Transdermal Blood Sampling for C-peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes

OBJECTIVE:C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative.RESEARCH DESIGN AND METHODS:Ninety-one individuals (71 with type 1 diabetes, 20 controls; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1–17.1], diabetes duration 4.0 years [1.5–7.7]; controls: 42.2 years [38.0–52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire.RESULTS:Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40–50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) <35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] – TCB ln[C-peptide] = 0.008, 95% CI [−0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided).CONCLUSIONS:Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research

The situation of nursing education in Latin America and the Caribbean towards universal health

Objetivo: evaluar la situación de la educación en enfermería y analizar en qué grado los programas de educación de enfermería a nivel de grado en América Latina y el Caribe están preparando a los graduados para contribuir al logro de la Salud Universal. Método: se llevó a cabo un estudio transversal, cuantitativo, descriptivo y exploratorio en 25 países. Resultados: participaron en el estudio 246 escuelas de enfermería. El porcentaje de profesores con títulos de doctorado fue de 31,3%; pero, si se excluye a Brasil esta cifra se reduce a 8,3%. La proporción de la experiencia clínica adquirida en los servicios de atención primaria de salud en relación con la adquirida en servicios hospitalarios fue de 0,63, lo que indica que los estudiantes adquieren la mayor parte de su experiencia clínica en entornos hospitalarios. Los resultados mostraron una necesidad de mejorar el acceso a internet; la tecnología de la información; la accesibilidad para las personas discapacitadas; la evaluación de los programas, de los profesores y de los estudiantes; y los métodos de enseñanza y aprendizaje. Conclusiones: hay heterogeneidad en la educación en enfermería en América Latina y el Caribe. En general, los programas de estudios de enfermería han adoptado los principios y los valores de la Salud Universal y la atención primaria de salud, así como los principios que sustentan las modalidades de educación transformadora, como son el desarrollo del pensamiento crítico y complejo, la solución de problemas, la toma de decisiones clínicas basadas en la evidencia y el aprendizaje a lo largo de toda la vida. Sin embargo, hay necesidad de promover un cambio en el paradigma de la educación en enfermería, a fin de que abarque más capacitación en la atención primaria de salud.Objetivo: avaliar a situação da educação em enfermagem e analisar o quanto os programas de educação em enfermagem, no nível de Bacharelado na América Latina e no Caribe, estão preparando graduados a contribuir para o alcance da Saúde Universal. Método: estudo quantitativo, descritivo/exploratório, transversal, realizado em 25 países. Resultados: um total de 246 escolas de enfermagem participaram do estudo. O corpo docente com nível de Doutorado totalizou 31,3%; sem o Brasil o número fica reduzido a 8,3%. A razão entre experiências clínicas nos serviços de atenção primária à saúde e nos serviços hospitalares foi de 0,63, indicando que os estudantes têm mais experiências clínicas nos cenários hospitalares. Os resultados sugeriram necessidade de aprimoramento relacionada ao acesso à Internet; tecnologia da informação; acesso para portadores de deficiências; avaliação do programa, do corpo docente e dos estudantes; e aos métodos de ensino/aprendizagem. Conclusão: há heterogeneidade na educação em enfermagem na América Latina e no Caribe. Os currículos de enfermagem incluem, geralmente, os princípios e valores da Saúde Universal e da atenção primária à saúde, bem como aqueles princípios subjacentes às modalidades de educação transformativa, como o desenvolvimento de pensamento crítico e complexo, a solução de problemas, a tomada de decisão clínica baseada em evidências, e aprendizagem contínua. No entanto, é preciso promover uma mudança de paradigma na educação em enfermagem que inclua mais treinamento na atenção primária à saúde.Objective: to assess the situation of nursing education and to analyze the extent to which baccalaureate level nursing education programs in Latin America and the Caribbean are preparing graduates to contribute to the achievement of Universal Health. Method: quantitative, descriptive/exploratory, cross-sectional study carried out in 25 countries. Results: a total of 246 nursing schools participated in the study. Faculty with doctoral level degrees totaled 31.3%, without Brazil this is reduced to 8.3%. The ratio of clinical experiences in primary health care services to hospital-based services was 0.63, indicating that students receive more clinical experiences in hospital settings. The results suggested a need for improvement in internet access; information technology; accessibility for the disabled; program, faculty and student evaluation; and teaching/learning methods. Conclusion: there is heterogeneity in nursing education in Latin America and the Caribbean. The nursing curricula generally includes the principles and values of Universal Health and primary health care, as well as those principles underpinning transformative education modalities such as critical and complex thinking development, problem-solving, evidence-based clinical decision-making, and lifelong learning. However, there is a need to promote a paradigm shift in nursing education to include more training in primary health care

Three low-mass companions around aged stars discovered by TESS

We report the discovery of three transiting low-mass companions to aged stars: a brown dwarf (TOI-2336b) and two objects near the hydrogen burning mass limit (TOI-1608b and TOI-2521b). These three systems were first identified using data from the Transiting Exoplanet Survey Satellite (TESS). TOI-2336b has a radius of $1.05\pm 0.04\ R_J$, a mass of $69.9\pm 2.3\ M_J$ and an orbital period of 7.71 days. TOI-1608b has a radius of $1.21\pm 0.06\ R_J$, a mass of $90.7\pm 3.7\ M_J$ and an orbital period of 2.47 days. TOI-2521b has a radius of $1.01\pm 0.04\ R_J$, a mass of $77.5\pm 3.3\ M_J$ and an orbital period of 5.56 days. We found all these low-mass companions are inflated. We fitted a relation between radius, mass and incident flux using the sample of known transiting brown dwarfs and low-mass M dwarfs. We found a positive correlation between the flux and the radius for brown dwarfs and for low-mass stars that is weaker than the correlation observed for giant planets.Comment: 20 pages, 13 figures; submitted to MNRA

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention