Evidence for prevention and screening: recommendations in adults.

A growing body of evidence supports preventive interventions in asymptomatic adults. Primary prevention, which includes counselling (in particular for smoking cessation) and review of immunisation status, has been shown to be more cost-effective than secondary prevention. Evidence supports screening for hypertension, hyperlipidaemia, cervical cancer, colorectal cancer, breast cancer and obesity. Screening for lung, pancreatic and ovarian cancer has no effect on outcome and should not be performed. Controversial preventive interventions include general screening for diabetes mellitus, thyroid disorders and prostate cancer. Physicians should be aware of a possible hidden agenda in patients presenting for a checkup

Are internists in an non-prescriptive setting favourable to guidelines? A survey in a Department of Internal Medicine in Switzerland.

A cross-sectional anonymous postal survey was carried out in a Department of Internal Medicine in order to assess physicians' knowledge about and attitudes towards clinical practice guidelines and to evaluate the role of age in determining their use and opinions. The study took place in a Swiss University Hospital where exposure to guidelines had been limited. The questionnaire was sent to the 174 physicians of the Department. The response rate was 67% (116/174). The spontaneous definitions of guidelines were heterogeneous and referred to information of uncertain validity. Most participants, especially the younger groups of junior and senior residents, reported using guidelines and were favourable to their development. Less favourable attitudes were observed among senior staff physicians and consultants. For instance, the latter more often held the opinion that guidelines are too rigid to apply to individual patients, were likely to decrease physician reimbursement and to hamper research (respectively, 32% vs 24%, 50% vs 31% and 18% vs 7% when compared with the opinions of residents). In conclusion, in a non-prescriptive hospital setting, where the development, dissemination and implementation of guidelines are emerging, the concept of 'guideline' was heterogeneous. Despite generally positive attitudes towards guidelines, the opinion of senior staff physicians constitute a barrier to their dissemination and implementation

Influence of body weight and UGT2B7 polymorphism on varenicline exposure in a cohort of smokers from the general population.

The abstinence rate to tobacco after varenicline treatment is moderate and might be partially affected by variability in varenicline concentrations. This study aimed at characterizing the sources of variability in varenicline pharmacokinetics and to relate varenicline exposure to abstinence. The population pharmacokinetic analysis (NONMEM®) included 121 varenicline concentrations from 82 individuals and tested the influence of genetic and non-genetic characteristics on apparent clearance (CL/F) and volume of distribution (V/F). Model-based average concentrations over 24 h (Cav) were used to test the impact of varenicline exposure on the input rate (Kin) expressed as a function of the number of cigarettes per day in a turnover model of 373 expired carbon monoxide levels. A one-compartment model with first-order absorption and elimination appropriately described varenicline concentrations. CL/F was 8.5 L/h (coefficient of variation, 26%), V/F was 228 L, and the absorption rate (k <sub>a</sub> ) was fixed to 0.98 h <sup>-1</sup> . CL/F increased by 46% in 100-kg individuals compared to 60-kg individuals and was found to be 21% higher in UGT2B7 rs7439366 TT individuals. These covariates explained 14% and 9% of the interindividual variability in CL/F, respectively. No influence of varenicline Cav was found on Kin in addition to the number of cigarettes. Body weight mostly and to a smaller extent genetic polymorphisms of UGT2B7 can influence varenicline exposure. Dose adjustment based on body weight and, if available, on UGT2B7 genotype might be useful to improve clinical efficacy and tolerability of varenicline

Influence of anthropometric parameters and biochemical markers of bone metabolism on quantitative ultrasound of bone in the institutionalized elderly

The assessment of bone quality by quantitative ultrasound (QUS), a transportable and relatively cheap method, shows some correlations with bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) and with fracture risk. To examine its correlation with bone metabolism in a population of institutionalized elderly people known to be at high risk for vitamin D deficiency and secondary hyperparathyroidism, QUS of the calcaneus and biochemical parameters were measured in 264 women aged 85±7 (SD) years and in 103 men aged 81±8 years living in 19 nursing homes. Vitamin D deficiency was frequent in this population: 41.9% of the women and 31.4% of the men had a serum 25-hydroxyvitamin (25OHD) level below the 2.5th percentile level of 3276 normal Swiss adults (6.2 µg/l or 15.5 mmol/l). Hyperparathyroidism was less frequent: serum parathyroid hormone (PTH) levels were above the 97.5th percentile level of normal adults (70 pg/l) in 18.9% of women and 9.8% of men. In women, QUS data correlated significantly with age (r=−0.297), body mass index (BMI) (r=0.403), calcium (r=0.220), PTH (r=−0.296), 25OHD (r=0.298) and alkaline phosphatase (AP) (r=−0.170) for broadband ultrasound attenuation (BUA), and with age (r=−0.195), BMI (r=0.208), PTH (r=−0.174), 25OHD (r=0.140) and AP (r=−0.130) for speed of sound (SOS). In men, ultrasound data correlated with BMI (r=0.326), calcium (r=0.199), 25OHD (r=0.258) and AP (r=−0.311) for BUA, and with AP (r=−0.196) for SOS. In women, but not in men because of their smaller number, a multivariate analysis was performed to examine relationships between age, BMI, biochemical markers and QUS. Age, BMI, PTH and phosphate explained 30% of the variance of BUA and 10% for SOS. In conclusion, QUS of bone evaluates characteristics of bone that are influenced, at least partially, by age, BMI and the secondary hyperparathyroidism due to vitamin D deficienc

Combining bone resorption markers and heel quantitative ultrasound to discriminate between fracture cases and controls

Summary: This nested case-control analysis of a Swiss ambulatory cohort of elderly women assessed the discriminatory power of urinary markers of bone resorption and heel quantitative ultrasound for non-vertebral fractures. The tests all discriminated between cases and controls, but combining the two strategies yielded no additional relevant information. Introduction: Data are limited regarding the combination of bone resorption markers and heel quantitative bone ultrasound (QUS) in the detection of women at risk for fracture. Methods: In a nested case-control analysis, we studied 368 women (mean age 76.2 ± 3.2years), 195 with low-trauma non-vertebral fractures and 173 without, matched for age, BMI, medical center, and follow-up duration, from a prospective study designed to predict fractures. Urinary total pyridinolines (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid chromatography. All women underwent bone evaluations using Achilles+ and Sahara heel QUS. Results: Areas under the receiver operating-characteristic curve (AUC) for discriminative models of the fracture group, with 95% confidence intervals, were 0.62 (0.56-0.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69) and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination of resorption markers and QUS added no significant discriminatory information to either measurement alone with an AUC of 0.66 (0.60-0.71) for Achilles+ with PYD and 0.68 (0.62-0.73) for Sahara with PYD. Conclusions: Urinary bone resorption markers and QUS are equally discriminatory between non-vertebral fracture patients and controls. However, the combination of bone resorption markers and QUS is not better than either test used alon

Association of nicotine metabolism and sex with relapse following varenicline and nicotine replacement therapy.

Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine, mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of varenicline in women and in nicotine normal metabolizers phenotypically determined by nicotine-metabolite ratio. Our objective was to study the influence of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine replacement therapy and varenicline. Data were extracted from a longitudinal study which included smokers participating in a smoking cessation program. Response to treatment was defined by the absence of relapse when a set threshold of reduction in cigarettes per day relative to the week before the study was no more reached. The analysis considered total and partial reduction defined by a diminution of 100% and of 90% in cigarettes per day, respectively. The hazard ratio of relapsing was estimated in multivariate Cox regression models including the sex and the nicotine metabolism determined by the phenotype or by CYP2A6 genotyping (rs1801272 and rs28399433). In the normal metabolizers determined by phenotyping and in women, the hazard ratio for relapsing was significantly lower with varenicline for a partial decrease (HR = 0.33, 95% CI [0.12, 0.89] and HR = 0.20, 95% CI [0.04, 0.91], respectively) and nonsignificantly lower for a total cessation (HR = 0.45, 95% CI [0.20, 1.0] and HR = 0.38, 95% CI [0.14, 1.0]). When compared with the normal metabolizers determined by phenotyping, the hazard ratio for a partial decrease was similar in the normal metabolizers determined by genotyping (HR = 0.42, 95% CI [0.18, 0.94]) while it was significantly lower with varenicline for a total cessation (HR = 0.50, 95% CI [0.26, 0.98]). Women and normal nicotine metabolizers may benefit more from varenicline over nicotine replacement therapy. (PsycINFO Database Recor

Association between smoking and recurrence of venous thromboembolism and bleeding in elderly patients with past acute venous thromboembolism.

BACKGROUND: While the association between smoking and arterial cardiovascular events has been well established, the association between smoking and venous thromboembolism (VTE) remains controversial. OBJECTIVES: To assess the association between smoking and the risk of recurrent VTE and bleeding in patients who have experienced acute VTE. PATIENTS/METHODS: This study is part of a prospective Swiss multicenter cohort that included patients aged ≥65years with acute VTE. Three groups were defined according to smoking status: never, former and current smokers. The primary outcome was the time to a first symptomatic, objectively confirmed VTE recurrence. Secondary outcomes were the time to a first major and clinically relevant non-major bleeding. Associations between smoking status and outcomes were analysed using proportional hazard models for the subdistribution of a competing risk of death. RESULTS: Among 988 analysed patients, 509 (52%) had never smoked, 403 (41%) were former smokers, and 76 (8%) current smokers. After a median follow-up of 29.6months, we observed a VTE recurrence rate of 4.9 (95% confidence interval [CI] 3.7-6.4) per 100 patient-years for never smokers, 6.6 (95% CI 5.1-8.6) for former smokers, and 5.2 (95% CI 2.6-10.5) for current smokers. Compared to never smokers, we found no association between current smoking and VTE recurrence (adjusted sub-hazard ratio [SHR] 1.05, 95% CI 0.49-2.28), major bleeding (adjusted SHR 0.59, 95% CI 0.25-1.39), and clinically relevant non-major bleeding (adjusted SHR 1.21, 95% CI 0.73-2.02). CONCLUSIONS: In this multicentre prospective cohort study, we found no association between smoking status and VTE recurrence or bleeding in elderly patients with VTE

Primary Care-Led Transition Clinics Hold Promise in Improving Care Transitions for Cancer Patients Facing Social Disparities: A Commentary.

Transitions in care are key junctions during which care coordination, communication, and individualized support are required to ensure optimal health outcomes for patients. This is particularly true for patients who face social disparities, such as poverty, limited health literacy, or belonging to a racial or ethnic minority, who are particularly at risk for experiencing poor care transitions. Interdisciplinary primary care-led transition clinics are an intervention that have shown promise in improving care transitions for diverse patient populations, including those that face social disparities, but their role in improving transitions in cancer care remains largely untapped. In this commentary we highlight why the time-limited support of an interdisciplinary primary care-led transition clinic that targets socially vulnerable cancer patients holds the promise of achieving more equitable healthcare access, healthcare quality, and ultimately more equitable health outcomes for cancer patients