CHRNA3/5, IREB2, and ADCY2 are associated with severe chronic obstructive pulmonary disease in Poland

We examined the association between single-nucleotide polymorphisms (SNPs) previously associated with chronic obstructive pulmonary disease (COPD) and/or lung function with COPD and COPD-related phenotypes in a novel cohort of patients with severe to very severe COPD. We examined 315 cases of COPD and 330 Caucasian control smokers from Poland. We included three SNPs previously associated with COPD: rs7671167 (FAM13A), rs13180 (IREB2), and rs8034191 (CHRNA 3/5), and four SNPs associated with lung function in a genome-wide association study of general population samples: rs2070600 (AGER), rs11134242 (ADCY2), rs4316710 (THSD4), and rs17096090 (INTS12). We tested for associations with severe COPD and COPD-related phenotypes, including lung function, smoking behavior, and body mass index. Subjects with COPD were older (average age 62 versus 58 years, P < 0.01), with more pack-years of smoking (45 versus 33 pack-years, P < 0.01). CHRNA3/5 (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.5-2.4; P = 7.4 × 10(-7)), IREB2 (OR, 0.69; 95% CI, 0.5-0.9; P = 3.4 × 10(-3)), and ADCY2 (OR, 1.35; 95% CI, 1.1-1.7; P = 0.01) demonstrated significant associations with COPD. FAM13A (OR, 0.8; 95% CI, 0.7-1.0; P = 0.11) approached statistical significance. FAM13A and ADCY2 also demonstrated a significant association with lung function. Thus, in severe to very severe COPD, we demonstrate a replication of association between two SNPs previously associated with COPD (CHRNA3/5 and IREB2), as well as an association with COPD of one locus initially associated with lung function (ADCY2).     

Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis

Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers.     

Efficacy of extended-release naltrexone in patients with relatively higher severity of alcohol dependence

Background: Because some literature reviews have suggested that naltrexone’s benefit may be limited to less‐severe alcohol dependence, and exclusively to reduction in heavy drinking rather than abstinence, we examined the efficacy of once per month, injectable extended‐release naltrexone (XR‐NTX 380 mg) in patients with relatively higher severity alcohol dependence. Methods: Post hoc analyses examined data from a multicenter, placebo‐controlled, 24‐week randomized trial of XR‐NTX for alcohol dependence (N = 624). We analyzed treatment effects in alcohol‐dependent patients who had higher baseline severity, as measured by: (i) the Alcohol Dependence Scale (ADS) or (ii) having been medically detoxified in the week before randomization. Efficacy was also examined via the relationship between pretreatment severity indices and reporting at least 4 days of lead‐in abstinence prior to treatment—a major predictor of good outcome in the original study. Results: Higher severity alcohol‐dependent patients, defined by the ADS, when receiving XR‐NTX 380 mg (n = 50) compared with placebo (n = 47), had significantly fewer heavy‐drinking days in‐trial (hazard ratio=0.583; p = 0.0049) and showed an average reduction of 37.3% in heavy‐drinking days compared with 27.4% for placebo‐treated patients (p = 0.039). Among those who had a detoxification just prior to randomization, these reductions were 48.9% (XR‐NTX 380 mg; n = 11) and 30.9% (placebo; n = 15) (p = 0.004). Subjects with at least 4 days of pretreatment abstinence (n = 82) versus those without (n = 542) had significantly higher pretreatment ADS scores (p = 0.002) and were more likely to require detoxification prior to randomization (p < 0.001). Patients with lead‐in abstinence experienced significantly better maintenance of initial and 6‐month abstinence. Conclusions: These secondary analyses support the efficacy of XR‐NTX 380 mg in relatively higher severity alcohol dependence for both reduction in heavy drinking and maintenance of abstinence, with implications for the role of adherence pharmacotherapy.     

Intimate partner violence and partner notification of sexually transmitted infections among adolescent and young adult family planning clinic patients

Patient-initiated partner notification of sexually transmitted infection (STI), i.e. patients informing their sexual partners of a diagnosis, is a cornerstone of STI prevention. Growing evidence suggests that women exposed to intimate partner violence (IPV) may fear such notification, or face negative consequences in response to STI disclosure. The current study assessed associations of IPV with fear of partner notification, and experiences of partner notification, among adolescent and young adult female family planning clinic patients. Women aged 16-29 years attending five family planning clinics in Northern California, USA (n = 1282) participated in a cross-sectional survey. A history of physical or sexual IPV was associated with fear of partner notification. Moreover, participants exposed to IPV were more likely to have partners say that it was not from them or otherwise accuse them of cheating in response to partner notification. Such partners were less likely to seek indicated STI treatment or testing. Current findings suggest that partner notification for STI may be compromised by IPV. Clinical practices and policies to support effective partner notification should include IPV assessment, and provide mechanisms to address related fears concerning partner notification.