Large-Scale Evidence for the Effect of the COLIA1 Sp1 Polymorphism on Osteoporosis Outcomes: The GENOMOS Study.

Background Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. Methods and Findings Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups ( p < 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), ( p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses. Conclusions Allowing for the inevitable heterogeneity between participating teams, this study—which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene—demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases

Physician Awareness of Alcohol Use Disorders Among Older Patients

OBJECTIVES: To determine primary care physicians' awareness of, and screening practices for, alcohol use disorders (AUDs) among older patients. DESIGN: Cross-sectional telephone survey of a national sample of primary care physicians. PARTICIPANTS: Physicians randomly sampled from the Masterfile database of the American Medical Association and stratified by specialty as family practice physicians, internal medicine physicians, and either family practice or internal medicine physicians with geriatric certification. MAIN RESULTS: A total of 171 physicians were contacted: 155 (91%) agreed to participate, and responses were analyzed from 150 (50 family practice, 50 internal medicine, 50 with geriatric certification). The median prevalence estimate of AUDs among older patients was 5% for each group of physicians. In contrast to published prevalence rates of AUDs ranging from 5% to 23%, 38% of physicians reported prevalence estimates of less than 5%, and 5% cited estimates of at least 25%. Compared with the other groups, the physicians with geriatric certification were more likely to report no regular screening (42% vs 20% for family practice vs 18% for internal medicine, p=.01), while younger (<40 years) and middle-aged physicians (40–55 years) reported higher annual screening rates relative to older physicians (>55 years) (77% vs 60% vs 44% respectively, p=.03). Among physicians who regularly screened (n=110), 100% asked quantity-frequency questions, 39% also used the CAGE questions, and 15% also cited use of biochemical markers. CONCLUSIONS: Primary care physicians may “underdetect” AUDs among older patients. The development of age-specific screening methods and physician education may facilitate detection of older patients with (or at risk for) these disorders

Antibiotics in the clinical pipeline in 2013

The continued emergence of multi-drug-resistant bacteria is a major public health concern. The identification and development of new antibiotics, especially those with new modes of action, is imperative to help treat these infections. This review lists the 22 new antibiotics launched since 2000 and details the two first-in-class antibiotics, fidaxomicin (1) and bedaquiline (2), launched in 2011 and 2012, respectively. The development status, mode of action, spectra of activity, historical discovery and origin of the drug pharmacophore (natural product, natural product derived, synthetic or protein/mammalian peptide) of the 49 compounds and 6 β-lactamase/β-lactam combinations in active clinical development are discussed, as well as compounds that have been discontinued from clinical development since 2011. New antibacterial pharmacophore templates are also reviewed and analyzed