Psychosocial and pharmacologic interventions for problematic methamphetamine use: Findings from a scoping review of the literature.

RATIONALE: Methamphetamine use and related harms have risen at alarming rates. While several psychosocial and pharmacologic interventions have been described in the literature, there is uncertainty regarding the best approach for the management of methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU). We conducted a scoping review of recent systematic reviews (SR), clinical practice guidelines (CPG), and primary controlled studies of psychosocial and pharmacologic treatments for MUD/PMU. METHODS: Guided by an a priori protocol, electronic database search updates (e.g., MEDLINE, Embase) were performed in February 2022. Screening was performed following a two-stage process, leveraging artificial intelligence to increase efficiency of title and abstract screening. Studies involving individuals who use methamphetamine, including key subgroups (e.g. those with mental health comorbidities; adolescents/youths; gay, bisexual, and other men who have sex with men) were sought. We examined evidence related to methamphetamine use, relapse, use of other substances, risk behaviors, mental health, harms, and retention. Figures, tables and descriptive synthesis were used to present findings from the identified literature. RESULTS: We identified 2 SRs, one CPG, and 54 primary studies reported in 69 publications that met our eligibility criteria. Amongst SRs, one concluded that psychostimulants had no effect on methamphetamine abstinence or treatment retention while the other reported no effect of topiramate on cravings. The CPG strongly recommended psychosocial interventions as well as self-help and family support groups for post-acute management of methamphetamine-related disorders. Amongst primary studies, many interventions were assessed by only single studies; contingency management was the therapy most commonly associated with evidence of potential effectiveness, while bupropion and modafinil were analogously the most common pharmacologic interventions. Nearly all interventions showed signs of potential benefit on at least one methamphetamine-related outcome measure. DISCUSSION: This scoping review provides an overview of available interventions for the treatment of MUD/PMU. As most interventions were reported by a single study, the effectiveness of available interventions remains uncertain. Primary studies with longer durations of treatment and follow-up, larger sample sizes, and of special populations are required for conclusive recommendations of best approaches for the treatment of MUD/PMU.

Safety of influenza vaccination during pregnancy: a systematic review.

OBJECTIVE: We conducted a systematic review to evaluate associations between influenza vaccination during pregnancy and adverse birth outcomes and maternal non-obstetric serious adverse events (SAEs), taking into consideration confounding and temporal biases. METHODS: Electronic databases (Ovid MEDLINE ALL, Embase Classic+Embase and the Cochrane Central Register of Controlled Trials) were searched to June 2021 for observational studies assessing associations between influenza vaccination during pregnancy and maternal non-obstetric SAEs and adverse birth outcomes, including preterm birth, spontaneous abortion, stillbirth, small-for-gestational-age birth and congenital anomalies. Studies of live attenuated vaccines, single-arm cohort studies and abstract-only publications were excluded. Records were screened using a liberal accelerated approach initially, followed by a dual independent approach for full-text screening, data extraction and risk of bias assessment. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence certainty. RESULTS: Of 9443 records screened, 63 studies were included. Twenty-nine studies (24 cohort and 5 case-control) evaluated seasonal influenza vaccination (trivalent and/or quadrivalent) versus no vaccination and were the focus of our prioritised syntheses; 34 studies of pandemic vaccines (2009 A/H1N1 and others), combinations of pandemic and seasonal vaccines, and seasonal versus seasonal vaccines were also reviewed. Control for confounding and temporal biases was inconsistent across studies, limiting pooling of data. Meta-analyses for preterm birth, spontaneous abortion and small-for-gestational-age birth demonstrated no significant associations with seasonal influenza vaccination. Immortal time bias was observed in a sensitivity analysis of meta-analysing risk-based preterm birth data. In descriptive summaries for stillbirth, congenital anomalies and maternal non-obstetric SAEs, no significant association with increased risk was found in any studies. All evidence was of very low certainty. CONCLUSIONS: Evidence of very low certainty suggests that seasonal influenza vaccination during pregnancy is not associated with adverse birth outcomes or maternal non-obstetric SAEs. Appropriate control of confounding and temporal biases in future studies would improve the evidence base.

Guidance for using artificial intelligence for title and abstract screening while conducting knowledge syntheses.

BACKGROUND: Systematic reviews are the cornerstone of evidence-based medicine. However, systematic reviews are time consuming and there is growing demand to produce evidence more quickly, while maintaining robust methods. In recent years, artificial intelligence and active-machine learning (AML) have been implemented into several SR software applications. As some of the barriers to adoption of new technologies are the challenges in set-up and how best to use these technologies, we have provided different situations and considerations for knowledge synthesis teams to consider when using artificial intelligence and AML for title and abstract screening. METHODS: We retrospectively evaluated the implementation and performance of AML across a set of ten historically completed systematic reviews. Based upon the findings from this work and in consideration of the barriers we have encountered and navigated during the past 24 months in using these tools prospectively in our research, we discussed and developed a series of practical recommendations for research teams to consider in seeking to implement AML tools for citation screening into their workflow. RESULTS: We developed a seven-step framework and provide guidance for when and how to integrate artificial intelligence and AML into the title and abstract screening process. Steps include: (1) Consulting with Knowledge user/Expert Panel; (2) Developing the search strategy; (3) Preparing your review team; (4) Preparing your database; (5) Building the initial training set; (6) Ongoing screening; and (7) Truncating screening. During Step 6 and/or 7, you may also choose to optimize your team, by shifting some members to other review stages (e.g., full-text screening, data extraction). CONCLUSION: Artificial intelligence and, more specifically, AML are well-developed tools for title and abstract screening and can be integrated into the screening process in several ways. Regardless of the method chosen, transparent reporting of these methods is critical for future studies evaluating artificial intelligence and AML.

Models of provider care in long-term care: A rapid scoping review.

INTRODUCTION: One of the current challenges in long-term care homes (LTCH) is to identify the optimal model of care, which may include specialty physicians, nursing staff, person support workers, among others. There is currently no consensus on the complement or scope of care delivered by these providers, nor is there a repository of studies that evaluate the various models of care. We conducted a rapid scoping review to identify and map what care provider models and interventions in LTCH have been evaluated to improve quality of life, quality of care, and health outcomes of residents. METHODS: We conducted this review over 10-weeks of English language, peer-reviewed studies published from 2010 onward. Search strategies for databases (e.g., MEDLINE) were run on July 9, 2020. Studies that evaluated models of provider care (e.g., direct patient care), or interventions delivered to facility, staff, and residents of LTCH were included. Study selection was performed independently, in duplicate. Mapping was performed by two reviewers, and data were extracted by one reviewer, with partial verification by a second reviewer. RESULTS: A total of 7,574 citations were screened based on the title/abstract, 836 were reviewed at full text, and 366 studies were included. Studies were classified according to two main categories: healthcare service delivery (n = 92) and implementation strategies (n = 274). The condition/ focus of the intervention was used to further classify the interventions into subcategories. The complex nature of the interventions may have led to a study being classified in more than one category/subcategory. CONCLUSION: Many healthcare service interventions have been evaluated in the literature in the last decade. Well represented interventions (e.g., dementia care, exercise/mobility, optimal/appropriate medication) may present opportunities for future systematic reviews. Areas with less research (e.g., hearing care, vision care, foot care) have the potential to have an impact on balance, falls, subsequent acute care hospitalization.

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.

Assessing how information is packaged in rapid reviews for policy-makers and other stakeholders: a cross-sectional study.

BACKGROUND: Rapid reviews (RRs) are useful products to healthcare policy-makers and other stakeholders, who require timely evidence. Therefore, it is important to assess how well RRs convey useful information in a format that is easy to understand so that decision-makers can make best use of evidence to inform policy and practice. METHODS: We assessed a diverse sample of 103 RRs against the BRIDGE criteria, originally developed for communicating clearly to support healthcare policy-making. We modified the criteria to increase assessability and to align with RRs. We identified RRs from key database searches and through searching organisations known to produce RRs. We assessed each RR on 26 factors (e.g. organisation of information, lay language use). Results were descriptively analysed. Further, we explored differences between RRs published in journals and those published elsewhere. RESULTS: Certain criteria were well covered across the RRs (e.g. all aimed to synthesise research evidence and all provided references of included studies). Further, most RRs provided detail on the problem or issue (96%; n = 99) and described methods to conduct the RR (91%; n = 94), while several addressed political or health systems contexts (61%; n = 63). Many RRs targeted policy-makers and key stakeholders as the intended audience (66%; n = 68), yet only 32% (n = 33) involved their tacit knowledge, while fewer (27%; n = 28) directly involved them reviewing the content of the RR. Only six RRs involved patient partners in the process. Only 23% (n = 24) of RRs were prepared in a format considered to make information easy to absorb (i.e. graded entry) and 25% (n = 26) provided specific key messages. Readability assessment indicated that the text of key RR sections would be hard to understand for an average reader (i.e. would require post-secondary education) and would take 42 (± 36) minutes to read. CONCLUSIONS: Overall, conformity of the RRs with the modified BRIDGE criteria was modest. By assessing RRs against these criteria, we now understand possible ways in which they could be improved to better meet the information needs of healthcare decision-makers and their potential for innovation as an information-packaging mechanism. The utility and validity of these items should be further explored. PROTOCOL AVAILABILITY: The protocol, published on the Open Science Framework, is available at: osf.io/68tj7.

Assessing the format and content of journal published and non-journal published rapid review reports: A comparative study.

BACKGROUND: As production of rapid reviews (RRs) increases in healthcare, knowing how to efficiently convey RR evidence to various end-users is important given they are often intended to directly inform decision-making. Little is known about how often RRs are produced in the published or unpublished domains, and what and how information is structured. OBJECTIVES: To compare and contrast report format and content features of journal-published (JP) and non-journal published (NJP) RRs. METHODS: JP RRs were identified from key databases, and NJP RRs were identified from a grey literature search of 148 RR producing organizations and were sampled proportionate to cluster size by organization and product type to match the JP RR group. We extracted and formally compared 'how' (i.e., visual arrangement) and 'what' information was presented. RESULTS: We identified 103 RRs (52 JP and 51 NJP) from 2016. A higher percentage of certain features were observed in JP RRs compared to NJP RRs (e.g., reporting authors; use of a traditional journal article structure; section headers including abstract, methods, discussion, conclusions, acknowledgments, conflict of interests, and author contributions; and use of figures (e.g., Study Flow Diagram) in the main document). For NJP RRs, a higher percentage of features were observed (e.g., use non-traditional report structures; bannering of executive summary sections and appendices; use of typographic cues; and including outcome tables). NJP RRs were more than double in length versus JP RRs. Including key messages was uncommon in both groups. CONCLUSIONS: This comparative study highlights differences between JP and NJP RRs. Both groups may benefit from better use of plain language, and more clear and concise design. Alternative innovative formats and end-user preferences for content and layout should be studied further with thought given to other considerations to ensure better packaging of RR results to facilitate uptake into policy and practice. STUDY REGISTRATION: The full protocol is available at: https://osf.io/29xvk/.

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 HTTPS: //bit.ly/2WGzi30.

Effectiveness of stop smoking interventions among adults: protocol for an overview of systematic reviews and an updated systematic review.

BACKGROUND: Tobacco smoking is the leading cause of cancer, preventable death, and disability. Smoking cessation can increase life expectancy by nearly a decade if achieved in the third or fourth decades of life. Various stop smoking interventions are available including pharmacotherapies, electronic cigarettes, behavioural support, and alternative therapies. This protocol outlines an evidence review which will evaluate the benefits and harms of stop smoking interventions in adults. METHODS: The evidence review will consist of two stages. First, an overview of systematic reviews evaluating the benefits and harms of various stop smoking interventions delivered in or referred from the primary care setting will be conducted. The second stage will involve updating a systematic review on electronic cigarettes identified in the overview; randomized controlled trials will be considered for outcomes relating to benefits while randomized controlled trials, non-randomized controlled trials, and comparative observational studies will be considered for evaluating harms. Search strategies will be developed and peer-reviewed by medical information specialists. The search strategy for the updated review on e-cigarettes will be developed using that of the candidate systematic review. The MEDLINE®, PsycINFO, Embase, and the Cochrane Library electronic databases will be searched as of 2008 for the overview of reviews and from the last search date of the selected review for the updated review. Organizational websites and trial registries will be searched for unpublished or ongoing reviews/studies. Two reviewers will independently screen the title and abstracts of citations using the liberal accelerated method. Full-text screening will be performed independently by two reviewers. Extracted data will be verified by a second reviewer. Disagreements regarding full-text screening and data extraction will be resolved by consensus or third-party adjudication. The methodological quality of systematic reviews, risk of bias of randomized and non-randomized trials, and methodological quality of cohort studies will be evaluated using AMSTAR 2, the Cochrane risk of bias tool, and a modified version of the Scottish Intercollegiate Guidelines Network critical appraisal tool, respectively. The GRADE framework will be used to assess the quality of the evidence for outcomes. DISCUSSION: The evidence review will evaluate the benefits and harms of various stop smoking interventions for adults. Findings will be used to inform a national tobacco cessation guideline by the Canadian Task Force on Preventive Health Care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42018099691, CRD42018099692).

Incidence, causes, and consequences of preventable adverse drug reactions occurring in inpatients: A systematic review of systematic reviews.

BACKGROUND: Preventable adverse drug reactions (PADRs) in inpatients are associated with harm, including increased length of stay and potential loss of life, and result in elevated costs of care. We conducted an overview of reviews (i.e., a systematic review of systematic reviews) to determine the incidence of PADRs experienced by inpatients. Secondary review objectives were related to assessment of the effects of patient age, setting, and clinical specialty on PADR incidence. METHODS: The protocol was registered in PROSPERO (CRD42016043220). We performed a search of Medline, Embase, and the Cochrane Library, limiting languages of publication to English and French. We included published systematic reviews that reported quantitative data on the incidence of PADRs in patients receiving acute or ambulatory care in a hospital setting. The full texts of all primary studies for which PADR data were reported in the included reviews were obtained and data relevant to review objectives were extracted. Quality of the included reviews was assessed using the AMSTAR-2 tool. Both narrative summaries of findings and meta-analyses of primary study data were undertaken. RESULTS: Thirteen systematic reviews encompassing 37 unique primary studies were included. Across primary studies, the PADR incidence was highly varied, ranging from 0.006 to 13.3 PADRs per 100 patients, with a pooled incidence estimate of 0.59 PADRs per 100 patients. Substantial heterogeneity was present across both reviews and primary studies with respect to review/study objectives, patient age, hospital setting, medical discipline, definitions and assessment tools used, event detection methods, endpoints of interest, and units of measure. Thirteen primary studies used prospective event detection methods and had a pooled PADR incidence of 3.13 (2.87-3.38) PADRs per 100 patients; however, extreme statistical heterogeneity (I2 = 97%) indicated this finding should be considered with caution. Subgroup meta-analyses demonstrated that PADR incidence varied significantly with event detection method (prospective > retrospective > voluntary reporting methods), hospital setting (ICU > wards), and medical discipline (medical > surgical). High statistical heterogeneity (I2 > 80%) was present across all analyses, indicating results should be interpreted with caution. Effects of patient age could not be assessed due to poor reporting of age groups used in primary studies. DISCUSSION: The method of event detection appeared to significantly influence PADR incidence, with prospective methods having the highest reported PADR rate. This finding is in agreement with the background literature. High methodological and statistical heterogeneity across primary studies evaluating adverse drug events reduces the validity of the overall PADR incidence derived from the meta-analyses of the pooled data. Data pooled from studies using only prospective methods of event detection should provide an overall estimate closest to the true PADR incidence; however, our estimate should be considered with caution due to the statistical heterogeneity found in this group of studies. Future studies should employ prospective methods of detection. This review demonstrates that the true overall incidence of PADRs is likely much greater than the overall pooled incidence estimate of 0.59 PADRs per 100 patients obtained when event detection method was not taken into consideration.

Risk factors associated with the onset and progression of Alzheimer's disease: A systematic review of the evidence.

A systematic review was conducted to identify risk factors associated with the onset and progression of Alzheimer's disease (AD). Moderate and high quality systematic reviews were eligible for inclusion. Primary studies reporting on non-genetic risk factors associated with neuropathologically or clinically confirmed AD were considered. Eighty one systematic reviews reporting on AD onset and 12 reporting on progression satisfied the eligibility criteria. Four hundred and thirty-two relevant primary studies reporting on onset were identified; however, only those published between 2010 and 2012 (n=65) were included in the qualitative synthesis. Several factors including statins, light-to-moderate alcohol consumption, compliance with a Mediterranean diet, higher educational attainment, physically and cognitively stimulating activities, and APOE ε2 appeared to be associated with a decreased risk of AD onset. The evidence was suggestive of an increased risk of AD associated with head injury in males, age, diabetes mellitus, conjugated equine estrogen use with medroxyprogesterone acetate, current smoking, and lower social engagement. With respect to genetic factors, APOE ε4 remained the strongest predictor of AD. Physical and cognitive activities were associated with a beneficial effect on cognitive function and other indicators of dementia progression while higher educational attainment was associated with faster cognitive decline. Although suggestive of an association, the current evidence for a majority of the identified putative factors for AD onset and progression was weak, at best due to conflicting findings across studies or inadequate evidence. Further research is required to confirm the etiological or protective role of a number of risk factors.

Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

Systematic reviews of factors associated with the onset and progression of neurological conditions in humans: A methodological overview.

As a component of the National Population Health Study of Neurological conditions, systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 priority neurological conditions. Between 2011 and 2013, electronic databases and grey literature sources were searched to identify systematic reviews and primary studies reporting on the onset and progression of each condition. Inclusion was restricted to studies of humans reported in English or French. Additional condition-specific eligibility criteria were also applied. Titles and abstracts were screened by one reviewer with excluded records verified by a second reviewer. Full-text reports were screened independently by two reviewers. Disagreements were resolved by consensus or third party adjudication. Systematic reviews were quality appraised using the AMSTAR criteria, with only moderate and high quality reviews considered for inclusion. Primary studies were also sought to ensure that evidence from existing systematic reviews was supplemented with recent primary study findings (i.e., those published after the most recent systematic review). Evidence from primary studies was also considered if a systematic review was unavailable or of poor quality. Data were extracted using standardized forms. Where feasible, data were extracted independently by two reviewers. Otherwise, data were extracted by a single reviewer and independent data extraction by a second reviewer was conducted for a randomly selected sample of studies. An updated search was conducted in 2016 to identify systematic reviews published since the initial search in 2011-2013. A summary of the methodology used to conduct the systematic reviews is described. Illustrative results are provided for the risk of amyotrophic lateral sclerosis in relation to occupational exposure to lead and other heavy metals.

Effectiveness of Personal Protective Equipment for Healthcare Workers Caring for Patients with Filovirus Disease: A Rapid Review.

BACKGROUND: A rapid review, guided by a protocol, was conducted to inform development of the World Health Organization's guideline on personal protective equipment in the context of the ongoing (2013-present) Western African filovirus disease outbreak, with a focus on health care workers directly caring for patients with Ebola or Marburg virus diseases. METHODS: Electronic databases and grey literature sources were searched. Eligibility criteria initially included comparative studies on Ebola and Marburg virus diseases reported in English or French, but criteria were expanded to studies on other viral hemorrhagic fevers and non-comparative designs due to the paucity of studies. After title and abstract screening (two people to exclude), full-text reports of potentially relevant articles were assessed in duplicate. Fifty-seven percent of extraction information was verified. The Grading of Recommendations Assessment, Development and Evaluation framework was used to inform the quality of evidence assessments. RESULTS: Thirty non-comparative studies (8 related to Ebola virus disease) were located, and 27 provided data on viral transmission. Reporting of personal protective equipment components and infection prevention and control protocols was generally poor. CONCLUSIONS: Insufficient evidence exists to draw conclusions regarding the comparative effectiveness of various types of personal protective equipment. Additional research is urgently needed to determine optimal PPE for health care workers caring for patients with filovirus.

Comparison of physical interventions, behavioral interventions, natural health products, and pharmacologics to manage hot flashes in patients with breast or prostate cancer: protocol for a systematic review incorporating network meta-analyses.

BACKGROUND: Breast and prostate cancers are the most commonly diagnosed non-dermatologic malignancies in Canada. Agents including endocrine therapies (e.g., aromatase inhibitors, gonadotrophin-releasing hormone analogs, anti-androgens, tamoxifen) and chemotherapy have improved survival for both conditions. As endocrine manipulation is a mainstay of treatment, it is not surprising that hot flashes are a common and troublesome adverse effect. Hot flashes can cause chills, night sweats, anxiety, and insomnia, lessening patients' quality of life. These symptoms impact treatment adherence, worsening prognosis. While short-term estrogen replacement therapy is frequently used to manage hot flashes in healthy menopausal women, its use is contraindicated in breast cancer. Similarly, testosterone replacement therapy is contraindicated in prostate cancer. It is therefore not surprising that non-hormonal pharmacological treatments (anti-depressants, anti-epilectics, anti-hypertensives), physical/behavioral treatments (e.g., acupuncture, yoga/exercise, relaxation techniques, cognitive behavioral therapy), and natural health products (e.g., black cohosh, flax, vitamin E, ginseng) have been studied for control of hot flashes. There is a need to identify which interventions minimize the frequency and severity of hot flashes and their impact on quality of life. This systematic review and network meta-analysis of randomized studies will synthesize available evidence addressing this knowledge gap. METHODS/DESIGN: An electronic search of Medline, Embase, AMED, PsycINFO, and the Cochrane Register of Controlled Trials has been designed by an information specialist and peer reviewed by a second information specialist. Study selection and data collection will be performed by two reviewers independently. Risk of bias assessments will be completed using the Cochrane Risk of Bias Scale. Outcomes of interest will include validated measures of hot flash severity, hot flash frequency, quality of life, and harms. Bayesian network meta-analyses will be performed where judged appropriate based on review of clinical and methodologic features of included studies. DISCUSSION: Our review will include a broad range of interventions that patients with breast and prostate cancer have attempted to use to manage hot flashes. Our work will establish the extent of evidence underlying these interventions and will employ an inclusive approach to analysis to inform comparisons between them. Our findings will be shared with Cancer Care Ontario for consideration in the development of guidance related to supportive care in these patients. PROSPERO: CRD42015024286.

Checking whether there is an increased risk of post-transplant lymphoproliferative disorder and other cancers with specific modern immunosuppression regimens in renal transplantation: protocol for a network meta-analysis of randomized and observational studies.

BACKGROUND: Patients undergoing renal transplant procedures require multi-agent immunosuppressive regimens both short term (induction phase) and long term (maintenance phase) to minimize the risk of organ rejection. There are several drug classes and agents for immunosuppression. Use of these agents may increase the risk of different harms including not only infections, but also malignancies including post-transplant lymphoproliferative disorder. There is a need to identify which regimens minimize the risk of such outcomes. The objective of this systematic review and network meta-analysis of randomized and observational studies is to explore whether certain modern regimens of immunosuppression used to prevent organ rejection in renal transplant patients are associated with an increased risk of post-transplant lymphoproliferative disorder and other malignancies. METHODS/DESIGN: 'Modern' regimens were defined to be those evaluated in controlled studies beginning in 1990 or later. An electronic literature search of Medline, Embase and the Cochrane Central Register of Controlled Trials has been designed by an experienced information specialist and peer reviewed by a second information specialist. Study selection and data collection will be performed by two reviewers. The outcomes of interest will include post-transplant lymphoproliferative disorder and other incident forms of malignancy occurring in adult renal transplant patients. Network meta-analyses of data from randomized and observational studies will be performed where judged appropriate based on a review of the clinical and methodological features of included studies. A sequential approach to meta-analysis will be used to combine data from different designs. DISCUSSION: Our systematic review will include both single-agent and multi-agent modern pharmacotherapy regimens in patients undergoing renal transplantation. It will synthesize malignancy outcomes. Our work will also add to the development of methods for network meta-analysis across study designs to assess treatment safety. TRIAL REGISTRATION: PROSPERO Registration Number: CRD42013006951.