Weight loss and metabolic outcomes in women with or without polycystic ovarian syndrome after Roux-en-Y gastric bypass: A case-matched study.

BACKGROUND AND OBJECTIVES: Weight loss is the mainstay of management for women with polycystic ovarian syndrome (PCOS). However, lifestyle and dietary modifications, and gastric banding have generally poor long-term efficacy. We aimed to investigate whether gastric bypass is equally efficacious in women with or without PCOS. METHODS: We performed a matched case-control study of primary Roux-en-Y gastric bypass surgery in women with PCOS (cases, n = 30) compared to women without PCOS (controls, n = 60) matched for baseline age, body mass index (BMI) and presence or absence of type 2 diabetes (T2D). Data shown represent mean values. RESULTS: At 24 months after surgery the 90 participants (age 36.1 years) experienced significant reductions in BMI (53.4 vs. 34.9 kg/m2, p < 0.0001), glycated haemoglobin (HbA1c) in 21 women with T2D (68.2 vs. 38.7 mmol/mol, p < 0.0001) and blood pressure (BP) in 29 women with hypertension (144/91 vs. 129/83 mmHg, p < 0.01), while obstructive sleep apnoea (OSA) resolved in 88.0% of the 25 affected patients. Women with PCOS compared to women without PCOS achieved equivalent reductions in percentage total weight loss (32.6% vs. 32.6% at 12 months and 34.8% vs. 36.1% at 24 months) and HbA1c (T2D subgroup; 38.3 vs. 41.6 mmol/mol at 12 months and 37.0 vs. 39.6 mmol/mol at 24 months) and comparable improvement in BP (hypertension subgroup) and resolution of OSA (87.5% vs. 88.2% at 24 months). CONCLUSION: In women with PCOS with morbid obesity, gastric bypass resulted in significant weight loss and metabolic outcomes similar to women without PCOS.

Effectiveness of fluticasone furoate/vilanterol versus fluticasone propionate/salmeterol on asthma control in the Salford Lung Study.

OBJECTIVE: The Asthma Salford Lung Study demonstrated the effectiveness of initiating once-daily fluticasone furoate/vilanterol (FF/VI) versus continuing usual care in asthma patients in UK primary care [ 1 ]. Here, we report a secondary analysis in a subset of patients with fluticasone propionate/salmeterol (FP/Salm) as their baseline intended maintenance therapy, to evaluate the relative effectiveness of initiating FF/VI versus continuing FP/Salm. METHODS: Adults with symptomatic asthma were randomised to initiate FF/VI 100[200]/25 µg or continue FP/Salm. The Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), Work Productivity and Activity Impairment Asthma questionnaire, severe exacerbations, salbutamol inhaler prescriptions and serious adverse events (SAEs) were recorded throughout the 12-month treatment period. RESULTS: One thousand two hundred and sixty-four patients (FF/VI 646; FP/Salm 618) were included in this subset analysis; 978 had baseline ACT score <20 and were included in the primary effectiveness analysis (PEA) population. At week 24, odds of patients being ACT responders (total score ≥20 and/or improvement from baseline ≥3) were significantly higher with FF/VI versus FP/Salm (71% vs. 56%; odds ratio 2.03 [95% CI: 1.53, 2.68]; p < 0.001 [PEA]). Significant benefit with FF/VI versus FP/Salm was also observed for AQLQ responders, activity impairment due to asthma, exacerbation rates, and salbutamol inhalers prescribed. No significant between-group differences were observed for impairment while working or work absenteeism due to asthma. CONCLUSIONS: For patients in primary care, initiating FF/VI was significantly better than continuing with FP/Salm for improving asthma control and quality of life, and reducing asthma exacerbations, with no notable difference in SAEs. ClinicalTrials.gov: NCT01706198.

Monitoring safety in a phase III real-world effectiveness trial: use of novel methodology in the Salford Lung Study.

