Genomic monitoring of SARS-CoV-2 variants using sentinel SARI hospital surveillance

Background

To support the COVID-19 pandemic response, many countries, including Belgium, implemented baseline genomic surveillance (BGS) programs aiming to early detect and characterize new SARS-CoV-2 variants. In parallel, Belgium maintained a sentinel network of six hospitals that samples patients with severe acute respiratory infections (SARI) and integrated SARS-CoV-2 detection within a broader range of respiratory pathogens. We evaluate the ability of the SARI surveillance to monitor general trends and early signals of viral genetic evolution of SARS-CoV-2 and compare it with the BGS as a reference model.

Methods

Nine-hundred twenty-five SARS-CoV-2 positive samples from patients fulfilling the Belgian SARI definition between January 2020 and December 2022 were sequenced using the ARTIC Network amplicon tiling approach on a MinION platform. Weekly variant of concern (VOC) proportions and types were compared to those that were circulating between 2021 and 2022, using 96,251 sequences of the BGS.

Results

SARI surveillance allowed timely detection of the Omicron (BA.1, BA.2, BA.4, and BA.5) and Delta (B.1.617.2) VOCs, with no to 2 weeks delay according to the start of their epidemic growth in the Belgian population. First detection of VOCs B.1.351 and P.1 took longer, but these remained minor in Belgium. Omicron BA.3 was never detected in SARI surveillance. Timeliness could not be evaluated for B.1.1.7, being already major at the start of the study period.

Conclusions

Genomic surveillance of SARS-CoV-2 using SARI sentinel surveillance has proven to accurately reflect VOCs detected in the population and provides a cost-effective solution for long-term genomic monitoring of circulating respiratory viruses.     

Mecamylamine treatment for alcohol dependence: a randomized controlled trial

Background and aims

The nicotinic acetylcholine receptor antagonist, mecamylamine, is a potential novel pharmacotherapy for alcohol use disorder. The aims were to compare alcohol consumption between mecamylamine and placebo and test if smoking status modified treatment effects.

Design

Out‐patient, randomized, double‐blind clinical trial for 12 weeks of treatment with mecamylamine (10 mg) (n = 65) versus placebo (n = 63).

Setting

Connecticut, USA.

Participants

Individuals had current alcohol dependence (n = 128), had an average age of 48.5 [standard deviation (SD) = 9.4], 110 (85.9%) were men, and included 74 smokers (57.8%) and 54 non‐smokers (42.2%). Participants were randomized to mecamylamine 10 mg per day or placebo. All subjects also received medical management therapy administered by trained research personnel.

Measurements

Primary outcome was percentage of heavy drinking days during the last month of treatment; other outcomes included drinking days, drinks per drinking days, alcohol craving, smoking, symptoms of nicotine withdrawal and side effects.

Findings

There were no significant differences in the percentage of heavy drinking days at 3 months between the mecamylamine (mean = 18.4, SD = 29.0) and placebo treatment groups (mean = 20.4, SD = 29.2) [F_{1, 100} = 1.3, P = 0.25; effect size d = 0.07; mean difference = 2.06, 95% confidence interval (CI) = ?8.96 to 13.08]. There were no significant differences in percentage of drinking days or in drinks per drinking day at month 3 between the mecamylamine and placebo groups; there were no significant interactions.

Conclusions

Mecamylamine 10 mg per day did not reduce alcohol consumption significantly in treatment‐seeking smokers and non‐smokers with alcohol use disorder.     

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.     

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.     

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal

Background and Aims

Cannabidiol (CBD), a non‐intoxicating cannabinoid found in cannabis, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side effects and research showing that it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette‐related stimuli and increased craving and withdrawal; and (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette‐related stimuli, craving and withdrawal and not produce any side effects.

Design

Randomized, double‐blind cross‐over study with a fixed satiated session followed by two overnight abstinent sessions.

Setting

UK laboratory.

Participants

Thirty non‐treatment‐seeking, dependent cigarette smokers recruited from the community.

Intervention and comparator

800 mg oral CBD, or matched placebo (PBO) in a counterbalanced order

Measurements

AB to pictorial tobacco cues was recorded using a visual probe task and an explicit rating task. Withdrawal, craving, side effects, heart rate and blood pressure were assessed repeatedly.

Findings

When participants received PBO, tobacco abstinence increased AB (P = 0.001, d = 0.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (P = 0.007, d = 0.704) and no longer differed from satiety (P = 0.82). Compared with PBO, CBD also reduced explicit pleasantness of cigarette images (P = 0.011; d = 0.514). Craving (Bayes factor = 7.08) and withdrawal (Bayes factor = 6.95) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence.

Conclusions

A single 800‐mg oral dose of cannabidiol reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. Cannabidiol did not influence tobacco craving or withdrawal or any subjectively rated side effects.     

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.     

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.     

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.     

Gender differences in individuals with obesity and binge eating disorder: A retrospective comparison of phenotypical features and treatment outcomes

Objective

Phenotypical comparisons between individuals with obesity without binge eating disorder (OB) and individuals with obesity and comorbid binge eating disorder (OB + BED) are subject to ongoing investigations. At the same time, gender-related differences have rarely been explored, raising the question whether men and women with OB and OB + BED may require differently tailored treatments.

Method

We retrospectively compared pre- versus post-treatment data in a matched sample of n = 180 men and n = 180 women with OB or OB + BED who received inpatient treatment.

Results

We found that men displayed higher weight loss than women independent of diagnostic group. In addition, men with OB + BED showed higher weight loss than men with OB after 7 weeks of treatment.

Conclusions

The present findings add to an emerging yet overall still sparse body of studies comparing phenotypical features and treatment outcomes in men and women with OB and OB + BED; implications for further research are discussed.

Clinical Trial Registration

The study was prospectively registered with the German Clinical Trial Register as part of application DRKS00028441.     

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).     

Steroid administration for ischemic complications after radiofrequency ablation: A retrospective study

Aim

The aim of this study was to evaluate the effects of steroids on ischemic complications after radiofrequency ablation.

Methods

A total of 58 patients with ischemic complications were divided into two groups according to corticosteroid use or non-use.

Results

A total of 13 patients who were administered steroids had a shorter duration of fever than those who were not administered steroids (median 6.0 vs. 2.0 days; p < 0.001). Linear regression analysis showed that steroid administration was associated with a reduction of 3.9 days in the duration of fever (p = 0.008).

Conclusions

Steroid administration for ischemic complications after radiofrequency ablation may reduce the risk of fatal outcomes by blocking systemic inflammatory reactions.     

New Institutionalization in Long‐Term Care After Hospital Discharge to Skilled Nursing Facility

Background/Objectives

Approximately half of individuals newly admitted to long‐term care (LTC) nursing homes (NHs) experienced a prior hospitalization followed by discharge to a skilled nursing facility (SNF). The objective was to examine characteristics associated with new institutionalizations of older adults on this care trajectory.

Design

Retrospective cohort study.

Setting

SNFs and LTC NHs.

Patients

Medicare fee‐for‐service beneficiaries admitted to 7,442 SNFs in 2013 (N = 597,986).

Measurements

We used demographic and clinical characteristics from Medicare data and the Minimum Data Set. We defined “new institutionalization” as LTC NH residence for longer than 90 non‐SNF days, starting within 6 months of hospital discharge.

Results

For individuals who survived 6 months after hospital discharge, the overall rate of new LTC institutionalizations was 10.0% (N = 59,736). Older age, white race, being unmarried, Medicaid eligibility, higher income, more comorbidities, cognitive impairment, depression, functional limitations, hallucinations and delusions, aggressive behavior, incontinence, and pressure ulcers were associated with higher adjusted odds of new LTC institutionalization. In analyses stratified according to race and ethnicity, higher income was associated with lower odds of LTC institutionalization for whites (odds ratio (OR) = 0.92, 95% confidence interval (CI) = 0.89–0.96) and greater odds for blacks (OR = 1.40, 95% CI = 1.27–1.55) and Hispanics (OR = 1.44, 95% CI = 1.25–1.66). Moderate or severe depression, functional limitations, hallucinations and delusions, aggressive behavior, and being unmarried were stronger risk factors for LTC for cognitively intact individuals than for those with moderate to severe cognitive impairment. Being unmarried and having more comorbidities were stronger predictors in those aged 66 to 70 than in those aged 81 to 85 and 91 and older.

Conclusion

Associations between risk factors and new LTC institutionalizations varied according to race and ethnicity, age, and level of cognitive function. Programs that target older adults at greater risk may be an effective strategy for reducing new institutionalizations and fostering aging in place.     

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.     

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.     

Reducing the standard serving size of alcoholic beverages prompts reductions in alcohol consumption

Aims

To test whether reducing the standard serving size of alcoholic beverages would reduce voluntary alcohol consumption in a laboratory (study 1) and a real‐world drinking environment (study 2). Additionally, we modelled the potential public health benefit of reducing the standard serving size of on‐trade alcoholic beverages in the United Kingdom.

Design

Studies 1 and 2 were cluster‐randomized experiments. In the additional study, we used the Sheffield Alcohol Policy Model to estimate the number of deaths and hospital admissions that would be averted per year in the United Kingdom if a policy that reduces alcohol serving sizes in the on‐trade was introduced.

Setting

A semi‐naturalistic laboratory (study 1), a bar in Liverpool, UK (study 2).

Participants

Students and university staff members (study 1: n = 114, mean age = 24.8 years, 74.6% female), residents from local community (study 2: n = 164, mean age = 34.9 years, 57.3% female).

Interventions and comparators

In study 1, participants were assigned randomly to receive standard or reduced serving sizes (by 25%) of alcohol during a laboratory drinking session. In study 2, customers at a bar were served alcohol in either standard or reduced serving sizes (by 28.6–33.3%).

Measurements

Outcome measures were units of alcohol consumed within 1 hour (study 1) and up to 3 hours (study 2). Serving size condition was the primary predictor.

Findings

In study 1, a 25% reduction in alcohol serving size led to a 20.7–22.3% reduction in alcohol consumption. In study 2, a 28.6–33.3% reduction in alcohol serving size led to a 32.4–39.6% reduction in alcohol consumption. Modelling results indicated that decreasing the serving size of on‐trade alcoholic beverages by 25% could reduce the number of alcohol‐related hospital admissions and deaths per year in the United Kingdom by 4.4–10.5% and 5.6–13.2%, respectively.

Conclusions

Reducing the serving size of alcoholic beverages in the United Kingdom appears to lead to a reduction in alcohol consumption within a single drinking occasion.     

Left atrial dyssynchrony in veteran endurance athletes with and without paroxysmal atrial fibrillation

Background

Prolonged endurance exercise increase the risk of atrial fibrillation (AF) in men. Functional parameters may help separate physiological from pathological atrial remodeling in athletes. LA mechanical dispersion (LA MD) is associated with AF in the general population, but the associations between prolonged exercise, LA MD and AF are not known.

Purpose

To describe LA MD in veteran athletes with and without paroxysmal AF (pAF) and to investigate LA MD's ability to identify veteran athletes with pAF.

Methods

Two hundred and ninety-three men, skiers with (n = 57) and without (n = 87) pAF, and controls with (n = 61) and without pAF (n = 88) underwent an echocardiographic exam in sinus rhythm. LA reservoir strain (LASr) was measured, and LA MD defined as the standard deviation of time-to-peak strain (SD-TPS).

Results

Skiers (mean age 70.7 ± 6.7 years) reported an average of 40–50 years of endurance exercise. LA volumes were associated with pAF and athletic status (p < .001). SD-TPS was associated with pAF (p < .001) but not athletic status (p = .173). We found no significant trend between years of exercise and SD-TPS in individuals without AF (p = .893). SD-TPS did not add incremental value in identifying athletes with pAF in addition to clinical markers, QRS width, LA volume, and LASr (p = .056).

Conclusion

LA MD was associated with pAF regardless of athletic status but not related to years of endurance exercise, suggesting LA MD could be a promising marker of pathological atrial remodeling in athletes. However, we found no incremental value of LA MD identifying athletes with pAF when LASr was included in the model.     

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.     

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.     

IN.PACT AV access randomized trial: Japan cohort outcomes through 12 months

Purpose

There is a lack of adjudicated and prospectively randomized published outcomes on the use of drug-coated balloons (DCB) to treat dysfunctional arteriovenous fistula in Asian patients. This post hoc subgroup analysis of 112 Japanese participants from the global IN.PACT AV Access trial reports outcomes through 12 months.

Materials and Methods

Participants were treated with DCB (n = 58) or standard non-coated percutaneous transluminal angioplasty (PTA) balloons (n = 54). Outcomes included target lesion primary patency (TLPP), access circuit primary patency, and safety.

Results

Through 6 months, TLPP was 86.0% (49/57) in the DCB group and 49.1% (26/53) in the PTA group (p < 0.001). Through 12 months, TLPP was 67.3% (37/55) in the DCB group and 43.4% (23/53) in the PTA group (p = 0.013).

Conclusion

In this post hoc analysis of Japanese participants from the IN.PACT AV Access trial, participants treated with DCB had higher TLPP through 6 and 12 months compared with PTA.     

Clinical,neuroimaging, and behavioural risk factors for neurocognitive impairment in Chinese patients with haemophilia: A multicentre study

Background

Few studies have evaluated the impact of subclinical microstructural changes and psychosocial factors on cognitive function in patients with haemophilia.

Objectives

To determine the prevalence and characteristics of cognitive impairment in patients with haemophilia, and identify associated risk factors.

Methods

We recruited haemophilia A or B patients who were aged ≥10 years old from three public hospitals in Hong Kong. A neurocognitive battery was administered to evaluate their attention, memory, processing speed and cognitive flexibility performances. They also underwent magnetic resonance imaging to identify cerebral microbleeds. Validated self-reported questionnaires were administered to assess their mental health status and adherence to prophylactic treatment. General linear modelling was used to investigate the association of neurocognitive outcomes with risks factors, adjusting for age and education attainment.

Results

Forty-two patients were recruited (median age 32.0 years; 78.6% haemophilia A; 80.9% moderate-to-severe disease). Six patients (14.3%) had developed cerebral microbleeds. A subgroup of patients demonstrated impairments in cognitive flexibility (30.9%) and motor processing speed (26.2%). Hemarthrosis in the previous year was associated with worse attention (Estimate = 7.62, 95% CI: 1.92–15.33; p = .049) and cognitive flexibility (Estimate = 8.64, 95% CI: 2.52–13.29; p = .043). Depressive (Estimate = 0.22, 95% CI: 0.10–0.55; p = .023) and anxiety (Estimate = 0.26, 95% CI: 0.19–0.41; p = .0069) symptoms were associated with inattentiveness. Among patients receiving prophylactic treatment (71.4%), medication adherence was positively correlated with cognitive flexibility (p = .037).

Conclusion

A substantial proportion of patients with haemophilia demonstrated cognitive impairment, particularly higher-order thinking skills. Screening for cognitive deficits should be incorporated into routine care. Future studies should evaluate the association of neurocognitive outcomes with occupational/vocational outcomes.