Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldTo determine if neuregulin 1 (NRG1) is associated with schizophrenia in Asian populations, we investigated a Han Chinese population using both a family trio design and a case-control design. A total of 25 microsatellite markers and single nucleotide polymorphisms (SNPs) were genotyped spanning the 1.1 Mb NRG1 gene including markers of a seven-marker haplotype at the 5' end of the gene found to be in excess in Icelandic and Scottish schizophrenia patients. The alleles of the individual markers forming the seven marker at-risk haplotype are not likely to be causative as they are not in excess in patients in the Chinese population studied here. However using unrelated patients, we find a novel haplotype (HAP(China 1)), immediately upstream of the Icelandic haplotype, in excess in patients (11.9% in patients vs 4.2% in controls; P=0.0000065, risk ratio (rr) 3.1), which was not significant when parental controls were used. Another haplotype (HAP(China 2)) overlapping the Icelandic risk haplotype was found in excess in the Chinese (8.5% of patients vs 4.0% of unrelated controls; P=0.003, rr 2.2) and was also significant using parental controls only (P=0.0047, rr 2.1). A four-marker haplotype at the 3' end of the NRG1 gene, HAP(China 3), was found at a frequency of 23.8% in patients and 13.7% in nontransmitted parental haplotypes (P=0.000042, rr=2.0) but was not significant in the case-control comparison. We conclude that different haplotypes within the boundaries of the NRG1 gene may be associated with schizophrenia in the Han Chinese

Current European guidelines for management of arterial hypertension: Are they adequate for use in primary care? Modelling study based on the Norwegian HUNT 2 population

<p>Abstract</p> <p>Background</p> <p>Previous studies indicate that clinical guidelines using combined risk evaluation for cardiovascular diseases (CVD) may overestimate risk. The aim of this study was to model and discuss implementation of the current (2007) hypertension guidelines in a general Norwegian population.</p> <p>Methods</p> <p>Implementation of the current <it>European Guidelines for the Management of Arterial Hypertension </it>was modelled on data from a cross-sectional, representative Norwegian population study (The Nord-Trøndelag Health Study 1995-97), comprising 65,028 adults, aged 20-89, of whom 51,066 (79%) were eligible for modelling.</p> <p>Results</p> <p>Among individuals with blood pressure ≥120/80 mmHg, 93% (74% of the total, adult population) would need regular clinical attention and/or drug treatment, based on their total CVD risk profile. This translates into 296,624 follow-up visits/100,000 adults/year. In the Norwegian healthcare environment, 99 general practitioner (GP) positions would be required in the study region for this task alone. The number of GPs currently serving the adult population in the study area is 87 per 100,000 adults.</p> <p>Conclusion</p> <p>The potential workload associated with the European hypertension guidelines could destabilise the healthcare system in Norway, one of the world's most long- and healthy-living nations, by international comparison. Large-scale, preventive medical enterprises can hardly be regarded as scientifically sound and ethically justifiable, unless issues of practical feasibility, sustainability and social determinants of health are considered.</p

Use and feasibility of delayed prescribing for respiratory tract infections: A questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Delayed prescribing of antibiotics for respiratory tract infections (RTIs) lowers the amount of antibiotics consumed. Several national treatment guidelines on RTIs recommend the strategy. When advocating treatment innovations, the feasibility and credibility of the innovation must be taken into account. The objective of this study was to explore GPs use and patients uptake of wait-and-see prescriptions for RTIs, and to investigate the feasibility of the strategy from GPs' and patients' perspectives.</p> <p>Methods</p> <p>Questionnaire survey among Norwegian GPs issuing and patients receiving a wait-and-see-prescription for RTIs. Patients reported symptoms, confidence and antibiotics consumption, GPs reported diagnoses, reason for issuing a wait-and-see-prescription and their opinion about the method.</p> <p>Results</p> <p>304 response pairs from consultations with 49 GPs were received. The patient response rate was 80%. The most common diagnosis for the GPs to issue a wait-and-see prescription was sinusitis (33%) and otitis (21%). 46% of the patients reported to consume the antibiotics. When adjusted for other factors, the diagnosis did not predict antibiotic consumption, but both being 16 years or more (p = 0,006) and reporting to have a fever (p = 0,012) doubled the odds of antibiotic consumption, while feeling very ill more than quadrupled the odds (p = 0,002). In 210 cases (69%), the GP found delayed prescribing a very reasonable strategy, and 270 patients (89%) would prefer to receive a wait-and-see prescription in a similar situation in the future. The GPs found delayed prescribing very reasonable most frequently in cases of sinusitis (79%, p = 0,007) and least frequently in cases of lower RTIs (49%, p = 0,002).</p> <p>Conclusion</p> <p>Most patients and GPs are satisfied with the delayed prescribing strategy. The patients' age, symptoms and malaise are more important than the diagnosis in predicting antibiotic consumption. The GP's view of the method as a reasonable approach depends on the patient's diagnosis. In our setting, delayed prescribing seems to be a feasible strategy, especially in cases of sinusitis and otitis. Educational efforts to promote delayed prescribing in similar settings should focus on these diagnoses.</p

Иммунно-нейроэндокринные взаимосвязи в развитии перименопаузальной патологии

Представлен современный патогенетический взгляд на происходящие в перименопаузальном периоде системные нарушения. Показано, что имунно-нейроэндокринный гомеостаз имеет определенные отличия в зависимости от клинической формы и степени тяжести перименопаузальных нарушений, что необходимо учитывать при проведении терапевтических мероприятий.Представлено сучасний патогенетичний погляд на системні порушення, що відбуваються в перименопаузальному періоді. Показано, що імунно-нейроендокринний гомеостаз має певні відмінності залежно від клінічної форми і ступеня тяжкості перименопаузальних порушень, що необхідно враховувати під час проведення терапевтичних заходів.A modern pathogenetic opinion about the systemic perimenopausal disorders is presented. It is shown that immunoneuroendocrine homeostatsis differs depending on the clinical form and degree of severity of perimenopausal disorders, which should be taken into consideration when taking therapeutic measures

Infectious disease management in primary care: perceptions of GPs

<p>Abstract</p> <p>Background</p> <p>It is important to keep the level of antibiotic prescribing low to contain the development of resistant bacteria. This study was conducted to reveal new knowledge about how GPs think in relation to the prescribing of antibiotics - knowledge that could be used in efforts toward rational treatment of infectious diseases in primary care. The aim was to explore and describe the variations in GPs' perceptions of infectious disease management, with special reference to antibiotic prescribing.</p> <p>Methods</p> <p>Twenty GPs working at primary care centres in a county in south-west Sweden were purposively selected based on the strategy of including GPs with different kinds of experience. The GPs were interviewed and perceptions among GPs were analysed by a phenomenographic approach.</p> <p>Results</p> <p>Five qualitatively different perceptions of infectious disease management were identified. They were: (A) the GP must help the patient to achieve health and well-being; (B) the management must meet the GP's perceived personal, professional and organisational demands; (C) restrictive antibiotic prescribing is time-consuming; (D) restrictive antibiotic prescribing can protect the effectiveness of antibiotics; and (E) patients benefit personally from restrictive antibiotic prescribing.</p> <p>Conclusions</p> <p>Restrictive antibiotic prescribing was considered important in two perceptions, was not an issue as such in two others, and was considered in one perception although the actual prescribing was greatly influenced by the interaction between patient and GP. Accordingly, to encourage restrictive antibiotic prescribing several aspects must be addressed. Furthermore, different GPs need various kinds of support. Infectious disease management in primary care is complex and time-consuming, which must be acknowledged in healthcare organisation and planning.</p

Benzodiazepine use among adults residing in the urban settlements of Karachi, Pakistan: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>There are hardly any studies carried out in Pakistan on the usage of benzodiazepines at the level of community. This research was aimed to determine the frequency of benzodiazepine use, along with its associations with socio-demographic and clinical characteristics among community dwelling adults, residing in two urban settlements of Karachi, Pakistan.</p> <p>Methods</p> <p>We performed a cross sectional study from August 2008 to December 2009, in 2 areas of Karachi, namely Garden and Sultanabad. We followed the systematic sampling strategy to randomly select the households, with an adult of either sex and of age 18 years or more. Data collection was carried out through interview, using a pre-tested questionnaire, with items on socio-demographic position, medical history and benzodiazepine use. Student's t-test and χ²test was employed to determine the associations between socio-demographic and clinical characteristics, and their relationship with benzodiazepine use was determined using applied logistic regression.</p> <p>Results</p> <p>The overall percentage of benzodiazepine consumption was estimated to be 14%. There were significantly more benzodiazepine users in the peri-urban Sultanabad community to the urban community of Garden (p-value = 0.001). The mean age (± SD) for users was 51.3 (± 15.6) years compared to 37.1 (± 14.4) years among non-users. Bromazepam was the most widely used benzodiazepine (29%); followed by diazepam, with a median duration on primary use being 144 weeks (IQR = 48-240). The adjusted logistic regression model revealed that increasing age, location, female sex, unemployment and psychiatric consultation were associated with increased likelihood of benzodiazepine use.</p> <p>Conclusion</p> <p>We believe the unregulated over-the-counter sales of benzodiazepines and social conditions might be playing a role in this high consumption of benzodiazepines in the community.</p

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5x10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci

Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations

Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10−9). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5–1,100). In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36–3.43). Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection