Interventions for great saphenous vein reflux: network meta-analysis of randomized clinical trials.

BACKGROUND: A variety of endovascular and open surgical interventions exist to treat great saphenous vein reflux. However, comparisons of treatment outcomes have been inconsistent. METHODS: A systematic review and network meta-analysis of RCTs was performed to compare rates of incomplete stripping or non-occlusion of the great saphenous vein with or without reflux (anatomical failure) at early, mid- and long-term follow-up; and secondary outcomes (reintervention and clinical recurrence) among intervention groups. The surface under the cumulative ranking curve (SUCRA) method was used to estimate the probability of the intervention with the lowest anatomical failure rates. RESULTS: Some 72 RCTs were included. Comparisons of endothermal techniques with open surgery were mostly not significantly different, except for endovenous laser ablation (EVLA), which had higher long-term anatomical failure rates (pooled risk ratio (RR) 1.87, 95 per cent c.i. 1.14 to 3.07). Mechanochemical ablation had higher anatomical failure rates than radiofrequency ablation (RFA) (pooled RR 2.77, 1.38 to 5.53), and cyanoacrylate closure (CAC) had a RR 0.56 (0.34 to 0.93) times lower than either RFA or EVLA at the early term. Ultrasound-guided foam sclerotherapy had a higher risk of anatomical failure and reintervention than open surgery, with the lowest SUCRA value, and CAC was ranked first, third and first for best intervention for anatomical failure at early, mid and long term respectively. However, clinical recurrence rates were not significantly different between all comparisons. CONCLUSION: Mechanochemical ablation and ultrasound-guided foam sclerotherapy performed poorly, with higher anatomical failure rates in the long term. The other treatment modalities had similar rates of anatomical failure in the short and mid term.

Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis.

BACKGROUND: The efficacy of hormonal regimens for the prevention of endometrioma recurrence in women who have undergone conservative surgery is still controversial. OBJECTIVE: To compare the efficacy of different hormonal regimens in this context and to rank them. SEARCH STRATEGY: MEDLINE and Scopus databases were searched through January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cohorts, comparing the effect of any pair of interventions (i.e. cyclic oral contraceptives [OC], continuous OC, gonadotropin-releasing hormone agonist [GnRHa], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNG-IUS] and expectant management) on endometrioma recurrence were selected. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA) and ranked in descending order. MAIN RESULTS: Six RCTs (675 patients) and 16 cohorts (3089 patients) were included. NMA of the RCTs involving expectant management, cyclic OC, continuous OC, GnRHa and GnRHa + LNG-IUS, showed that all hormonal regimens had a nonsignificant lower risk of endometrioma recurrence compared with expectant management. NMA of the cohorts involving expectant, cyclic OC, continuous OC, GnRHa, DNG, LNG-IUS, GnRHa + OC, and GnRHa + LNG-IUS indicated that LNG-IUS, DNG, continuous OC, GnRHa + OC and cyclic OC had a significantly lower risk of endometrioma recurrence than expectant management. LNG-IUS was ranked highest, followed by DNG and GnRHa + LNG-IUS. Long-term use of hormonal treatment either OC or progestin had a significantly lower risk of endometrioma recurrence than expectant treatment. CONCLUSION: In the NMA of RCTs, there was no evidence supporting hormonal treatment for postoperative prevention of endometrioma recurrence. This was at odds with the cohort evidence, which found the protective effect of OC and progestin regimens, especially long-term treatment. Large-scale RCTs of these agents are still required. TWEETABLE ABSTRACT: Hormonal regimens given as long-term treatment tend to reduce risk of endometrioma recurrence after conservative surgery.

Efficacy of an agonist of α-MSH, the palmitoyl tetrapeptide-20, in hair pigmentation.

OBJECTIVE: Hair greying (i.e., canities) is a component of chronological ageing and occurs regardless of gender or ethnicity. Canities is directly linked to the loss of melanin and increase in oxidative stress in the hair follicle and shaft. To promote hair pigmentation and reduce the hair greying process, an agonist of α-melanocyte-stimulating hormone (α-MSH), a biomimetic peptide (palmitoyl tetrapeptide-20; PTP20) was developed. The aim of this study was to describe the effects of the designed peptide on hair greying. METHODS: Effect of the PTP20 on the enzymatic activity of catalase and the production of H2 O2 by Human Follicle Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression of melanocortin receptor-1 (MC1-R) and the production of melanin were investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20 was also determined. Ex vivo studies using human micro-dissected hairs allowed to visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP-1, TRP-2, Melan-A, ASIP, and MC1-R. These investigations were completed by a clinical study on 15 human male volunteers suffering from premature canities. RESULTS: The in vitro and ex vivo studies revealed the capacity of the examined PTP20 peptide to enhance the expression of catalase and to decrease (30%) the intracellular level of H2 O2 . Moreover, PTP20 was shown to activate in vitro and ex vivo the melanogenesis process. In fact, an increase in the production of melanin was shown to be correlated with elevated expression of MC1-R, TRP-1, and Melan-A, and with the reduction in ASIP expression. A modulation on TRP-2 was also observed. The pivotal role of MC1-R was confirmed on protein expression analysed on volunteer's plucked hairs after 3 months of the daily application of lotion containing 10 ppm of PTP20 peptide. CONCLUSION: The current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of α-MSH to promote hair pigmentation and thus, reduce the hair greying process.

Insulin resistance correlates with maculopathy and severity of retinopathy in young adults with Type 1 Diabetes Mellitus.

AIMS: To assess the relationship between insulin resistance (IR), retinopathy and maculopathy in young adults with Type 1 diabetes mellitus. METHODS: A cross-sectional study at a regional Australian tertiary hospital. Retinal pathology, assessed by colour fundus photography, was correlated with two surrogate measures of IR: estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS), where lower scores reflect greater IR. RESULTS: 107 patients were recruited, with mean age 24.7years, 53% male, and mean duration of disease 10.8years. Mean eGDR scores (5.6vs 8.0 p<0.001) and ISS (4.7vs 7.9, p<0.001) were lower in subjects having at least moderate non-proliferative diabetic retinopathy (NPDR; relative to nil/mild-NPDR). Similarly, mean eGDR (4.2vs 6.2, p=0.001) and ISS (3.8vs 6.1, p=0.003) were lower in patients with maculopathy. Multivariate logistic regression modelling was used to control for confounding. For retinopathy severity, a unit increase in eGDR or ISS (representing lower IR) was associated with a 50% decrease in odds of moderate-NPDR or worse (eGDR OR 0.5, 95%CI 0.32-0.77, p=0.002; ISS OR 0.49, 95%CI 0.29-0.84, p=0.01). A unit increase in eGDR or ISS was associated with a 46-56% decrease in odds of maculopathy (eGDR OR 0.54, 95%CI 0.37-0.81, p=0.003; ISS OR 0.44, 95%CI 0.22-0.88, p=0.02). CONCLUSIONS: IR correlates with more severe retinopathy in young adults with Type 1DM. This is the first description of a correlation between IR and maculopathy in Type 1DM, warranting further evaluation. Prospective studies examining whether reducing IR can improve microvascular complications are required.

Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

Predicting type 2 diabetes using genetic and environmental risk factors in a multi-ethnic Malaysian cohort.

OBJECTIVE: Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation. STUDY DESIGN: This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project. METHODS: The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R2 and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants. RESULTS: The models including environmental risk factors only had pseudo R2 values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10-4-4.83 × 10-12) and increased the pseudo R2 by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 < P < 0.05. CONCLUSION: This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene-environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.

Prenatal microarray comparative genomic hybridization: Experience from the two first years of activity at the Lyon university-hospital.

OBJECTIVES: This study aims to describe how microarray comparative genomic hybridization (aCGH) has shifted to become a prenatal diagnosis tool at the Lyon university-hospital. MATERIALS AND METHODS: This retrospective study included all patients who were referred in the 3 pluridisciplinary centers for prenatal diagnosis of the Lyon university-hospital and who received a prenatal aCGH between June 2013 and June 2015. aCGH was systematically performed in parallel with a karyotype, using the PréCytoNEM array design. RESULTS: A total of 260 microarrays were performed for the following indications: 249 abnormal ultrasounds (95.8%), 7 characterizations of chromosomal rearrangements (2.7%), and 4 twins with no abnormal ultrasounds (1.5%). With a resolution of 1 mega base, we found 235 normal results (90.4%), 23 abnormal results (8.8%) and 2 non-returns (0.8%). For the chromosomal rearrangements visible on the karyotype, aCGH identified all of the 12 unbalanced rearrangements and did not identify the 2 balanced rearrangements. Among the fetuses with normal karyotypes, 11 showed abnormal microarray results, corresponding to unbalanced cryptic chromosomal rearrangements (4.2%). CONCLUSION: Transferring aCGH to a prenatal diagnosis at the Lyon university-hospital has increased the detection rate of chromosomal abnormalities by 4.2% compared to the single karyotype.

Increasing the protein quantity in a meal results in dose-dependent effects on postprandial glucose levels in individuals with Type 1 diabetes mellitus.

AIM: To determine the glycaemic impact of increasing protein quantities when consumed with consistent amounts of carbohydrate in individuals with Type 1 diabetes on intensive insulin therapy. METHODS: Participants with Type 1 diabetes [aged 10-40 years, HbA1c ≤ 64 mmol/mol (8%), BMI ≤ 91st percentile] received a 30-g carbohydrate (negligible fat) test drink daily over 5 days in randomized order. Protein (whey isolate 0 g/kg carbohydrate, 0 g/kg lipid) was added in amounts of 0 (control), 12.5, 25, 50 and 75 g. A standardized dose of insulin was given for the carbohydrate. Postprandial glycaemia was assessed by 5 h of continuous glucose monitoring. RESULTS: Data were collected from 27 participants (15 male). A dose-response relationship was found with increasing amount of protein. A significant negative relationship between protein dose and mean excursion was seen at the 30- and 60-min time points (P = 0.007 and P = 0.002, respectively). No significant relationship was seen at the 90- and 120-min time points. Thereafter, the dose-response relationship inverted, such that there was a significant positive relationship for each of the 150-300-min time points (P < 0.004). Mean glycaemic excursions were significantly greater for all protein-added test drinks from 150 to 300 min (P < 0.005) with the 75-g protein load, resulting in a mean excursion that was 5 mmol/l higher when compared with the control test drink (P < 0.001). CONCLUSIONS: Increasing protein quantity in a low-fat meal containing consistent amounts of carbohydrate decreases glucose excursions in the early (0-60-min) postprandial period and then increases in the later postprandial period in a dose-dependent manner.

Reduced prevalence of pain and distress during 4 years of screening with QUICATOUCH in Australian oncology patients.

While psychosocial screening has been recommended in oncology for some time, widespread adoption in clinical practice has lagged. The QUICATOUCH program is one example of sustained clinic-level screening, assessment and referral. We examined whether this program was associated with reductions in pain or distress. Oncology outpatients completed a brief, computerised assessment using Distress and Pain Thermometers. We describe population levels of pain and distress and model pain and distress scores over 4 years of the program. 9,133 patients were screened on 26,385 occasions over 48 months (October 2007-September 2011). Pain over threshold (1/10) reduced over time, from 33% in the first 3 months to 16% in the final quarter of the evaluation. Distress over threshold (4/10) reduced from 28% to 10%. A reduction was also observed when restricted to patients screened for the first time. Our analysis demonstrated this effect was not explained by measured potential confounders (gender, age, treatment status) and was unlikely to be attributable to regression to the mean. Observational studies cannot prove causation. However, the significant reduction in pain and distress levels in the 48 months following commencement of QUICATOUCH is consistent with a beneficial effect of the program.

The duration of intrapartum maternal hyperglycaemia predicts neonatal hypoglycaemia in women with pre-existing diabetes.

AIM: There is a high incidence of neonatal hypoglycaemia in neonates born to mothers with pre-existing diabetes. This often necessitates admission to the neonatal intensive care. Guidelines suggest maintaining intrapartum blood glucose levels (BGLs) of 4-7 mmol/l in women with diabetes to reduce the risk of neonatal hypoglycaemia. This study assessed whether intrapartum BGLs in women with pre-gestational Type 1 and 2 diabetes were predictive of neonatal hypoglycaemia. METHODS: A retrospective analysis of 261 births delivered at a tertiary hospital in Australia from 2009 to 2014. RESULTS: There were 122 cases of neonatal hypoglycaemia (glucose ≤ 2.6 mmol/l) in 261 births (47%). The mothers in the neonatal hypoglycaemia group spent less time with BGL in the range 4-7 mmol/l [55 ± 37% vs. 65 ± 35%, P = 0.02; odds ratio (OR) 0.992, P = 0.03] and more time with BGL in the 7-10 mmol/l range (31 ± 34% vs. 18 ± 27%, P = 0.003; OR 1.013, P = 0.003) compared with those without neonatal hypoglycaemia. Although statistically significant, receiver operating characteristic (ROC) curve analysis showed that time spent with maternal BGLs in the range 4-7 mmol/l [area under the curve (AUC) = 0.58] or 7-10 mmol (AUC = 0.60) was not strong enough to be a useful clinical predictor of neonatal hypoglycaemia. HbA1c in the second trimester of pregnancy (P = 0.02, OR 1.42) and percentage time spent in BGL range of 7-10 mmol/l (P = 0.001, OR 1.02) were both associated with a risk of neonatal hypoglycaemia in a logistic regression model. HbA1c in the third trimester (P = 0.07, OR 1.28) approached, but did not reach, significance. CONCLUSIONS: These data support a BGL range of 4-7 mmol/l as an intrapartum target. Glycaemic control in the second trimester is associated with neonatal hypoglycaemia. Improvement in ante- and intrapartum glycaemic control may reduce neonatal hypoglycaemia in women with pre-existing diabetes.

Network meta-analysis of antibiotic prophylaxis for prevention of surgical-site infection after groin hernia surgery.

BACKGROUND: First-generation cephalosporins (such as cefazolin) are recommended as antibiotic prophylaxis in groin hernia repair, but other broad-spectrum antibiotics have also been prescribed in clinical practice. This was a systematic review and network meta-analysis to compare the efficacy of different antibiotic classes for prevention of surgical-site infection (SSI) after hernia repair. METHODS: RCTs were identified that compared efficacy of antibiotic prophylaxis on SSI after inguinal or femoral hernia repair from PubMed and Scopus databases up to March 2016. Data were extracted independently by two reviewers. Network meta-analysis was applied to assess treatment efficacy. The probability of being the best antibiotic prophylaxis was estimated using surface under the cumulative ranking curve (SUCRA) analysis. RESULTS: Fifteen RCTs (5159 patients) met the inclusion criteria. Interventions were first-generation (7 RCTs, 1237 patients) and second-generation (2 RCTs, 532) cephalosporins, ß-lactam/ß-lactamase inhibitors (6 RCTs, 619) and fluoroquinolones (2 RCTs, 581), with placebo as the most common comparator (14 RCTs, 2190). A network meta-analysis showed that ß-lactam/ß-lactamase inhibitors and first-generation cephalosporins were significantly superior to placebo, with a pooled risk ratio of 0·44 (95 per cent c.i. 0·25 to 0·75) and 0·62 (0·42 to 0·92) respectively. However, none of the antibiotic classes was significantly different from the others. SUCRA results indicated that ß-lactam/ß-lactamase inhibitors and first-generation cephalosporins were ranked first and second respectively for best prophylaxis. CONCLUSION: ß-Lactam/ß-lactamase inhibitors followed by first-generation cephalosporins ranked as the most effective SSI prophylaxis for adult patients undergoing groin hernia repair.

Cautionary tales in the interpretation of observational studies of effects of clinical interventions.

Observational studies of the effectiveness of clinical interventions are proliferating as more 'real-world' clinical data (so called 'big data') are gathered from clinical registries, administrative datasets and electronic health records. While well-conducted randomised controlled trials (RCT) remain the scientific standard in assessing the efficacy of clinical interventions, well-designed observational studies may add to the evidence base of effectiveness in situations where RCT are of limited value or very difficult to perform. Rather than dismissing observational studies, we need to determine what circumstances may justify doing an observational study and when the study is sufficiently rigorous to be considered reasonably trustworthy. This article proposes criteria by which users of the literature might make such determinations.

Elevation of post mortem vitreous humour sodium and chloride levels can be used as a reliable test in cases of suspected salt water drowning when the immersion times are less than one hour.

BACKGROUND: Previous studies in salt water drowning deaths (SWD) demonstrated an observable elevation of post mortem vitreous sodium and chloride (PMVSC) levels. It remains unclear what the underlying mechanism responsible for this change is: whether this is due to rapid electrolyte changes from salt water inhalation/ingestion during drowning or from electrolyte diffusion and/or osmosis across the outer coats of the eyeballs during immersion. A recent animal study using sacrificed bovine eyeballs immersed in salt water demonstrated no significant elevations in PMVSC when immersed for less than one hour. Assuming similar physical properties between human and bovine, we extrapolate that an elevation in PMVSC in SWD with immersion times of less than one hour (SWD-1) would not be from immersion, but from drowning. AIM: Investigate whether there is an elevation in PMVSC in SWD-1. METHODS: Retrospective study comparing PMVSC in SWD-1 with controls from 2012 to 2015 inclusive. RESULTS: PMVSC in SWD-1 was significantly elevated compared with controls. A PMVSC of 259mmol/L has a sensitivity, specificity and likelihood ratio of 0.9, 0.9 and 7.6, respectively. CONCLUSION: The elevation in PMVSC in SWD-1 is due to drowning. A PMVSC of 259mmol/L and above is a reliable ancillary test in diagnosing drowning in bodies immersed in salt water for less than one hour.

