A survey of obstetricians' attitudes to induction of labour at 39 weeks gestation with the intention of reducing caesarean section rates.

BACKGROUND: Induction of labour (IOL) and caesarean section (CS) rates continue to increase in Australia, New Zealand and globally. There is evidence that CS rates are decreased in the context of medically indicated and elective IOL; therefore, the emerging concept of using IOL as means of preventing CS warrants investigation. AIMS: To assess obstetricians' opinions of elective IOL at 39 weeks gestation, its feasibility, generalisability and utility as a means of preventing CS in Australia and New Zealand. MATERIALS AND METHODS: A de-identified cross-sectional survey was distributed electronically to all Fellows and trainees of The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). The survey was voluntary and distributed with the approval of the RANZCOG Continuing Education Committee. The survey addressed opinions relating to rates of and indications for IOL, the perceived validity of those indications and explored the acceptability of using a screening tool to predict women at increased risk of intra-partum CS and tailoring obstetric management to include the option of IOL at 39 weeks gestation. RESULTS: The overall response rate was 34% (492/1423) (including trainees) and the response rate was 53% (394/750) for currently practising obstetricians. The majority (90%) of responders agreed on medical and clinical indications for IOL. There was no consensus on the validity of IOL if a woman were at apparent high risk of intra-partum CS; however, 81% (360/443) of clinicians would be interested in a tool that could predict those women at risk. CONCLUSIONS: There is heterogeneity of obstetrician's beliefs on using IOL at 39 weeks as a mechanism to reduce the CS rate.

Uric acid predicts long-term cardiovascular risk in type 2 diabetes but does not mediate the benefits of fenofibrate: The FIELD study.

AIM: To explore the relationship between baseline uric acid (UA) levels and long-term cardiovascular events in adults with type 2 diabetes (T2D) and to determine whether the cardioprotective effects of fenofibrate are partly mediated through its UA-lowering effects. METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial were utilized, comprising 9795 adults with T2D randomly allocated to treatment with fenofibrate or matching placebo. Plasma UA was measured before and after a 6-week, active fenofibrate run-in phase in all participants. Cox proportional hazards models were used to explore the relationships between baseline UA, pre-to-post run-in reductions in UA and long-term cardiovascular outcomes. RESULTS: Mean baseline plasma UA was 0.33 mmol/L (SD 0.08). Baseline UA was a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L higher UA conferring a 21% increase in event rate (HR 1.21, 95% CI 1.13-1.29, P < .001). This remained significant after adjustment for treatment allocation, cardiovascular risk factors and renal function. The extent of UA reduction during fenofibrate run-in was also a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L greater reduction conferring a 14% lower long-term risk (HR 0.86, 95% CI 0.76-0.97, P = .015). This effect was not modified by treatment allocation (Pinteraction = .77). CONCLUSIONS: UA is a strong independent predictor of long-term cardiovascular risk in adults with T2D. Although greater reduction in UA on fenofibrate is predictive of lower cardiovascular risk, this does not appear to mediate the cardioprotective effects of fenofibrate.

Epidemiological data of type 1 diabetes mellitus in children in Uzbekistan, 1998-2014.

AIMS: We aimed to determine the incidence, prevalence and mortality of type 1 diabetes (T1D) in Uzbekistan in children <15 years old. METHODS: In a prospective study from 1998 to 2014 the primary ascertainment of incidence, prevalence and mortality, and cause of death was via data collected by endocrinology dispensaries in Uzbekistan's 14 administrative divisions. A second data collection for 2008-2010 from a national audit in 2011 was used to determine age structure. RESULTS: Over 1998-2014 T1D prevalence roughly doubled (7.8 to 15.3/100,000 population aged <15 years, P = .10), following a doubling of incidence (1.5 to 3.1/100 000 < 15 years), a 5.6% annualized increase, P = .001), with a fall in mortality per 1000 patient years (24.5 to 2.0, P = .001). There was a female preponderance, with a male:female ratio of 0.89 in 2008-2010. In every year, T1D incidence was highest in the 10-14.99 year age-group, although the proportion of diagnoses under 5 years of age increased from 6.0% of total diagnoses in 1998-2002, to 13.4% in 2008-2010. Peak age of onset in 2008-2010 was 13 years. Notable regional variation was evident, with incidence being highest in Tashkent-City (P = .005). The most common cause of death was chronic renal failure-responsible for 31 deaths in children <15 years during the study period. CONCLUSIONS: Our results provide the first long-term epidemiological data for T1D in Uzbekistan and the region. Uzbekistan is country of low but rising T1D incidence and prevalence, and falling mortality. Attention to improving clinical care is warranted, to reduce long-term complications.

Baseline Circulating FGF21 Concentrations and Increase after Fenofibrate Treatment Predict More Rapid Glycemic Progression in Type 2 Diabetes: Results from the FIELD Study.

BACKGROUND: It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS: Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of ß-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. RESULTS: Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). CONCLUSIONS: Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetes patients. This association may be partly explained by hepatic function.

A New Scope of Practice: Adult Pulmonary Aspiration Managed With a Pediatric Gastroscope: A Case Report.

Pulmonary aspiration continues to be a major cause of anesthesia-related mortality. Anesthesiologists are encouraged to perform bronchoscopy to manage aspiration of particulate matter; however, they have limited training and experience in clearing luminal obstructions endoscopically. In our report, an adult with achalasia aspirated during induction for a per-oral endoscopic myotomy (POEM), resulting in desaturation and high airway pressures. Bronchoscopy by the anesthesiologist was ineffective. However, bronchoscopy by the gastroenterologist using a pediatric gastroscope cleared the bronchi of debris and led to immediate clinical improvement. Anesthesiologists, faced with particulate matter aspiration, could consider assistance from a gastrointestinal endoscopist.

Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study.

BACKGROUND: Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. METHODS: In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up. We did a post-hoc analysis of recorded on-study gout attacks and plasma uric acid concentrations according to treatment allocation. The outcomes of this analysis were change in uric acid concentrations and risk of on-study gout attacks. The FIELD study is registered with ISRCTN, number ISRCTN64783481. FINDINGS: Between Feb 23, 1998, and Nov 3, 2000, 9795 patients were randomly assigned to fenofibrate (n=4895) or placebo (n=4900) in the FIELD study. Uric acid concentrations fell by 20·2% (95% CI 19·9-20·5) during the 6-week active fenofibrate run-in period immediately pre-randomisation (a reduction of 0·06 mmol/L or 1 mg/dL) and remained -20·1% (18·5-21·7, p<0·0001) lower in patients taking fenofibrate than in those on placebo in a random subset re-measured at 1 year. With placebo allocation, there were 151 (3%) first gout events over 5 years, compared with 81 (2%) among those allocated fenofibrate (HR with treatment 0·54, 95% CI 0·41-0·70; p<0·0001). In the placebo group, the cumulative proportion of patients with first gout events was 7·7% in patients with baseline uric acid concentration higher than 0·36 mmol/L and 13·9% in those with baseline uric acid concentration higher than 0·42 mmol/L, compared with 3·4% and 5·7%, respectively, in the fenofibrate group. Risk reductions were similar among men and women and those with dyslipidaemia, on diuretics, and with elevated uric acid concentrations. For participants with elevated baseline uric acid concentrations despite taking allopurinol at study entry, there was no heterogeneity of the treatment effect of fenofibrate on gout risk. Taking account of all gout events, fenofibrate treatment halved the risk (HR 0·48, 95% CI 0·37-0·60; p<0·0001) compared with placebo. INTERPRETATION: Fenofibrate lowered uric acid concentrations by 20%, and almost halved first on-study gout events over 5 years of treatment. Fenofibrate could be a useful adjunct for preventing gout in diabetes. FUNDING: None.

HDL as a Target for Glycemic Control.

HDL has long been known for its role in reverse cholesterol transport, thought in part to explain the well-recognized links between low levels of HDL-C and cardiovascular disease. The past decade has seen increasing evidence from epidemiological, basic science and early human intervention studies that HDL biology is more complex and may influence the onset and progression of type 2 diabetes. Research has identified multiple potential pathways by which higher HDL particle concentrations or functional improvements may ameliorate the development and progression of the disease. These include promotion of insulin secretion and pancreatic islet beta-cell survival, promotion of peripheral glucose uptake, and suppression of inflammation. The relationships between HDL-C levels, commonly used in clinical practice, and HDL particle number, size and various HDL functions is complex, and is intimately linked with triglyceride metabolism. The complexity of these relationships is amplified in diabetes, which negatively impacts multiple aspects of lipoprotein biology. This article reviews the rationale for, and potential of, HDL-based anti-diabetic pharmacotherapy, with an emphasis on the particular challenges posed by diabetes-related HDL dysfunction, and on the difficulties of selecting appropriate targets and HDL-related biomarkers for research and for clinical practice. We discuss aspects of HDL metabolism that are known to be altered in type 2 diabetes, potentially useful measures of HDL-targeted therapy in diabetes, and review early intervention studies in humans. These areas provide a firm foundation for further research and knowledge expansion in this intriguing area of human health and disease.

HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes.

OBJECTIVE: Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control. RESEARCH DESIGN AND METHODS: The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated ß-cell function (homeostasis model assessment of ß-cell function [HOMA-B]) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin. RESULTS: Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = -0.233, -0.134, and -0.230; all P < 0.001; n = 8,271) but not related to HbA1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = -0.063; P = 0.002; n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio [HR] 1.13 [CI 1.07-1.19], P < 0.001; and HR 1.16 [CI 1.10-1.23], P < 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P < 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant. CONCLUSIONS: HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.