Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.

Estimation of population attributable fraction (PAF) for disease occurrence in a cohort study design.

The population attributable fraction (PAF) is a useful measure for describing the expected change in an outcome if its risk factors are modified. Cohort studies allow researchers to assess the predictive value of the risk factor modification on the incidence of the outcome during a certain follow-up. Estimation of PAF for both mortality and morbidity in cohort studies with censored survival data has been developed in the recent years. So far, however, censoring due to death in the estimation of PAF for morbidity has been ignored, resulting in estimation of a quantity which is not relevant in practice as some people are likely to die during the follow-up. The risk factors related to the disease incidence may also be related to mortality, and modification of these risk factors is likely to delay the occurrence of both events. Thus, censoring due to death and the impact of risk factor modification must be considered when estimating PAF for disease incidence. We consider both and introduce two measures of disease burden: PAF for the incidence of disease during lifetime and PAF for the prevalence of disease in the population at a certain time. We demonstrate how consideration of censoring due to death changes the estimated PAF for disease incidence and its confidence interval. This underlines the importance of choosing a correct PAF measure depending on the outcome of interest and the risk factors of interest to obtain accurate and interpretable results.

Demographic, social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. METHODS: Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04-1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24-2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08-1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08-2.64), and current (OR 3.42, 95% CI 1.81-6.47) or former (OR 1.95, 95% CI 1.33-2.86) smokers. CONCLUSION: The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.

Health-related predictors of cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: The relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain. METHODS: A prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, health service records 4-27 months prior to diagnosis, and mortality data. We compared individuals with incident registry-notified CUP (n = 327; 90% C80) to two sets of randomly selected controls (3:1): (i) incident metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted models incorporating sociodemographic and lifestyle factors, people with cancer registry-notified CUP were more likely to have fair compared with excellent self-rated overall health (OR 1.78, 95% CI 1.01-3.14) and less likely to self-report anxiety (OR 0.48, 95% CI 0.24-0.97) than those registered with metastatic cancer of known primary. Compared to general cohort population controls, people registered with CUP were more likely to have poor rather than excellent self-rated overall health (OR 6.22, 95% CI 1.35-28.6), less likely to self-report anxiety (OR 0.28, 95% CI 0.12-0.63), and more likely to have a history of diabetes (OR 1.89, 95% CI 1.15-3.10) or cancer (OR 1.62, 95% CI 1.03-2.57). Neither tertiary nor community-based health service use independently predicted CUP risk. CONCLUSION: Low self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted.

Prospective study of coffee consumption and risk of Parkinson's disease.

OBJECTIVE: To examine the prediction of coffee consumption on the incidence of Parkinson's disease. SUBJECTS AND METHODS: The study population comprised 6710 men and women, aged 50-79 years and free from Parkinson's disease at the baseline. At baseline, enquiries were made about coffee consumption in a self-administered questionnaire as the average number of cups per day. During a 22-year follow-up, 101 incident cases of Parkinson's disease occurred. Parkinson's disease cases were identified through a nationwide registry of patients receiving medication reimbursement, which is based on certificates from neurologist. RESULTS: After adjustments for age, sex, marital status, education, community density, alcohol consumption, leisure-time physical activity, smoking, body mass index, hypertension and serum cholesterol, the relative risk for subjects drinking 10 or more cups of coffee per day compared with non-drinkers was 0.26 (95% confidence interval 0.07-0.99, P-value for trend=0.18). The association was stronger among overweight persons and among persons with lower serum cholesterol level (P-value for interaction=0.04 and 0.03, respectively). CONCLUSIONS: The results support the hypothesis that coffee consumption reduces the risk of Parkinson's disease, but protective effect of coffee may vary by exposure to other factors.

Psychological predictors on the outcome of short-term psychodynamic psychotherapy and solution-focused therapy in the treatment of mood and anxiety disorder.

OBJECTIVE: Patient's pre-treatment suitability for short-term psychodynamic psychotherapy (STPP) and solution-focused therapy (SFT) has not been compared. The aim of this study was to compare the prediction of psychological suitability measures on outcome of STPP vs. SFT. METHOD: Altogether 198 patients with mood or anxiety disorder were randomized to STPP or SFT. A 7-item Suitability for Psychotherapy Scale (SPS) was assessed at baseline and a cumulative SPS score was formed. Psychiatric symptoms were measured using SCL-90-GSI at baseline and seven times during a 3-year follow-up. RESULTS: The SPS score predicted the outcome of both short-term psychotherapies; for patients with a good score short-term therapies seemed beneficial, whereas for patients with a poor score they did not seem sufficient. There was no difference between STPP and SFT in the prediction of the SPS score. CONCLUSIONS: Psychological suitability measures may apparently be useful in the prediction of overall short-term psychotherapy outcomes.

Prediction of the outcome of short- and long-term psychotherapy based on socio-demographic factors.

BACKGROUND: Socio-demographic factors predict the outcome of short-term psychotherapy (STT) in the treatment of mood and anxiety disorders, but information on the prediction for long long-term therapy (LPP) is lacking. We aimed to compare the prediction of changes in psychiatric symptoms afforded by socio-demographic factors across two treatment conditions, short- versus long-term psychotherapy. METHODS: In the Helsinki Psychotherapy Study, 326 outpatients with mood or anxiety disorders, aged 20-46 years, were randomly assigned to STT or LPP. Socio-demographic factors (i.e. age, gender, education, employment status, marital status, and living arrangement) were self-reported. Psychiatric symptoms were measured by the Symptom Check List, Global Severity Index (SCL-90-GSI) and Anxiety scale (SCL-90-Anx), and the Beck Depression Inventory (BDI) at baseline and seven times during a three-year follow-up period. RESULTS: Socio-demographic factors were found to predict symptom development during follow-up irrespective of the baseline symptom level. Patients in a relatively good position, i.e. married and highly educated patients benefited from STT, whereas patients in less advantaged positions, i.e. homemakers, lone parents, and divorced patients needed LPP or did not benefit from either therapy. In several categories of socio-demographic factors, the extent to which a patient's background predicted the outcome of the psychotherapy varied according to whether general, anxiety or depressive symptoms were studied. LIMITATIONS: We were unable to assess widows and pensioners. For ethical reasons, a no-treatment control group with a long follow-up could not be included in the study design. CONCLUSIONS: Socio-demographic factors may need to be considered in the selection of patients for short- and long-term therapy.

Changes in lifestyle for psychiatric patients three years after the start of short- and long-term psychodynamic psychotherapy and solution-focused therapy.

OBJECTIVES: Lifestyle is less favourable among individuals suffering from psychiatric disorders. We studied whether psychotherapy brings along changes in lifestyle and whether these changes differ between short-term and long-term psychodynamic psychotherapy (SPP and LPP) and solution-focused therapy (SFT). METHODS: A total of 326 outpatients, 20-46 years of age, with mood or anxiety disorder were randomly assigned to LPP, SPP and SFT. The lifestyle variables considered were alcohol consumption, smoking, body mass index (BMI), leisure time exercise and serum cholesterol. The patients were monitored for three years from the start of treatment. RESULTS: During the three-year follow-up, BMI and serum cholesterol rose statistically significantly although no statistically significant trends were shown for alcohol consumption, smoking or exercise. SPP showed a disadvantage of increased alcohol consumption and serum cholesterol level when compared with LPP. SFT showed an advantage of reduced smoking in comparison with SPP. DISCUSSION: Small therapy-specific changes in lifestyle may be a result from psychotherapy treatment. These lifestyle changes are apparently more common in short-term therapy. More studies are needed to verify these findings.

Randomized trial on the effectiveness of long-and short-term psychodynamic psychotherapy and solution-focused therapy on psychiatric symptoms during a 3-year follow-up.

BACKGROUND: Insufficient evidence exists for a viable choice between long- and short-term psychotherapies in the treatment of psychiatric disorders. The present trial compares the effectiveness of one long-term therapy and two short-term therapies in the treatment of mood and anxiety disorders. METHOD: In the Helsinki Psychotherapy Study, 326 out-patients with mood (84.7%) or anxiety disorder (43.6%) were randomly assigned to three treatment groups (long-term psychodynamic psychotherapy, short-term psychodynamic psychotherapy, and solution-focused therapy) and were followed up for 3 years from start of treatment. Primary outcome measures were depressive symptoms measured by self-report Beck Depression Inventory (BDI) and observer-rated Hamilton Depression Rating Scale (HAMD), and anxiety symptoms measured by self-report Symptom Check List Anxiety Scale (SCL-90-Anx) and observer-rated Hamilton Anxiety Rating Scale (HAMA). RESULTS: A statistically significant reduction of symptoms was noted for BDI (51%), HAMD (36%), SCL-90-Anx (41%) and HAMA (38%) during the 3-year follow-up. Short-term psychodynamic psychotherapy was more effective than long-term psychodynamic psychotherapy during the first year, showing 15-27% lower scores for the four outcome measures. During the second year of follow-up no significant differences were found between the short-term and long-term therapies, and after 3 years of follow-up long-term psychodynamic psychotherapy was more effective with 14-37% lower scores for the outcome variables. No statistically significant differences were found in the effectiveness of the short-term therapies. CONCLUSIONS: Short-term therapies produce benefits more quickly than long-term psychodynamic psychotherapy but in the long run long-term psychodynamic psychotherapy is superior to short-term therapies. However, more research is needed to determine which patients should be given long-term psychotherapy for the treatment of mood or anxiety disorders.