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.     

Education is the strongest socio‐economic predictor of smoking in pregnancy

Aims

To investigate socio‐economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions.

Design

Cross‐sectional analysis with linked survey and register data.

Setting

South‐western Finland.

Participants

A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study.

Measurements

The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire‐based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio‐economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated.

Findings

Mother's education was the strongest socio‐economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2–3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1–9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95% CI = 1.4–6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0–18.2; P < 0.001) for vocational secondary education and 14.4 (95% CI = 6.3–33.0; P < 0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1–3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4–2.8; P < 0.001), but did not attenuate its socio‐economic disparities.

Conclusions

In Finland, socio‐economic disparities in smoking in pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general).     

Major life events and risk of alcohol use disorders: a prospective cohort study

Aims

To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD).

Design

Prospective cohort study with baseline examination in 1991–93 and linkage to national registers to identify AUD at follow‐up.

Setting

Copenhagen, Denmark.

Participants

Individuals (aged 21–93 years) who participated in the Copenhagen City Heart Study in 1991–93 (n = 8758).

Measurements

The primary outcome was first registration with AUD during follow‐up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity.

Findings

Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD.

Conclusions

Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.     

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.     

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.     

Medications That Cause Dry Mouth As an Adverse Effect in Older People: A Systematic Review and Metaanalysis

Objectives

To assess and quantify the risk of drug‐induced dry mouth as a side effect in older people.

Design

Systematic review and metaanalysis.

Setting

A search of the literature was undertaken using Medline, Embase, Cochrane, Web of Science, and PubMed from 1990 to 2016.

Participants

Older people (aged ≥60) who participated in intervention or observational studies investigating drug use as an exposure and xerostomia or salivary gland hypofunction as adverse drug outcomes.

Measurements

Two pairs of authors screened titles and abstracts of studies for relevance. Two authors independently extracted data, including study characteristics, definitions of exposure and outcome, and methodological quality. For the metaanalyses, random‐effects models were used for pooling the data and I² statistics for exploring heterogeneity.

Results

Of 1,544 potentially relevant studies, 52 were deemed eligible for inclusion in the final review and 26 in metaanalyses. The majority of studies were of moderate methodological quality. In the intervention studies, urological medications (odds ratio (OR) = 5.91, 95% confidence interval (CI) = 4.04–8.63; I² = 62%), antidepressants (OR = 4.74, 95% CI = 2.69–8.32, I² = 21%), and psycholeptics (OR = 2.59, 95% CI = 1.79–3.95, I² = 0%) were significantly associated with dry mouth. In the observational studies, numbers of medications and several medication classes were significantly associated with xerostomia and salivary gland hypofunction.

Conclusion

Medication use was significantly associated with xerostomia and salivary gland hypofunction in older adults. The risk of dry mouth was greatest for drugs used for urinary incontinence. Future research should develop a risk score for medication‐induced dry mouth to assist with prescribing and medication management.     

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 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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Food consumption by degree of processing is associated with nocturnal dipping and blood pressure variability: The ELSA-Brasil study

Background and aimsAmbulatory blood pressure monitoring (ABPM) allows the assessment of cardiovascular risk markers that cannot be obtained by casual measurements; however, the evidence on the association between food consumption and blood pressure (BP) assessed by ABPM is scarce. We aimed to evaluate the association between food consumption by degree of processing and ambulatory BP.Methods and resultsCross-sectional analysis (2012–2014) of data from a subsample (n = 815) of ELSA-Brasil cohort participants who performed 24-h ABPM was conducted. Systolic (SBP) and diastolic (DBP) BP means and variability during the 24 h and subperiods (sleep and wake), nocturnal dipping, and morning surge were evaluated. Food consumption was classified according to NOVA. Associations were tested by generalized linear models. The consumption of unprocessed, minimally processed foods, and culinary ingredients (U/MPF&CI) was 63.1% of daily caloric intake, 10.8% of processed (PF), and 24.8% of ultraprocessed (UPF). A negative association was found between U/MPF&CI consumption and extreme dipping (T2: odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.55–0.58; T3: OR = 0.55; 95% CI = 0.54–0.57); and between UPF consumption and nondipping (T2: OR = 0.68, 95% CI = 0.55–0.85) and extreme dipping (T2: OR = 0.63, 95% CI = 0.61–0.65; T3: OR = 0.95, 95% CI = 0.91–0.99). There was a positive association between PF consumption and extreme dipping (T2: OR = 1.22, 95% CI = 1.18–1.27; T3: OR = 1.34, 95% CI = 1.29–1.39) and sleep SBP variability (T3: Coef = 0.56, 95% CI = 0.03–1.10).ConclusionsThe high consumption of PF was associated with greater BP variability and extreme dipping, while the U/MPF&CI and UPF consumption were negatively associated with alterations in nocturnal dipping.     

Pain in individuals with idiopathic inflammatory myopathies,other systemic autoimmune rheumatic diseases,and without rheumatic diseases: A report from the COVAD study

Objectives

To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs).

Methods

Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores.

Results

Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0–5.0), 3.0 (IQR = 1.0–6.0), and 1.0 (IQR = 0–2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5–4.5, and NRS = 3.6, 95% CI = 3.1–4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios.

Conclusion

Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.     

Risk of hospitalization for upper gastrointestinal tract complications associated with non‐selective non‐steroidal anti‐inflammatory drugs in Malaysia: a retrospective case control study

Aims: To assess the association between non‐steroidal anti‐inflammatory drug (NSAID) use and upper gastrointestinal (GI) tract‐related hospitalizations and to evaluate inpatient healthcare resource utilization associated with these complications in Malaysia. Methods: A retrospective case control study was performed using medical records of patients admitted to two Malaysian hospitals during 1999 and 2000. Cases were identified based on mode of presentation at hospital admission. One control was identified for each case, matched by age, sex and admission date. NSAID exposure was determined by drug use during one year prior to admission. Conditional logistic regression analysis was used to determine the association between NSAID use and upper GI complications, adjusting for predictors. Results: The 273 cases were significantly more likely to have used NSAIDs in the year prior to hospitalization than controls (27.8%vs. 6.2% of patients; P < 0.0001). Conditional logistic regression analysis adjusting for other predictors showed that the odds of being hospitalized for upper GI tract complications were 4.1 times higher among NSAID users than non‐users (95% CI = 1.88–9.12). Other risk factors for GI‐related hospitalizations were a history of upper GI tract complications (OR = 5.8, 95% CI = 1.28–26.53), use of gastroprotective agents (OR = 5.3, 95% CI = 1.67–16.79), and use of antacids (OR = 5.0, 95% CI = 2.10–11.91) in the previous year. Conclusion: This study demonstrated that NSAID exposure was significantly higher among patients hospitalized for GI‐related complications than for other reasons, indicating that NSAID use is an independent risk factor for upper GI tract complications in this Malaysian sample.     

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.