BACKGROUND: The Salford Lung Study (SLS) programme, encompassing two phase III pragmatic randomised controlled trials, was designed to generate evidence on the effectiveness of a once-daily treatment for asthma and chronic obstructive pulmonary disease in routine primary care using electronic health records. OBJECTIVE: The objective of this study was to describe and discuss the safety monitoring methodology and the challenges associated with ensuring patient safety in the SLS. Refinements to safety monitoring processes and infrastructure are also discussed. The study results are outside the remit of this paper. The results of the COPD study were published recently and a more in-depth exploration of the safety results will be the subject of future publications. ACHIEVEMENTS: The SLS used a linked database system to capture relevant data from primary care practices in Salford and South Manchester, two university hospitals and other national databases. Patient data were collated and analysed to create daily summaries that were used to alert a specialist safety team to potential safety events. Clinical research teams at participating general practitioner sites and pharmacies also captured safety events during routine consultations. Confidence in the safety monitoring processes over time allowed the methodology to be refined and streamlined without compromising patient safety or the timely collection of data. The information technology infrastructure also allowed additional details of safety information to be collected. CONCLUSION: Integration of multiple data sources in the SLS may provide more comprehensive safety information than usually collected in standard randomised controlled trials. Application of the principles of safety monitoring methodology from the SLS could facilitate safety monitoring processes for future pragmatic randomised controlled trials and yield important complementary safety and effectiveness data. © 2016 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in chronic obstructive pulmonary disease.

BACKGROUND: New treatments need to be evaluated in real-world clinical practice to account for co-morbidities, adherence and polypharmacy. METHODS: Patients with chronic obstructive pulmonary disease (COPD), ≥ 40 years old, with exacerbation in the previous 3 years are randomised 1:1 to once-daily fluticasone furoate 100 µg/vilanterol 25 µg in a novel dry-powder inhaler versus continuing their existing therapy. The primary endpoint is the mean annual rate of COPD exacerbations; an electronic medical record allows real-time collection and monitoring of endpoint and safety data. CONCLUSIONS: The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in COPD. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01551758.

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma.

BACKGROUND: Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. METHODS/DESIGN: The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 µg or 200 µg)/vilanterol 25 µg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors. PRIMARY ENDPOINT: Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data. DISCUSSION: The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01706198; 04 October 2012.

Using an electronic medical record (EMR) to conduct clinical trials: Salford Lung Study feasibility.

BACKGROUND: Real-world data on the benefit/risk profile of medicines is needed, particularly in patients who are ineligible for randomised controlled trials conducted for registration purposes. This paper describes the methodology and source data verification which enables the conduct of pre-licensing clinical trials of COPD and asthma in the community using the electronic medical record (EMR), NorthWest EHealth linked database (NWEH-LDB) and alert systems. METHODS: Dual verification of extracts into NWEH-LDB was performed using two independent data sources (Salford Integrated Record [SIR] and Apollo database) from one primary care practice in Salford (N = 3504). A feasibility study was conducted to test the reliability of the NWEH-LDB to support longitudinal data analysis and pragmatic clinical trials in asthma and COPD. This involved a retrospective extraction of data from all registered practices in Salford to identify a cohort of patients with a diagnosis of asthma (aged ≥18) and/or COPD (aged ≥40) and ≥2 prescriptions for inhaled bronchodilators during 2008. Health care resource utilisation (HRU) outcomes during 2009 were assessed. Exacerbations were defined as: prescription for oral corticosteroids (OCS) in asthma and prescription of OCS or antibiotics in COPD; and/or hospitalisation for a respiratory cause. RESULTS: Dual verification demonstrated consistency between SIR and Apollo data sources: 3453 (98.6%) patients were common to both systems; 99.9% of prescription records were matched and of 29,830 diagnosis records, one record was missing from Apollo and 272 (0.9%) from SIR. Identified COPD patients were also highly concordant (Kappa coefficient = 0.98). A total of 7981 asthma patients and 4478 COPD patients were identified within the NWEH-LDB. Cohort analyses enumerated the most commonly prescribed respiratory medication classes to be: inhaled corticosteroids (ICS) (42%) and ICS plus long-acting ß2-agonist (LABA) (40%) in asthma; ICS plus LABA (55%) and long-acting muscarinic antagonists (36%) in COPD. During 2009 HRU was greater in the COPD versus asthma cohorts, and exacerbation rates in 2009 were higher in patients who had ≥2 exacerbations versus ≤1 exacerbation in 2008 for both asthma (137.5 vs. 20.3 per 100 person-years, respectively) and COPD (144.6 vs. 41.0, respectively). CONCLUSION: Apollo and SIR data extracts into NWEH-LDB showed a high level of concordance for asthma and COPD patients. Longitudinal data analysis characterized the COPD and asthma populations in Salford including medications prescribed and health care utilisation outcomes suitable for clinical trial planning.

Obtaining real-world evidence: the Salford Lung Study.

We need to assess clinical treatments in real-life settings outside of randomised controlled trials (RCTs). Pragmatic RCT (pRCT) data can supplement RCTs by providing effectiveness information to support healthcare decisions. Electronic health records can facilitate concurrent safety monitoring and data collection without direct patient contact for large randomised study populations in pRCTs. The Salford Lung Study is the world's first phase III pRCT in asthma and chronic obstructive pulmonary disease (COPD), which aims to randomise over 7000 patients. This paper describes the hurdles overcome and the enormous effort and resource required to establish this comparative effectiveness study of a prelicence intervention. GLAXOSMITHKLINE PROTOCOL: HZC115151 ASTHMA STUDY CLINICALTRIALSGOV REGISTRATION: NCT01706198 COPD STUDY CLINICALTRIALSGOV REGISTRATION: NCT01551758.

Does preoperative weight loss in a specialist medical weight management centre influence postoperative weight loss after bariatric surgery?

Weight loss of 5%-10% is advised in medical weight management (MWM) programmes prior to bariatric surgery but it remains to be established whether it influences postoperative weight loss outcomes. We studied postoperative percent total weight loss (%TWL) in 168 patients categorized by preoperative referral weight loss <5% or ≥5% in a UK NHS bariatric centre. Eighty-six (51.2%) patients achieved sustained referral weight loss <5% (Group A) and 82 (48.8%) ≥5% (Group B). Overall postoperative %TWL in Group A compared with Group B was 30.0% versus 28.3% (p = .30) at 12 months and 32.5% versus 29.6% (p = .20) at 24 months. There were no significant differences in postoperative %TWL at 12 and 24 months when categorized by procedure (gastric bypass, n = 106; or sleeve gastrectomy, n = 62), age or sex. Preoperative weight loss during intensive specialist MWM did not influence postoperative weight loss up to 24 months with gastric bypass or sleeve gastrectomy.

Metabolic outcomes 1 year after gastric bypass surgery in obese people with type 2 diabetes.

OBJECTIVE: To assess metabolic outcomes in obese people with type 2 diabetes (T2D) in the first year following gastric bypass surgery. SUBJECTS AND METHODS: Forty-nine obese patients with T2D who had undergone gastric bypass surgery 12 or more months previously were identified. Body weight and glycosylated haemoglobin (HbA(1c)) pre-operatively and 3, 6 and 12 months postoperatively, changes to glucose-lowering therapies, and blood pressure (BP) and total and high-density lipoprotein (HDL) cholesterol pre-operatively and 12 months postoperatively were recorded. The primary outcome measure was change in HbA(1c); secondary outcomes included changes in BP and lipid profile. RESULTS: The mean pre-operative body weight was 141.4 kg, the body mass index 49.4 and HbA(1c) 8.1%. The mean postoperative percentage of excess body weight loss at 3, 6 and 12 months was 39.0, 53.9 and 71.1 with reduction in HbA(1c) to 6.6, 6.2 and 5.8%, respectively (p < 0.0001). Remission of diabetes (HbA(1c) <6.5%) occurred in 12 of 18 patients (67%) at 3 months, 20 of 27 (74%) at 6 months and 21 of 25 (84%) at 12 months; of 41 patients under glucose-lowering treatment, 26 (63%) achieved complete withdrawal of treatment and 7 (17%) had their doses reduced. The mean of differences between baseline and 12-month measurements of systolic BP was 10.5 mm Hg (p = 0.021) and the total-to-HDL cholesterol ratio 0.9 (p < 0.002). CONCLUSION: Our study confirmed the finding of previous studies that gastric bypass surgery in obese people with T2D results in significant weight loss, and improved glycaemic, BP and lipid profiles. Bariatric surgery should be regarded as an effective therapeutic intervention in this patient population.

The use of eGFR and ACR to predict decline in renal function in people with diabetes.

BACKGROUND: There have been few attempts to estimate progression of kidney disease in people with diabetes in a single large population with predictive modelling. The aim of this study was to investigate the rate of progression of chronic kidney disease in people with diabetes according to their estimated glomerular filtration rate (eGFR) and presence of albuminuria. METHODS: Data were collected on all people with diabetes in Salford, UK, where an eGFR could be calculated using the four-variable MDRD formula and urinary albumin-creatinine ratio (uACR) was available. All data between 2001 and 2007 were used in the model. Classification of albuminuria status was based on the average of their first two uACR measurements. A longitudinal mixed effect dynamic regression model was fitted to the data. Parameters were estimated by maximum likelihood. RESULTS: For the analysis of the population, average progression of eGFR, uACR and drug prescribing were available in 3431 people. The regression model showed that in people with diabetes and macroalbuminuria, eGFR declined at 5.7% per annum, while the eGFR of those with microalbuminuria or without albuminuria declined at 1.5% and 0.3% per annum, respectively, independently of age (P < 0.0001). CONCLUSIONS: The longitudinal effect of time on eGFR showed that people with diabetes and macroalbuminuria have an estimated 19 times more rapid decline in renal function compared with those without albuminuria. This study demonstrates that the progression of kidney disease in diabetic people without albuminuria is relatively benign compared with those with albuminuria.

Effect of patient age on airway response by paramedics: frailty or futility?

OBJECTIVE: We studied patterns related to patient age and indication for airway interventions delivered by paramedics from 2000 through 2004. METHODS: The study population included patients ≥ 15 years old managed by paramedics. Outcomes were the frequencies of definitive airway, ventilatory techniques, and oxygenation techniques. Independent variables were patient age, gender, race, hospital drive time, do-not-resuscitate status, and two trauma indicators of the American College of Surgeons Committee on Trauma (anatomic injury and mechanism of injury). Subset analysis was performed with the presence or absence of a set of recorded conditions. RESULTS: A total of 827,772 paramedic transports were studied; 233,470 were identified with at least one indication for airway intervention. Patients older than 65 years were, when compared with patients 65 years old or younger, 1) less likely to receive ventilatory interventions with any indication; 2) more likely to receive ventilatory intervention without an indication; and 3) more likely to receive oxygenation interventions whether indications were present or not. We considered age in five-year intervals and noted a consistent biphasic pattern for all interventions, regardless of indications. The odds ratios for interventions for patients in each block compared with those for 15- to 29-year-old patients increased with age until about 70 years of age, then gradually declined. CONCLUSIONS: Patterns of age-related variations in airway interventions cannot be explained by the application of protocols. The reason for the peak rate of interventions at age 70 years is unknown. Explanations need to consider the influence on paramedic behavior of a number of factors, including frailty and futility. Additional paramedic training may be needed to change these patterns.

Implications of COVID-19 labour market shocks for inequality in financial wellbeing.

Australia's economy abruptly entered into a recession due to the COVID-19 pandemic of 2020. Related labour market shocks on Australian residents have been substantial due to business closures and social distancing restrictions. Government measures are in place to reduce flow-on effects to people's financial situations, but the extent to which Australian residents suffering these shocks experience lower levels of financial wellbeing, including associated implications for inequality, is unknown. Using novel data we collected from 2078 Australian residents during April to July 2020, we show that experiencing a labour market shock during the pandemic is associated with a 29% lower level of perceived financial wellbeing, on average. Unconditional quantile regressions indicate that lower levels of financial wellbeing are present across the entire distribution, except at the very top. Distribution analyses indicate that the labour market shocks are also associated with higher levels of inequality in financial wellbeing. Financial counselling and support targeted at people who experience labour market shocks could help them to manage financial commitments and regain financial control during periods of economic uncertainty.

The impact of fluticasone furoate/vilanterol on healthcare resource utilisation in the Salford Lung Study in chronic obstructive pulmonary disease.

AIM: The Salford Lung Study (SLS) in chronic obstructive pulmonary disease (COPD) was a randomised controlled trial evaluating the effectiveness and safety of initiating fluticasone furoate/vilanterol (FF/VI) 100/25 µg versus continuing usual care (UC) in patients with COPD and a history of exacerbations. Here, we investigate the impact of initiating FF/VI on healthcare resource utilisation (HRU) in SLS COPD. METHODS: HRU and interventions were determined from patients' electronic health records. Annual rates of on-treatment all-cause and COPD-related secondary care contacts (SCCs) and primary care contacts (PCCs) for FF/VI versus UC were analysed using a general linear model. Costs were derived from national data sources. RESULTS: Least-squares (LS) mean annual rates of all-cause (9.81 versus 9.36) and COPD-related (1.57 versus 1.48) SCCs were similar for FF/VI and UC, as were rates of all-cause hospitalisations (0.87 versus 0.82). Mean duration of hospital stay/patient was 4.5 and 4.2 days, respectively. COPD-related SCC mean total cost/patient was £484 FF/VI and £475 UC. LS mean annual rates of all-cause PCCs were significantly higher for FF/VI (21.20 versus 18.88 UC; p < 0.001). LS mean annual rates of COPD-related PCCs were similar for FF/VI and UC (2.42 versus 2.46). All-cause PCC mean total cost/patient was £900 FF/VI versus £811 UC, but COPD-related PCC costs were similar (£116 versus £114). Direct COPD-related total medical costs/patient were significantly lower for FF/VI (LS geometric mean £806 versus £963 UC; p < 0.001). DISCUSSION: In patients with COPD and exacerbation history, FF/VI may represent a less costly alternative to current therapies.GlaxoSmithKline plc. study HZC115151; ClinicalTrials.gov NCT01551758.The reviews of this paper are available via the supplemental material section.

Safety data in randomised real-world evidence studies: Salford Lung Study learnings.

Evidence to support clinical decision making must be based on safety data that have been captured, analysed and interpreted in a robust and reliable way. Randomised real-world evidence (RRWE) studies provide the opportunity to evaluate the use of medicines in patients and settings representative of routine clinical practice. However, elements that underpin the design of RRWE studies can have a significant impact upon the analysis, interpretation and implications of safety data. In this narrative review, we use data from the Salford Lung Study; two prospective, 12-month, open-label, parallel-group, phase III randomised controlled trials conducted in primary care in the UK; to highlight the importance of capturing treatment modifications when attempting to evaluate safety events according to actual treatment exposure. We demonstrate that analysing safety data by actual treatment received (i.e. accounting for the treatment modifications that occur routinely in the primary care setting) provides additional insight beyond analysing according to randomised treatment strategy only. It is therefore proposed that understanding of safety data from RRWE trials can be optimised by analysing both by randomised group and by actual treatment received.

Haemoglobin and Hematinic Status Before and After Bariatric Surgery over 4 years of Follow-Up.

PURPOSE: Bariatric surgery is associated with deficiencies of vitamins and minerals, and patients are routinely advised supplements postoperatively. We studied prevalence of vitamin B12, folate and iron deficiencies and anaemia before and after bariatric surgery over 4 years of follow-up. MATERIALS AND METHODS: We performed a retrospective cohort analysis of 353 people with obesity, including 257 (72.8%) women, who underwent gastric bypass (252, 71.4%) or sleeve gastrectomy (101, 28.6%) at our National Health Service bariatric centre in Northwest England. RESULTS: At baseline, mean (standard error) age was 46.0 (0.6) years, body mass index 53.1 (0.4) kg/m2, serum vitamin B12 400.2 (16.4) pg/L, folate 7.7 (0.2) µg/L, iron 12.0 (0.3) µmol/L, ferritin 118.3 (8.4) µg/L and haemoglobin 137.9 (0.8) g/L. Frequency of low vitamin B12 levels reduced from 7.5% preoperatively to 2.3% at 48 months (P < 0.038). Mean folate levels increased from baseline to 48 months by 5.3 µg/L (P < 0.001) but frequency of low folate levels increased from 4.7% preoperatively to 10.3% (P < 0.048). Ferritin levels increased from baseline to 48 months by 51.3 µg/L (P < 0.009). Frequency of low ferritin levels was greater in women (39.1%) than in men (8.9%) at baseline (P < 0.001) and throughout the study period. Haemoglobin was low in 4.6% of all patients at baseline with no significant change over the study period. CONCLUSION: There were notable rates of haematinic insufficiencies in bariatric surgical candidates preoperatively. Our study lends further support to regular supplementation with vitamin B12, folic acid, and iron in people undergoing bariatric surgery.

Factors associated with kidney disease progression and mortality in a referred CKD population.

BACKGROUND: Knowing how kidney disease progresses is important for decision making in patients with chronic kidney disease (CKD) and for designing clinical services. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We examined renal function trajectories in CRISIS (Chronic Renal Insufficiency Standards Implementation Study), in which 1,325 patients with CKD stages 3-5 and mean age of 65.1 years were followed up prospectively for a median of 26 months after referral to a regional nephrology center in the United Kingdom. By protocol, estimated glomerular filtration rate was determined every 12 months. PREDICTORS: CKD stage defined as estimated glomerular filtration rate ≥ 45 (stage 3a), 30-44 (3b), 15-29 (4), and < 15 (5) mL/min/1.73 m². OUTCOMES: Onset of renal replacement therapy (RRT), death, the composite end point of RRT or death, or decreasing CKD stage. RESULTS: During a median follow-up of 26 months, 13% reached the end point of RRT (5.1 events/100 patient-years), 20% died (9.6 deaths/100 patient-years), and 33% reached the combined end point of RRT or death (14.7 events/100 patient-years). For stage 3a, baseline prevalence and annual probabilities of decreasing CKD stage, RRT, and death were 18.0%, 0.41, 0.01, and 0.02, respectively. Corresponding values for stage 3b were 32.5%, 0.22, < 0.01, and 0.06; for stage 4, 36.5%, 0.17, 0.03, and 0.10; and for stage 5, 13.2%, zero (by definition), 0.31, and 0.08, respectively. Markov model projections suggested a steady decrease for proportions with stages 3a, 3b, and 4; a steady increase for death and RRT; and a biphasic pattern for (non-RRT) stage 5, with a plateau in the first 2 years followed by a steady decrease. LIMITATIONS: Single-center observational study. CONCLUSION: This study suggests that death and RRT are the dominant outcomes in patients referred for management of CKD and that most patients spend comparatively little time in late stages without RRT.

Vitamin D Status After Gastric Bypass or Sleeve Gastrectomy over 4 Years of Follow-up.

BACKGROUND: Bariatric surgery for severe obesity can lead to micronutrient/vitamin deficiencies. AIMS: To study baseline and post-surgical prevalence of vitamin D deficiency in patients undergoing bariatric surgery. PARTICIPANTS AND SETTING: Patients undergoing bariatric surgery in a university teaching hospital in North West England. METHODS: We performed an observational cohort analysis of longitudinal data on vitamin D and related parameters in patients who underwent bariatric surgery. Patients were routinely recommended daily combined calcium and vitamin D supplementation post-surgery. RESULTS: We studied 460 patients who had completed at least 12 months post-operatively; mean (standard deviation) age was 48.0 (10.5) years, weight 144.7 (27.3) kg and body mass index 50.0 (7.6) kg/m2; 292 (63.5%) underwent gastric bypass and 168 (36.5%) sleeve gastrectomy. Vitamin D level was 33.1 (23.9) nmol/L at baseline, rising to 57.1 (23.1) nmol/L at 12 months post-surgery. Whereas 43.2% had vitamin D deficiency and 34.7% insufficiency preoperatively, 8.9% and 26.7% had deficiency and insufficiency, respectively, at 12 months with similar trends up to 4 years of follow-up. There were no significant differences between procedures or sexes in vitamin D levels or sufficiency rates. CONCLUSION: Vitamin D deficiency and insufficiency were prevalent pre-surgery and reduced significantly with routine supplementation post-surgery.

Benefit and safety of fluticasone furoate/vilanterol in the Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD) according to baseline patient characteristics and treatment subgroups.

