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.     

Diminishing benefit of smoking cessation medications during the first year: a meta‐analysis of randomized controlled trials

Background and aims

Although smoking cessation medications have shown effectiveness in increasing abstinence in randomized controlled trials (RCTs), it is unclear to what extent benefits persist over time. This paper assesses whether the benefits of smoking cessation medications decline over the first year.

Methods

We selected studies from three systematic reviews published by the Cochrane Collaboration. RCTs of first‐line smoking cessation medications, with 6‐ and 12‐month follow‐up, were eligible for inclusion. Meta‐analysis was used to synthesize information on sustained abstinence (SA) at 6 versus 12 months and 3 versus 6 months, using the risk difference (RD) (‘net benefit’) between intervention and control group quit rates, the relative risk (RR) and the odds ratio (OR).

Results

Sixty‐one studies (27 647 participants) were included. Fewer than 40% of intervention group participants were sustained abstinent at 3 months (bupropion: 37.1%; nicotine replacement therapy (NRT): 34.8%; varenicline: 39.3%); approximately a quarter were sustained abstinent at 6 months (bupropion: 25.9%; NRT: 26.6%; varenicline: 25.4%), and approximately a fifth were sustained abstinent at 12 months (bupropion: 19.9%; NRT: 19.8%%; varenicline: 18.7%). There was only a small decline in RR (3 months: 1.95 [95% confidence interval (CI) = 1.74–2.18, P < 0.0001]; 6 months: 1.87 (95% CI = 1.67–2.08 P < 0.0001); 12 months: 1.75 (95% CI = 1.56–1.95, P < 0.0001) between intervention and control groups over time, but a substantial decline in net benefit [3 months: RD = 17.3% (14.5–20.1%); 6 months: RD = 11.8% (10.0–13.7%); 12 months: RD = 8.2% (6.8–9.6%)]. The decline in net benefit was statistically significant between 3 and 6 [RD = 4.95% (95% CI = 3.49–6.41%), P < 0.0001] and 6 and 12 months [RD = 3.00% (95% CI = 2.36%–3.64%), P < 0.0001)] for medications combined and individual medications.

Conclusions

The proportion of smokers who use smoking cessation medications who benefit from doing so decreases during the course of the first year, but a net benefit still remains at 12 months.     

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.     

Assessment of factors associated with smoking cessation at diagnosis or during follow‐up of Crohn's disease

Background and Aim

Smoking cessation is known to improve the course of Crohn's disease (CD). However, the factors associated with smoking cessation after CD diagnosis have not been well established.

Methods

Clinical characteristics and change in smoking status were evaluated in 445 current smokers at the time of CD diagnosis. Patients were classified into three subgroups based on their final smoking status and time of smoking cessation: non‐quitters, quitters at diagnosis, and quitters during follow‐up.

Results

The overall smoking cessation rate was 55.7% (248 of 445 patients). The diagnosis of CD was the main reason for quitting (41.5%, 103 of 248 patients). Smoking cessation at the time of CD diagnosis was associated with intestinal resection within 3 months from CD diagnosis (odds ratio [OR] 2.355, 95% confidence interval [CI] 1.348–4.116, P = 0.003), light smoking (OR 2.041, 95% CI 1.157–3.602, P = 0.014), and initiation of smoking before 18 years of age (OR 0.570, 95% CI 0.327–0.994, P = 0.047). Light smoking (OR 1.762, 95% CI 1.019–3.144, P = 0.043) and initiation of smoking before 18 years (OR 0.588, 95% CI 0.381–0.908, P = 0.017) were also associated with overall smoking cessation.

Conclusion

Quitters after CD diagnosis, including quitters at diagnosis and quitters during follow‐up, had features distinct from those of non‐quitters. Given the motivation at CD diagnosis, a detailed history of smoking habits should be taken and all current smokers should be encouraged to quit smoking at the time of CD diagnosis.     

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.     

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.     

Epidemiology of low back pain in the United Arab Emirates

Aims: Low back pain (LBP), a common presenting problem in general practice in the United Arab Emirates (UAE), has received increasing attention in recent decades. We seek to investigate the prevalence of LBP and associated risk factors among people living in the typically hot, humid desert environment of the UAE. Methods: A cross‐sectional questionnaire survey was conducted. The setting was the Primary Health Care (PHC) Clinics in Al‐Ain, UAE. The subjects were a multistage stratified sample of 1304 UAE nationals, 15–70 years of age, who attended PHC clinics for any reason. All subjects were invited to participate. The questionnaire used in the survey is a modified version of the Roland‐Morris scale for evaluating low back pain. The questionnaires were administered during face‐to‐face interviews conducted in Arabic by qualified nurses. Results: Of the total 1304 subject, 1103 (84.5%) living in both urban and rural areas agreed to participate and responded to the study; 586 (53.1%) were men and 517 (46.9%) women. The mean ages and SD of the subjects were 34.9 ± 13.4 years for the men and 33.5 ± 11.8 years for the women. The prevalence of LBP in the present study was 64.6% (95% CI = 60.7–68.5). The results revealed that there were statistically significant differences between men and women with respect to LBP and body mass index (BMI) (P < 0.001), marital status (P < 0.001), occupational status (P < 0.001), housing condition (P < 0.001), and smoking habits (P < 0.001). Back pain had a greater influence on the lifestyle habits of the women than men. Stepwise multiple regression analysis showed that only BMI (OR = 2.54, 95% CI = 2.30–281; P < 0.001), prolonged standing (OR = 6.22, 95% CI = 4.01–9.67; P < 0.0001), weakness in leg (OR = 2.11, 95% CI = 1.16–3.85; P = 0.0142), lifting heavy weights (OR = 6.34, 95% CI = 4.09–9.84; P = 0.019) regular exercise (OR = 12.47, 95% CI = 7.50–20.71; P < 0.001) and smoking habits (OR = 1.61, 95% CI = 1.08–2.38; P < 0.05) had a significant effect on the presence of LBP in these patients. Conclusions: The study showed that the prevalence of back‐related disability was higher among women than men in the UAE. Also, low socio‐economic status and adverse lifestyle habits may constitute risk factors and predictors of LBP.     

Maternal hepatitis B and hepatitis C infection and neonatal neurological outcomes

To examine the associations between maternal hepatitis B (HBV) and hepatitis C (HCV) infection status and selected infant neurological outcomes diagnosed at birth, we conducted a population‐based, retrospective cohort study on singleton live births in Florida from 1998 to 2009. Primary exposures included maternal HBV and HCV monoinfection. The neurological outcomes included brachial plexus injury, cephalhematoma, foetal distress, feeding difficulties, intraventricular h aemorrhage and neonatal seizures. Multivariable logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) that were adjusted for socio‐demographic characteristics, risky behaviours, pregnancy complications and pre‐existing medical conditions, and timing of delivery. The risk of an adverse neurological outcome was higher in infants born to mothers with hepatitis viral infection (7.2% for HCV, 5.0% for HBV), compared with infants of hepatitis virus‐free mothers (4.2%). After adjusting for potential confounders, women with HBV were twice as likely to have infants who suffered from brachial plexus injury (OR = 2.04, 95% CI = 1.15–3.60), while those with HCV had an elevated odds of having an infant with feeding difficulties (OR: 1.32, 95% CI = 1.06–1.64) and a borderline increased likelihood for neonatal seizures (OR = 1.74, 95% CI = 0.98–3.10). Additionally, HCV+ mothers had a 22% increased odds of having an infant with some type of adverse neurological outcome (OR: 1.22, 95% CI = 1.03–1.44). Our findings add to current understanding of the association between maternal HBV/HCV infections and infant neurological outcomes. Further research evaluating the role of maternal HBV and HCV infections (including viraemia, treatment) on pregnancy outcomes is warranted.     

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.     

Life‐course socio‐economic position,area deprivation and Type 2 diabetes: findings from the British Women's Heart and Health Study

Objectives We examined whether area deprivation influenced risk of Type 2 diabetes, fasting blood glucose and insulin resistance over and above the effect of individual socio‐economic position (SEP) measured across the life course. Methods A cross‐sectional analysis of 4286 women aged 60 to 79 years from 457 British electoral wards in 23 towns. Results Area deprivation was positively associated with diagnosed [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.13, 1.53, per quintile of area deprivation, n = 2895], but not undiagnosed Type 2 diabetes after adjustment for individual life‐course SEP. This association was robust to adjustment for adult health behaviours and physiological risk factors. Insulin resistance [homeostasis model assessment (HOMA) score] increased by 1.90% (95% CI 0.01, 3.82, n = 2526) per quintile of area deprivation after adjustment for individual SEP, while fasting blood glucose increased by 0.69% (95% CI 0.16, 1.22, n = 2875) after adjustment for individual SEP. Conclusions Area level deprivation independently influences diagnosed Type 2 diabetes, insulin resistance and fasting blood glucose. Examination of more specific characteristics of places is needed to understand the mechanisms by which these effects arise.     

Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria

Objectives

Malaria infection may impact on mother‐to‐child transmission (MTCT) of HIV‐1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV‐1 MTCT in southern Mozambique.

Methods

A total of 207 HIV‐positive Mozambican pregnant women were enrolled in the study as part of a randomized placebo‐controlled trial of two‐dose sulfadoxine‐pyrimethamine (SP) IPTp in women receiving single‐dose nevirapine to prevent MTCT of HIV. HIV RNA viral load, maternal anaemia and peripheral and placental malaria were assessed at delivery. Infant HIV status was determined by DNA polymerase chain reaction (PCR) at 1 month of age.

Results

There were 19 transmissions of HIV in 153 mother–infant pairs. IPTp with SP did not have a significant impact on MTCT (11.8% in the SP group vs. 13.2% in the placebo group; P=0.784) or on maternal HIV RNA viral load [16 312 (interquartile range {IQR} 4076–69 296) HIV‐1 RNA copies/mL in the SP group vs. 18 274 (IQR 5471–74 104) copies/mL in the placebo group; P=0.715]. In multivariate analysis, maternal HIV RNA viral load [adjusted odds ratio (AOR) 19.9; 95% confidence interval (CI) 2.3–172; P=0.006] and anaemia (haematocrit <33%; AOR 7.5; 95% CI 1.7–32.4; P=0.007) were independent risk factors for MTCT. Placental malaria was associated with a decrease in MTCT (AOR 0.23; 95% CI 0.06–0.89; P=0.034).

Conclusions

IPTp with SP was not associated with a significant impact on MTCT of HIV. Maternal anaemia was an independent risk factor for MTCT.     

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.     

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.     

The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom

Aims

To estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all‐cause mortality (ACM) and opioid drug‐related poisoning (DRP) mortality.

Design

Cohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register.

Setting

UK primary care.

Participants

A total of 11 033 opioid‐dependent patients who received OST from 1998 to 2014, followed‐up for 30 410 person‐years.

Measurements

Exposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed‐up for 16 363 person‐years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone and buprenorphine. Inverse probability weights were included to adjust for confounding and balance characteristics of patients prescribed methadone or buprenorphine.

Findings

ACM and DRP rates were 1.93 and 0.53 per 100 person‐years, respectively. DRP was elevated during the first 4 weeks of OST [incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97–3.82], the first 4 weeks off OST (IRR = 8.15, 95% CI = 5.45–12.19) and the rest of time out of OST (IRR = 2.13, 95% CI = 1.47–3.09) compared with mortality risk from 4 weeks to end of treatment. Patients on buprenorphine compared with methadone had lower ACM rates in each treatment period. After adjustment, there was evidence of a lower DRP risk for patients on buprenorphine compared with methadone at treatment initiation (IRR = 0.08, 95% CI = 0.01–0.48) and rest of time on treatment (IRR = 0.37, 95% CI = 0.17–0.79). Treatment duration (mean and median) was shorter on buprenorphine than methadone (173 and 40 versus 363 and 111, respectively). Model estimates suggest that there was a low probability that methadone or buprenorphine reduced the number of DRP in the population: 28 and 21%, respectively.

Conclusions

In UK general medical practice, opioid substitution treatment with buprenorphine is associated with a lower risk of all‐cause and drug‐related poisoning mortality than methadone. In the population, buprenorphine is unlikely to give greater overall protection because of the relatively shorter duration of treatment.     

Meta‐analysis: Association between hepatitis B virus preS mutation and hepatocellular carcinoma risk

Previous observational studies suggested that hepatitis B virus (HBV) preS mutation plays an important role in the existence of HBV‐related hepatocellular carcinoma (HCC). However, the results are still debatable. With an increasing number of studies about this topic, this study employed a meta‐analysis to identify the association between HBV preS mutation and HCC risk. We searched for eligible studies from PubMed, ProQuest, CINAHL, ScienceDirect and Springer databases to assess the association between HBV mutation and HCC risk. This meta‐analysis was conducted using RevMan 5.3 to provide pooled estimate for odds ratio (ORs) with 95% confidence intervals (95% CIs). Twenty‐one clinical studies were included in this meta‐analysis study which consisted of 1738 participants with HBV‐related HCC and 3740 HBsAg‐positive patients without HCC. All studies used samples of Asian population. PreS deletion was the most common mutation found in all studies. We found that ORs of HBV overall preS deletion was associated with HCC (OR = 3.28; 95% CI = 2.32‐4.65; P < .00001; random‐effects model). Each preS1 and preS2 deletion was associated with increased risk of HCC, with OR 2.42 (95% CI = 1.25‐4.68, P = .008) and 3.36 (95% CI = 2.04‐5.55, P < .00001), respectively. PreS2 start codon mutation was also significantly associated with HCC risk (OR = 2.47; 95% CI: 1.15‐5.27; P = .02; random‐effect model). The result of this meta‐analysis suggested that HBV preS deletion (all, preS1 and preS2) and preS2 start codon mutation might contribute to the increased risk of HBV‐related HCC.     

The interferon‐gamma (IFN‐γ) +874T allele reduces the risk of hepatitis B infection in an Asian population

Increasing evidence suggests that polymorphism of the interferon‐gamma (IFN‐γ) gene in the first intron at position +874 may be associated with chronic hepatitis B virus (HBV) infection and/or HBV clearance. However, the results of relevant studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta‐analysis. In total, 10 independent studies including 1661 chronic HBV‐infected patients and 1142 controls were included in this meta‐analysis. In studies following Hardy–Weinberg equilibrium (HWE), a significantly decreased risk of chronic HBV infection was associated with the IFN‐γ + 874TT genotype in the overall population (TT vs AA: odds ratio (OR) = 0.714, 95% confidence interval (CI) = 0.526–0.969, P = 0.031) when compared with a spontaneously recovered population. Subgroup analysis by ethnicity revealed a similar association in Asian individuals (TT vs AA: OR = 0.706, 95% CI = 0.518–0.962, P = 0.028). Moreover, when compared with a healthy control group, the 874T allele was associated with a significant lower risk of chronic HBV infection in the overall populations (TA vs AA: OR = 0.439, 95% CI = 0.193–0.997, P = 0.049; TT + TA vs AA: OR = 0.475, 95% CI = 0.271–0.832, P = 0.009) and in Asian individuals (TA vs AA: OR = 0.862, 95% CI = 0.744–0.999, P = 0.048). In conclusion, the IFN‐γ + 874TT genotype and 874T allele reduce the risk of chronic HBV infection in Asian individuals.     

Association Between Knee Pain,Impaired Function,and Development of Depressive Symptoms

Objectives

To examine the association between knee pain and function and depressive symptoms in older Japanese adults.

Design

Community‐based prospective cohort study.

Setting

Kurabuchi Town, Gumma Prefecture, Japan.

Participants

Individuals aged 65 and older (N = 573; n = 260 men, n = 313 women) without depressive symptoms participated in baseline examinations in 2005 and 2006; 95.6% participated in follow‐up interviews (2007–08).

Measurements

Degree of knee pain and functional impairment was assessed at baseline using a self‐administered questionnaire in Japanese based on an English version of the Western Ontario and McMaster Universities Osteoarthritis Index. The Geriatric Depression Scale was used to identify depressive symptoms in face‐to‐face home‐visit interviews conducted 2 years later, and the association between knee pain and functional impairment and depressive symptoms was assessed using logistic regression.

Results

During the 2‐year follow‐up, 11.9% of participants developed depressive symptoms, and pain and functional impairment were found to be associated with development of these symptoms. Pain at night while in bed (adjusted odds ratio (aOR) = 2.6, 95% confidence interval (CI) = 1.4–4.9) and difficulty putting on socks (aOR = 3.7, 95% CI: 1.8–7.5), getting into and out of a car (aOR = 3.4, 95% CI = 1.8–6.5), and taking off socks (aOR = 3.1, 95% CI = 1.5–6.5) were found to be most strongly associated with development of depressive symptoms.

Conclusion

Examining elderly people's responses to questions about pain at night and difficulties performing daily activities may be an efficient way of identifying those at high risk of developing depressive symptoms.