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Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse. To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment). Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms. We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05-1.00, p = 0.03) with minimal heterogeneity (I(2) = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27-2.61, p = 0.02) however significant heterogeneity was observed (I(2) = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response. Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers.

Multimorbidity, the presence of two or more (2+) chronic conditions, presents significant challenges for healthcare delivery, particularly among populations with opioid use disorder (OUD). Multimorbidity patterns among individuals with OUD are not well established, and minimal research exists examining the impact of clustering methods on identifying these patterns. Our study aimed to assess multimorbidity prevalence, explore associated sociodemographic and clinical characteristics, and determine multimorbidity patterns using hierarchical cluster analysis (HCA) and K-means clustering among people receiving treatment for OUD in Ontario, Canada between 2011 and 2021. Data from two prospective cohort studies were merged and linked to Ontario provincial health administrative databases. We identified 16 chronic conditions, used in prior research examining multimorbidity in Ontario, using ICD-10-CA diagnostic codes and the diagnostic codes of physician billing claims using a 2-year lookback. Multimorbidity was defined as the presence of 2+ of the above conditions, excluding the diagnosis of OUD. We conducted a retrospective cohort study, following the participants for eight years in the data holdings to ascertain the prevalence of multimorbidity. Sociodemographic and clinical characteristics were analyzed using modified Poisson regression models, and multimorbidity patterns were identified through HCA and K-means clustering. Among 3,430 people with OUD, 32.5% (n = 1,114, 95% confidence interval (CI)=30.9, 34.1) experienced multimorbidity over an eight-year period, with older age (Prevalence Ratio (PR)=3.39, 95% CI = 2.36, 4.87) and unemployment (PR = 1.31, 95% CI = 1.13, 1.54) associated with increased prevalence. HCA identified six distinct disease clusters, whereas K-means clustering identified four clusters. Both methods identified groupings of cardiovascular (coronary syndrome), cardiometabolic (diabetes, hypertension), and respiratory (chronic obstructive pulmonary disease) diseases, reflecting shared comorbidities among people with OUD. Our findings highlight the substantial burden of multimorbidity among populations with OUD, and the importance of considering sociodemographic factors in understanding multimorbidity prevalence. Moreover, the choice of clustering method significantly influences the identification and interpretation of multimorbidity patterns, with HCA providing more clinically meaningful groupings compared to K-means clustering. Our findings highlight the need for clinicians to tailor care plans and for policymakers to prioritize integrated healthcare delivery strategies to address the complex health needs of people with OUD.

Individuals with opioid use disorder (OUD) have a high prevalence of co-occurring mental health disorders; however, there exists little information on mental health service use for this population. We aimed to determine the prevalence of non-substance use-related mental health emergency department (ED) visits, hospitalizations, and outpatient physician visits for individuals receiving treatment for OUD over one year. We also explored individual-level characteristics associated with mental health care service use and estimated the costs of this care. We linked observational cohort data collected from 3,430 individuals receiving treatment for OUD in Ontario, Canada, with health administrative records available for all individuals enrolled in Ontario's public health insurance program. Eligible participants were receiving medication treatment for OUD and were recruited between 2011 and 2021 Starting on the day of cohort enrolment, we included health service data for up to 12 months. We identified ED visits and hospitalizations for non-substance use-related mental health disorders using ICD-10-CA diagnostic codes. Outpatient mental health visits to primary care providers and psychiatrists were ascertained by examining the diagnostic codes of physician billing claims. We used logistic regression to explore the association between demographic and clinical factors of interest and mental health-related ED visits or hospitalizations. Mean one-year mental healthcare costs, calculated in 2022 Canadian dollars, were estimated. We fit a two-part zero-inflated negative binomial model to explore the association between factors of interest and healthcare costs. Altogether, 14.9% of individuals had mental health-related acute care ED visits or hospitalizations and 37.3% had outpatient mental health visits during the follow up period. For participants with at least one visit, we determined the mean number of ED visits (1.93, standard deviation [SD] = 2.15), hospitalizations (1.46, SD = 1.05), primary care visits (3.51, SD = 4.31), and psychiatry visits (4.04, SD = 4.73). Lower odds of ED use and hospitalization were associated with older age (46+ compared to less than 25 years: odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.29, 0.63) and being employed (OR 0.48, 95% CI 0.37, 0.61). Higher odds of ED use and hospitalization was associated with positive opioid urine drug screens (50% positive urine drug screens compared to 0%: OR 1.45, 95% CI 1.05, 2.01), having more comorbid conditions (7+ health conditions compared to 0-2 health conditions: OR 3.76, 95% CI 2.60, 5.44), and receipt of outpatient mental healthcare (OR 2.38, 95% CI 1.95, 2.92) were associated with higher odds of ED visits or hospitalizations. Mean one-year mental healthcare costs for individuals receiving ED visits or hospitalizations totaled $9,117.80 (95% CI 7,372.90, 10,862.70) per person. Mean one-year costs for individuals with outpatient mental healthcare alone totaled $382.30 (95% CI 343.20, 421.30) per person. Individuals receiving treatment for OUD receive care in EDs, inpatient units, and outpatient clinics for mental health conditions other than substance use-related diagnoses. Healthcare costs were considerably higher for those receiving acute care treatment for mental health conditions. Studying integrated mental health and substance use disorder treatment in the outpatient setting should be a priority to bolster care for this population.

