Genome-wide association study of male sexual orientation

Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10 -5 , including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10 -7 ) and 14 (p = 4.7 × 10 -7 ). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10 -3 ) for a SNP association previously reported (rs77013977, p = 7.1 × 10 -8 ), with the combined analysis yielding p = 6.7 × 10 -9 , i.e., a genome-wide significant association

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Burden of heart failure on patients from China: results from a cross-sectional survey

James DS Jackson,1 Sarah E Cotton,1 Sara Bruce Wirta,2 Catia C Proenca,3 Milun Zhang,4 Raquel Lahoz,5 Frederico J Calado5 1Real World Research, Adelphi Real World, Bollington, UK; 2Real World Evidence, Cardio-Metabolics Franchise, Novartis Sweden AB, Stockholm, Sweden; 3Wellmera AG, Basel, Switzerland; 4Health Economics and Outcomes Research and Access Strategy, Novartis Pharma China, Beijing, China; 5Real World Evidence, Cardio-Metabolics Franchise, Novartis Pharma AG, Basel, Switzerland Purpose: Little evidence exists on the burden that chronic heart failure (HF) poses specifically to patients in China. The objective of this study, therefore, was to describe the burden of HF on patients in China.Materials and methods: A cross-sectional survey of cardiologists and their patients with HF was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Patients for whom a patient record form was completed were invited to complete a patient questionnaire.Results: Most of the 933 patients (mean [SD] age 65.8 [10.2] years; 55% male; 80% retired) included in the study received care in tier 2 and 3 hospitals in large cities. Patients gave a median score of 4 on a scale from 1 (no disruption) to 10 (severe disruption) to describe how much HF disrupts their everyday life. Patients in paid employment (8%) missed 10% of work time and experienced 29% impairment in their ability to work due to HF in the previous week. All aspects of patients&rsquo; health-related quality of life (QoL) were negatively affected by their condition. Mean &plusmn; SD utility calculated by the 3-level 5-dimension EuroQol questionnaire was 0.8&plusmn;0.2, and patients rated their health at 70.3 (11.5) on a 100 mm visual analog scale. Patients incurred costs associated with HF treatment, travel, and professional caregiving services.Conclusion: HF is associated with poor health-related QoL and considerable disruption in patients&rsquo; lives. Novel and improved therapies are needed to reduce the burden of HF on patients and the health care system. Keywords: patient burden, health-related quality of life, heart failure, survey, real-world&nbsp

Perceptions of heart failure symptoms, disease severity, treatment decision-making and side effects by patients and cardiologists: a multinational survey in a cardiology setting

Sara Bruce Wirta,1 Bogdan Balas,2 Catia C Proenca,3 Hollie Bailey,4 Zoe Phillips,4 James Jackson,4 Sarah Cotton4 1Real World Evidence, Cardio-Metabolic Franchise, Novartis Sweden, Stockholm, Sweden; 2Real World Evidence, Cardio-Metabolic Franchise, Novartis Pharma, Basel, Switzerland; 3Wellmera AG, Basel, Switzerland; 4Real World Research, Adelphi Real World, Bollington, UK Purpose: Explore the extent to which heart failure (HF) symptoms and side effects of HF treatment experienced by patients are recognized by cardiologists, and concordance between patient&ndash;cardiologist perceptions of HF severity and patients&rsquo; contributions to treatment decision-making. Methods: A multinational, cross-sectional survey of cardiologists and patients with HF was conducted. Patient-record forms (PRFs) were completed by cardiologists for consecutive consulting patients with HF, who completed a patient self-completion questionnaire (PSC). Responses from PRFs with an associated PSC were analyzed to compare patient- and cardiologist-reported occurrences of HF symptoms and treatment side effects, patient-perceived severity of HF and cardiologists&rsquo; perceived risk of death within 12 months, and patient input into treatment decisions. Concordance was calculated as the number of response agreements between PSCs and PRFs for total number of matched pairs. Over- or underreporting of symptoms and side effects by cardiologists relative to patient-reported occurrences were calculated. Results: Overall, 2,454 patient&ndash;cardiologist pairs were identified. High levels of concordance between matched pairs were observed for the occurrence of reported HF symptoms (93%), side effects (77%&ndash;98%) and degree of patient input into treatment decisions (74%); for perceived HF severity, concordance was 54%. Most symptoms (except dyspnea when active and fatigue/weakness, experienced by &gt;50% of patients) were underreported by cardiologists. Of patients reporting to have been informed by their cardiologist that their HF was mild, 28% were perceived by their cardiologist to have a moderate&ndash;high/very high risk of death within 12 months. Treatment choice was not discussed with almost a third of patients. When discussed, 94% of patients (n=1,540) reported the cardiologist made the final decision. Cardiologists more often under- than overreported the occurrence of side effects reported by patients. Conclusion: Improved patient&ndash;cardiologist dialogue and shared decision-making is required for optimizing patient care and outcomes in HF. Keywords: patient influence, disease awareness, treatment decision-making, patient-reported outcomes, disease-specific program, real worl

Burden of heart failure on caregivers in China: results from a cross-sectional survey

James DS Jackson,1 Sarah E Cotton,1 Sara Bruce Wirta,2 Catia C Proenca,3 Milun Zhang,4 Raquel Lahoz,5 Frederico J Calado5 1Real World Research, Adelphi Real World, Bollington, Cheshire, UK; 2Real World Evidence Center of Excellence, Novartis Sweden AB, Stockholm, Sweden; 3Wellmera AG, Basel, Switzerland; 4Health Economics and Outcomes Research &amp; Access Strategy, Novartis Pharma China, Beijing, China; 5Real World Evidence Center of Excellence, Novartis Pharma AG, Basel, Switzerland Purpose: Family and friends play a pivotal role in caring for patients with heart failure (HF); however, evidence of the impact of caregiving is limited. The objectives of this study were to describe the burden of caregiving on informal caregivers of patients with chronic HF in China.Materials and methods: A cross-sectional survey of cardiologists, their patients with HF, and those patients&rsquo; caregivers was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Caregivers of these patients were invited to complete a questionnaire.Results: Overall, 458 caregivers completed a questionnaire (mean &plusmn; standard deviation age 60.1&plusmn;10.6 years; 60% female; 77% spouses; 74% retired). Caregivers spent a mean of 24.5 (16.9) hours caregiving per week, and a third reported a reduction in their social activity, time for themselves, or time for family. Caregivers in employment took several days off work in the past 3&nbsp;months owing to caregiving, sometimes resulting in reduced income. Up to 79% of caregivers reported an impact on their physical or emotional well-being, and 57% reported deterioration in their objective health status. Inconsistencies stemming from differences in the three-level five-dimension EuroQol questionnaire and HF Caregiver Questionnaire were observed for the impact of caregiving on caregivers&rsquo; health-related quality of life. Conclusion: Assisting patients with HF is associated with caregiver burden. Addressing the needs of caregivers may help to promote their continued support and improve patient outcomes.Keywords: burden, caregiver, China, health-related quality of life, heart failure&nbsp

Care pathways and treatment patterns for patients with heart failure in China: results from a cross-sectional survey

James DS Jackson,1 Sarah E Cotton,1 Sara Bruce Wirta,2 Catia C Proenca,3 Milun Zhang,4 Raquel Lahoz,5 Bogdan Balas,5 Frederico J Calado5 1Real World Research, Adelphi Real World, Bollington, UK; 2Real World Evidence, Cardio-Metabolic Franchise, Novartis Sweden AB, Stockholm, Sweden; 3Wellmera AG, Basel, Switzerland; 4Health Economics and Outcomes Research, Novartis Pharma China, Beijing, China; 5Medical Affairs, Cardio-Metabolic Franchise, Novartis Pharma AG, Basel, Switzerland Purpose: The objective of this study was to describe the clinical care pathways, management and treatment patterns, and hospitalizations for patients with heart failure (HF) in China. Subjects and methods: A cross-sectional survey of cardiologists and their patients with HF was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Patients for whom a patient record form was completed were invited to complete a patient self-completion questionnaire. Results: Most of the 1,500 patients (mean [SD] age 66 [10] years; 55% male) included in the study received care in tier-2 and -3 hospitals in large cities. Cardiologists were responsible for initial consultation, diagnosis, and treatment of patients with HF. The use of guideline-recommended diagnostics was high. However, guideline-recommended double- and triple-combination therapy was received by only 51% and 18% of patients, respectively. In total, 20% of patients with HF reported that they were not consulted on the choice of therapy. Concordance was high (&ge;80%) between matched cardiologist and patient pairs for the occurrence of side effects, while cardiologists more often under- than overreported the occurrence of side effects of treatment reported by patients. Conclusion: The management of HF was predominantly overseen by cardiologists. The use of diagnostic tests was high, but the use of guideline-recommended treatment was low in this population. Improved communication between patients and cardiologists is essential to optimize treatment decision making and to increase awareness of treatment side effects. Keywords: heart failure, disease management, patient preference, treatment satisfaction, real-world evidenc