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Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic progressive illness with a spectrum of disease severity from steatosis to end-stage liver disease. Emerging evidence suggests total serum bilirubin levels are inversely related to the prevalence of metabolic syndrome including NAFLD. We investigated the effects of bilirubin on all-cause and cause-specific mortality stratified by NAFLD status. Methods: We used the third National Health and Nutrition Examination Survey Cohort (1988-1994) and linked mortality dataset through 2019. Cox-regression models were constructed to assess the association between bilirubin levels categorized by quartile with all-cause and cause-specific mortality. Results: During the median follow-up of 324 months (n=11,078), higher bilirubin levels were associated with a reduction in risk of all-cause mortality in the multivariable model [hazard ratio (HR): 0.83, 95% confidence interval (CI): 0.71-0.97 for quartile 4 (highest bilirubin levels) vs. quartile 1 (lowest bilirubin levels), p for trend=0.033]. Higher bilirubin levels were associated with a lower risk for all-cause mortality in individuals with NAFLD (HR=0.68, 95%CI: 0.55-0.86 for quartile 4, p for trend=0.010); however, this protective association with higher bilirubin levels was not noted in those without NAFLD. Higher bilirubin levels were associated with a lower risk for cardiovascular and cancer-related mortality in individuals with NAFLD. Conclusions: In this large national representative sample of American adults, higher bilirubin levels in NAFLD were associated with a lower risk of all-cause mortality, which may be derived from a lower risk of cardiovascular/cancer-related mortality. [ABSTRACT FROM AUTHOR]

The impact of different types of physical activity (PA) on mortality in the context of nonalcoholic fatty liver disease (NAFLD) is not clearly defined and was investigated. This prospective study was performed using the 2007–2014 US National Health and Nutrition Examination Survey with mortality follow-up through 2019. Over a median follow-up of 8.6 years, leisure-time and transportation-related PA that fulfilled the criteria outlined in the PA guidelines (≥150 min/week) in NAFLD were associated with a risk reduction in all-cause mortality (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.59–0.98 for leisure-time PA; HR: 0.62, 95% CI: 0.45–0.86 for transportation-related PA). Leisure-time and transportation-related PA in NAFLD were inversely associated with all-cause mortality in a dose-dependent manner (p for trends <0.01). Furthermore, the risk for cardiovascular mortality was lower in those meeting the PA guidelines for leisure-time PA (HR: 0.63, 95% CI: 0.44–0.91) and transportation-related PA (HR: 0.38, 95% CI: 0.23–0.65). Increasing sedentary behavior was linked to an increased risk of all-cause and cardiovascular mortality (p for trend <0.01). Meeting PA guidelines (≥150 min/week) for leisure-time and transportation-related PA has beneficial health effects on all-cause and cardiovascular mortality among individuals with NAFLD. Sedentary behavior in NAFLD showed harmful effects on all-cause and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Muscle strength in non-alcoholic fatty liver disease and all-cause and cause-specific mortality Keywords: death; handgrip strength; hepatic steatosis; nhanes; sarcopenia EN death handgrip strength hepatic steatosis nhanes sarcopenia 513 516 4 01/27/23 20230201 NES 230201 Abbreviations BMI body mass index CI confidence interval HIS hepatic steatosis index HR hazard ratio NAFLD non-alcoholic fatty liver disease NHANES National Health and Nutrition Examination Survey UCOD underlying cause of death Key points Higher muscle strength among individuals with non-alcoholic fatty liver disease is associated with a lower risk of all-cause and cardiovascular mortality independent of known demographic, clinical and metabolic risk factors. 8 Range of combined grip strength/body mass index for women: quartile 1: <1.437, quartile 2: >=1.437 and <1.712, quartile 3: >=1.712 and <2.025, quartile 4: >=2.025. First, we used a non-invasive marker to define NAFLD, which may misclassify the true prevalence of NAFLD, because NHANES 2011-2014 data lack radiological or histological information, which is considered the gold standard for the diagnosis of NAFLD. [Extracted from the article]

Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease. We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic. Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes. The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men. The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)‐related end‐stage liver disease (ESLD). We assess aetiology‐based hospitalizations for ESLD in the United States, 2016–2019. Methods: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision. Results: National hospitalization rates for non‐alcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100 000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100 000 persons in 2016 to 58.5 in 2019 (−6.5% AAPC). Hospitalizations for ESLD in alcohol‐related liver disease (ALD) increased as well. Conclusions: Hospitalization rates for NAFLD‐ and ALD‐related ESLD increased steadily, while those for HCV‐related ESLD decreased during the direct‐acting antivirals era. [ABSTRACT FROM AUTHOR]

Background & Aims: With the recent improvement in the treatment of hepatitis C virus (HCV) infection, a better understanding of the infection burden is needed. We aimed to (a) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (b) identify at‐risk populations for HCV infection in the United States (US) general population. Methods: Population‐based analyses using the National Health and Nutrition Examination Survey (2013‐2018) were performed with a focus on HCV infection. We analysed the prevalence of HCV infection based on the health insurance status before the direct‐acting antiviral (DAA) era (2013‐2014) and during the DAA era (2015‐2018). Results: The age‐adjusted prevalence of active HCV infection (HCV RNA [+]) was 0.92% (95% confidence interval, 0.71%‐1.19%) in the US non‐institutionalized civilian population. Although the prevalence of active HCV infection has remained stable, the prevalence of resolved HCV infection has increased after the introduction of DAA. In terms of health insurance coverage, the prevalence of active HCV infection decreased, and the prevalence of resolved HCV infection increased among individuals who had health insurance, especially private health insurance. The independent risk factors of active HCV infection were 40‐69 years group, male, less than high school education, unmarried, below poverty status, being born in the US, history of blood transfusion and not having private health insurance. Conclusion: The burden of active HCV infection has decreased among individuals who had health insurance, especially private health insurance, during the DAA era. [ABSTRACT FROM AUTHOR]

Background: The 3 Wishes Project (3WP) promotes a personalized dying experience by eliciting and facilitating individualized terminal wishes for patients, families and the clinicians caring for them. We aimed to evaluate the adaptability of the 3WP to a community intensive care unit (ICU), and to describe the patients cared for with this palliative approach, as well as local implementation strategies. Methods: The 3WP was implemented in a 15-bed community hospital ICU in southern Ontario from 2017 to 2019. In this observational, descriptive study, we invited adult patients (≥ 18 yr) whose risk of death was deemed to be 95% or greater by the attending physician, or patients undergoing withdrawal of life-support to participate. We abstracted patient data from medical records, as well as the type, timing and cost of each wish, which person or service made and facilitated each wish, and if and why wishes were completed or not. We summarized data both narratively and quantitatively. Results: The 3WP helped to realize 479 (99.2%) of 483 terminal wishes for 101 dying patients. This initiative was introduced as an interprofessional intervention and championed by nursing staff who were responsible for most patient enrolment and wish facilitation. Wishes included humanizing the ICU environment for the patient with belongings and blankets, musical performances, smudging and bathing ceremonies, and keepsakes. The cost was $5.39 per patient (standard deviation $22.40), with 430 (89.8%) wishes incurring no cost. Wishes made directly by patients accounted for 30 (6.2%) of wishes; those from family members and ICU staff accounted for 236 (48.9%) and 238 (49.3%) of wishes, respectively. The program comforted patients and their loved ones, motivating clinicians to sustain this end-of-life intervention. Interpretation: We documented successful implementation of the 3WP in a community hospital, showing program adaptability and uptake outside of academic centres at relatively low cost. The lack of strict protocolization and personalized design of this intervention underscores its inherent flexibility, with potential to promote individualized end-of-life care in nonacademic hospital wards, homes or hospice. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected the hospital experience for patients, visitors, and staff.Objective: To understand clinician perspectives on adaptations to end-of-life care for dying patients and their families during the pandemic.Design: Mixed-methods embedded study. (ClinicalTrials.gov: NCT04602520).Setting: 3 acute care medical units in a tertiary care hospital from 16 March to 1 July 2020.Participants: 45 dying patients, 45 family members, and 45 clinicians.Intervention: During the pandemic, clinicians continued an existing practice of collating personal information about dying patients and "what matters most," eliciting wishes, and implementing acts of compassion.Measurements: Themes from semistructured clinician interviews that were summarized with representative quotations.Results: Many barriers to end-of-life care arose because of infection control practices that mandated visiting restrictions and personal protective equipment, with attendant practical and psychological consequences. During hospitalization, family visits inside or outside the patient's room were possible for 36 patients (80.0%); 13 patients (28.9%) had virtual visits with a relative or friend. At the time of death, 20 patients (44.4%) had a family member at the bedside. Clinicians endeavored to prevent unmarked deaths by adopting advocacy roles to "fill the gap" of absent family and by initiating new and established ways to connect patients and relatives.Limitation: Absence of clinician symptom or wellness metrics; a single-center design.Conclusion: Clinicians expressed their humanity through several intentional practices to preserve personalized, compassionate end-of-life care for dying hospitalized patients during the SARS-CoV-2 pandemic.Primary Funding Source: Canadian Institutes of Health Research and Canadian Critical Care Trials Group Research Coordinator Fund. [ABSTRACT FROM AUTHOR]

Background: Depression impacts the lives of millions of people worldwide. Behavioral activation (BA), derived from cognitive behavioral therapy, has the potential for improving depressive symptoms in patients with depression. Studies evaluating the effectiveness of BA specifically in the context of group therapy programs in a hospital setting for patients with depression are limited. In this study, we report findings from a pilot trial evaluating group BA for major depressive disorder. Objective: The objectives of this pilot trial are to assess the potential of a full trial of BA group therapy in a large-scale tertiary care setting and to provide preliminary information about possible results regarding mood symptoms and quality of life in adults with depression. Methods: Using a parallel single-cohort pragmatic pilot randomized controlled trial design, we evaluated the potential of conducting a large trial of BA effectiveness among adults with depression. Participants were randomized to the intervention (BA in addition to usual care) or control (support group in addition to usual care) groups and were assessed weekly for 18 consecutive weeks. Participants randomized to intervention underwent 28 2-h group BA therapy visits administered by trained therapists and completed assessments to examine treatment outcomes. Feasibility was measured in terms of enrollment rates (min. 20%), completion rates of study (min. 80%), and completion rates of weekly measurement scales (min. 80%). The reporting of this pilot trial is in accordance with the CONSORT extension for randomized pilot and feasibility trials. Results: We randomized 20 individuals of mean age of 48.8 years (standard deviation = 9.7) with a DSM-5 diagnosis of major depressive disorder to intervention (n = 10) or control (n = 10) groups. Based on our feasibility criteria, our recruitment rate was excellent (20/27; 74%), study completion was found to be a moderate (80% of the total participants in both arms completed the study; BA = 100%, control = 60%), and completeness of measurements on a weekly basis was adequate overall (82%; BA = 86%, control = 79%). Conclusions: The study has demonstrated the potential feasibility to perform a larger scale trial upon modifications to the control group to avoid the low rate of study completion (60%) in this group. Trial registration: ClinicalTrials NCT02045771, Registered January 22, 2014 [ABSTRACT FROM AUTHOR]

Objective To assess which mental health-related states of being are perceived as diseases by psychiatrists, nonpsychiatric physicians, nurses, parliament members and laypeople. Design and setting A population-based, mailed survey in Finland. Participants Respondents from a random sample of 3000 laypeople, 1500 physicians, 1500 nurses and all 200 members of the parliament (MPs) of Finland. Primary outcome measures Respondents' perspectives on 20 mental health-related states of being as diseases, measuring the extent of agreement with the claim: '[This state of being] is a disease'. Results Of the 6200 people approached, we received 3259 eligible responses (53%). Two conditions (schizophrenia and autism) were considered to be diseases by at least 75% and two states (grief and homosexuality) were considered not to be diseases by at least 75% in each group. A majority (at least 50% in each group) considered seven states as diseases (anorexia, attention deficit hyperactivity disorder, bulimia, depression, generalised anxiety disorder, panic disorder and personality disorder) and three not to be diseases (absence of sexual desire, premature ejaculation and transsexualism). In six states, there was a wide divergence of opinion (alcoholism, drug addiction, gambling addiction, insomnia, social anxiety disorder and work exhaustion). Psychiatrists were significantly more inclined to considering states of being as diseases relative to other groups, followed by non-psychiatric physicians, nurses, MPs and laypeople. Conclusions Respondents agreed that some conditions, such as schizophrenia and autism, are diseases and other states, such as grief and homosexuality, are not; for others, there was considerable disagreement. Psychiatrists are more inclined to consider mental health-related states of being as diseases compared with other physicians, who, in turn, are more inclined than other constituencies. Understanding notions of disease may underlie important debates in public policy and practice in areas of mental health and behaviour, and have implications for resource allocation and stigma. [ABSTRACT FROM AUTHOR]

Background: Pneumocephalus, illustrated by air in the cranial vault is relatively infrequent and generally associated with neurosurgery, trauma, meningitis and barotrauma. However cases of spontaneous non-traumatic pneumocephalus remain rare. While the relationship between continuous positive airway pressure (CPAP) and atraumatic pneumocephalus has been previously reported, to our knowledge the rare presentation associated with sinus wall osteomyelitis has never been described. We summarize here the case of a 67-year-old woman's acute presentation of Streptococcus salvarius infection after a sudden drop in her consciousness.Case Presentation: The patient was brought to hospital by family reporting a one week history of sudden deterioration, cognitive decline, and lethargy. The patient presented with reduced arousal, cognitive function (Glasgow Coma Scale: 10, Abbreviated Mental Test Score:CS, 0 AMTS), and no history of trauma. Computed Tomography (CT) imaging was ordered and identified a significant pneumocephalus with no cranial defect. Further investigations acknowledged possible sinus or middle ear disease, which was highlighted by the discovery of S. salivarius by polymerase chain reaction (PCR) and potentially exacerbated by the use of nocturnal continuous positive airway pressure (CPAP). The patient made a complete recovery by eliminating likely causative factors and long term regimental antibiotics administration.Conclusion: This case highlights a rare neurological presentation of S. salivarius infection with a mixed aetiology of spontaneous pneumocephalus. This case features an atypical complication associated with CPAP use, and to our knowledge is the first case to be associated with sinus wall osteomyelitis. Recognition of the clinical features and risk factors for spontaneous pneumocephalus -while rare-serve to broaden our clinical index of suspicion when presented with patients experiencing neurological deficit. Information from this case may also aid in improving prevention, early diagnosis, and future management. [ABSTRACT FROM AUTHOR]

Objective: There is a significant interindividual variability in treatment outcomes in methadone maintenance treatment (MMT) for opioid use disorder (OUD). This prospective cohort study examines the impact of comorbid psychiatric disorders on continued illicit opioid use in patients receiving MMT for OUD. Methods: Data were collected from 935 patients receiving MMT in outpatient clinics between June 2011 and June 2015. Using linear regression analysis, we evaluated the impact of having a comorbid psychiatric disorder on continued illicit opioid use during MMT, adjusting for important confounders. The main outcome measure was percentage of opioid-positive urine screens for 6 months. We conducted a subgroup analysis to determine the influence of specific comorbid psychiatric disorders, including substance use disorders, on continued illicit opioid use. Results: Approximately 80% of participants had at least one comorbid psychiatric disorder in addition to OUD, and 42% of participants had a comorbid substance use disorder. There was no significant association between having a psychiatric comorbidity and continuing opioid use (P=0.248). Results from subgroup analysis, however, suggest that comorbid tranquilizer (ß=20.781, P,0.001) and cocaine (ß=6.344, P=0.031) use disorders are associated with increased rates of continuing opioid use. Conclusion: Results from our study may serve to guide future MMT guidelines. Specifically, we find that cocaine or tranquilizer use disorder, comorbid with OUD, places patients at high risk for poor MMT outcomes. Treatment centers may choose to gear more intensive therapy toward such populations. [ABSTRACT FROM AUTHOR]

Regardless of whether a randomized trial finds a statistically significant effect for an intervention or not, readers often wonder if the trial was large enough to be conclusive. To answer this question, we can estimate the required sample size for a trial by considering how commonly the outcome occurs, the smallest effect of clinical importance and the acceptable risk of falsely detecting or rejecting that effect. But when is a meta-analysis conclusive? We explain and illustrate the interpretation of Trial Sequential Analysis (TSA), a method increasingly used to answer this question. We conducted a conventional meta-analysis which suggested that, in adults undergoing cardiac surgery, remote ischemic preconditioning does not provide a statistically significant reduction in acute kidney injury (AKI) [12 trials, 4230 patients; relative risk 0.87 (95% confidence interval 0.74-1.02); P = 0.08; I2= 35%] or the risk of receiving acute dialysis [5 trials, 2111 patients; relative risk 1.15 (95% confidence interval 0.42-3.19); P = 0.78; I2 = 59%]. TSA demonstrates that as little as a 20% relative risk reduction in AKI is unlikely. Reliably finding effects on acute dialysis and smaller effects on AKI would require much more evidence. Notably, conventional meta-analyses conducted at one of the two earlier time points may have prematurely declared a statistically significant reduction in AKI, even though at no point in the TSA was there sufficient evidence to support such an effect. With this and other examples, we demonstrate that the TSA can prevent premature conclusions from meta-analyses. [ABSTRACT FROM AUTHOR]

Public health concerns for the independent management of obesity and suicidal behavior are rising. Emerging evidence suggests body weight plays an important role in quantifying the risk of suicide. In light of these findings, we aimed to clarify the association between body mass index (BMI) and suicidal behavior by systematically reviewing and evaluating the literature. Studies were identified by searching MEDLINE, EMBASE, PsycINFO, and CINAHL from inception to January 2015, supplemented by hand and grey literature searches. Study screening, data extraction, and risk of bias assessment were conducted in duplicate. We included 38 observational studies. Meta-analyses supported an inverse association between BMI and completed suicide. Pooled summary estimates demonstrated that underweight was significantly associated with an increased risk of completed suicide (HR = 1.21, 95% CI 1.07 to 1.36, p = .002), and obesity (HR = 0.71, 95% CI 0.56 to 0.89, p = .003) and overweight (HR = 0.78, 95% CI 0.75 to 0.82, p < .0001) were significantly associated with a decreased risk of completed suicide relative to normal weight. A qualitative summary of the literature demonstrated conflicting evidence regarding the association between BMI and attempted suicide and revealed no association between BMI and suicidal ideation. BMI may be used to aid the assessment of suicide risk, especially that of completed suicide. However, unmeasured confounders and systematic biases of individual studies limit the quality of evidence. [ABSTRACT FROM AUTHOR]

Background: Stepped wedge design (SWD) is a cluster randomized controlled trial (RCT) design that sequentially rolls out intervention to all clusters at varying time points. Being a relatively new design method, reporting quality has yet to be explored, and this review will seek to fill this gap in knowledge. Objectives: The objectives of this review are: 1) to assess the quality of SWD trial reports based on the CONSORT guidelines or CONSORT extension to cluster RCTs; 2) to assess the completeness of reporting of SWD trial abstracts using the CONSORT extension for abstracts; 3) to assess the reporting of sample size details in SWD trial reports or protocols; 4) to assess the completeness of reporting of SWD trial protocols according to SPIRIT guidelines; 5) to assess the consistency between the trial registration information and final SWD trial reports; and 6) to assess the consistency of what is reported in the abstracts and main text of the SWD trial reports. We will also explore factors that are associated with the completeness of reporting. Methods: We will search MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for all randomized controlled trials utilizing SWD. Details from eligible papers will be extracted in duplicate. Demographic statistics obtained from the data extraction will be analyzed to answer the primary objectives pertaining to the reporting quality of several aspects of a published paper, as well as to explore possible temporal trends and consistency between abstracts, trial registration information, and final published articles. Discussion: Findings from this review will establish the reporting quality of SWD trials and inform academics and clinicians on their completeness and consistency. Results of this review will influence future trials and improve the overall quality and reporting of SWD trials. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Concomitant opioid abuse is a serious problem among patients receiving methadone maintenance treatment (MMT) for opioid use disorder. This is an exploratory study that aims to identify predictors of the length of time a patient receiving MMT for opioid use disorder remains abstinent (relapse-free). METHODS: Data were collected from 250 MMT patients enrolled in addiction treatment clinics across Southern Ontario. The impact of certain clinical and socio-demographic factors on the outcome (time until opioid relapse) was determined using a Cox proportional hazard model. RESULTS: History of injecting drug use behavior (hazard ratio (HR): 2.26, P = 0.042), illicit benzodiazepine consumption (HR: 1.07, P = 0.002), and the age of onset of opioid abuse (HR: 1.10, P < 0.0001) are important indicators of accelerated relapse among MMT patients. Conversely, current age is positively associated with duration of abstinence from illicit opioid use, serving as a protective factor against relapse (HR: 0.93, P = 0.003). CONCLUSION: This study helps to identify patients at increased risk of relapse during MMT, allowing health care providers to target more aggressive adjunct therapies toward high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Despite the growing numbers of men and women with opioid use disorder in Canada, sex-specific issues in treatment have not been re-examined in the current population of patients with opioid addiction. We aimed to evaluate sex differences in substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid use disorder in Ontario, Canada. Methods: We recruited 503 participants with opioid dependence disorder receiving methadone maintenance treatment. We collected data on demographics, treatment characteristics, psychiatric history, addiction severity, and drug use patterns through urinalysis. We performed adjusted univariate analyses and logistic regression to identify distinct factors affecting men and women. Results: Among our sample of 54 % (n = 266) men and 46 % women (n = 226) with mean age 38.3 years, less than half of participants were employed (35.6 %) and married (31.8 %) and had completed a high school education (27.9 %). Compared to men, women had frequent physical and psychological health problems, family history of psychiatric illness, and childcare responsibilities and began using opioids through a physician prescription. Men had higher rates of employment, cigarette smoking, and cannabis use compared to women. Conclusions: Our results have revealed different patterns of substance use, health, and social functioning among men and women currently receiving methadone treatment for opioid addiction in Ontario, Canada. This information can be used to develop an integrative treatment regimen that caters to the individual needs of men and women, as well as to inform methadone treatment protocols to include specialized services (including vocational counseling, childcare and parenting assistance, medical assistance, relationship or domestic violence counseling, etc.) and increase their availability and accessibility on a larger scale. [ABSTRACT FROM AUTHOR]

Background: Eligibility criteria that result in the exclusion of a substantial number of patients from randomized trials jeopardize the generalizability of treatment effect to much of the clinical population. This is important when evaluating opioid substitution and antagonist therapies (OSATs), especially given the challenges associated with treating the opioid-dependent population. We aimed to identify OSAT trials' eligibility criteria, quantify the percentage of the clinical population excluded by these criteria, and determine how OSAT guidelines incorporate evidence from these trials.Methods: We performed a systematic review to identify the eligibility criteria used across trials. We searched Medline, EMBASE, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry (CTR), World Health Organization International CTR Platform Search Portal, and the National Institutes of Health CTR databases from inception to January 1, 2014. To quantify the effect of trials' eligibility criteria on generalizability, we applied these criteria to data from an observational study of opioid-dependent patients (n = 394). We then accessed the Canadian, American, British, and World Health Organization (WHO) OSAT guidelines to evaluate how evidence is used in the recommendations.Results: Among the 60 trials identified the majority (≥50 % of trials) exclude patients with psychiatric (60 %) and physical comorbidity (51.7 %). Additionally, we found 19 trials exclude patients with current alcohol/substance-use problems (31.7 %), and 29 (48.3 %) exclude patients taking psychotropic medications. These criteria were restrictive and in some cases rendered 70 % of the observational sample ineligible. North American OSAT guidelines made strong recommendations supported by evidence with poor generalizability. National Institute of Health and Care Excellence (NICE) and WHO guidelines for opioid misuse provide a critical assessment of the literature used to inform their recommendations.Conclusions: Trials assessing OSATs often exclude patients with concurrent disorders. If the excluded patients respond differently to treatment, results from these trials are likely to overestimate the true effectiveness of OSATs. North American guidelines should consider these limitations when drafting clinical recommendations. [ABSTRACT FROM AUTHOR]

Background: The heritability of opioid use disorder has been widely investigated; however, the influence of specific genes on methadone treatment outcomes is not well understood. The association between response to methadone treatment and genes that are involved in substance use behaviors and reward mechanisms is poorly understood, despite evidence suggesting their contribution to opioid use disorder. The aim of this study was to investigate the effect of brain-derived neurotrophic factor (BDNF) and dopamine receptor D2 (DRD2) polymorphisms on continued opioid use among patients on methadone treatment for opioid use disorder. Methods: BDNF 196G>A (rs6265) and DRD2-241A>G (rs1799978) genetic variants were examined in patients with opioid use disorder who were recruited from methadone treatment clinics across Southern Ontario, Canada. We collected demographic information, substance use history, blood for genetic analysis, and urine to measure opioid use. We used regression analysis to examine the association between continued opioid use and genetic variants, adjusting for age, sex, ethnicity, methadone dose, duration in treatment, and number of urine screens. Results: Among 240 patients treated with methadone for opioid use disorder, 36.3 percent (n = 87) and 11.3 percent (n = 27) had at least one risk allele for rs6265 and rs1799978, respectively. These genetic variants were not significantly associated with continued opioid use while on methadone maintenance treatment [rs6265: odds ratio (OR) = 1.37, 95 % confidence interval (CI) = 0.792, 2.371, p = 0.264; rs1799978: OR 1.27, 95 % CI 0.511, 3.182, p = 0.603]. Conclusions: Despite an association of BDNF rs6265 and DRD2 rs1799978 with addictive behaviors, these variants were not associated with continued illicit opioid use in patients treated with methadone. Problematic use of opioids throughout treatment with methadone may be attributed to nongenetic factors or a polygenic effect requiring further exploration. Additional research should focus on investigating these findings in larger samples and different populations. [ABSTRACT FROM AUTHOR]