Influenza vaccine effectiveness: Maintained protection throughout the duration of influenza seasons 2010-2011 through 2013-2014.

BACKGROUND: Factors, such as age, comorbidities, vaccine type, herd immunity, previous influenza exposure, and antigenic shift may impact the immune response to the influenza vaccine, protection against circulating strains, and antibody waning. Evaluating vaccine effectiveness (VE) is important for informing timing of vaccine administration and evaluating overall vaccine benefit. METHODS: VE was assessed using febrile respiratory illness surveillance among Department of Defense non-active duty beneficiaries from influenza seasons 2010-2011 through 2013-2014. Respiratory specimens were taken from participants meeting the case definition and tested by polymerase chain reaction for influenza. VE was calculated using logistic regression and by taking 1 minus the odds ratio of being vaccinated in the laboratory confirmed positive influenza cases versus laboratory confirmed negative controls. RESULTS: This study included 1486 participants. We found an overall adjusted VE that provided significant and fairly consistent protection ranging from 54% to 67% during 0-180days postvaccination. This VE dropped to -11% (95% confidence interval: -102% to 39%) during 181-365days. CONCLUSIONS: Our study found moderate VE up to 6months postvaccination. Since the influenza season starts at different times each year, optimal timing is difficult to predict. Consequently, early influenza vaccination may still offer the best overall protection.

Women in Radiology: Exploring the Gender Disparity.

PURPOSE: In 2015, only 1.5% of female Canadian medical students pursued radiology as a specialty, versus 5.6% of men. The aim of this study was to determine what factors attract and deter Canadian medical students from pursuing a career in radiology, and why fewer women than men pursue radiology as a specialty. METHODS: An anonymous online survey was e-mailed to English-speaking Canadian medical schools, and 12 of 14 schools participated. Subgroup analyses for gender and radiology interest were performed using the Fisher exact test (P < .05). RESULTS: In total, 917 students (514 women; 403 men) responded. Direct patient contact was valued by significantly more women who were not considering specialization in radiology (87%), compared with women who were (70%; P < .0001). Physics deterred more women (47%) than it did men (21%), despite similar educational backgrounds for the two gender groups in physical sciences (P < .0001). More women who were considering radiology as a specialty rated intellectual stimulation as being important to their career choice (93%), compared with women who were not (80%; P = .002). Fewer women who were not interested in radiology had done preclinical observerships in radiology (20%), compared with men who were not interested in radiology (28%; P = .04). CONCLUSIONS: A perceived lack of direct patient contact dissuades medical students from pursuing radiology as a career. Women have less preclinical radiology exposure than do men. Programs that increase preclinical exposure to radiology subspecialties that have greater patient contact should be initiated, and an effort to actively recruit women to such programs should be made.

Perception of radiation exposure and risk among patients, medical students, and referring physicians at a tertiary care community hospital.

BACKGROUND: It is important for physicians to be aware of the radiation doses as well as the risks associated with diagnostic imaging procedures that they are ordering. METHODS: A survey was administered to patients, medical students, and referring physicians from a number of specialties to determine background knowledge regarding radiation exposure and risk associated with commonly ordered medical imaging tests. RESULTS: A total of 127 patients, 32 referring physicians, and 30 medical students completed the survey. The majority of patients (92%) were not informed of the radiation risks associated with tests that they were scheduled to receive and had false perceptions about the use of radiation and its associated risks. Physicians and medical students had misconceptions about the use of ionizing radiation in a number of radiologic examinations; for example, 25% and 43% of physicians and medical students, respectively, were unaware that interventional procedures used ionizing radiation, and 28% of physicians were unaware that mammography used ionizing radiation. Computed tomographies and barium studies were thought to be associated with the least ionizing radiation among physicians. CONCLUSION: There is a need for educating the public, medical students, and referring physicians about radiation exposure and associated risk so that (1) patients receiving multiple medical imaging tests are aware of the radiation that they are receiving and (2) physicians and future physicians will make informed decisions when ordering such tests to limit the amount of radiation that patients receive and to promote informed consent among patients.

Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.

BACKGROUND: Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. METHODS: We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. FINDINGS: We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. INTERPRETATION: Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention. FUNDING: arcOGEN was funded by a special purpose grant from Arthritis Research UK.

Incidental discovery of a membranous ventricular septal aneurysm in two dissimilar patients.

A ventricular septal aneurysm (VSA) is a rare cardiac anomaly, and an accurate statistic of its prevalence has not been reported in the literature. True incidence is likely underestimated as most patients are thought to be asymptomatic. As a result, most VSAs are discovered incidentally on echocardiography, during angiography, or at autopsy. Potential complications include rupture, bacterial endocarditis, right ventricular outflow tract obstruction, and thromboembolic disease. It has been proposed that VSAs occur in association with ventricular septal defects (VSDs) and other congenital cardiac abnormalities. It is uncommon for a VSA to exist in the absence of a known prior ventricular septal defect. We present two cases, each highlighting an incidental intact aneurysm involving the membranous interventricular septum. We discuss the contrast in the two patients with regard to their age, accompanying cardiac anomalies and cardiovascular fitness. Clinical implications of the condition are reviewed.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer.

We conducted a genome-wide association study for testicular germ cell tumor, genotyping 298,782 SNPs in 979 affected individuals and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three new susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5, which has previously been associated with multiple other cancers (rs4635969, OR=1.54, P=1.14x10(-23); rs2736100, OR=1.33, P=7.55x10(-15)). We also identified a locus on chromosome 12 (rs2900333, OR=1.27, P=6.16x10(-10)) that contains ATF7IP, a regulator of TERT expression. Finally, we identified a locus on chromosome 9 (rs755383, OR=1.37, P=1.12x10(-23)), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice.