Depression and anxiety in adolescents and adults with cystic fibrosis in the UK: A cross-sectional study

Background The International Depression/anxiety Epidemiological Study (TIDES) in the UK aimed: (i) to establish the prevalence of anxiety and depression amongst people with CF compared to a normative sample; (ii) to establish the association between mood, demographic and clinical variables; and (iii) to provide guidance for specialist-referral decision-making. Methods Patients (≥ 12 years) completed the Hospital Anxiety and Depression Scale (HADS). CF-HADS scores, expressed as percentiles, were compared with a normative sample. Multiple-regression analysis explored associations between demographic, clinical and mood variables. Results Thirty-nine CF centres recruited 2065 patients. Adults with CF were similar in terms of anxiety and depression to the general population. Adolescents with CF were less anxious and depressed. For adult patients, older age, unemployment for health reasons and poor lung function were associated with disordered mood. Gender-specific CF-percentile scores were calculated. Conclusion Surveillance, with attention to gender and risk factors is advocated. This work provides unique benchmark scores to aid referral decision-making

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

Gender differences and determinants of health related quality of life in coronary patients: a follow-up study

<p>Abstract</p> <p>Background</p> <p>The role of gender differences in Health Related Quality Life (HRQL) in coronary patients is controversial, so understanding the specific determinants of HRQL in men and women might be of clinical importance. The aim of this study was to know the gender differences in the evolution of HRQL at 3 and 6 months after a coronary event, and to identify the key clinical, demographic and psychological characteristics of each gender associated with these changes.</p> <p>Methods</p> <p>A follow-up study was carried out, and 175 patients (112 men and 63 women) with acute myocardial infarction (AMI) or unstable angina were studied. The SF-36v1 health questionnaire was used to assess HRQL, and the GHQ-28 (General Health Questionnaire) to measure mental health during follow-up. To study the variables related to changes in HRQL, generalized estimating equation (GEE) models were performed.</p> <p>Results</p> <p>Follow-up data were available for 55 men and 25 women at 3 months, and for 35 men and 12 women at 6 months. Observations included: a) Revascularization was performed later in women. b) The frequency of rehospitalization between months 3 and 6 of follow-up was higher in women c) Women had lower baseline scores in the SF-36. d) Men had progressed favourably in most of the physical dimensions of the SF-36 at 6 months, while at the same time women's scores had only improved for Physical Component Summary, Role Physical and Social Functioning; e) the variables determining the decrease in HRQL in men were: worse mental health and angina frequency; and in women: worse mental health, history of the disease, revascularization, and angina frequency.</p> <p>Conclusions</p> <p>There are differences in the evolution of HRQL, between men and women after a coronary attack. Mental health is the determinant most frequently associated with HRQL in both genders. However, other clinical determinants of HRQL differed with gender, emphasizing the importance of individualizing the intervention and the content of rehabilitation programs. Likewise, the recognition and treatment of mental disorders in these patients could be crucial.</p

Genetic association of zinc transporter 8 (ZnT8) autoantibodies in type 1 diabetes cases

Autoantibodies to zinc transporter 8 (ZnT8A) are associated with risk of type 1 diabetes. Apart from the SLC30A8 gene itself, little is known about the genetic basis of ZnT8A. We hypothesise that other loci in addition to SLC30A8 are associated with ZnT8A. The levels of ZnT8A were measured in 2,239 British type 1 diabetic individuals diagnosed before age 17 years, with a median duration of diabetes of 4 years. Cases were tested at over 775,000 loci genome wide (including 53 type 1 diabetes associated regions) for association with positivity for ZnT8A. ZnT8A were also measured in an independent dataset of 855 family members with type 1 diabetes. Only FCRL3 on chromosome 1q23.1 and the HLA class I region were associated with positivity for ZnT8A. rs7522061T &gt; C was the most associated single nucleotide polymorphism (SNP) in the FCRL3 region (p = 1.13 x 10(-16)). The association was confirmed in the family dataset (p a parts per thousand currency signaEuro parts per thousand 9.20 x 10(-4)). rs9258750A &gt; G was the most associated variant in the HLA region (p = 2.06 x 10(-9) and p = 0.0014 in family cases). The presence of ZnT8A was not associated with HLA-DRB1, HLA-DQB1, HLA-A, HLA-B or HLA-C (p &gt; 0.05). Unexpectedly, the two loci associated with the presence of ZnT8A did not alter risk of having type 1 diabetes, and the 53 type 1 diabetes risk loci did not influence positivity for ZnT8A, despite them being disease specific. ZnT8A are not primary pathogenic factors in type 1 diabetes. Nevertheless, ZnT8A testing in combination with other autoantibodies facilitates disease prediction, despite the biomarker not being under the same genetic control as the disease

Characterizing hospital workers' willingness to report to duty in an influenza pandemic through threat- and efficacy-based assessment

<p>Abstract</p> <p>Background</p> <p>Hospital-based providers' willingness to report to work during an influenza pandemic is a critical yet under-studied phenomenon. Witte's Extended Parallel Process Model (EPPM) has been shown to be useful for understanding adaptive behavior of public health workers to an unknown risk, and thus offers a framework for examining scenario-specific willingness to respond among hospital staff.</p> <p>Methods</p> <p>We administered an anonymous online EPPM-based survey about attitudes/beliefs toward emergency response, to all 18,612 employees of the Johns Hopkins Hospital from January to March 2009. Surveys were completed by 3426 employees (18.4%), approximately one third of whom were health professionals.</p> <p>Results</p> <p>Demographic and professional distribution of respondents was similar to all hospital staff. Overall, more than one-in-four (28%) hospital workers indicated they were not willing to respond to an influenza pandemic scenario if asked but not required to do so. Only an additional 10% were willing if required. One-third (32%) of participants reported they would be unwilling to respond in the event of a more severe pandemic influenza scenario. These response rates were consistent across different departments, and were one-third lower among nurses as compared with physicians. Respondents who were hesitant to agree to work additional hours when required were 17 times less likely to respond during a pandemic if asked. Sixty percent of the workers perceived their peers as likely to report to work in such an emergency, and were ten times more likely than others to do so themselves. Hospital employees with a perception of high efficacy had 5.8 times higher declared rates of willingness to respond to an influenza pandemic.</p> <p>Conclusions</p> <p>Significant gaps exist in hospital workers' willingness to respond, and the EPPM is a useful framework to assess these gaps. Several attitudinal indicators can help to identify hospital employees unlikely to respond. The findings point to certain hospital-based communication and training strategies to boost employees' response willingness, including promoting pre-event plans for home-based dependents; ensuring adequate supplies of personal protective equipment, vaccines and antiviral drugs for all hospital employees; and establishing a subjective norm of awareness and preparedness.</p

Strain-Dependent Differences in Bone Development, Myeloid Hyperplasia, Morbidity and Mortality in Ptpn2-Deficient Mice

Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2ex2−/ex2− mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2−/− mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2ex2−/ex2− mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2−/− (BALB/c) mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea) evident in Ptpn2−/− (BALB/c) mice were not detected in Ptpn2ex2−/ex2− mice. At 14 days of age, bone development was delayed in Ptpn2−/− (BALB/c) mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2ex2−/ex2− mice. Ptpn2ex2−/ex2− mice had defects in erythropoiesis and B cell development as evident in Ptpn2−/− (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2−/− (BALB/c) mice. Moreover, thymic atrophy, another feature of Ptpn2−/− (BALB/c) mice, was delayed in Ptpn2ex2−/ex2− mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2−/− (BALB/c) mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2ex2−/ex2− mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent

Guidelines for the management of pregnancy in women with cystic fibrosis

Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF