Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Contributions of the social environment to first-onset and recurrent mania.

In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=33 375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study's 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71, 2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways.

Do sport-specific stressors predict athletic injury?

Previous research concerning the relation between life stress and athletic injury has not assessed the separate predictive contribution of sport-related stress and stressors in other life domains. We propose that stressful life events that occur within the same environmental context as the outcome may have an impact that goes beyond general life stress. The present study eliminates the potential confounding of the two classes of life events, as well as potential masking effects of social desirability. In a prospective study involxing 425 high school athletes (236 males and 189 females) in four sports, preseason measures of both sport-specific and non-sport stressful life events were administered. Injury time loss was tracked during the subsequent season. The results indicated that sport-specific stressful events accounted for statistically significant injury time loss variance beyond that accounted for by general negative life stress only for female athletes. Implications of the findings for interpreting previous research and for designing future studies are discussed.

Economics of antihypertensive therapy in the elderly.

Because of the high incidence of morbidity and mortality associated with hypertension in the elderly, the treatment of hypertension in this patient group must involve consideration of clinical, humanistic and economic outcomes. The most frequently used method of pharmacoeconomic analysis for antihypertensive therapy involves cost-effectiveness analysis, although several other methods are available. Current evidence reveals a trend toward cost effectiveness of antihypertensive treatment in elderly patients. However, these formal analyses are limited by the need for extrapolation of data regarding efficacy and level of risk from epidemiological and randomised trials, information which is often lacking. To incorporate economic factors into clinical decision making, other measures of economic impact should be explored. The economic impact of antihypertensive therapy is affected by the level of risk for the patient and the efficacy of the treatment. Data indicate that the risk of morbidity and mortality related to hypertension increases with age and that current antihypertensive drugs reduce this risk. When choosing an antihypertensive agent, the following parameters should be considered: acquisition cost, likelihood of adverse effects and other determinants of treatment adherence, and individual predictors of response. The economic outcomes will be maximised if prudent drug selection is supplemented by appropriate diagnostic and classification procedures and reduction of cardiovascular risk factors other than hypertension. The accumulation of data addressing the risks and benefits of therapy for the very old and the comparative efficacy of newer antihypertensive therapies will further clarify the decision-making process.

Results of a community pharmacy-based breast cancer risk-assessment and education program.

We tested the hypothesis that an education program addressing breast cancer screening schedules and modalities coupled with a breast cancer risk assessment provided by community pharmacists can increase women's confidence in performing screening practices endorsed by the American Cancer Society (ACS). This randomized, paired, pre-post study was conducted in six community pharmacies and two health-screening fairs; subjects were 140 women over 18 years of age. The pharmacist-administered program used the Breast Cancer Risk-Assessment Tool (Gail model) software provided by the National Cancer Institute of the National Institutes of Health. In addition, pharmacists provided education and training on breast self-examination (BSE), clinical breast examination (CBE), and mammography. Adherence to ACS guidelines for monthly BSE increased from 31% to 56% (p<0.001) for all women 6 months after the program. Performance of monthly BSE by women considered at high risk for developing breast cancer increased from 20% to 60% (p<0.005). The mean number of BSEs performed over 6 months increased from 2.69 to 4.09 (p<0.001). Women's confidence performing correct BSE improved from 6.41 to 7.04 (p<0.001) on a scale of 0-10. Adherence to ACS guidelines for CBE and mammography did not reveal statistically significant improvements except for better adherence to CBE in women aged 40-49 years (81% to 97%, p<0.025). The strength of the pharmacists' intervention may not appear as manipulation of high-risk patients' behavior but as improvement of self-directed behaviors, such as BSE, across all age groups.

Giant cell tumor of the intermediate cuneiform. A case report.

Although it has yet to be determined which surgical procedure provides the least chance for recurrence, surgical treatment remains the preferred therapy for giant cell tumors of bone. Few cases of giant cell tumor of the tarsus have been reported in the literature, with less than 10 of these cases occurring in the cuneiforms. When the extent of the tumor is questionable, definitive radiologic techniques should be used to aid in the selection of the most appropriate surgical procedure. Follow-up radiographic examination is critical to ensure that the patient remains tumor free. Yearly chest x-rays are recommended to rule out pulmonary metastasis. Although giant cell tumors represent only 5% to 8% of all benign primary osseous neoplasms of the foot, they have the potential to undergo malignant transformation, increasing the morbidity and mortality to the patient. Giant cell tumors of bone are locally aggressive, often occurring adjacent to articular surfaces, and usually are large when diagnosed. It is essential for the surgeon to plan a treatment that not only minimizes the chance of recurrence, but also attempts to preserve function of the involved part.

Operative treatment of Brodie's abscess.

This manuscript deals with a unique operative management of unilateral Brodie's abscess in a 16-year-old male. Brodie's abscess is a common finding in childhood osteomyelitis. A review of the radiographic appearance, clinical presentation, and surgical management is presented.

Systemic lupus erythematosus and right recurrent laryngeal nerve palsy.

A 52-year-old woman presenting with systemic lupus erythematosus (SLE) and a right recurrent laryngeal nerve palsy is described. The symptoms and signs resolved within days of initiating steroid therapy. This is the first reported case of recurrent laryngeal nerve palsy associated with SLE in the absence of pulmonary hypertension or laryngeal lupus.