Prevention of alcohol withdrawal seizure recurrence and treatment of other alcohol withdrawal symptoms in the emergency department: a rapid review.

BACKGROUND: Patients who experience harms from alcohol and other substance use often seek care in the emergency department (ED). ED visits related to alcohol withdrawal have increased across the world during the COVID-19 pandemic. ED clinicians are responsible for risk-stratifying patients under time and resource constraints and must reliably identify those who are safe for outpatient management versus those who require more intensive levels of care. Published guidelines for alcohol withdrawal are largely limited to the primary care and outpatient settings, and do not provide specific guidance for ED use. The purpose of this review was to synthesize published evidence on the treatment of alcohol withdrawal syndrome in the ED. METHODS: We conducted a rapid review by searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (1980 to 2020). We searched for grey literature on Google and hand-searched the conference abstracts of relevant addiction medicine and emergency medicine professional associations (2015 to 2020). We included interventional and observational studies that reported outcomes of clinical interventions aimed at treating alcohol withdrawal syndrome in adults in the ED. RESULTS: We identified 13 studies that met inclusion criteria for our review (7 randomized controlled trials and 6 observational studies). Most studies were at high/serious risk of bias. We divided studies based on intervention and summarized evidence narratively. Benzodiazepines decrease alcohol withdrawal seizure recurrence and treat other alcohol withdrawal symptoms, but no clear evidence supports the use of one benzodiazepine over another. It is unclear if symptom-triggered benzodiazepine protocols are effective for use in the ED. More evidence is needed to determine if phenobarbital, with or without benzodiazepines, can be used safely and effectively to treat alcohol withdrawal in the ED. Phenytoin does not have evidence of effectiveness at preventing withdrawal seizures in the ED. CONCLUSIONS: Few studies have evaluated the safety and efficacy of pharmacotherapies for alcohol withdrawal specifically in the ED setting. Benzodiazepines are the most evidence-based treatment for alcohol withdrawal in the ED. Pharmacotherapies that have demonstrated benefit for treatment of alcohol withdrawal in other inpatient and outpatient settings should be evaluated in the ED setting before routine use.

Risk Factors for Misuse of Prescribed Opioids: A Systematic Review and Meta-Analysis.

STUDY OBJECTIVE: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective is to synthesize the available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing misuse among patients prescribed opioids for noncancer pain. METHODS: We performed a systematic search of the scientific and gray literature for studies reporting on risk factors for prescription opioid misuse. Two reviewers independently reviewed titles, abstracts, and full texts; extracted data; and assessed study quality. We excluded studies with greater than 50% cancer patients, palliative patients, and illicit opioid initiation. When possible, we synthesized the effect sizes of dichotomous risk factors and their associations with opioid misuse, using inverse-variance random-effects meta-analysis. We calculated the mean difference between opioid misusers and nonmisusers for continuous risk factors. When studies lacked homogeneity, we synthesized their results qualitatively. RESULTS: Of 9,629 studies, 65 met our inclusion criteria. Among patients with outpatient opioid prescriptions, the following factors were associated with the development of misuse: any current or previous substance use (odds ratio [OR] 3.55; 95% confidence interval [CI] 2.62 to 4.82), any mental health diagnosis (OR 2.45; 95% CI 1.91 to 3.15), younger age (OR 2.19; 95% CI 1.81 to 2.64), and male sex (OR 1.23; 95% CI 1.10 to 1.36). CONCLUSION: Although clinicians should endeavor to offer alternative pain management strategies to all patients, those who are younger, are male patients, and report a history of or current substance use or mental health diagnoses were associated with a greater risk of developing opioid misuse. Clinicians should consider prioritizing alternative pain management strategies for these higher-risk patients.

Adverse drug event reporting systems: a systematic review.

AIM: Adverse drug events (ADEs) are harmful and unintended consequences of medications. Their reporting is essential for drug safety monitoring and research, but it has not been standardized internationally. Our aim was to synthesize information about the type and variety of data collected within ADE reporting systems. METHODS: We developed a systematic search strategy, applied it to four electronic databases, and completed an electronic grey literature search. Two authors reviewed titles and abstracts, and all eligible full-texts. We extracted data using a standardized form, and discussed disagreements until reaching consensus. We synthesized data by collapsing data elements, eliminating duplicate fields and identifying relationships between reporting concepts and data fields using visual analysis software. RESULTS: We identified 108 ADE reporting systems containing 1782 unique data fields. We mapped them to 33 reporting concepts describing patient information, the ADE, concomitant and suspect drugs, and the reporter. While reporting concepts were fairly consistent, we found variability in data fields and corresponding response options. Few systems clarified the terminology used, and many used multiple drug and disease dictionaries such as the Medical Dictionary for Regulatory Activities (MedDRA). CONCLUSION: We found substantial variability in the data fields used to report ADEs, limiting the comparability of ADE data collected using different reporting systems, and undermining efforts to aggregate data across cohorts. The development of a common standardized data set that can be evaluated with regard to data quality, comparability and reporting rates is likely to optimize ADE data and drug safety surveillance.

Using Economic Evidence to Set Healthcare Priorities in Low-Income and Lower-Middle-Income Countries: A Systematic Review of Methodological Frameworks.

Policy makers in low-income and lower-middle-income countries (LMICs) are increasingly looking to develop 'evidence-based' frameworks for identifying priority health interventions. This paper synthesises and appraises the literature on methodological frameworks--which incorporate economic evaluation evidence--for the purpose of setting healthcare priorities in LMICs. A systematic search of Embase, MEDLINE, Econlit and PubMed identified 3968 articles with a further 21 articles identified through manual searching. A total of 36 papers were eligible for inclusion. These covered a wide range of health interventions with only two studies including health systems strengthening interventions related to financing, governance and human resources. A little under half of the studies (39%) included multiple criteria for priority setting, most commonly equity, feasibility and disease severity. Most studies (91%) specified a measure of 'efficiency' defined as cost per disability-adjusted life year averted. Ranking of health interventions using multi-criteria decision analysis and generalised cost-effectiveness were the most common frameworks for identifying priority health interventions. Approximately a third of studies discussed the affordability of priority interventions. Only one study identified priority areas for the release or redeployment of resources. The paper concludes by highlighting the need for local capacity to conduct evaluations (including economic analysis) and empowerment of local decision-makers to act on this evidence.

The effect of early in-hospital medication review on health outcomes: a systematic review.

AIMS: Adverse drug events are an important cause of emergency department visits, unplanned admissions and prolonged hospital stays. Our objective was to synthesize the evidence on the effect of early in-hospital pharmacist-led medication review on patient-oriented outcomes based on observed data. METHODS: We systematically searched eight bibliographic reference databases, electronic grey literature, medical journals, conference proceedings, trial registries and bibliographies of relevant papers. We included studies that employed random or quasi-random methods to allocate subjects to pharmacist-led medication review or control. Medication review had to include, at a minimum, obtaining a best possible medication history and reviewing medications for appropriateness and adverse drug events. The intervention had to be initiated within 24 h of emergency department presentation or 72 h of admission. We extracted data in duplicate and pooled outcomes from clinically homogeneous studies of the same design using random effects meta-analysis. RESULTS: We retrieved 4549 titles of which seven were included, reporting the outcomes of 3292 patients. We pooled data from studies of the same design, and found no significant differences in length of hospital admission (weighted mean difference [WMD] -0.04 days, 95% confidence interval [CI] -1.63, 1.55), mortality (odds ratio [OR] 1.09, 95% CI 0.69, 1.72), readmissions (OR 1.15, 95% CI 0.81, 1.63) or emergency department revisits at 3 months (OR 0.60, 95% CI 0.27, 1.32). Two large studies reporting reductions in readmissions could not be included in our pooled estimates due to differences in study design. CONCLUSIONS: Wide confidence intervals suggest that additional research is likely to influence the effect size estimates and clarify the effect of medication review on patient-oriented outcomes. This systematic review failed to identify an effect of pharmacist-led medication review on health outcomes.

The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review.

STUDY OBJECTIVE: We synthesize the available evidence on the effect of ketamine on intracranial and cerebral perfusion pressures, neurologic outcomes, ICU length of stay, and mortality. METHODS: We developed a systematic search strategy and applied it to 6 electronic reference databases. We completed a gray literature search and searched medical journals as well as the bibliographies of relevant articles. We included randomized and nonrandomized prospective studies that compared the effect of ketamine with another intravenous sedative in intubated patients and reported at least 1 outcome of interest. Two authors independently performed title, abstract, and full-text reviews, and abstracted data from all studies, using standardized forms. Data from randomized controlled trials and prospective studies were synthesized in a qualitative manner because the study designs, patient populations, reported outcomes, and follow-up periods were heterogeneous. We used the Jadad score and Cochrane Risk of Bias tool to assess study quality. RESULTS: We retrieved 4,896 titles, of which 10 studies met our inclusion criteria, reporting data on 953 patients. One study was deemed at low risk of bias in all quality assessment domains. All others were at high risk in at least 1 domain. Two of 8 studies reported small reductions in intracranial pressure within 10 minutes of ketamine administration, and 2 studies reported an increase. None of the studies reported significant differences in cerebral perfusion pressure, neurologic outcomes, ICU length of stay, or mortality. CONCLUSION: According to the available literature, the use of ketamine in critically ill patients does not appear to adversely affect patient outcomes.

Screening for harmful substance use in emergency departments: a systematic review.

BACKGROUND: Substance use-related emergency department (ED) visits have increased substantially in North America. Screening for substance use in EDs is recommended; best approaches are unclear. This systematic review synthesizes evidence on diagnostic accuracy of ED screening tools to detect harmful substance use. METHODS: We included derivation or validation studies, with or without comparator, that included adult (≥ 18 years) ED patients and evaluated screening tools to identify general or specific substance use disorders or harmful use. Our search strategy combined concepts Emergency Department AND Screening AND Substance Use. Trained reviewers assessed title/abstracts and full-text articles for inclusion, extracted data, and assessed risk of bias (QUADAS-2) independently and in duplicate. Reviewers resolved disagreements by discussion. Primary investigators adjudicated if necessary. Heterogeneity precluded meta-analysis. We descriptively summarized results. RESULTS: Our search strategy yielded 2696 studies; we included 33. Twenty-one (64%) evaluated a North American population. Fourteen (42%) applied screening among general ED patients. Screening tools were administered by research staff (n = 21), self-administered by patients (n = 10), or non-research healthcare providers (n = 1). Most studies evaluated alcohol use screens (n = 26), most commonly the Alcohol Use Disorders Identification Test (AUDIT; n = 14), Cut down/Annoyed/Guilty/Eye-opener (CAGE; n = 13), and Rapid Alcohol Problems Screen (RAPS/RAPS4/RAPS4-QF; n = 12). Four studies assessing six tools and screening thresholds for alcohol abuse/dependence in North American patients (AUDIT ≥ 8; CAGE ≥ 2; Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-2] ≥ 1; RAPS ≥ 1; National Institute on Alcohol Abuse and Alcoholism [NIAAA]; Tolerance/Worry/Eye-opener/Amnesia/K-Cut down [TWEAK] ≥ 3) reported both sensitivities and specificities ≥ 83%. Two studies evaluating a single alcohol screening question (SASQ) (When was the last time you had more than X drinks in 1 day?, X = 4 for women; X = 5 for men) reported sensitivities 82-85% and specificities 70-77%. Five evaluated screening tools for general substance abuse/dependence (Relax/Alone/Friends/Family/Trouble [RAFFT] ≥ 3, Drug Abuse Screening Test [DAST] ≥ 4, single drug screening question, Alcohol, Smoking and Substance Involvement Screening Test [ASSIST] ≥ 42/18), reporting sensitivities 64%-90% and specificities 61%-100%. Studies' risk of bias were mostly high or uncertain. CONCLUSIONS: Six screening tools demonstrated both sensitivities and specificities ≥ 83% for detecting alcohol abuse/dependence in EDs. Tools with the highest sensitivities (AUDIT ≥ 8; RAPS ≥ 1) and that prioritize simplicity and efficiency (SASQ) should be prioritized.

The human health effects of unconventional oil and gas development (UOGD): A scoping review of epidemiologic studies.

OBJECTIVE: Unconventional oil and gas development (UOGD, sometimes termed "fracking" or "hydraulic fracturing") is an industrial process to extract methane gas and/or oil deposits. Many chemicals used in UOGD have known adverse human health effects. Canada is a major producer of UOGD-derived gas with wells frequently located in and around rural and Indigenous communities. Our objective was to conduct a scoping review to identify the extent of research evidence assessing UOGD exposure-related health impacts, with an additional focus on Canadian studies. METHODS: We included English- or French-language peer-reviewed epidemiologic studies (January 2000-December 2022) which measured exposure to UOGD chemicals directly or by proxy, and where health outcomes were plausibly caused by UOGD-related chemical exposure. Results synthesis was descriptive with results ordered by outcome and hierarchy of methodological approach. SYNTHESIS: We identified 52 studies from nine jurisdictions. Only two were set in Canada. A majority (n = 27) used retrospective cohort and case-control designs. Almost half (n = 24) focused on birth outcomes, with a majority (n = 22) reporting one or more significant adverse associations of UOGD exposure with: low birthweight; small for gestational age; preterm birth; and one or more birth defects. Other studies identified adverse impacts including asthma (n = 7), respiratory (n = 13), cardiovascular (n = 6), childhood acute lymphocytic leukemia (n = 2), and all-cause mortality (n = 4). CONCLUSION: There is a growing body of research, across different jurisdictions, reporting associations of UOGD with adverse health outcomes. Despite the rapid growth of UOGD, which is often located in remote, rural, and Indigenous communities, Canadian research on its effects on human health is remarkably sparse. There is a pressing need for additional evidence.

RéSUMé: OBJECTIF: L'exploitation pétrolière et gazière non conventionnelle (EPGNC, parfois appelée « fracturation ¼ ou « fracturation hydraulique ¼) est un processus industriel d'extraction du méthane et/ou de gisements de pétrole. De nombreux produits chimiques utilisés dans l'EPGNC ont des effets indésirables connus sur la santé humaine. Le Canada est un grand producteur de gaz dérivé de l'EPGNC, dont les puits sont souvent situés à l'intérieur et autour de communautés rurales et autochtones. Nous avons mené une étude de champ pour déterminer l'étendue des données de recherche évaluant les effets sur la santé de l'exposition à l'EPGNC, en nous concentrant plus particulièrement sur les études canadiennes. MéTHODE: Nous avons inclus des études épidémiologiques en anglais ou en français évaluées par les pairs (janvier 2000 à décembre 2022) qui mesuraient l'exposition directe ou indirecte aux produits chimiques de l'EPGNC et dans lesquelles les résultats cliniques étaient plausiblement causés par l'exposition aux produits chimiques liés à l'EPGNC. La synthèse des résultats est descriptive, et les résultats sont ordonnés selon les résultats cliniques et l'approche méthodologique. SYNTHèSE: Nous avons identifié 52 études menées dans neuf juridictions. Deux seulement étaient canadiennes. La majorité (n = 27) faisaient appel à des cohortes rétrospectives ou étaient des études cas-témoins. Près de la moitié (n = 24) portaient sur les issues de la grossesse, et la majorité (n = 22) déclaraient une ou plusieurs associations indésirables significatives entre l'exposition à l'EPGNC et : l'insuffisance de poids à la naissance; la petite taille du bébé pour son âge gestationnel; la naissance avant terme; et une ou plusieurs anomalies congénitales. D'autres études faisaient état d'effets indésirables, dont l'asthme (n = 7), les troubles respiratoires (n = 13), les troubles cardiovasculaires (n = 6), la leucémie aiguë lymphoblastique infantile (n = 2) et la mortalité toutes causes confondues (n = 4). CONCLUSION: Il existe dans différents pays un corpus croissant d'études qui font état d'associations entre l'EPGNC et des résultats sanitaires indésirables. Malgré la croissance rapide de l'EPGNC, souvent présente dans des communautés éloignées, rurales et autochtones, la recherche canadienne sur ses effets sur la santé humaine est remarquablement clairsemée. Il y a un besoin urgent de recueillir d'autres données probantes à ce sujet.

Evaluating treatment outcomes in pharmacogenomic-guided care for major depression: A rapid review and meta-analysis.

Pharmacogenomic (PGx) testing may increase the probability of remission and response in patients with major depressive disorder (MDD) undergoing pharmacotherapy. Given the potential implications of these outcomes and recent proliferation of PGx studies, we conducted a systematic review to evaluate the effectiveness of PGx testing on clinical outcomes in patients with MDD as compared to treatment as usual (TAU). MEDLINE, Embase, PsycInfo, and CENTRAL were searched for English-language articles from 2000 to 2021 for randomized controlled trials (RCTs) comparing PGx-guided treatment vs. TAU in patients with MDD. Meta-analyses were conducted in R. Ten RCTs were included: eight reported remission and seven reported response. The best available evidence suggests that PGx-guided care for moderate-to-severe adult depression is more likely to result in remission and response than TAU (both risk ratios significant). However, there are limitations in the evidence base, including high risk of bias and inconsistency between trials. Despite the consequent very low certainty in the magnitude of effect, there is confidence in the direction. Though modest, the beneficial effects of PGx for adults with moderate-severe MDD could - as a result of the scope and scale of the condition and its impacts - have important ramifications for patients and the health system.

A Systematic Review of Kidney Transplantation Decision Modelling Studies.

BACKGROUND: Genome-based precision medicine strategies promise to minimize premature graft loss after renal transplantation, through precision approaches to immune compatibility matching between kidney donors and recipients. The potential adoption of this technology calls for important changes to clinical management processes and allocation policy. Such potential policy change decisions may be supported by decision models from health economics, comparative effectiveness research and operations management. OBJECTIVE: We used a systematic approach to identify and extract information about models published in the kidney transplantation literature and provide an overview of the status of our collective model-based knowledge about the kidney transplant process. METHODS: Database searches were conducted in MEDLINE, Embase, Web of Science and other sources, for reviews and primary studies. We reviewed all English-language papers that presented a model that could be a tool to support decision making in kidney transplantation. Data were extracted on the clinical context and modelling methods used. RESULTS: A total of 144 studies were included, most of which focused on a single component of the transplantation process, such as immunosuppressive therapy or donor-recipient matching and organ allocation policies. Pre- and post-transplant processes have rarely been modelled together. CONCLUSION: A whole-disease modelling approach is preferred to inform precision medicine policy, given its potential upstream implementation in the treatment pathway. This requires consideration of pre- and post-transplant natural history, risk factors for allograft dysfunction and failure, and other post-transplant outcomes. Our call is for greater collaboration across disciplines and whole-disease modelling approaches to more accurately simulate complex policy decisions about the integration of precision medicine tools in kidney transplantation.

Short communication: Systematic review on effectiveness of micro-induction approaches to buprenorphine initiation.

BACKGROUND/OBJECTIVES: Micro-induction is a novel buprenorphine induction approach that seeks to avoid withdrawal and minimize precipitated withdrawal, both barriers to standard inductions. We aimed to synthesize evidence on micro-induction effectiveness, and regimens described. METHODS: We searched scientific databases and grey literature for studies including adolescents or adults with opioid use disorder who received buprenorphine micro-induction. Study selection, data extraction and quality assessments occurred in duplicate. We narratively synthesized results. RESULTS: We screened 4,752 citations and included 19 case studies/series and one feasibility study (n = 57 patients; mean age 38 years [SD 12.0]; 57.9% male [33/57]). Studies described 26 regimens; starting and maintenance doses ranged from 0.03 to 1.0 mg, and 8 to 32 mg, respectively. We calculated rate of increase to 8 mg. All patients achieved the desired maintenance dose. Among 54 patients in whom precipitated withdrawal was not reported, mean increases were 1.36 mg/day (SD 0.41). For three patients in whom precipitated withdrawal was specifically reported, mean increase was 1.17 mg/day (SD 0.11). All studies were low quality. DISCUSSION: Described regimens are highly variable. Inconsistent reporting, selection bias, and poor quality evidence limit conclusions regarding optimal dosing, and patient characteristics and clinical settings in which micro-induction is likely beneficial. CONCLUSIONS: This systematic review provides the most up-to-date synthesis on buprenorphine micro-induction regimens. Rigorous studies evaluating effectiveness and safety of micro-induction, and patient and clinical factors influencing its success, are needed.

The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review.

STUDY OBJECTIVE: To synthesize the evidence on the effect of a bolus dose of etomidate on adrenal function, mortality, and health services utilization compared with other induction agents used for rapid sequence intubation. METHODS: We developed a systematic search strategy and applied it to 10 electronic bibliographic databases. We hand searched journals; reviewed conference proceedings, gray literature, and bibliographies of relevant literature; and contacted content experts for studies comparing a bolus dose of etomidate with other induction agents. Retrieved articles were reviewed and data were abstracted with standardized forms. Data were pooled with the random-effects model if at least 4 clinically homogenous studies of the same design reported the same outcome measure. All other data were reported qualitatively. RESULTS: From 3,083 titles reviewed, 20 met our inclusion criteria. Pooled mean cortisol levels were lower in elective surgical patients induced with etomidate compared with those induced with other agents between 1 and 4 hours postinduction. The differences varied from 6.1 microg/dL (95% confidence interval [CI] 2.4 to 9.9 microg/dL; P=.001) to 16.4 microg/dL (95% CI 9.7 to 23.1 microg/dL; P<.001). Two studies in critically ill patients reported significantly different cortisol levels up to 7 hours postinduction. None of the studies reviewed, nor our pooled estimate (odds ratio 1.14; 95% CI 0.81 to 1.60), showed a statistically significant effect on mortality. Only one study reported longer ventilator, ICU, and hospital lengths of stay in patients intubated with etomidate. CONCLUSION: The available evidence suggests that etomidate suppresses adrenal function transiently without demonstrating a significant effect on mortality. However, no studies to date have been powered to detect a difference in hospital, ventilator, or ICU length of stay or in mortality.

Effectiveness of micro-induction approaches to buprenorphine initiation: A systematic review protocol.

BACKGROUND: Buprenorphine is first-line opioid agonist therapy for opioid use disorder. Standard regimens require that patients be in opioid withdrawal prior to induction, which is a barrier for many. Micro-induction is a novel induction approach that does not require patients to be in withdrawal. Our primary objective is to synthesize available evidence on the effectiveness of micro-inductions on patient and clinical outcomes compared to standard dosing or other approaches, or evaluated without a comparator group. Secondary objectives are to synthesize evidence on clinical factors that influence micro-induction effectiveness, and to summarize micro-induction regimens described in the literature. METHODS: We will search MEDLINE, Embase, CINAHL, Psycinfo, Science Citation Index, and the grey literature for studies that include adolescents or adults with opioid use disorder who received a buprenorphine micro-induction regimen. We will consider any patient or clinical outcomes defined by study authors. We will include controlled and non-controlled interventional studies, observational studies, case reports/series and reports from relevant organizations or guidelines pertinent to our third objective. We will select studies, extract data and assess study quality (using the Downs and Black, and Cochrane Risk of Bias tools) in duplicate. We will narratively synthesize our results, and will meta-analyze outcome measures if multiple studies report common outcomes with acceptably low heterogeneity. DISCUSSION: Our review will include the most up-to-date available data on buprenorphine micro-inductions. We anticipate limitations relating to study heterogeneity and quality. We will disseminate study results widely to inform updated guidelines for opioid agonist therapy prescribers.

Patient-oriented research competencies in health (PORCH) for researchers, patients, healthcare providers, and decision-makers: results of a scoping review.

PLAIN ENGLISH SUMMARY: Background The Canadian Institutes of Health Research funded a program, "patient-oriented research" (POR), to change the way health research is done. POR involves patients and their families/caregivers as equal partners on research teams with researchers, healthcare providers and decision-makers. The authors of this paper work through a unit in British Columbia, Canada that functions to help research teams learn how to do patient-oriented research. We felt that we could not train people if we didn't first understand what others had learned about what competencies (knowledge, skills and attitudes) were helpful for members of these research teams. Method We used a method called a scoping review to search literature on patient-involved research. Our search included papers in academic journals as well as information on websites, training manuals, conference proceedings, governmental documents and statements from health organizations. Findings Writers reported the usefulness of many competencies for researchers and patients, with fewer competencies for healthcare providers or decision-makers. The main competencies for researchers had to do with participation, communication and conflict management; for patients they had to do with research knowledge and skills, cultural competence and participation. It was helpful that all team members want to work as part of a group for the public good. Conclusions We worked with an advisory group of people representing patients and their families/caregivers, researchers, healthcare providers and decision-makers to review our findings. We concluded that our competency statements are helpful for people to determine what they need to know or learn as they join research teams. ABSTRACT: Background The Canadian Institutes of Health Research (CIHR) launched an initiative called the Strategy for Patient-Oriented Research (SPOR) encouraging patient-oriented research (POR) that engages patients as equal partners in research teams alongside researchers, healthcare providers and health system decision-makers. Other countries have launched similar initiatives (POR-related work) yet there has never been full review of the competencies needed by individuals engaging in this work. Purpose and methods Our purpose was to summarize existing knowledge on POR and POR-related competencies by conducting a scoping review of peer-reviewed and grey literature. Our objectives were to systematically explore literature, articulate competencies necessary for research team members, identify research gaps and provide recommendations for further research. Using standard health databases and search methods, a total of 2036 sources was retrieved. Data were extracted from 35 peer-reviewed papers and 38 grey literature sources. We used an iterative process to reach consensus on competency statements. Findings and conclusions The main competencies for researchers were in categories of participation, communication and teamwork and conflict/tension management; for patients the main competencies were in research knowledge and skills, cultural competence/context and participation. While fewer competencies were documented for the other stakeholder groups, the need for understanding patient involvement in research and knowledge of the needs that research partners have are noted as competencies for healthcare providers and decision-makers. Attitudes demonstrating inclination to conduct the work were noted for all. The competencies can be used to consider learning needs of research team members and for team members wishing to assess their own readiness to serve on a POR or POR-related research team. Incidentally, we noted the lack of a common vocabulary used to describe patient-involved research, a situation making research and literature review/retrieval quite challenging. Recommendations for future research and for achieving consistency in language are addressed.

Naloxone dosing in the era of ultra-potent opioid overdoses: a systematic review.

OBJECTIVES: Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses. METHODS: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old. RESULTS: A total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions. CONCLUSIONS: Practitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.

Economic burden of asthma: a systematic review.

BACKGROUND: Asthma is associated with enormous healthcare expenditures that include both direct and indirect costs. It is also associated with the loss of future potential earnings related to both morbidity and mortality. The objective of the study is to determine the burden of disease costs associated with asthma. METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL, CDSR, OHE-HEED, and Web of Science Databases between 1966 and 2008. RESULTS: Sixty-eight studies met the inclusion criteria. Hospitalization and medications were found to be the most important cost driver of direct costs. Work and school loss accounted for the greatest percentage of indirect costs. The cost of asthma was correlated with comorbidities, age, and disease severity. CONCLUSION: Despite the availability of effective preventive therapy, costs associated with asthma are increasing. Strategies including education of patients and physicians, and regular follow-up are required to reduce the economic burden of asthma.

Naloxone interventions in opioid overdoses: a systematic review protocol.

BACKGROUND: North America is in the midst of an unabated opioid overdose epidemic due to the increasing non-medical use of fentanyl and ultra-potent opioids. Naloxone is an effective antidote to opioid toxicity, yet its optimal dosing in the context of fentanyl and ultra-potent opioid overdoses remains unknown. This review aims to determine the relationship between the first empiric dose of naloxone and reversal of toxicity, adverse events, and the total cumulative dose required among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Secondary objectives include evaluating the relationship between the cumulative naloxone dose and toxicity reversal and adverse events, among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. METHODS: To identify studies, we will search MEDLINE, Embase, CENTRAL, DARE, CDAG, CINAHL, Science Citation Index, multiple trial registries, and the gray literature. Included studies will evaluate patients with suspected or confirmed opioid toxicity from undifferentiated opioids and ultra-potent opioids, who received an empiric and possibly additional doses of naloxone. The main outcomes of interest are the relationship between naloxone dose and toxicity reversal and adverse events. We will include controlled and non-controlled interventional studies, observational studies, case reports/series, and reports from poison control centers. We will extract data and assess study quality in duplicate with discrepancies resolved by consensus or a third party. We will use the Downs and Black and Cochrane risk of bias tools for observational and randomized controlled studies. If we find sufficient variation in dose, we will fit a random effects one-stage model to estimate a dose-response relationship. We will conduct multiple subgroup analyses, including by type of opioid used and by suspected high and low prevalence of ultra-potent opioid use based on geographic location and time of the original studies. DISCUSSION: Our review will include the most up-to-date available data including ultra-potent opioids to inform the current response to the opioid epidemic, addressing the limitations of recent reviews. We anticipate limitations relating to study heterogeneity. We will disseminate study results widely to update overdose treatment guidelines and naloxone dosing in Take Home Naloxone programs.

Patient-Oriented Research Competencies in Health (PORCH) for patients, healthcare providers, decision-makers and researchers: protocol of a scoping review.

BACKGROUND: Patient-Oriented Research (POR) is a Canadian initiative for health research that refers to research processes informed by full and active patient involvement in all aspects of the research. Ideally, POR results in a wide dissemination of the research findings and the uptake of such findings in both clinical practice and health policy. The Canadian Institute for Health Research (CIHR) identifies four stakeholder groups that are involved in POR who are envisioned to take on a collaborative role in enacting this approach to research. Those stakeholder groups are patients, researchers, health care providers and healthcare decision-makers. To achieve collaboration among stakeholders in POR, tools, resources, education/training and capacity building are required for each stakeholder group engaged in this work. Therefore, this review focuses on understanding and articulating competencies needed by participants to engage in POR. The aim is to summarize existing knowledge on discrete POR competencies for the four stakeholder groups; to support collaboration among them for uptake and strengthening of POR; and to inform policy, education and future research. Accordingly, our research question is 'What are the POR core competencies needed by patients, researchers, healthcare providers, and decision-makers?' The main objectives are to (1) systematically explore the academic and grey literature on competencies needed for these stakeholder groups to engage in POR; (2) map the eligible publications and research gaps in this area; (3) gain knowledge to support collaboration among stakeholders; and (4) provide recommendations for further research to use competencies that emerge in developing stakeholder groups' readiness to conduct POR. METHODS/DESIGN: We will use a methodologically rigorous scoping review approach including formulation of the research question and development of the protocol; screening and identification of the literature; selection of relevant studies; data extraction; and collation, summary and report of the results. Our eligibility criteria include elements of population (patients, researchers, healthcare providers and decision-makers); concept (competencies: knowledge, skills, attitudes; and POR); context (level of involvement in research, settings, funding sources); study design (sample, stakeholder group, methodology, grey literature, theoretical framework); outcomes (primary: relevant to decision-making/policy and practice; and secondary: relevant to education and research); language (English, French); and timing (1990-2017). Registration with PROSPERO is not eligible for scoping reviews; so, it has not been registered. DISCUSSION: Research on core competencies required to enact POR is in its infancy. In this review, we can articulate what is known and thought about competencies (knowledge, skills and attitudes) needed by individuals on POR research teams and ultimately provide knowledge that could impact research, practice, education and policy. Identification of competencies can contribute to design of healthcare professionals' basic and ongoing educational programmes, patient training in research, and professional development activities for health care providers and decision-makers. In addition, knowledge of core competencies can permit individuals to evaluate their own readiness to enter POR research teams.