Excess overdose mortality immediately following transfer of patients and their care as well as after cessation of opioid substitution therapy

Aims

To investigate clustering of all‐cause and overdose deaths after a transfer of patients and their care to alternative treatment provider and after the end of opioid substitution therapy (OST) in opioid‐dependent individuals in specialist addiction treatment.

Design, Setting and Participants

Mortality data were identified within a sample of 5335 patients with opioid use disorder who had received OST treatment between 1 April 2008 and 31 December 2013 from a large mental health‐care provider in the United Kingdom. We investigated the circumstances and distribution of the 332 deaths identified within the observation window with a specific focus on overdose deaths (n = 103) after a planned discharge, dropout and transfer between services.

Measurements

Crude mortality rates for overdose mortality 14 days, 28 days and more than 1 month after the end of treatment/transfer for overdose mortality.

Findings

Of 47 individuals who died from overdose after having been transferred between services, nine died during the first 2 weeks [crude mortality rate (CMR) = 136.4, 95% confidence interval (CI) = 64.3–243.1] and a further five died during the first month post‐transfer (CMR= 79.5, 95% CI = 44.2–129.7). Of the 32 individuals who died from overdose after planned OST cessation, five died during the first 2 weeks (CMR = 151.5, 95% CI = 51.1–319.0) and a further four died during the first month post‐discharge (CMR = 82.6, 95% CI = 38.4–151.0).

Conclusions

In the United Kingdom, opioid‐dependent people who are transferred to an alternative treatment provider for continuation of their opioid substitution therapy experience high overdose mortality rates, with substantially higher rates during the first month (especially during the first 14 days) following transfer.     

Extended‐release injectable naltrexone for opioid use disorder: a systematic review

Aims

To review systematically the published literature on extended‐release naltrexone (XR‐NTX, Vivitrol^®), marketed as a once‐per‐month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR‐NTX; (2) what are adherence rates to XR‐NTX; and (3) does XR‐NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined.

Methods

We searched PubMed and used Google Scholar for forward citation searches of peer‐reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR‐NTX were included.

Results

We identified and included 34 studies. Pooled estimates showed that XR‐NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5–70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0–90.1%); 44.2% (95% CI = 33.1–55.9%) of individuals took all scheduled injections of XR‐NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6‐month rates: 46.7%, 95% CI = 34.5–59.2% versus 10.5%, 95% CI = 4.6–22.4%, respectively). Compared with referral to treatment, XR‐NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR‐NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR‐NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification.

Conclusions

Many individuals intending to start extended‐release naltrexone (XR‐NTX) do not and most who do start XR‐NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR‐NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.     

The short‐term impact of the alcohol act on alcohol‐related deaths and hospital admissions in Scotland: a natural experiment

Background and aim

The introduction of the Alcohol Act in Scotland on 1 October 2011, which included a ban on multi‐buy promotions, was probably associated with a fall in off‐trade alcohol sales in the year after its implementation. The aim of this study was to test if the same legislation was associated with reduced levels of alcohol‐related deaths and hospital admissions in the 3‐year period after its introduction.

Design

A natural experiment design using time–series data to assess the impact of the Alcohol Act legislation in Scotland. Comparisons were made with unexposed populations in the rest of Great Britain.

Setting

Scotland with comparable data obtained for geographical control groups in other parts of Great Britain.

Participants

For alcohol‐related deaths, a total of 17 732 in Scotland and 88 001 in England and Wales throughout 169 4‐week periods between January 2001 and December 2013 and for alcohol‐related hospital admissions, a total of 121 314 in Scotland and 696 892 in England throughout 182 4‐week periods between January 2001 and December 2014.

Measurements

Deaths and hospital admissions in Scotland and control groups that were wholly attributable to alcohol for consecutive 4‐week periods between January 2001 and December 2014. Data were obtained by age, sex and area‐based socio‐economic position.

Findings

There was no evidence to suggest that the Alcohol Act was associated with changes in the overall rate of alcohol‐related deaths [incidence rate ratio (IRR) = 0.99, 95% confidence interval (CI) = 0.91–1.07)] or hospital admissions (IRR = 0.98, 95% CI = 0.95–1.02) in Scotland. In control group analyses, the pseudo intervention variable was not associated with a change in alcohol‐related death rates in England/Wales (IRR = 0.99, 95% CI = 0.95–1.02), but was associated with an increase in alcohol‐related hospital admission rates in England (IRR = 1.05, 95% CI = 1.03–1.07). In combined models, the interaction analysis did not provide support for a ‘net effect’ of the legislation on alcohol‐related deaths in Scotland compared with England/Wales (IRR 0.99, 95% CI = 0.95–1.04), but suggested a net reduction in hospital admissions for Scotland compared with England (IRR = 0.93, 95% CI = 0.87–0.98).

Conclusion

The implementation of the Alcohol Act in Scotland has not been associated clearly with a reduction in alcohol‐related deaths or hospital admissions in the 3‐year period after it was implemented in October 2011.     

Needle and syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta‐analysis

Aims

To estimate the effects of needle and syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of hepatitis C virus (HCV) in people who inject drugs (PWID).

Methods

Systematic review and meta‐analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within the last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥ 100% coverage (receiving sufficient or greater number of needles and syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non‐randomized studies tool. Random‐effects models were used in meta‐analysis.

Results

We identified 28 studies (n = 6279) in North America (13), United Kingdom (five), Europe (four), Australia (five) and China (one). Studies were at moderate (two), serious (17) critical (seven) and non‐assessable risk of bias (two). Current OST is associated with 50% [risk ratio (RR) =0.50, 95% confidence interval (CI) = 0.40–0.63] reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I² = 0, P = 0.889). Weaker evidence was found for high NSP coverage (RR = 0.79, 95% CI = 0.39–1.61) with high heterogeneity (I² = 77%, P = 0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR = 0.44, 95% CI = 0.24–0.80) with low heterogeneity (I² = 12.3%, P = 0.337), but not in North America (RR = 1.58, I² = 89.5%, P = < 0.001). Combined OST/NSP is associated with a 74% reduction in HCV acquisition risk (RR = 0.26, 95% CI = 0.07–0.89, I² = 80% P = 0.007). According to Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria, the evidence on OST and combined OST/NSP is low quality, while NSP is very low.

Conclusions

Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle and syringe programmes (NSP). There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe.     

Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES

Aims

To assess (1) how far the efficacies of front‐line smoking cessation pharmacotherapies vary as a function of smoker characteristics and (2) associations between these characteristics and success of smoking cessation attempts.

Design

Prospective correlational study in the context of a double‐blind randomized trial. The outcome was regressed individually onto each covariate after adjusting for treatment, and then a forward stepwise model constructed. Treatment moderator effects of covariates were tested by treatment × covariate interactions.

Setting

Health service facilities in multiple countries.

Participants

Data came from 8120 smokers willing to make a quit attempt, randomized to varenicline, bupropion, nicotine replacement therapy (NRT) or placebo in Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) between 30 November 2011 and 13 January 2015.

Measurements

Smoker characteristics measured at baseline were country, psychiatric history, sex, age, body mass index (BMI), ethnic group, life‐time suicidal ideation/behaviour, anxiety, depression, aggression, psychotropic medication, history of alcohol/substance use disorder, age of starting smoking, cigarette dependence [Fagerström Test for Cigarette Dependence (FTCD)] and prior use of study medicines. Outcome was biochemically confirmed continuous abstinence at weeks 9–24 from start of treatment.

Findings

No statistically significant treatment × covariate interactions were found. Odds of success were associated independently positively with age [odds ratio (OR) = 1.01; 95% confidence interval (CI) = 1.00, 1.01], BMI (1.01; 95% CI = 1.00, 1.02) and age of starting smoking (1.03; 95% CI = 1.02, 1.04). Odds were associated independently negatively with US (versus non‐US) study site (0.53; 95% CI = 0.46, 0.61), black (versus white) ethnic group (0.57; 95% CI = 0.45, 0.72), mood disorder (0.85; 95% CI = 0.73, 0.99), anxiety disorder (0.71; 95% CI = 0.55, 0.90) and psychotic disorder (0.73; 95% CI = 0.50, 1.07), taking psychotropic medication (0.81; 95% CI = 0.68, 0.95), FTCD (0.89; 95% CI = 0.87, 0.92) and previous use of NRT (0.78; 95% CI = 0.67, 0.91).

Conclusions

While a range of smoker characteristics—including psychiatric history, cigarette dependence and prior use of nicotine replacement therapy (NRT)—are associated with lower cessation rates, they do not substantially influence the efficacy of varenicline, bupropion or NRT.     

Effects of opiate substitution treatment on mortality for opioids users: a systematic review and meta-analysis

Background

Opioid dependence is associated with high risk of premature death. Opiate-substitution treatment (OST) is the major treatment in community for opioid dependence worldwide. We aimed to estimate crude mortality rates (CMRs) and the effects of OST on mortality risk by meta-analysis.

Effects of comorbid substance use disorders on outcomes in a Housing First intervention for homeless people with mental illness

Background and Aims

Evidence supports the effectiveness of Housing First (HF) programmes for people who are experiencing homelessness and mental illness; however, questions remain about its use in people with comorbid substance use disorders (SUD). The aim of this project was to test whether SUD modifies the effectiveness of an HF intervention.

Design

Secondary analysis of data from a randomized controlled trial of HF versus treatment‐as‐usual (TAU) with 24‐month follow‐up, comparing those with and without SUD at trial entry.

Setting

Vancouver, Toronto, Winnipeg, Moncton and Montreal, Canada.

Participants

A total of 2154 participants recruited from 2009 to 2013 and randomized to HF versus TAU (67% male, mean age 40.8 ± 11.2, 25% ethno‐cultural minority). All were homeless and had a mental disorder at baseline; 35% reported symptoms consistent with SUD.

Intervention

Housing paired with Intensive Case Management or Assertive Community Treatment.

Measurements

Primary outcomes were days housed and community functioning. Secondary outcomes were general and health‐related quality of life and mental health symptoms. Predictors were SUD status crossed with intervention group (HF versus TAU).

Findings

People with SUD in both the HF and TAU groups spent less time in stable housing, but the effect of HF did not vary by SUD status [odds ratio (OR) = 1.17, 95% confidence interval (CI) = ?0.77, 1.76]. Similarly, there was no difference between those with and without SUD in the effect of HF (over TAU) on community functioning (b = 0.75, 95% CI = ?0.36, 1.87), quality of life (b = ?1.27, 95% CI = ?4.17, 1.63), health‐related quality of life (b = ?0.01, 95% CI = ?0.03, 0.02) or mental health symptoms (b = 0.43, 95% CI = ?0.99, 1.86).

Conclusions

Housing First programs in Canada are equally effective in people with and without comorbid substance use disorder (SUD). Overall, the intervention appears to be able to engage people with SUD and is reasonably successful at housing them, without housing being contingent upon abstinence or treatment.     

Childhood traumatic experiences and the association with marijuana and cocaine use in adolescence through adulthood

Background and aims

Examination of longitudinal relationships between childhood traumatic experiences and drug use across the life‐course at the national level, with control of confounding by other forms of trauma, is needed. We aimed to estimate the prevalence of nine typologies of childhood traumas and the cumulative number experienced, correlation between traumas and associations between individual and cumulative number of traumas with drug use during adolescence, emerging adulthood and adulthood.

Design

Secondary data analysis using the National Longitudinal Study of Adolescent to Adult Health.

Setting

United States.

Participants

A nationally representative sample of individuals in grades 7–12 (aged 11–21 years) during 1994–95, who were re‐interviewed during emerging adulthood (2001–02; aged 18–28) and adulthood (2007–08; aged 24–34). The analytical sample comprised 12 288 participants with data at all three waves.

Measurements

Nine typologies of childhood traumas: neglect; emotional, physical and sexual abuse; parental incarceration and binge drinking; and witnessing, being threatened with and experiencing violence. Indicators of each were summed to measure cumulative dose. Outcomes were marijuana and cocaine use during adolescence, emerging adulthood and adulthood.