BACKGROUND: SLS COPD was the first open-label randomised controlled trial demonstrating a reduction in moderate/severe COPD exacerbations with once-daily inhaled fluticasone furoate/vilanterol (FF/VI) in everyday clinical practice. Here we report FF/VI effectiveness and safety in predefined patient subgroups. METHODS: Patients with COPD, exacerbation history, and receiving maintenance inhaler therapy, were randomised to initiate FF/VI 100/25 µg or continue usual care (UC) with 12 months' follow-up. Annual rates of moderate/severe exacerbations (primary outcome), selected secondary outcomes, and incidence of pneumonia serious adverse events of special interest (SAESI) were compared between randomisation groups across various patient subgroups/baseline treatment strata. SAESI rates by actual treatment were also assessed. RESULTS: Lower exacerbation rates were observed for FF/VI versus UC across all subgroups/strata, including ICS + LABA therapy subset (8.0% [0.1, 15.4]), except in patients without baseline airflow limitation (-0.5% [-29.8, 22.1]). Larger reductions compared to the overall analysis were observed for patients on ICS-containing regimens (excluding LAMA) before the study (15.6% [3.4, 26.3]), and with baseline CAT score <10 (25.3% [-0.4, 44.4]). Pneumonia SAESI rates were similar for FF/VI versus UC across all subgroups/strata, except the LABA, LAMA or LABA + LAMA stratum (incidence ratio 2.8 [0.9, 8.5]). SAESI rates were not increased for FF/VI versus other ICS + LABA. CONCLUSIONS: Initiating FF/VI versus continuing UC reduced exacerbation rates without increased pneumonia SAESI risk compared to other ICS-containing regimens and in various patient subgroups, consistent with primary study findings. FF/VI may be a therapeutic option for a broad population of COPD patients, including those with more severe disease.

Bariatric surgery as a model to explore the basis and consequences of the Reaven hypothesis: Small, dense low-density lipoprotein and interleukin-6.

BACKGROUND: Reaven originally described the clustering of insulin resistance/hyperinsulinaemia, obesity (particularly visceral), altered cytokine levels, glucose intolerance, hypertriglyceridaemia and low high-density lipoprotein cholesterol. Subsequently, a potentially highly atherogenic small, dense low-density lipoprotein was also reported. We have studied the effect of bariatric surgery on this and other risk factors for atherosclerosis. METHODS: Forty patients (20 with type 2 diabetes mellitus) undergoing bariatric surgery were studied before and 1 year after bariatric surgery. RESULTS: Twelve months after bariatric surgery, median body mass index had decreased from 49.5 to 36.5 kg/m2, fasting insulin from 21.3 to 7.8 mU/L and insulin resistance (homeostatic model assessment of insulin resistance) from 5.9 to 1.8 (all p < 0.001). Thirteen out of 20 patients had remission from type 2 diabetes mellitus. Highly sensitive C-reactive protein, interleukin-6, fasting triglycerides ( p < 0.001) and small, dense low-density lipoprotein ( p < 0.001) decreased, while high-density lipoprotein cholesterol increased ( p < 0.001) significantly, irrespective of having type 2 diabetes mellitus and/or being treated with statin therapy before surgery. CONCLUSION: The association between marked weight loss and change in insulin resistance and hyperinsulinaemia with the change in small, dense low-density lipoprotein and interleukin-6 warrants further investigation. Bariatric surgery provides a model for investigating the mechanisms linking insulin resistance/hyperinsulinaemia to atherosclerosis.

Derivation and validation of a prediction score for major coronary heart disease events in a U.K. type 2 diabetic population.

OBJECTIVE: To derive and validate an absolute risk algorithm for major coronary heart disease (CHD) events in the U.K. population with type 2 diabetes. RESEARCH DESIGN AND METHODS: A population cohort with type 2 diabetes was constructed in Tayside, Scotland, U.K., and longitudinally followed-up to June 2004. Participants were all people with type 2 diabetes registered with general practices and the Diabetes Audit and Research in Tayside, Scotland, database (97% sensitive) with no previous CHD event and with complete measurements (n = 4,569). The main outcome measure was risk of CHD defined as fatal or nonfatal myocardial infarction or CHD death, derived from the Weibull accelerated failure-time model. Validation of the algorithm was performed on an independent dataset from Salford, England, U.K. RESULTS: There were a total of 243 subjects (5.3%) with a fatal or nonfatal myocardial infarction or CHD death over the follow-up period from 1 January 1995 to 30 June 2004 (maximum follow-up 9.5 years). The final Weibull model included the significant predictors of age at diagnosis, duration of diabetes, HbA(1c), smoking (current, past, never), sex, systolic blood pressure, treated hypertension, total cholesterol, and height. Assessment of discrimination and calibration in the Salford validation dataset demonstrated a good fit (c = 0.71 [95% CI 0.63-0.79]). CONCLUSIONS: This study provides the first validated, population-derived model for prediction of absolute risk of CHD in people with type 2 diabetes. It provides a useful additional decision aid for the clinician treating type 2 diabetes by indicating appropriate early action to decrease the risk of adverse outcomes.