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Background and aims: Varenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care. Design Case–cross‐over study. Setting: UK‐based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality data sets. Participants: Adult smokers (n =282,429) observed during periods when exposed and not exposed to either varenicline or NRT. Measurements Main outcomes included suicide, self‐harm, myocardial infarction (MI), all‐cause death and cause‐specific death [MI, chronic obstructive pulmonary disease (COPD)]. In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure during the risk period (90 days prior to the event) with the chance of exposure during an earlier single reference period (91–180 days prior to the event) or multiple 90‐day reference periods to increase statistical power. Findings In the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, while NRT was associated with MI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.18–1.67]. Using multiple reference periods, varenicline was associated with an increased risk of self‐harm (OR = 1.32, 95% CI = 1.12–1.56) and suicide (OR = 3.56, 95% CI = 1.32–9.60) but a reduction in all‐cause death (OR = 0.75, 95% CI = 0.61–0.93). NRT was associated with MI (OR = 1.54, 95% CI = 1.36–1.74), self‐harm (OR = 1.30, 95% CI = 1.18–1.44) and deaths from MI (OR = 1.53, 95% CI = 1.11–2.10), COPD (OR = 1.33, 95% CI = 1.14–1.56) and all causes (OR = 1.28, 95% CI = 1.18–1.40) when using multiple reference periods. Conclusions: There appear to be positive associations between (1) nicotine replacement therapy (NRT) and myocardial infarction, death and risk of self‐harm and (2) varenicline and increased risk of self‐harm and suicide, as well as a negative association between varenicline and all‐cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (nicotine replacement therapy is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self‐harm). [ABSTRACT FROM AUTHOR]

OBJECTIVE To aid the interpretation of the trends in prostate cancer mortality, which declined in the UK in the early 1990s for unknown reasons, by investigating prostate cancer death rates, incidence and treatments in England and Wales in 1975–2004. METHODS Join-point regression was used to assess secular trends in mortality and incidence (source: Office of National Statistics), radical prostatectomy and orchidectomy (source: Hospital Episode Statistics database) and androgen-suppression drugs (source: Intercontinental Medical Statistics). RESULTS Prostate cancer mortality declined from 1992 (95% confidence interval, CI, 1990–94). The relative decline in mortality to 2004 was greater and more sustained amongst men aged 55–74 years (annual percentage mortality reduction 2.75%; 95% CI 2.33–3.18%) than amongst those aged ≥75 years (0.71%, 0.26–1.15%). The use of radical prostatectomy increased between 1991 (89 operations) and 2004 (2788) amongst men aged 55–74 years. The prescribing of androgen suppression increased between 1987 (33 000 prescriptions) and 2004 (470 000). CONCLUSIONS The decrease in prostate cancer mortality was greater amongst men aged 55–74 years than in those aged ≥75 years, but pre-dated the substantial use of prostate-specific antigen screening and radical prostatectomy in the UK. An increase in radical therapy amongst younger groups with localized cancers and screen-detected low-volume locally advanced disease as a result of stage migration, as well as prolonged survival from increased medical androgen suppression therapy, might partly explain recent trends. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the morbidity and mortality after radical prostatectomy (RP) in relation to the numbers of RPs carried out at individual hospitals, as recent studies of complex surgery report worse outcomes in low-volume hospitals, and there has been a large increase in RPs for localized prostate cancer. METHODS We analysed hospital episode statistics data for all 18 027 RPs in English National Health Service hospitals between 1997 and 2004. RESULTS In multivariate analysis, there was a U–shaped association of hospital volume with mortality ( P for nonlinear trend, 0.004), but this finding was based on only 59 (0.3%) deaths. The mean length of stay was 6 days and decreased by 2.96% (95% confidence interval, CI, 1.98–3.92; P < 0.001) per quintile increase in hospital volume. In all, 16.1% of men had 30-day in-hospital complications; 20.3% were readmitted with complications within a year. The odds of 30-day in-hospital wound/bleeding complications decreased by 6% (95% CI 1–11; P = 0.02), and miscellaneous medical complications decreased by 10% (0–19; P = 0.04) per increase in hospital volume quintile. For re-admissions within a year, the hazard of vascular complications decreased by 15% (6–22; P = 0.001), wound/bleeding complications decreased by 8% (2–13; P = 0.01) and genitourinary complications decreased by 5% (2–8; P = 0.002), per increase in hospital volume quintile. CONCLUSION In men undergoing RP the length of hospital stay and rates of some short- and long-term postoperative complications afterward are lower in high-volume hospitals. The magnitudes of these effects on the outcomes studied may be too small and inconsistent to indicate a policy of selective referral to high-volume hospitals. Quality of life and oncological outcomes, however, could not be investigated in this dataset. [ABSTRACT FROM AUTHOR]