Findings

Approximately half experienced at least one childhood trauma; traumas were not highly correlated. We observed a dose–response relationship between the number of traumas and drug use in adolescence [marijuana, adjusted odds ratio (aOR) one trauma versus none = 1.65, 95% confidence interval (CI) = 1.42, 1.92; two traumas = 2.58, 95% CI = 2.17, 3.06; ≥ four traumas = 6.92, 95% CI = 5.17, 9.26; cocaine, aOR one trauma = 1.87, 95% CI = 1.23, 2.84; two traumas = 2.80, 95% CI = 1.74, 4.51; ≥ four traumas = 9.54, 95% CI = 5.93, 15.38]. Similar dose–response relationships with drug use were observed in emerging adulthood and adulthood. Each individual trauma was associated independently with either marijuana or cocaine use in adolescence, emerging adulthood and/or adulthood.

Conclusions

Childhood trauma is prevalent in the United States, and individual types as well as the total number experienced are associated significantly with marijuana and cocaine use throughout the life‐course.     

Neonatal outcomes after fetal exposure to methadone and buprenorphine: national registry studies from the Czech Republic and Norway

Background and Aims

Opioid maintenance treatment (OMT) is recommended to opioid‐dependent females during pregnancy. However, it is not clear which medication should be preferred. We aimed to compare neonatal outcomes after prenatal exposure to methadone (M) and buprenorphine (B) in two European countries.

Design

Nation‐wide register‐based cohort study using personalized IDs assigned to all citizens for data linkage.

Setting

The Czech Republic (2000–14) and Norway (2004–13). [Correction added after online publication on 26 April 2018: The Czech Republic (2000–04) corrected to (2000–14).]

Participants

Opioid‐dependent pregnant Czech (n = 333) and Norwegian (n = 235) women in OMT who received either B or M during pregnancy and their newborns.

Measurements

We linked data from health registries to identify the neonatal outcomes: gestational age, preterm birth, birth weight, length and head circumference, small for gestational age, miscarriages and stillbirth, neonatal abstinence syndrome (NAS) and Apgar score. We performed multivariate linear regression and binary logistic regression to explore the associations between M and B exposure and outcomes. Regression coefficient (β) and odds ratio (OR) were computed.

Findings

Most neonatal outcomes were more favourable after exposure to B compared with M, but none of the differences was statistically significant. For instance, in the multivariate analysis, birth weight was β = 111.6 g [95% confidence interval (CI) = ?10.5 to 233.6 and β = 83.1 g, 95% CI = ?100.8 to 267.0] higher after B exposure in the Czech Republic and Norway, respectively. Adjusted OR of NAS for B compared with M was 0.94 (95% CI = 0.46–1.92) in the Norwegian cohort.

Conclusions

Two national cohorts of women receiving opioid maintenance treatment during pregnancy showed small but not statistically significant differences in neonatal outcomes in favour of buprenorphine compared with methadone.

     

Prognosis for older people at presentation to emergency department based on frailty and aggregated vital signs

Background

Risk stratification for older people based on aggregated vital signs lack the accuracy to predict mortality at presentation to the Emergency Department (ED). We aimed to develop and internally validate the Frailty adjusted Prognosis in ED tool (FaP-ED) for 30-day mortality combining frailty and aggregated vital signs.

Methods

Single-center prospective cohort of undifferentiated ED patients aged 65 or older, consecutively sampled upon ED presentation from a tertiary Emergency Center. Vital signs were aggregated using the National Early Warning Score (NEWS) as a measure of illness or injury severity and frailty was assessed with the Clinical Frailty Scale (CFS). The FaP-ED was constructed by combining NEWS and CFS in multivariable logistic regression. The primary outcome was 30-day mortality. Measures of discrimination and calibration were assessed to evaluate predictive performance and internally validated using bootstrapping.

Results

2250 patients were included, 67 (1.8%) were omitted from analyses due to missing CFS, loss to follow-up, or terminal illness. Thirty-day mortality rate was 5.4% (N = 122, 95% CI = 4.5%–6.4%). Median NEWS was 1 (Inter-Quartile Range (IQR): 0–3) and median CFS was 4 (IQR: 3–5). The Area Under Receiver Operating Characteristic (AUROC) for FaP-ED was 0.86 (95% CI = 0.83–0.90). This was significantly higher than NEWS (0.81, 95% CI = 0.77–0.85, DeLong: Z = 3.5, p < 0.001) or CFS alone (0.82, 95% CI = 0.78–0.86, DeLong: Z = 4.4, p < 0.001). Bootstrapped estimates of FaP-ED AUROC, calibration slope, and intercept were 0.86, 0.95, and −0.09, respectively, suggesting internal validity. A decision-threshold of CFS 5 and NEWS 3 was proposed based on qualitative comparison of positive Likelihood Ratio at all relevant FaP-ED cutoffs.

Conclusion

Combining aggregated vital signs and frailty accurately predicted 30-day mortality at ED presentation and illustrated an important clinical interaction between frailty and illness severity. Pending external validation, the Fap-ED operationalizes the concept of such “geriatric urgency” for the ED setting.     

Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients

Aims To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet. Design Patients were randomized to receive buprenorphine or methadone over a 13‐week treatment period in a double‐blind, double‐dummy trial. Setting Three methadone clinics in Australia. Participants Four hundred and five opioid‐dependent patients seeking treatment. Intervention Patients received buprenorphine or methadone as indicated clinically using a flexible dosage regime. During weeks 1–6, patients were dosed daily. From weeks 7–13, buprenorphine patients received double their week 6 dose on alternate days. Measurements Retention in treatment, and illicit opioid use as determined by urinalysis. Self‐reported drug use, psychological functioning, HIV‐risk behaviour, general health and subjective ratings were secondary outcomes. Findings Intention‐to‐treat analyses revealed no significant difference in completion rates at 13 weeks. Methadone was superior to buprenorphine in time to termination over the 13‐week period (Wald χ² = 4.371, df = 1, P = 0.037), but not separately for the single‐day or alternate‐day dosing phases. There were no significant between‐group differences in morphine‐positive urines, or in self‐reported heroin or other illicit drug use. The majority (85%) of the buprenorphine patients transferred to alternate‐day dosing were maintained in alternate‐day dosing. Conclusions Buprenorphine did not differ from methadone in its ability to suppress heroin use, but retained approximately 10% fewer patients. This poorer retention was due possibly to too‐slow induction onto buprenorphine. For the majority of patients, buprenorphine can be administered on alternate days.     

Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment

Aim   To compare retention in treatment and mortality among people entering methadone and buprenorphine treatment for opioid dependence.
Data sources   The Pharmaceutical Drugs of Abuse System (PHDAS) database records start- and end-dates of all episodes of methadone and buprenorphine treatment in New South Wales, and the National Death Index (NDI) records all reported deaths.
Methods   Data linkage study. First entrants to treatment between June 2002 and June 2006 were identified from the PHDAS database. Retention in treatment was compared between methadone and buprenorphine. Names were linked to the NDI database, and 'good matches' were identified. Deaths were classified as occurring during induction, maintenance and either post-methadone or post-buprenorphine, depending on the latest episode of treatment prior to death. The numbers of inductions into treatment, of total person-years spent in each treatment, and person-years post-methadone or buprenorphine, were calculated. Risk of death in different periods, and different treatments, was analysed using Poisson regression.
Results   A total of 5992 people entered their first episode of treatment—3349 (56%) on buprenorphine, 2643 on methadone. Median retention was significantly longer in methadone (271 days) than buprenorphine (40 days). During induction, the risk of death was lower for buprenorphine (relative risk = 0.114, 95% confidence interval = 0.002–0.938, P  = 0.02, Fisher's exact test). Risk of death was lowest during treatment, significantly higher in the first 12 months after leaving both methadone and buprenorphine. Beyond 12 months after leaving treatment, risk of death was non-significantly higher than during treatment.
Conclusions   Buprenorphine was safer during induction. Despite shorter retention in treatment, buprenorphine maintenance was not associated with higher risk of death.     

Exposure to opioid maintenance treatment reduces long-term mortality

AIMS: To (i) examine the predictors of mortality in a randomized study of methadone versus buprenorphine maintenance treatment; (ii) compare the survival experience of the randomized subject groups; and (iii) describe the causes of death. DESIGN: Ten-year longitudinal follow-up of mortality among participants in a randomized trial of methadone versus buprenorphine maintenance treatment. SETTING: Recruitment through three clinics for a randomized trial of buprenorphine versus methadone maintenance. PARTICIPANTS: A total of 405 heroin-dependent (DSM-IV) participants aged 18 years and above who consented to participate in original study. MEASUREMENTS: Baseline data from original randomized study; dates and causes of death through data linkage with Births, Deaths and Marriages registries; and longitudinal treatment exposure via State health departments. Predictors of mortality examined through survival analysis. FINDINGS: There was an overall mortality rate of 8.84 deaths per 1000 person-years of follow-up and causes of death were comparable with the literature. Increased exposure to episodes of opioid treatment longer than 7 days reduced the risk of mortality; there was no differential mortality among methadone versus buprenorphine participants. More dependent, heavier users of heroin at baseline had a lower risk of death, and also higher exposure to opioid treatment. Older participants randomized to buprenorphine treatment had significantly improved survival. Aboriginal or Torres Strait Islander participants had a higher risk of death. CONCLUSIONS: Increased exposure to opioid maintenance treatment reduces the risk of death in opioid-dependent people. There was no differential reduction between buprenorphine and methadone. Previous studies suggesting differential effects may have been affected by biases in patient selection.     

Buprenorphine versus methadone maintenance treatment in an ambulant setting: a health-related quality of life assessment

Background To compare the effects on quality of life (QOL) of oral methadone with sublingual buprenorphine. Methods We performed an open‐label, non‐randomized, two‐site (methadone–buprenorphine) study. During 6 months we assessed the quality of life status of 53 opioid‐dependent patients admitted to a methadone or buprenorphine maintenance programme using the German version (Berlin Quality of Life Profile) of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opioid Withdrawal Scale. Five hundred and thirty urine screening tests were carried out randomly to detect additional consumption. Results Sixty‐seven opioid‐dependent subjects (38 on methadone and 29 on buprenorphine) were enrolled in the study, and 53 completed it (30 subjects treated with buprenorphine and 23 subjects with racemic methadone). The subjects were comparable on all baseline measures. At the first follow‐up (week 8), the buprenorphine‐maintained group showed significantly less additional consumption of opioids (P = 0.013) compared with the methadone group. Patients retained in the buprenorphine or methadone programme (week 24) showed no significant differences in all quality of life scores. At the end of the study period, the buprenorphine‐maintained group showed significantly less additional consumption of opioids (P = 0.001) and cocaine (P = 0.018) compared with the methadone group. The outcome measures for withdrawal symptoms after 24 weeks of treatment with buprenorphine showed slight advantages in stomach cramps, fatigue or tiredness, feelings of coldness and heart pounding. Conclusions These results suggest that buprenorphine treatment is as effective as methadone regarding effects on quality of life and withdrawal symptoms. Buprenorphine has the potential to reduce the harm caused by drug abuse. Further research is needed to determine if buprenorphine is more effective than methadone in particular subgroups of patients.     

Syncope,Hypotension, and Falls in the Treatment of Hypertension: Results from the Randomized Clinical Systolic Blood Pressure Intervention Trial

Objective

To determine predictors of serious adverse events (SAEs) involving syncope, hypotension, and falls, with particular attention to age, in the Systolic Blood Pressure Intervention Trial.

Design

Randomized clinical trial.

Setting

Academic and private practices across the United States (N = 102).

Participants

Adults aged 50 and older with a systolic blood pressure (SBP) of 130 to 180 mmHg at high risk of cardiovascular disease events, but without diabetes, history of stroke, symptomatic heart failure or ejection fraction less than 35%, dementia, or standing SBP less than 110 mmHg (N = 9,361).

Intervention

Treatment of SBP to a goal of less than 120 mmHg or 140 mmHg.

