity; (3) a triage-conditional rule, in which the value of 1 test serves to triage the use of another test; (4) an arithmetic operation on the values of 2 tests; and (5) a model-based prediction rule based on a fitted model applied to biomarker values. CONCLUSIONS: Clinicians can initiate their diagnostic process with a type-II Boolean combination of serum C-reactive protein (CRP) and interleukin-6 (IL-6). False negatives of the combination can be minimized when the threshold is chosen to reach 90% to 95% sensitivity for each test. Once a joint infection is suspected on the basis of serum testing, joint aspiration should be performed. If joint aspiration yields a wet tap, a leukocyte esterase (LER) strip is highly recommended for point-of-care testing, with a reading of ++ or greater indicating PJI; a reading below ++ should be followed by one of the laboratory-based synovial tests. If joint aspiration yields a dry tap, clinicians should rely on preoperative tissue culture and histological analysis for diagnosis. Combinations based on triage-conditional, arithmetic, and model-based prediction rules require further research. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Pharmacologic and surgical therapies for patients with Meniere's disease: A systematic review and network meta-analysis.

BACKGROUND: Meniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs). METHODS: Our published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes. RESULTS: We identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002). CONCLUSION: To achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence.

Comparing Interventions for Management of Hot Flashes in Patients With Breast and Prostate Cancer: A Systematic Review With Meta-Analyses.

PROBLEM IDENTIFICATION: Hot flashes are common and bothersome in patients with breast and prostate cancer and can adversely affect patients' quality of life. LITERATURE SEARCH: Databases were searched for randomized controlled trials (RCTs) evaluating the effects of one or more interventions for hot flashes in patients with a history of breast or prostate cancer. DATA EVALUATION: Outcomes of interest included changes in hot flash severity, hot flash frequency, quality of life, and harms. Pairwise meta-analyses and network meta-analyses were performed where feasible, with narrative synthesis used where required. SYNTHESIS: 40 RCTs were included. Findings from network meta-analysis for hot flash frequency suggested that several therapies may offer benefits compared to no treatment, but little data suggested differences between active therapies. Findings from network meta-analysis for hot flash score were similar. IMPLICATIONS FOR RESEARCH: Although many interventions may offer improvements for hot flashes versus no treatment, minimal data suggest important differences between therapies. SUPPLEMENTARY MATERIALS CAN BE FOUND BY VISITING&NBSP;HTTPS: //bit.ly/2WGzi30.

A scoping review of network meta-analyses assessing the efficacy and safety of complementary and alternative medicine interventions.

BACKGROUND: Network meta-analysis (NMA) has rapidly grown in use during the past decade for the comparison of healthcare interventions. While its general use in the comparison of conventional medicines has been studied previously, to our awareness, its use to assess complementary and alternative medicines (CAM) has not been studied. A scoping review of the literature was performed to identify systematic reviews incorporating NMAs involving one or more CAM interventions. METHODS: An information specialist executed a multi-database search (e.g., MEDLINE, Embase, Cochrane), and two reviewers performed study selection and data collection. Information on publication characteristics, diseases studied, interventions compared, reporting transparency, outcomes assessed, and other parameters were extracted from each review. RESULTS: A total of 89 SR/NMAs were included. The largest number of NMAs was conducted in China (39.3%), followed by the United Kingdom (12.4%) and the United States (9.0%). Reviews were published between 2010 and 2018, with the majority published between 2015 and 2018. More than 90 different CAM therapies appeared at least once, and the median number per NMA was 2 (IQR 1-4); 20.2% of reviews consisted of only CAM therapies. Dietary supplements (51.1%) and vitamins and minerals (42.2%) were the most commonly studied therapies, followed by electrical stimulation (31.1%), herbal medicines (24.4%), and acupuncture and related treatments (22.2%). A diverse set of conditions was identified, the most common being various forms of cancer (11.1%), osteoarthritis of the hip/knee (7.8%), and depression (5.9%). Most reviews adequately addressed a majority of the PRISMA NMA extension items; however, there were limitations in indication of an existing review protocol, exploration of network geometry, and exploration of risk of bias across studies, such as publication bias. CONCLUSION: The use of NMA to assess the effectiveness of CAM interventions is growing rapidly. Efforts to identify priority topics for future CAM-related NMAs and to enhance methods for CAM comparisons with conventional medicine are needed. SYSTEMATIC REVIEW REGISTRATION: https://ruor.uottawa.ca/handle/10393/35658.

Screening for esophageal adenocarcinoma and precancerous conditions (dysplasia and Barrett's esophagus) in patients with chronic gastroesophageal reflux disease with or without other risk factors: two systematic reviews and one overview of reviews to inform a guideline of the Canadian Task Force on Preventive Health Care (CTFPHC).

BACKGROUND: Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS: Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS: Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS: Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS: PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).

Diagnostic Accuracy of Serum, Synovial, and Tissue Testing for Chronic Periprosthetic Joint Infection After Hip and Knee Replacements: A Systematic Review.

BACKGROUND: Chronic periprosthetic joint infection (PJI) is a devastating complication that can occur following total joint replacement. Patients with chronic PJI report a substantially lower quality of life and face a higher risk of short-term mortality. Establishing a diagnosis of chronic PJI is challenging because of conflicting guidelines, numerous tests, and limited evidence. Delays in diagnosing PJI are associated with poorer outcomes and morbid revision surgery. The purpose of this systematic review was to compare the diagnostic accuracy of serum, synovial, and tissue-based tests for chronic PJI. METHODS: This review adheres to the Cochrane Collaboration's diagnostic test accuracy methods for evidence searching and syntheses. A detailed search of MEDLINE, Embase, the Cochrane Library, and the grey literature was performed to identify studies involving the diagnosis of chronic PJI in patients with hip or knee replacement. Eligible studies were assessed for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analyses were performed on tests with sufficient data points. Summary estimates and hierarchical summary receiver operating characteristic (HSROC) curves were obtained using a bivariate model. RESULTS: A total of 12,616 citations were identified, and 203 studies met the inclusion criteria. Of these 203 studies, 170 had a high risk of bias. Eighty-three unique PJI diagnostic tests were identified, and 17 underwent meta-analyses. Laboratory-based synovial alpha-defensin tests and leukocyte esterase reagent (LER) strips (2+) had the best performance, followed by white blood-cell (WBC) count, measurement of synovial C-reactive protein (CRP) level, measurement of the polymorphonuclear neutrophil percentage (PMN%), and the alpha-defensin lateral flow test kit (Youden index ranging from 0.78 to 0.94). Tissue-based tests and 3 serum tests (measurement of interleukin-6 [IL-6] level, CRP level, and erythrocyte sedimentation rate [ESR]) had a Youden index between 0.61 to 0.75 but exhibited poorer performance compared with the synovial tests mentioned above. CONCLUSIONS: The quality of the literature pertaining to chronic PJI diagnostic tests is heterogeneous, and the studies are at a high risk for bias. We believe that greater transparency and more complete reporting in studies of diagnostic test results should be mandated by peer-reviewed journals. The available literature suggests that several synovial fluid-based tests perform well for diagnosing chronic PJI and their use is recommended in the work-up of any suspected case of chronic PJI. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Intrathecal Analgesia for Chronic Refractory Pain: Current and Future Prospects.

The intrathecal drug-delivery system (IDDS) is one mode of infusing analgesic medications directly into the cerebrospinal fluid in close proximity to their site of action. This modality has been employed in patients with refractory pain either due to malignant or non-malignant causes for over 30 years. Unfortunately, and despite the number of years it has been in use, there is still a scarcity of rigorous evidence to guide its integration into clinical practice. Current best evidence is inconclusive as to the comparative effectiveness and harms of the IDDS relative to routine medical care of patients. There are far more systematic reviews than high-quality primary comparative studies of the IDDS vs. conventional pain treatment. Existing clinical practice recommendations are best viewed as expert opinion with competing interests. This article will review the existing literature for indications, contraindications, consensus statements, different technologies, and complications of the IDDS. Although approved analgesics for IDDS delivery are limited to morphine and ziconotide, many other analgesics, alone or in combination, are routinely used in this setting. This review will also focus on the pharmacology, clinical efficacy, and safety of intrathecal medications extensively used in clinical practice; including agents approved, unapproved, and under development.

Mitral Valve Clip for Treatment of Mitral Regurgitation: An Evidence-Based Analysis.

BACKGROUND: Many of the 500,000 North American patients with chronic mitral regurgitation may be poor candidates for mitral valve surgery. OBJECTIVE: The objective of this study was to investigate the comparative effectiveness, harms, and cost-effectiveness of percutaneous mitral valve repair using mitral valve clips in candidates at prohibitive risk for surgery. DATA SOURCES: We searched articles in MEDLINE, Embase, and the Cochrane Library published from 1994 to February 2014 for evidence of effectiveness and harms; for economic literature we also searched NHS EED and Tufts CEA registry. Grey literature was also searched. REVIEW METHODS: Primary studies were sought from existing systematic reviews that had employed reliable search and screening methods. Newer studies were sought by searching the period subsequent to the last search date of the review. Two reviewers screened records and assessed study validity. We used the Cochrane risk of bias tool for randomized, generic assessment for non-randomized studies, and the Phillips checklist for economic studies. RESULTS: Ten studies including 1 randomized trial were included. The majority of the direct comparative evidence compared the mitral valve clip repair with surgery in patients not particularly at prohibitive surgical risk. Irrespective of degenerative or functional chronic mitral regurgitation etiology, evidence of effectiveness and harms is inconclusive and of very low quality. Very-low-quality evidence indicates that percutaneous mitral valve clip repair may provide a survival advantage, at least during the first 1 to 2 years, particularly in medically managed chronic functional mitral regurgitation. Because of limitations in the design of studies, the cost-effectiveness of mitral valve clips in patients at prohibitive risk for surgery also could not be established. LIMITATIONS: Because of serious concerns of risk of bias, indirectness, and imprecision, evidence is of very low quality. CONCLUSIONS: No meaningful conclusions can be drawn about the comparative effectiveness, harms, and cost-effectiveness of mitral valve clips in the population with chronic mitral regurgitation who are at prohibitive risk for surgery.