A cohort of Indigenous Australian women and their children through pregnancy and beyond: the Gomeroi gaaynggal study.

Indigenous Australians have high rates of chronic diseases, the causes of which are complex and include social and environmental determinants. Early experiences in utero may also predispose to later-life disease development. The Gomeroi gaaynggal study was established to explore intrauterine origins of renal disease, diabetes and growth in order to inform the development of health programmes for Indigenous Australian women and children. Pregnant women are recruited from antenatal clinics in Tamworth, Newcastle and Walgett, New South Wales, Australia, by Indigenous research assistants. Measures are collected at three time points in pregnancy and from women and their children at up to eight time points in the child's first 5 years. Measures of fetal renal development and function include ultrasound and biochemical biomarkers. Dietary intake, infant feeding and anthropometric measurements are collected. Standardized procedures and validated tools are used where available. Since 2010 the study has recruited over 230 women, and retained 66 postpartum. Recruitment is ongoing, and Gomeroi gaaynggal is currently the largest Indigenous pregnancy-through-early-childhood cohort internationally. Baseline median gestational age was 39.1 weeks (31.5-43.2, n=110), median birth weight was 3180 g (910-5430 g, n=110). Over one third (39.3%) of infants were admitted to special care or neonatal nursery. Nearly half of mothers (47.5%) reported tobacco smoking during pregnancy. Results of the study will contribute to knowledge about origins of chronic disease in Indigenous Australians and nutrition and growth of women and their offspring during pregnancy and postpartum. Study strengths include employment and capacity-building of Indigenous staff and the complementary ArtsHealth programme.

Suicidal ideation reported by adults with Type 1 or Type 2 diabetes: results from Diabetes MILES-Australia.

AIMS: To examine the prevalence and correlates of suicidal ideation (SI) in a community-based sample of adults with Type 1 or Type 2 diabetes. METHODS: Participants were 3338 adults aged 18-70 years with Type 1 diabetes (n = 1376) or Type 2 diabetes (non-insulin: n = 1238; insulin: n = 724) from a national survey administered to a random sample registered with the National Diabetes Services Scheme. Depression and SI were assessed using the Patient Health Questionnaire, and diabetes-specific distress with the Problem Areas In Diabetes scale. Separate logistic regression analyses by diabetes type/treatment were used to determine relative contribution to SI. RESULTS: Overall, we observed a SI rate of 14% in our sample. Participants with Type 2 diabetes using insulin reported more frequent depressive symptoms, and were more likely to report recent SI (19%) compared with those with either Type 1 diabetes or Type 2 diabetes not using insulin (14 and 12%, respectively). After controlling for depression, there was little difference in the prevalence of SI between diabetes types/treatments, but higher diabetes-specific distress significantly increased the odds of SI. CONCLUSIONS: As SI is a significant risk factor for a suicide attempt, the findings have implications for healthcare professionals, pointing to the importance of adequate screening and action plans for appropriate follow-up of those reporting depression. Our findings are also indicative of the psychological toll of diabetes more generally, and the need to integrate physical and mental healthcare for people with diabetes.

Influence of dietary protein on postprandial blood glucose levels in individuals with Type 1 diabetes mellitus using intensive insulin therapy.