Measurements

Outcomes were SAEs involving syncope, hypotension, and falls. Predictors were treatment assignment, demographic characteristics, comorbidities, baseline measurements, and baseline use of cardiovascular medications.

Results

One hundred seventy‐two (1.8%) participants had SAEs involving syncope, 155 (1.6%) hypotension, and 203 (2.2%) falls. Randomization to intensive SBP control was associated with greater risk of an SAE involving hypotension (hazard ratio (HR) = 1.67, 95% confidence interval (CI) = 1.21–2.32, P = .002), and possibly syncope (HR = 1.32, 95% CI = 0.98–1.79, P = .07), but not falls (HR = 0.98, 95% CI = 0.75–1.29, P = .90). Risk of all three outcomes was higher for participants with chronic kidney disease or frailty. Older age was also associated with greater risk of syncope, hypotension, and falls, but there was no age‐by‐treatment interaction for any of the SAE outcomes.

Conclusions

Participants randomized to intensive SBP control had greater risk of hypotension and possibly syncope, but not falls. The greater risk of developing these events associated with intensive treatment did not vary according to age.     

A survey of tobacco dependence treatment guidelines content in 61 countries

Aims

To assess tobacco dependence treatment guidelines content in accordance with Article 14 of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) and its guidelines, and association between content and country income level.

Design

Cross‐sectional study.

Setting

On‐line survey from March to July 2016.

Participants

Contacts in 77 countries, including 68 FCTC Parties, six Signatories and three non‐Parties which had indicated having guidelines in previous surveys, or had not been surveyed before.

Measurements

A nine‐item questionnaire on guidelines content, key recommendations, writing and dissemination.

Findings

We received responses from contacts in 63 countries (82%); 61 had guidelines. The majority are for doctors (93%), primary care (92%) and nurses (75%). All recommend brief advice, 82% recording tobacco use in medical notes, 98% nicotine replacement therapy (NRT), 61% quitlines, 31% text messaging and 87% intensive specialist support, and 54% stress the importance of health‐care workers not using tobacco. Only 57% have a dissemination strategy, and 62% have not been updated for 5 or more years. Compared with high‐income countries, quitlines are less likely to be recommended in upper middle‐income countries guidelines [odds ratio (OR) = 0.15, 95% confidence interval (CI) = 0.04–0.61] and intensive specialist support in lower middle‐income countries guidelines (OR = 0.01, 95% CI = 0.00–0.20). Guidelines updating is associated positively with country income level (P = 0.027).

Conclusions

Although most tobacco dependence treatment guidelines in the 61 countries assessed in 2016 follow the World Health Organization's Framework Convention on Tobacco Control Article 14 recommendations and do not differ significantly by income level, improvements are needed in keeping guidelines up‐to‐date, applying good writing practices and developing a dissemination strategy.     

Preoperative atrial fibrillation and long-term survival after open heart surgery in a rural tertiary heart institute

Background

Preoperative atrial fibrillation (AF) is associated with increased morbidity and mortality after open heart surgery. However, the impact of preoperative AF on long-term survival after open heart surgery has not been widely examined in rural populations. Patients from rural regions are less likely to receive treatment for cardiac conditions and to have adequate medical insurance coverage.

Objective

To examine the influence of preoperative AF on long-term survival following open heart surgery in rural eastern North Carolina.

Methods

Long-term survival was compared in patients with and without preoperative AF after coronary artery bypass grafting (CABG) and CABG plus valve (CABG + V) surgery between 2002 and 2011. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model.

Results

The study population consisted of 5438 patients. A total of 263 (5%) patients had preoperative AF. Preoperative AF was an independent predictor of long-term survival (open heart surgery: adjusted HR = 1.6, 95% CI = 1.3–2.0; CABG: adjusted HR = 1.6, 95% CI = 1.3–2.1; CABG + V: adjusted HR = 1.6, 95% CI = 1.1–2.3).

Conclusion

Preoperative AF is an important predictor of long-term survival after open heart surgery in this rural population.     

Sickness absence diagnoses among abstainers,low‐risk drinkers and at‐risk drinkers: consideration of the U‐shaped association between alcohol use and sickness absence in four cohort studies

Aims

To estimate differences in the strength and shape of associations between alcohol use and diagnosis‐specific sickness absence.

Design

A multi‐cohort study. Participants (n = 47 520) responded to a survey on alcohol use at two time‐points, and were linked to records of sickness absence. Diagnosis‐specific sickness absence was followed for 4–7 years from the latter survey.

Setting and participants

From Finland, we had population cohort survey data from 1998 and 2003 and employee cohort survey data from 2000–02 and 2004. From France and the United Kingdom, we had employee cohort survey data from 1993 and 1997, and 1985–88 and 1991–94, respectively.

Measurements

We used standard questionnaires to assess alcohol intake categorized into 0, 1–11 and > 11 units per week in women and 0, 1–34 and > 34 units per week in men. We identified groups with stable and changing alcohol use over time. We linked participants to records from sickness absence registers. Diagnoses of sickness absence were coded according to the International Classification of Diseases. Estimates were adjusted for sex, age, socio‐economic status, smoking and body mass index.

Findings

Women who reported drinking 1–11 units and men who reported drinking 1–34 units of alcohol per week in both surveys were the reference group. Compared with them, women and men who reported no alcohol use in either survey had a higher risk of sickness absence due to mental disorders [rate ratio = 1.51, 95% confidence interval (CI) = 1.22–1.88], musculoskeletal disorders (1.22, 95% CI = 1.06–1.41), diseases of the digestive system (1.35, 95% CI = 1.02–1.77) and diseases of the respiratory system (1.49, 95% CI = 1.29–1.72). Women who reported alcohol consumption of > 11 weekly units and men who reported alcohol consumption of > 34 units per week in both surveys were at increased risk of absence due to injury or poisoning (1.44, 95% CI = 1.13–1.83).

Conclusions

In Finland, France and the United Kingdom, people who report not drinking any alcohol on two occasions several years apart appear to have a higher prevalence of sickness absence from work with chronic somatic and mental illness diagnoses than those drinking below a risk threshold of 11 units per week for women and 34 units per week for men. Persistent at‐risk drinking in Finland, France and the United Kingdom appears to be related to increased absence due to injury or poisoning.     

Social participation and incident disability and mortality among frail older adults: A JAGES longitudinal study

Background

Frailty is the highest risk factor for incident disability and mortality. Social participation is a modifiable factor for reducing adverse outcomes among independent older adults. However, the association between social participation and incident disability and mortality among frail older adults remains unclear. Therefore, we examined the association between various social activities and incident disability and mortality.

Methods

This nationwide prospective cohort study (The Japan Gerontological Evaluation Study) recruited older adults with frailty, aged 65 years and older (N = 9090) who were followed up for 6 years (2010–2016). We examined incident disability and all-cause mortality at the end of the follow-up period. Frailty was assessed using the Kihon Checklist. The independent variable was social participation in 2010, grouped into the following seven categories: hobby groups, sports groups or clubs, volunteer groups, senior citizens' clubs, industries, neighborhood communities, and paid work.

Results

The incidence of disability among participants was 19.5% (1770) and that of mortality was 19.2% (1753). Belonging to sports groups or clubs (Hazard Ratios [HR] = 0.74; 95% Confidence Interval [CI] = 0.57, 0.98) or hobby groups (HR = 0.77; 95% CI = 0.60, 0.98) was significantly associated with a lower risk of incident disability. Meanwhile, hobby groups (HR = 0.68; 95% CI = 0.56, 0.83), sports groups or clubs (HR = 0.71; 95% CI = 0.57, 0.88), volunteer groups (HR = 0.69; 95% CI = 0.54, 0.88), and senior citizens' club (HR = 0.75; 95% CI = 0.61, 0.90) were associated with lower risk of incident mortality.

Conclusions

Social participation was associated with a lower risk of incident disability and mortality, not only in healthy older adults but also in frail older adults who are at higher risk of incident disability and mortality. This suggests that frail older adults should be encouraged to participate in all the seven types of social participation examined in this study, as this may lower the risk of subsequent disability and mortality.