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.

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. 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. 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 ( =0.248). Results from subgroup analysis, however, suggest that comorbid tranquilizer (β=20.781, <0.001) and cocaine (β=6.344, =0.031) use disorders are associated with increased rates of continuing opioid use. 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.

Background/AimThe prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear.MethodWe identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations.ResultThere were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09–1.16]), 53% lower in Blacks (RR: 0.47 [0.45–0.49]) and 5% lower among other racial minorities (0.95 [0.91–0.99]). The rate was higher among females (RR:4.02 [3.93–4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03–2.10] and 1.33 [0.96–1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites.ConclusionThe hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.

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Background Given the complex nature of opioid addiction treatment and the rising number of available opioid substitution and antagonist therapies (OSAT), there is no ‘gold standard’ measure of treatment effectiveness, and each successive trial measures a different set of outcomes which reflect success in arbitrary or opportune terms. We sought to describe the variation in current outcomes employed across clinical trials for opioid addiction, as well as determine whether a discrepancy exists between the treatment targets that patients consider important and how treatment effectiveness is measured in the literature. Methods We searched nine commonly used databases (e.g., EMBASE, MEDLINE) from inception to August 1, 2015. Outcomes used across trials were extracted and categorized according to previously established domains. To evaluate patient-reported goals of treatment, semi-structured interviews were conducted with 18 adults undergoing methadone treatment. Results We identified 60 trials eligible for inclusion. Once outcomes were categorized into eight broad domains (e.g., abstinence/substance abuse), we identified 21 specific outcomes with furthermore 53 subdomains and 118 measurements. Continued opioid use and treatment retention were the most commonly reported measures (46%, n  = 28). The majority of patients agreed that abstinence from opioids was a primary goal in their treatment, although they also stressed goals under-reported in clinical trials. Conclusions There is inconsistency in the measures used to evaluate the effectiveness of OSATs. Individual and population level decision making is being guided by a standard of effect considered useful to researchers yet in direct conflict with what patients deem important. Trial registration PROSPERO, CRD42013006507.

ObjectivesTo compare the effectiveness of buprenorphine-naloxone (bup/nal) and methadone maintenance therapy (MMT) in the treatment of patients with opioid use disorder (OUD) during the fentanyl era.DesignSecondary analysis of prospective cohort study data.SettingData for the study were collected from 54 clinical sites across Ontario, Canada, between May 2018 and January 2023.ParticipantsTo be included in the present study, participants had to be at least 16 years of age, have provided written informed consent and be receiving either MMT or bup/nal therapy for OUD. This study includes data from 2601 participants, of whom 2068 were receiving MMT and 533 were receiving bup/nal for OUD. The mean age of participants was 39.4 years (SD: 10.9), and 45% were female.InterventionsMMT or bup/nal treatment for OUD.Outcome measuresWe employed a propensity score matched analysis to compare treatment outcomes among patients receiving MMT compared with bup/nal. We used ongoing illicit opioid use as an indicator of treatment outcome. We considered participants with >50% of urine drug screens in the past 12 months positive for non-prescribed opioids to be ‘non-responders’. We conducted subgroup analyses to identify whether treatment type was associated with ongoing non-prescribed opioid use among patients with and without a history of intravenous drug use (IVDU), and whether treatment type was associated with retention in treatment.ResultsEight per cent of patients on bup/nal were considered non-responders, compared with 11.9% of patients on MMT. We did not find a statistically significant association between treatment type and treatment response. However, we did find that patients on MMT were more likely to stay in treatment for 12 months (OR 1.79, 95% CI 1.45 to 2.22, p<0.001). We also found that, among patients without a history of IVDU, those on MMT were more likely to continue using non-prescribed opioids, compared with those on bup/nal (OR 1.72, 95% CI 1.07 to 2.77, p=0.023).ConclusionsAmong a cohort of patients with OUD receiving treatment during the fentanyl era, we find that there is no statistically significant difference in ongoing non-prescribed opioid use between patients receiving MMT compared with bup/nal. Future studies should aim to further compare treatment effectiveness using patient-centred outcomes and pragmatic trial designs.