AIM: To determine the effects of protein alone (independent of fat and carbohydrate) on postprandial glycaemia in individuals with Type 1 diabetes mellitus using intensive insulin therapy. METHODS: Participants with Type 1 diabetes mellitus aged 7-40 years consumed six 150 ml whey isolate protein drinks [0 g (control), 12.5, 25, 50, 75 and 100] and two 150 ml glucose drinks (10 and 20 g) without insulin, in randomized order over 8 days, 4 h after the evening meal. Continuous glucose monitoring was used to assess postprandial glycaemia. RESULTS: Data were collected from 27 participants. Protein loads of 12.5 and 50 g did not result in significant postprandial glycaemic excursions compared with control (water) throughout the 300 min study period (P > 0.05). Protein loads of 75 and 100 g resulted in lower glycaemic excursions than control in the 60-120 min postprandial interval, but higher excursions in the 180-300 min interval. In comparison with 20 g glucose, the large protein loads resulted in significantly delayed and sustained glucose excursions, commencing at 180 min and continuing to 5 h. CONCLUSIONS: Seventy-five grams or more of protein alone significantly increases postprandial glycaemia from 3 to 5 h in people with Type 1 diabetes mellitus using intensive insulin therapy. The glycaemic profiles resulting from high protein loads differ significantly from the excursion from glucose in terms of time to peak glucose and duration of the glycaemic excursion. This research supports recommendations for insulin dosing for large amounts of protein.

Evidence of effectiveness of a fracture liaison service to reduce the re-fracture rate.

SUMMARY: We assessed the ability of a fracture liaison service (FLS) to directly reduce re-fracture risk. Having a FLS is associated with a ∼40% reduction in the 3-year risk of major bone and ∼30% of any bone re-fracture. The number needed to treat to prevent a re-fracture is 20. INTRODUCTION: FLS have been promoted as the most effective interventions for secondary fracture prevention, and while there is evidence of increased rate of investigation and treatment at institutions with a FLS, only a few studies have considered fracture outcomes directly. We therefore sought to evaluate the ability of our FLS to reduce re-fracture risk. METHODS: Historical cohort study of all patients ≥50 years presenting over a 6-month period with a minimal trauma fracture (MTF) to the emergency departments of a tertiary hospital with a FLS, and one without a FLS. Baseline characteristics, mortality and MTFs over a 3-year follow-up were recorded. RESULTS: Five hundred fifteen patients at the FLS hospital and 416 patients at the non-FLS hospital were studied. Over 3 years, 63/515 (12%) patients at the FLS hospital and 70/416 (17%) at the non-FLS hospital had a MTF. All patients were analysed in an intention-to-treat analysis regardless of whether they were seen in the FLS follow-up clinic. Statistical analysis using Cox proportional hazard models in the presence of a competing risk of death from any cause was used. After adjustment for baseline characteristics, there was a ∼30% reduction in rate of any re-fracture at the FLS hospital (hazard ratio (HR) 0.67, confidence interval (CI) 0.47-0.95, p value 0.025) and a ∼40% reduction in major re-fractures (hip, spine, femur, pelvis or humerus) (HR 0.59, CI 0.39-0.90, p value 0.013). CONCLUSIONS: We found a ∼30% reduction in any re-fractures and a ∼40% reduction in major re-fractures at the FLS hospital compared with a similar non-FLS hospital. The number of patients needed to treat to prevent one new fracture over 3 years is 20.

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Autoantibodies are not predictive markers for the development of depressive symptoms in a population-based cohort of older adults.

BACKGROUND: Autoantibodies have been implicated in the etiologic pathway of depressive disorders. Here, we determine the association between the presence of a panel of autoantibodies at baseline and change in depression symptom score over 5-year follow-up in a cohort of healthy elderly Australians. METHODS: Serum samples from 2049 randomly selected subjects enrolled in the Hunter Community Study (HCS) aged 55-85 years were assayed for a range of autoimmune markers (anti-nuclear autoantibodies, extractable nuclear antigen autoantibodies, anti-neutrophil cytoplasmic autoantibodies, thyroid peroxidase autoantibodies, tissue transglutaminase autoantibodies, anti-cardiolipin autoantibodies, rheumatoid factor and cyclic citrullinated peptide autoantibodies) at baseline. Depression symptom score was assessed using the Centre for Epidemiological Study (CES-D) scale at baseline and 5 years later. RESULTS: Autoantibody prevalence varied amongst our sample with ANA being the most prevalent; positive in 16% and borderline in 36% of study population. No evidence for a relationship was found between change in CES-D score over time and any autoimmune marker. Statins and high cholesterol were significantly associated with change in CES-D score over time in univariate analysis; however, these were probably confounded since they failed to remain significant following multivariable analysis. CONCLUSIONS: Autoantibodies were not associated with change in CES-D score over time. These findings point to an absence of autoimmune mechanisms in the general population or in moderate cases of depression.

Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.

AIMS: To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. METHODS: We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. RESULTS: After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. CONCLUSION: This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations.