Inhaled corticosteriod use and the risk of pneumonia and COPD exacerbations in the UPLIFT study

Rationale Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases. This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population. Objectives We aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS. Methods The UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS. Poisson regression was used to compare the frequency of respiratory adverse events. Measurements and main results At entry, the groups were well matched apart from a higher FEV1% predicted (38 vs. 41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs. 36%; ICS vs. no ICS, respectively). Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs. 0.056 respectively; p = 0.012). When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs. 0.058, respectively; p < 0.001). COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs. 0.84 respectively; p = 0.013). Conclusions ICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown. In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation

Soy protein improves cardiovascular risk in subclinical hypothyroidism : a randomized double-blinded crossover study

© 2017 Endocrine Society. Background: Soy protein with isoflavones appears to have an adverse effect on thyroid function, but it is not known whether it is the protein or isoflavone component that is deleterious. The effect of isoflavone-free soy on thyroid function was determined in patients with subclinical hypothyroidism, with a secondary aim of assessing its effect on cardiovascular risk indices. Methods: This was a randomized, double-blind, crossover study involving 80 patients with subclinical (compensated) hypothyroidism. Patients were randomly assigned to either isolated soy (isoflavone-free) protein (SP) or casein protein (CP) supplementation for 8 weeks, washed out for 8 weeks, and then crossed over for a further 8-week period. Results: Thyroid function was unaffected by either a SP or CP. There were significant decreases in fasting glucose (4.760.6 vs 5.561.4, P < 0.01), insulin resistance (3.3±3.0 vs 3.8±3.4, P = 0.05), total cholesterol (4.4 ± 0.9 vs 5.3 ± 1.2, P < 0.01), triglycerides (0.9 ± 0.5 vs 1.7 ± 0.9, P < 0.1), and highly sensitive C-reactive protein (hsCRP; 0.8 ± 0.7 vs 2.6 ± 2.8, P < 0.01) in the SP group compared with the CP group. Blood pressure, low-density lipoprotein, and high-density lipoprotein remained unchanged in both groups. Conclusion: SP alone had no effect on thyroid function in patients with subclinical hypothyroidism and resulted in a significant reduction in fasting glucose, insulin resistance, total cholesterol, triglycerides, and hsCRP compared with CP

An audit of COPD: Diagnosis and management in general practice

Introduction: COPD is a spectrum of disorders primarily caused by smoking and characterised by progressive, not fully reversible airflow obstruction with a forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. Methods: From November 2016 to March 2017 we audited patients with COPD in five general practices in Hull and East Riding, UK. We looked at deviation from the locally agreed guidelines. We extracted data on severity, exacerbations, medication and eosinophil count. Results: We assessed 1088 records. Median age was 70.9 years; 577 (53%) were male. About two-thirds of patients on the COPD register have an FEV1/FVC ratio in the diagnostic range for COPD, however, 388 (36%) out of 1088 had a ratio of ⩾0.7. In the patients with a ratio of ⩾0.7, 259 (67%) out of 388 had an FEV1 <80% of predicted. Patients with frequent exacerbations were more likely to be prescribed inhaled corticosteroid (ICS)-containing inhalers (incidence rate ratio of 2). FEV1 % predicted was a poor indicator of exacerbation frequency; however, the presence of elevated blood eosinophil counts (EOS) on at least two occasions was highly predictive of exacerbations. When ICSs, FEV1, EOS were examined in combination, they were highly significant predictors for exacerbations. Conclusion: FEV1 maybe a more accurate diagnostic parameter in primary care. Historical evidence of blood eosinophilia is a better predictor than FEV1. The combination of biomarkers may prove more accurate indicator of future exacerbation frequency, leading to targeted intervention

Effect of soy in men with type 2 diabetes mellitus and subclinical hypogonadism: a randomised controlled study

Context: Isoflavones found in soy products have a chemical structure similar to estrogen, leading to concerns of an adverse estrogenic effect in men, particularly in those with type 2 diabetes mellitus (T2DM) who have low testosterone levels due to hypogonadism. Objective: The primary outcome was change in total testosterone levels. The secondary outcomes were the changes in glycaemia and cardiovascular risk markers. Design: Randomised double blind parallel study. Setting: Secondary care setting in UK. Participants: 200 men with T2DM with a total testosterone level≤12nmol/L Intervention: 15g soy protein with 66mg of isoflavones (SPI) or 15g soy protein alone without isoflavones (SP) daily as snack bars for three months. Results: There was no change in either total testosterone or in absolute free testosterone levels with either SPI or SP. There was an increase in TSH and reduction in fT4 (p&lt;0.01) after SPI supplementation. Glycaemic control improved with a significant reduction in HbA1c (-4.19(7.29)mmol/mol,p&lt;0.01) and HOMA-IR after SPI. Cardiovascular risk improved with a reduction in triglycerides, CRP and diastolic BP (p&lt;0.05) with SPI versus SP supplementation. There was 6% improvement in 10-year coronary heart disease risk after three months of SPI supplementation. Endothelial function improved with both SPI and SP supplementation (p&lt;0.01) with an increased reactive hyperemia index that was greater for the SPI group (p&lt;0.05). Conclusions: Testosterone levels were unchanged and there was a significant improvement in glycaemia and cardiovascular risk markers with SPI compared to SP alone over three months. There was significant increase in TSH and a reduction in fT4

Development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure

Objective: Cardiopulmonary exercise testing (CPET) is used to predict outcome in patients with mild-to-moderate heart failure (HF). Single CPET-derived variables are often used, but we wanted to see if a composite score achieved better predictive power. Methods: Retrospective analysis of patient records at the Department of Cardiology, Castle Hill Hospital, Kingston-upon-Hull. 387 patients [median (25th-75th percentile)] [age 65 (56-72) years; 79% males; LVEF 34 (31-37) %] were included. Patients underwent a symptomlimited, maximal CPET on a treadmill. During a median follow up of 8.6 ± 2.1 years in survivors, 107 patients died. Survival models were built and validated using a hybrid approach between the bootstrap and Cox regression. Nine CPET-derived variables were included. Z-score defined each variable's predictive strength. Model coefficients were converted to a risk score. Results: Four CPET-related variables were independent predictors of all-cause mortality in the survival model: the presence of exertional oscillatory ventilation (EOV), increasing slope of the relation between ventilation and carbon dioxide production (VE/VCO2 slope), decreasing oxygen uptake efficiency slope (OUES), and an increase in the lowest ventilatory equivalent for carbon dioxide (VEqCO2 nadir). Individual predictors of mortality ranged from 0.60 to 0.71 using Harrell’s C-statistic, but the optimal combination of EOV + VE/VCO2 slope + OUES + VEqCO2 nadir reached 0.75. The Hull CPET risk score had a significantly higher area under the curve (0.78) when compared to the Heart Failure Survival Score (AUC=0.70;

Pilot investigation of a virtual gastric band hypnotherapy intervention

This was a pilot investigation of 30 men and women with a BMI > 27kg/m² over a 24 week period. It aimed to determine whether virtual gastric band (VGB) hypnotherapy has an effect on weight loss in overweight adults, compared to relaxation hypnotherapy and a self-directed diet. Levels of weight loss and gain ranged from -17kg to +4.7kg in the VGB hypnotherapy group and -9.3kg to +7.8kg in the relaxation group. There was no significant difference between VGB hypnotherapy as a main effect on weight loss (Chi²=0.67, p=0.41, df=1) and there was no evidence of differential weight loss over time (Chi²=4.2, p=0.64, df=6). Therefore, this study concludes that there was no significant difference between VGB hypnotherapy and the relaxation hypnotherapy

The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: A randomized, double-blind, crossover study

Context: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism. Objective: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism. Design and Setting: We conducted a randomized, double-blind, crossover study in a tertiary care setting. Participants: Sixty patients with subclinical hypothyroidism participated in the study. Intervention: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2 mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16 mg phytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period. Main Outcome Measures: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP). Results: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2 mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged. Conclusion: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients. Copyright © 2011 by The Endocrine Society

Effect of Glucose Variability on the Long-Term Risk of Microvascular Complications in Type 1 Diabetes

OBJECTIVE This study analyzed data from the Epidemiology of Diabetes Interventions and Complications (EDIC) study to see whether longer-term follow-up of Diabetes Control and Complications Trial (DCCT) patients reveals a role for glycemic instability in the development of microvascular complications.RESEARCH DESIGN AND METHODS The mean area under the curve glucose and the within-day glucose variability (SD and mean amplitude of glycemic excursions [MAGE]) during the DCCT were assessed to see whether they contributed to the risk of retinopathy and nephropathy by year 4 of the EDIC.RESULTS Logistic regression analysis showed that mean glucose during the DCCT and mean A1C during EDIC were independently predictive of retinopathy (each P 0.25 using SD or MAGE).CONCLUSIONS Glucose variability in the DCCT did not predict the development of retinopathy or nephropathy by EDIC year 4.Analysis of the Diabetes Control and Complications Trial (DCCT) dataset has shown that glucose variability did not appear to be a further factor in the development or progression of either retinopathy or nephropathy (1,2). More recently, variability in A1C, a longer-term marker of glycemic control, during the DCCT has been found to add to the risk already indicated by the mean A1C value (3).This current study has examined data from the first 4 years of the DCCT extension study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. The EDIC has already shown the long-term beneficial effects of intensive treatment on microvascular complications (4–6). Our goal was to establish whether the follow-up study also unearths a longer-term relationship between glucose variability during the DCCT and subsequent retinopathy and nephropathy

Evaluating the Role of Ultrasound in Prostate cancer (ERUP) trial – Phase 1 early experience of micro-ultrasound in the UK

Purpose: To evaluate if the use of micro-ultrasound (microUS) can detect significant prostate (csPCa) pathology when compared to histology obtained during a transperineal prostate biopsy.Methods: Patients suspected of having prostate cancer, who had a prebiopsy MRI and could tolerate a transrectal examination were prospectively recruited. All patients had a microUS scan prior to their biopsy. The findings of MRI, microUS, and histology were risk stratified in accordance with local pathways. Comparison of assigned risk scores were made using histology as the reference standard.Results: Data from 101 patients were evaluated. Histology showed that csPCa was detected in 48.5% (n = 49/101) of patients. Moderate inter-rater agreement was found in both MRI and MicroUS with К of 0.31 in both modalities. High risk findings were identified in 81% (n = 82/101) patients at MRI and in 66% (n = 67/101) patients at microUS. Sensitivity and specificity of MRI was found to be 87% and 34.6% and for microUS 73.3% and 53.8% respectively.Conclusion: A limitation of this study was that the biopsy was not performed with microUS which may have resulted in unidentified cancers and lowered the apparent accuracy of the technique. However, we conclude that whilst microUS was diagnostic, MRI demonstrated higher sensitivity in our local population and remains the pre-biopsy imaging modality of choice. However, the higher specificity of microUS identified does indicate that it may be of value when MRI is contraindicated. The role of microUS, within an active surveillance pathway for prostate cancer, warrants further investigation