3,011 research outputs found
Diabetes in the Torres Strait Islands of Australia: better clinical systems but significant increase in weight and other risk conditions among adults, 1999-2005
OBJECTIVES: To (i) assess changes in clinical indicators of adults diagnosed with diabetes and (ii) estimate changes in risk factors and incidence of diabetes among adults without diabetes living in the Torres Strait and Northern Peninsula Area Health Service District in Queensland from 1999 to 2005.
DESIGN AND PARTICIPANTS: (i) Annual audit of clinical records of Torres Strait Islander adults on diabetes registers in 21 primary care clinics, and (ii) a 5-year follow up of a community cohort of 207 Torres Strait Islander adults without diabetes who participated in the Well Person's Health Check in 2000-01 and 2005-06.
MAIN OUTCOME MEASURES: Weight, height, waist circumference, fasting blood sugar (those without diabetes) and glycated haemoglobin (HbA1c; those with diabetes) levels, blood pressure (BP), fasting triglyceride and high-density lipoprotein cholesterol levels, urinary albumin-to-creatinine ratio and smoking status.
RESULTS: The number of adults included on the diabetes register increased from 555 in 1999 to 1024 in 2005. The mean age of patients diagnosed with diabetes decreased from 53.3 to 51.5 years, and their mean weight increased from 86.8 kg to 95.6 kg. Mean HbA1c level remained unchanged at about 9%, but the proportion with HbA1c level < 7% increased from 18.4% to 26.1%, and the proportion prescribed insulin increased from 14% in 2002 to 22% in 2005. The proportion with BP < 140/90 mmHg increased from 40.3% in 1999 to 66.8% in 2005. In the sample of 207 adults without diabetes, from 2000 to 2006, there was a weight gain of about 1 kg per person per year, and an annual increase in waist circumference of 0.8 cm in men and 1.2 cm in women. Crude incidence of diabetes was 29 (95% CI, 19-41) per 1000 person-years. There was a significant increase in diastolic blood pressure and fasting blood sugar levels, and no change in smoking habits.
CONCLUSIONS: Clinical care of adults with diabetes has improved and more people with diabetes are being diagnosed. However, weight gain and high rates of glycaemia remain a challenge and will result in a large burden of complications, including renal failure. Incidence data from this sample extrapolate to 120 (95% CI, 103-147) new cases of diabetes in the District each year. Urgent action to improve nutrition, decrease smoking and increase physical activity is required to improve metabolic fitness in younger people
Pre-pregnancy predictors of hypertension in pregnancy among Aboriginal and Torres Strait Islander women in north Queensland, Australia; a prospective cohort study
BACKGROUND Compared to other Australian women, Indigenous women are frequently at greater risk for hypertensive disorders of pregnancy. We examined pre-pregnancy factors that may predict hypertension in pregnancy in a cohort of Aboriginal and Torres Strait Islander women in north Queensland. METHODS Data on a cohort of 1009 Indigenous women of childbearing age (15–44 years) who participated in a 1998–2000 health screening program in north Queensland were combined with 1998–2008 Queensland hospitalisations data using probabilistic data linkage. Data on the women in the cohort who were hospitalised for birth (n = 220) were further combined with Queensland perinatal data which identified those diagnosed with hypertension in pregnancy. RESULTS Of 220 women who gave birth, 22 had hypertension in the pregnancy after their health check. The mean age of women with and without hypertension was similar (23.7 years and 23.9 years respectively) however Aboriginal women were more affected compared to Torres Strait Islanders. Pre-pregnancy adiposity and elevated blood pressure at the health screening program were predictors of a pregnancy affected by hypertension. After adjusting for age and ethnicity, each 1 cm increase in waist circumference showed a 4% increased risk for hypertension in pregnancy (PR 1.04; 95% CI; 1.02-1.06); each 1 point increase in BMI showed a 9% adjusted increase in risk (1.09; 1.04-1.14). For each 1 mmHg increase in baseline systolic blood pressure there was an age and ethnicity adjusted 6% increase in risk and each 1 mmHg increase in diastolic blood pressure showed a 7% increase in risk (1.06; 1.03-1.09 and 1.07; 1.03-1.11 respectively). Among those free of diabetes at baseline, the presence of the metabolic syndrome (International Diabetes Federation criteria) predicted over a three-fold increase in age-ethnicity-adjusted risk (3.5; 1.50-8.17). CONCLUSIONS Pre-pregnancy adiposity and features of the metabolic syndrome among these young Aboriginal and Torres Strait Islander women track strongly to increased risk of hypertension in pregnancy with associated risks to the health of babies.Sandra K Campbell, John Lynch, Adrian Esterman and Robyn McDermot
Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial
Background: Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best practice model that applies major elements of case management, including patient education, can improve antithrombotic management in primary health care in terms of reducing major thromboembolic and bleeding events.
Methods: This 24-month cluster-randomized trial will be performed in 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, health care assistants and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, health care assistants will be trained in case management and will use the Coagulation-Monitoring-List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment-as-usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization, and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients' assessment of chronic illness care, self-reported adherence to medication, general practitioners' and health care assistants' knowledge, patients' knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline (T0), follow-up after 12 (T1) and after 24 months (T2).
Discussion: The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients and the methodological tool, case-management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment
Self-assembled monolayer-based immunoassays for okadaic acid detection in seawater as monitoring tools
Rapid and cost-effective methods to monitor the presence of diarrhetic shellfish poisoning (DSP) toxins in seawater samples in an easy and reliable manner are required to protect human health and avoid economic losses to shellfish industry. Immunoassays for the detection of okadaic acid (OA) and dinophysistoxin-1 and dinophysistoxin-2 are developed by immobilising OA on self-assembled monothiols or dithiols in an ordered and oriented way, providing an effective limit of detection of ∼1 ng OA equiv./mL seawater. The immunoassays are applied to the analysis of the particulate fraction of seawater samples from two Catalan harbours (NW Mediterranean) and samples collected periodically from the Galician Rias (E Atlantic), as well as a reference mussel sample. Results are in agreement with LC-MS/MS and the certified values. OA concentration in seawater correlates with Dinophysis cell abundance, with a 1–2 weeks lag. The immunoassays provide powerful high-throughput analytical methods potentially applicable as alternative monitoring tools.info:eu-repo/semantics/acceptedVersio
Improving care for patients with osteoarthritis in five european countries: the jigsaw-e patient panel
info:eu-repo/semantics/publishedVersio
Educational outreach to general practitioners reduces children's asthma symptoms: a cluster randomised controlled trial
<p>Abstract</p> <p>Background</p> <p>Childhood asthma is common in Cape Town, a province of South Africa, but is underdiagnosed by general practitioners. Medications are often prescribed inappropriately, and care is episodic. The objective of this study is to assess the impact of educational outreach to general practitioners on asthma symptoms of children in their practice.</p> <p>Methods</p> <p>This is a cluster randomised trial with general practices as the unit of intervention, randomisation, and analysis. The setting is Mitchells Plain (population 300,000), a dormitory town near Cape Town. Solo general practitioners, without nurse support, operate from storefront practices. Caregiver-reported symptom data were collected for 318 eligible children (2 to 17 years) with moderate to severe asthma, who were attending general practitioners in Mitchells Plain. One year post-intervention follow-up data were collected for 271 (85%) of these children in all 43 practices.</p> <p>Practices randomised to intervention (21) received two 30-minute educational outreach visits by a trained pharmacist who left materials describing key interventions to improve asthma care. Intervention and control practices received the national childhood asthma guideline. Asthma severity was measured in a parent-completed survey administered through schools using a symptom frequency and severity scale. We compared intervention and control group children on the change in score from pre-to one-year post-intervention.</p> <p>Results</p> <p>Symptom scores declined an additional 0.84 points in the intervention vs. control group (on a nine-point scale. p = 0.03). For every 12 children with asthma exposed to a doctor allocated to the intervention, one extra child will have substantially reduced symptoms.</p> <p>Conclusion</p> <p>Educational outreach was accepted by general practitioners and was effective. It could be applied to other health care quality problems in this setting.</p
Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signalling
Transferrin receptor 2 (Tfr2) is mainly expressed in the liver and controls iron homeostasis. Here, we identify Tfr2 as a regulator of bone homeostasis that inhibits bone formation. Mice lacking Tfr2 display increased bone mass and mineralization independent of iron homeostasis and hepatic Tfr2. Bone marrow transplantation experiments and studies of cell-specific Tfr2 knockout mice demonstrate that Tfr2 impairs BMP-p38MAPK signaling and decreases expression of the Wnt inhibitor sclerostin specifically in osteoblasts. Reactivation of MAPK or overexpression of sclerostin rescues skeletal abnormalities in Tfr2 knockout mice. We further show that the extracellular domain of Tfr2 binds BMPs and inhibits BMP-2-induced heterotopic ossification by acting as a decoy receptor. These data indicate that Tfr2 limits bone formation by modulating BMP signaling, possibly through direct interaction with BMP either as a receptor or as a co-receptor in a complex with other BMP receptors. Finally, the Tfr2 extracellular domain may be effective in the treatment of conditions associated with pathological bone formation
Caveolin 1 protein expression in renal cell carcinoma predicts survival
<p>Abstract</p> <p>Background</p> <p>Caveolae play a significant role in disease phenotypes such as cancer, diabetes, bladder dysfunction, and muscular dystrophy. The aim of this study was to elucidate the caveolin-1 <it>(</it>CAV1<it>) </it>protein expression in renal cell cancer (RCC) and to determine its potential prognostic relevance.</p> <p>Methods</p> <p>289 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Both cytoplasmic and membranous CAV1 expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 169 evaluable patients with a median follow up of 80.5 months (interquartile range (IQR), 24.5 - 131.7 months).</p> <p>Results</p> <p>A high CAV1 expression in the tumor cell cytoplasm was significantly associated with male sex (p = 0.04), a positive nodal status (p = 0.04), and poor tumor differentiation (p = 0.04). In contrast, a higher than average (i.e. > median) CAV1 expression in tumor cell membranes was only linked to male sex (p = 0.03). Kaplan-Meier analysis disclosed significant differences in 5-year overall (51.4 vs. 75.2%, p = 0.001) and tumor specific survival (55.3 vs. 80.1%, p = 0.001) for patients with higher and lower than average cytoplasmic CAV1 expression levels, respectively. Applying multivariable Cox regression analysis a high CAV1 protein expression level in the tumor cell cytoplasm could be identified as an independent poor prognostic marker of both overall (p = 0.02) and tumor specific survival (p = 0.03) in clear cell RCC patients.</p> <p>Conclusion</p> <p>Over expression of caveolin-1 in the tumour cell cytoplasm predicts a poor prognosis of patients with clear cell RCC. CAV1 is likely to be a useful prognostic marker and may play an important role in tumour progression. Therefore, our data encourage further investigations to enlighten the role of CAV1 and its function as diagnostic and prognostic marker in serum and/or urine of RCC patients.</p
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
Increased risk of type I errors in cluster randomised trials with small or medium numbers of clusters: a review, reanalysis,and simulation study
Background: Cluster randomised trials (CRTs) are commonly analysed using mixed-effects models or generalised estimating equations (GEEs). However, these analyses do not always perform well with the small number of clusters typical of most CRTs. They can lead to increased risk of a type I error (finding a statistically significant treatment effect when it does not exist) if appropriate corrections are not used.
Methods: We conducted a small simulation study to evaluate the impact of using small-sample corrections for mixed-effects models or GEEs in CRTs with a small number of clusters. We then reanalysed data from TRIGGER, a CRT with six clusters, to determine the effect of using an inappropriate analysis method in practice. Finally, we reviewed 100 CRTs previously identified by a search on PubMed in order to assess whether trials were using appropriate methods of analysis. Trials were classified as at risk of an increased type I error rate if they did not report using an analysis method which accounted for clustering, or if they had fewer than 40 clusters and performed an individual-level analysis without reporting the use of an appropriate small-sample correction.
Results: Our simulation study found that using mixed-effects models or GEEs without an appropriate correction led to inflated type I error rates, even for as many as 70 clusters. Conversely, using small-sample corrections provided correct type I error rates across all scenarios. Reanalysis of the TRIGGER trial found that inappropriate methods of analysis gave much smaller P values (P ≤ 0.01) than appropriate methods (P = 0.04–0.15). In our review, of the 99 trials that reported the number of clusters, 64 (65 %) were at risk of an increased type I error rate; 14 trials did not report using an analysis method which accounted for clustering, and 50 trials with fewer than 40 clusters performed an individual-level analysis without reporting the use of an appropriate correction.
Conclusions: CRTs with a small or medium number of clusters are at risk of an inflated type I error rate unless appropriate analysis methods are used. Investigators should consider using small-sample corrections with mixed-effects models or GEEs to ensure valid results.
Abbreviations: CRT, Cluster randomised trial; CI, Confidence interval; GEE, Generalised estimating equations; TRIGGER, Trial in Gastrointestinal Transfusio
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