Exploring the use of adjusted body mass index thresholds based on equivalent insulin resistance for defining overweight and obesity in UK South Asian children

Background Body mass index (BMI) overweight/obesity thresholds in South Asian (SA) adults, at equivalent type-2 diabetes risk are lower than for white Europeans (WE). We aimed to define adjusted overweight/obesity thresholds for UK–SA children based on equivalent insulin resistance (HOMA-IR) to WE children. Methods In 1138 WE and 1292 SA children aged 9.0–10.9 years, multi-level regression models quantified associations between BMI and HOMA-IR by ethnic group. HOMA-IR levels for WE children were calculated at established overweight/obesity thresholds (at 9.5 years and 10.5 years), based on UK90 BMI cut-offs. Quantified associations in SA children were then used to estimate adjusted SA weight-status thresholds at the calculated HOMA-IR levels. Results At 9.5 years, current WE BMI overweight and obesity thresholds were 19.2 kg/m2, 21.3 kg/m2 (boys) and 20.0 kg/m2, 22.5 kg/m2 (girls). At equivalent HOMA-IR, SA overweight and obesity thresholds were lower by 2.9 kg/m2 (95% CI: 2.5–3.3 kg/m2) and 3.2 kg/m2 (95% CI: 2.7–3.6 kg/m2) in boys and 3.0 kg/m2 (95% CI: 2.6–3.4 kg/m2) and 3.3 kg/m2 (95% CI: 2.8–3.8 kg/m2) in girls, respectively. At these lower thresholds, overweight/obesity prevalences in SA children were approximately doubled (boys: 61%, girls: 56%). Patterns at 10.5 years were similar. Conclusions SA adjusted overweight/obesity thresholds based on equivalent IR were markedly lower than BMI thresholds for WE children, and defined more than half of SA children as overweight/obese

Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man

Measures of satisfaction with care during labour and birth: a comparative review

Background Satisfaction is the one of the most frequently reported outcome measures for quality of care. Assessment of satisfaction with maternity services is crucial, and psychometrically sound measures are needed if this is to inform health practices. This paper comparatively reviews current measures of satisfaction with care during labour and birth. Methods A review of the literature was conducted. Studies were located through computerised databases and hand searching references of identified articles and reviews. Inclusion criteria were that the questionnaire was a multi-item scale of satisfaction with care during labour and birth, and some form of psychometric information (either information about questionnaire construction, or reliability, or validity) had to be reported. Results Nine questionnaires of satisfaction with care during labour and birth were identified. Instruments varied in psychometric properties and dimensions. Most described questionnaire construction and tested some form of reliability and validity. Measures were generally not based on the main theoretical models of satisfaction and varied in scope and application to different types of samples (e.g. satisfaction following caesarean section). For an in-depth measure of satisfaction with intrapartum care, the Intrapartal-Specific Quality from the Patient’s Perspective questionnaire (QPP-I) is recommended. Brief measures with good reliability and validity are provided by the Six Simple Questions (SSQ) or Perceptions of Care Adjective Checklist (PCACL-R). Conclusions Despite the interest in measures of satisfaction there are only a small number of validated measures of satisfaction with care during labour and birth. It is important that brief, reliable and valid measures are available for use in general and specific populations in order to assist research and inform practice

Evaluating ethnic variations in the risk of infections in people with prediabetes and type 2 diabetes: a matched cohort study

Objective People living with type 2 diabetes (T2DM) are at higher infection risk, but it is unknown how this risk varies by ethnicity, or whether the risk is similarly observed in people with non-diabetic hyperglycaemia (“prediabetes”). Research Design and Methods We included 527,151 patients in England with T2DM and 273,216 with prediabetes, aged 18-90 and alive on 1st January 2015 on the Clinical Practice Research Datalink. Each were matched to 2 patients without diabetes or prediabetes on age, sex and ethnic group. Infections during 2015-9 were collated from primary care and linked hospitalisation records. Infection incidence rate ratios (IRR) for prediabetes or T2DM were estimated, unadjusted and adjusted for confounders. Results People with T2DM had increased risk for infections presenting in primary care (IRR=1.51, 95%CI 1.51-1.52) and hospitalisations (IRR=1.91, 1.90-1.93). This was broadly consistent overall within each ethnic group, though younger White T2DM patients (age <50) experienced a greater relative risk. Adjustment for socio-economic deprivation, smoking and co-morbidity attenuated associations, but IRRs remained similar by ethnicity. For prediabetes, a significant but smaller risk was observed (primary care IRR=1.35 1.34-1.36, hospitalisation IRR=1.33, 1.31-1.35); these were similar within each ethnicity for primary care infections, but less consistent for infection related hospitalisations. Conclusions The elevated infection risk for people with T2DM appears similar for different ethnic groups and is also seen in people with prediabetes. Infections are a substantial cause of ill-health and health service use for people with prediabetes and T2DM. This has public health implications with rising prediabetes and diabetes prevalence

Early onset lactating adenoma and the role of breast MRI: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lactating adenoma is a benign condition, representing the most prevalent breast lesion in pregnant women and during puerperium; in this paper, a case of a woman with lactating adenoma occurring during the first trimester of pregnancy is reported. There have been no reports in the literature, according to our search, focusing on magnetic resonance imaging findings in cases of lactating adenomas. Also the early onset of the lesion during the first trimester of pregnancy is quite unusual and possibly unique.</p> <p>Case presentation</p> <p>We report the case of a primiparous 30-year-old Caucasian woman, who noted an asymptomatic lump within her left breast during the 9^thweek of gestation, slightly increasing in size over the next few weeks. Ultrasound demonstrated a hypoecoic solid mass, hypervascularized and measuring 4 cm. On magnetic resonance imaging, performed in the first month after delivery, the lesion appeared as an ovoidal homogeneous mass, with regular margins and a significant contrast enhancement indicative of a giant adenoma.</p> <p>Conclusion</p> <p>Magnetic resonance imaging could play an important role in the differential diagnosis of pregnancy-related breast lumps, particularly during puerperium, thus avoiding unnecessary surgical biopsies.</p

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies

BACKGROUND: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE: The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS: The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS: Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS: The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION: ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13696

Visceral leishmaniasis caused by Leishmania infantum in a Spanish patient in Argentina: What is the origin of the infection? Case report

BACKGROUND: The question "Where have you been?" is a common one asked by doctors in Northern Europe and America when faced with clinical symptoms not typical of their country. This question must also arise in the clinics of developing countries in which non-autochthonous cases such as the one described here can appear. Important outbreaks of Leishmania infantum have been recorded in the last decade in several Latin American countries but its presence has not yet been recorded in Argentina. We report the first case of visceral leishmaniasis owing to L. infantum in this country. CASE PRESENTATION: A 71-year-old Spanish woman who has been living in Mendoza, Argentina, during the last 40 years presented with a history of high fever and shivering, anemia, leukopenia and splenomegaly over two years. Argentinian doctors did not suspect visceral leishmaniasis even when the histological analysis revealed the presence of "intracytoplasmatic spheroid particles compatible with fungal or parasitic infection". After a serious deterioration in her health, she was taken to Spain where she was evaluated and visceral leishmaniasis was established. Specific identification of the parasite was done by PCR-ELISA, isoenzyme electrophoresis and RAPD-PCR. CONCLUSION: We would like to point out that: i) cases such as the one described here, which appear in non-endemic areas, can pass unnoticed by the clinical physician. ii) in countries in which these introduced cases reside, in-depth parasitological studies are required into vectors and possible reservoirs to rule out the rare case of local infection and, once infection has taken place, to ensure that this does not spread by anthroponotic transmission or a competent reservoir

Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein as an apoptotic milk factor in mammary gland involution

The mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation. However, little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2 to 3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis/involution.<br /