Diagnosis of metaphyseal fractures in infants and young children with suspected inflicted injury: a systematic review of cross-sectional imaging techniques.

AIM: To compare the diagnostic accuracy, advantages, and disadvantages of different medical imaging techniques for detecting metaphyseal fractures (also known as classic metaphyseal lesions [CMLs]) in infants and young children with suspected inflicted trauma. MATERIALS AND METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool criteria. Predefined keywords were used to search online databases for English articles published between 1 January 1980 and 31 March 2023. RESULTS: The initial search revealed 83 studies, only five of which met the inclusion criteria. The sensitivity and specificity of positron-emission tomography (PET) were 67% and 99%, respectively. The sensitivity and specificity of ultrasound were 55-61% and 96-97%, respectively. The sensitivity of magnetic resonance imaging (MRI) whole-body screening was 31%. The sensitivity of bone scintigraphy was 17% in one and 35% in a second study. Computed tomography was not used to detect CMLs in any diagnostic accuracy study. CONCLUSION: This systematic review has identified only a small number of relevant studies. In addition to the skeletal survey, PET and ultrasound may be helpful for the diagnosis of CMLs in infants and young children with suspected abuse; however, ultrasound has greater potential than PET due to its higher specificity, lack of radiation exposure, low cost, and wider availability.

The repeatability of the abbreviated (4-h) Oral Fat Tolerance Test and influence of prior acute aerobic exercise.

PURPOSE: The Oral Fat Tolerance Test (OFTT) is regarded as a repeatable measure used to assess postprandial triglyceride (TAG) levels, with higher levels observed in cardio-metabolic disorders. Acute aerobic exercise intervention before OFTT reduces the TAG response, but the repeatability of this effect is unknown. The aim of this study was to determine the repeatability of the abbreviated 4-h OFTT with and without immediate prior aerobic exercise. METHODS: On four separate days, healthy adult male participants underwent two 4-h OFTT (n = 10) and another two 4-h OFTT with 1-h of standardised moderate intensity aerobic exercise performed immediately before meal ingestion (n = 11). The OFTT meal composition included 75.4 g total fat, 21.7 g carbohydrate and 13.7 g protein. Venous blood was sampled at baseline and hourly up to 4 h after the OFTT meal ingestion, and TAG area under the curve (AUC) was calculated. RESULTS: Nonparametric Bland-Altman analysis of 4-h TAG AUC revealed that 9 of 10 repeat measurements fell within ±15 % of the median TAG AUC for the OFTT. By contrast, two of 11 repeat measurements fell within ±15 % of the median TAG AUC for the OFTT undertaken with 1-h prior aerobic exercise. CONCLUSIONS: The 4-h OFTT is a repeatable test of postprandial TAG responses in healthy men. However, aerobic exercise performed immediately before OFTT considerably increases the variability of TAG AUC. These findings have implications for interpretation of research studies investigating exercise intervention performed immediately before OFTT. Future studies should also investigate the repeatability of exercise performed 8-24 h before OFTT.

Soy isoflavones improve cardiovascular disease risk markers in women during the early menopause.

BACKGROUND: Hormone replacement therapy may be beneficial for cardiovascular disease risk (CVR) in post-menopausal women. Soy isoflavones may act as selective estrogen receptor modulators. The aim of this study was to evaluate whether soy isoflavones had an effect on CVR markers. METHODS: The expected 10-year risk of cardiovascular disease and mortality were calculated as a secondary endpoint from a double blind randomised parallel study involving 200 women (mean age 55 years, Caucasian, Hull, UK, 2012) in the early menopause who were randomised to 15 g soy protein with 66 mg isoflavone (SPI) or 15 g soy protein alone (depleted of all isoflavones; SP) given as a snack bar between meals daily for 6 months. Age, diabetes, smoking, blood pressure and lipid profiles were used to calculate CVR using the Framingham CVR engine. RESULTS: SPI treatment resulted in a significant reduction in the metabolic parameters and systolic blood pressure compared to SP (p < 0.01). There were no changes in fasting lipid profile and diastolic blood pressure with either treatment. At 6 months, changes in these parameters with SPI treatment were reflected in a calculated 27% (p < 0.01) reduction in 10 year coronary heart disease risk, a 37% (p < 0.01) reduction in myocardial infarction risk, a 24% (p < 0.04) reduction in cardiovascular disease and 42% (p < 0.02) reduction in cardiovascular disease death risk. CONCLUSIONS: Supplementation with soy protein with isoflavones for 6 months significantly improved CVR markers and calculated CVR at 6 months during early menopause compared to soy protein without isoflavones. ISRCTN REGISTRY: ISRCTN34051237.

Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been linked to polycystic ovary syndrome (PCOS) and carries an increased risk of liver cirrhosis. Procollagen type 3 amino-terminal peptide (PIIINP) is an independent predictor of liver cirrhosis. OBJECTIVE: To assess whether 6-month treatment with GLP-1 analogue, liraglutide, improves markers of liver fibrosis. DESIGN: A case-control study comparing women with PCOS to age- and weight-matched controls. PCOS was diagnosed according to the Rotterdam criteria. All participants underwent liver function tests and liver ultrasound scan to assess for fatty infiltration. Serum marker for liver fibrosis, PIIINP, was measured at baseline and after 6-month treatment with liraglutide 1·8 mg od. RESULTS: Nineteen women with PCOS and 17 controls were recruited, age 32·8 ± 7·2 vs 33·5 ± 6·7 years and weight 100·9 ± 16·7 vs 99·3 ± 14·7 kg, respectively. At baseline, the PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nm (P = 0·01), HOMA-IR 5·1 ± 2·6 vs 3·5 ± 1·3 (P = 0·03), AST 22·4 ± 5·2 vs 18·8 ± 3·4 u/l (P = 0·04), PIIINP 4·4 ± 0·8 vs 3·5 ± 0·8 ug/ml (P = 0·01) and NAFLD seven (35%) vs none (P = 0·005), respectively. Twenty-five (69%) participants completed the study (13 PCOS, 12 controls). Following treatment, weight was reduced by 3·0 ± 4·2 kg (P = 0·01) and 3·8 ± 3·4 kg (P = 0·001), respectively. Similarly, HOMA-IR, hsCRP, triglycerides and urinary isoprostane significantly reduced in both groups. PIIINP significantly reduced the in PCOS group 4·4 ± 0·8 vs 3·7 ± 0·9 ug/ml (P < 0·01), but not in controls 3·5 ± 0·8 vs 3·2 ± 0·7 ug/ml (P = 0·08). CONCLUSIONS: Treatment with liraglutide, and/or associated weight loss, significantly reduced PIIINP levels in obese women with PCOS. This may be an additional beneficial factor when considering the use of liraglutide in women with PCOS, obesity and NAFLD.

Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome.

AIM: This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. METHODS: In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention. RESULTS: By 12 weeks, niacin/laropiprant lowered low-density lipoprotein cholesterol (LDL-c) (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP. CONCLUSIONS: In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced ß-cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.

Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity.

INTRODUCTION: Previous studies investigating cardiovascular (CV) risk in obese women with polycystic ovary syndrome (PCOS) have been potentially confounded by not adequately accounting for body weight. OBJECTIVE: To assess if PCOS increases CV risk independently in young obese women by examining carotid intima-media wall thickness (cIMT) and platelet function. DESIGN: A case-control study comparing women with PCOS (n = 21) to age (32·8 ± 7·2 vs 33·5 ± 6·7 years), and weight (100·9 ± 16·7 vs 99·3 ± 14·7 kg)-matched controls (n = 19). Platelet function was examined by flow cytometry, clot structure and fibrinolysis by turbidimetric assays and endothelial function by ELISA and post ischaemic reactive hyperaemia. RESULTS: The PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nmol/l (P = 0·01), HOMA-IR 2·5 ± 1·7 vs 1·7 ± 1·0 (P = 0·08), impaired glucose regulation 33·3% vs 5·3% (P = 0·02), and urinary isoprostane 16·0 ± 4·4 vs 11·8 ± 7·1 ng/ml (P = 0·04) compared to controls. Mean cIMT 0·5 ± 0·05 vs 0·48 ± 0·06 mm (P = 0·36), and basal platelet surface expression (percentage of positive cells) of P-selectin 0·52 ± 0·3 vs 0·43 ± 0·23 (P = 0·40) and fibrinogen binding 0·97 ± 0·4 vs 0·83 ± 0·3 (P = 0·48) did not significantly differ between the PCOS and control groups respectively. Furthermore, platelets sensitivity to stimulation with adenosine-5'-diphosphate or inhibition with prostacyclin, clot structure and fibrinolytic efficiency ex vivo, endothelial reactive hyperaemic index (RHI), inflammation (hsCRP) and adhesion markers (sE-selectin, sP-selectin, sVCAM-1 and sICAM-1) were not significantly different between the two groups. CONCLUSIONS: PCOS appeared not to independently increase atherothrombotic risk when matched for obesity. It is likely that any excess CV risk in young obese women with PCOS can either be attributed to obesity or is not yet apparent at this early stage of the condition.

Implications of new European Union driving regulations on patients with Type 1 diabetes who participated in the Diabetes Control and Complications Trial.

AIMS: Recurrent severe hypoglycaemia in a patient with diabetes is strongly associated with a crash risk while driving. To help ensure road safety, recent changes were made to European Union driving regulations for patients with diabetes. These included the recommendation that more than one episode of severe hypoglycaemia within 12 months would lead to the loss of a driving licence. This study has assessed the impact of this regulation if applied to patients who participated in the Diabetes Control and Complications Trial. METHODS: All patients in the Diabetes Control and Complications Trial were assumed to be drivers. Repeated hypoglycaemic episodes within a year were determined during the mean 6.5 years of the study. RESULTS: Of the 1441 patients in the Diabetes Control and Complications Trial, 439 (30%) had more than one severe hypoglycaemic episode during a 12-month period of their study participation. Amongst the study groups, 312/711 (44%) of intensively treated and 127/730 (17%) of conventionally treated patients would have lost their licence at some point during the trial. The risk of licence loss increased with lower mean HbA1c , longer duration of diabetes and younger age (all P < 0.001). CONCLUSIONS: More than one episode of severe hypoglycaemia within a year was a frequent event in subjects in the Diabetes Control and Complications Trial, especially in intensively treated patients. If applied to current practice, improving road safety through these changes to European Union regulations could have a substantial impact on drivers who have Type 1 diabetes. This emphasizes the need to take into account the potential effects of severe hypoglycaemia in those who rely on a driving licence.

Extension MRI is clinically useful in cervical myelopathy.

INTRODUCTION: Cervical spine MRI with the neck in extension has been well described over the last 10 years, but its clinical value remains unknown. METHODS: We performed extension imaging in 60 patients in whom the initial neutral study showed borderline cord compression. Images were assessed using a previously validated grading system for cord compression. Multiple linear and area measurements were also obtained. Images were scored blindly and randomly. Inter- and intra-rater variability were determined in a subset of 20 cases. Independent clinical assessment utilised the Ranwat criteria. RESULTS: For most parameters inter/intra-observer variance of kappa/ICC > 0.6 was highly satisfactory. Standard MR was poor at discriminating between patients with and without myelopathy (ROC analysis, area under the curve (AUC), 0.52). This was considerably improved with extension imaging (AUC, 0.60), or by using the change in compression score between neutral and extension studies. Most measurements were not helpful; however, the ratio of cord area/CSF area at the level of maximum compression on extended images was the best discriminator (AUC, 0.71), as well as the presence of T2 change in cord substance (AUC, 0.68). CONCLUSION: This is the first study to demonstrate added clinical value utilising extension MRI. In this cohort of difficult patients, when there was no T2 signal change in the cord, the presence of clinical myelopathy could only be predicted by utilising the data from extension imaging.

Are non-invasive estimations of plasma volume an accurate measure of congestion in patients with chronic heart failure?

AIMS: We report associations between different formulae for estimating plasma volume status (PVS) and clinical and ultrasound markers of congestion in patients with chronic heart failure (CHF) enrolled in the Hull Lifelab registry. METHODS AND RESULTS: Cohort 1 comprised patients with data on signs and symptoms at initial evaluation (n = 3505). Cohort 2 included patients with ultrasound assessment of congestion [lung B-line count, inferior vena cava (IVC) diameter, jugular vein distensibility (JVD) ratio] (N = 341). Two formulae for PVS were used: (a) Hakim (HPVS) and (b) Duarte (DPVS). Results were compared with clinical and ultrasound markers of congestion. Outcomes assessed were mortality and the composite of heart failure (HF) hospitalisation and all-cause mortality. In cohort 1, HPVS was associated with mortality [hazard ratio (HR) per unitary increase = 1.02 (1.01-1.03); P < 0.001]. In cohort 2, HPVS was associated with B-line count (HR) = 1.05 [95% confidence interval (CI) (1.01-1.08); P = 0.02] and DPVS with the composite outcome [HR = 1.26 (1.01-1.58); P = 0.04]. HPVS and DPVS were strongly related to haemoglobin concentration and HPVS to weight. After multivariable analysis, there were no strong or consistent associations between PVS and measures of congestion, severity of symptoms, or outcome. By contrast, log[NTproBNP] was strongly associated with all three. CONCLUSION: Amongst patients with CHF, HPVS and DPVS are not strongly or consistently associated with clinical or ultrasound evidence of congestion, nor clinical outcomes after multivariable adjustment. They appear only to be surrogates of the variables from which they are calculated with no intrinsic clinical utility.

Does severe hypoglycaemia influence microvascular complications in Type 1 diabetes? An analysis of the Diabetes Control and Complications Trial database.

AIMS: Severe hypoglycaemia may have a role in aggravating micro- and macrovascular disease in diabetes. Data from the Diabetes Control and Complication Trial have been reanalysed to ascertain whether the frequency of severe hypoglycaemia exerted an influence on the development and progression of retinopathy or nephropathy in people with Type 1 diabetes. METHODS: Using binary longitudinal multiple logistic regression, HbA(1c) at study baseline, mean HbA(1c) throughout the study and the number of severe hypoglycaemic episodes during the trial were compared to examine the risk of development/progression of retinopathy and nephropathy. RESULTS: Average HbA(1c) during the study and/or HbA(1c) at baseline were independently predictive of retinopathy and nephropathy both in the intensively and the conventionally treated patients (all P ≤ 0.001). However, the number of hypoglycaemic episodes did not add to HbA(1c) in predicting retinopathy [odds ratio (95% CI) 0.99 (0.96-1.01), P = 0.51 in intensively treated patients, 0.94 (0.89-1.00), P = 0.05, conventional] or nephropathy [odds ratio (95% CI) 0.98 (0.95-1.01), P = 0.48 intensive, 1.03 (0.98-1.10), P = 0.17 conventional]. CONCLUSIONS: The frequency of exposure to severe hypoglycaemia did not predict a different risk of developing retinopathy or nephropathy in either treatment group of the Diabetes Control and Complications Trial at any given HbA(1c) .

The effect of extensive flooding in Hull on the glycaemic control of patients with diabetes.

AIMS: To examine the impact of extensive flooding in a UK city in 2007 on the glycaemic control of patients with diabetes mellitus. METHODS: This was a longitudinal study in patients with diabetes mellitus 12 months before and after the floods in Hull and East Yorkshire, UK. All patients registered with diabetes mellitus were sent questionnaires about their experiences during and after the floods. Glycaemic control for patients directly affected by the floods was compared against those unaffected. RESULTS: Of 1743 respondents, 296 patients had been affected by the floods (110 insulin treated, 186 lifestyle and oral agents) and 1447 unaffected (482 insulin treated, 965 lifestyle and oral agents). There was a rise in mean HbA(1c) of affected individuals comparing 12 months before the floods with 12 months after [mean (95% confidence interval), 7.6% (7.5-7.7) vs. 7.9% (7.7-8.0), P = 0.002], but not those unaffected [7.5% (7.4-7.6) vs. 7.5% (7.4-7.6), P = 0.46]. The difference was mainly in insulin-treated patients [8.6% (8.3, 8.9) affected vs. 8.2% (8.1, 8.3) unaffected, (P = 0.002)]. CONCLUSIONS: Glycaemic control deteriorated in diabetes patients following the floods but was almost exclusively confined to patients taking insulin and was worst at 6-9 months following the event. Insulin-treated patients may need specific targeting in the event of a natural disaster.

Insulin resistance variability in women with anovulatory and ovulatory polycystic ovary syndrome, and normal controls.

Women with polycystic ovary syndrome (PCOS) were found to have a higher biological variability in insulin resistance (IR) compared to controls, but it is unknown whether this variability in IR differs between PCOS who are anovulatory compared to those who have an ovulatory cycle. The primary aim of this study was to compare and contrast the variability of IR in women with ovulatory and anovulatory PCOS, in comparison to normal subjects. 53 Caucasian women with PCOS and 22 normal ovulating women were recruited. Fasting blood was collected each day on 10 consecutive occasions at 3-4 day intervals for analysis of insulin, glucose, progesterone, and testosterone. Analysis of progesterone levels showed 22 of 53 women with PCOS to have had an ovulatory cycle. Insulin resistance was calculated by HOMA method. Women with anovulatory PCOS had higher mean and variability of IR compared to those having an ovulatory cycle, and both were significantly higher than controls (mean ± SEM; HOMA-IR 4.14 ± 0.14 vs. 3.65 ± 0.15 vs. 2.21 ± 0.16, respectively) after adjustment or BMI. The mean BMI for individual PCOS patients correlated with mean HOMA-IR (p=0.009). Insulin resistance in women with anovulatory PCOS is both higher and more variable than in ovulatory PCOS. Since anovulatory PCOS therefore mimics the IR features of type 2 diabetes more closely, anovulation may be particularly associated with a higher cardiovascular risk compared to PCOS patients who ovulate.

Safety, efficacy and tolerability of exenatide in combination with insulin in the Association of British Clinical Diabetologists nationwide exenatide audit*.

AIM: To assess the extent, safety, efficacy and tolerability of reported off-licence exenatide use through a nationwide audit. METHODS: The Association of British Clinical Diabetologists hosted a password-protected, online collection of anonymized data of exenatide use in real clinical practice. Three hundred and fifteen contributors from 126 centres across UK provided data on 6717 patients. HbA1c and weight changes, exenatide discontinuation, adverse events and treatment satisfaction were compared between non-insulin and insulin-treated patients. RESULTS: Four thousand eight hundred and fifty-seven patients had baseline and follow-up treatment status with mean (±s.d.) baseline HbA1c 9.45 ± 1.69% and BMI 40.0 ± 8.2 kg/m(2) . Of the 4857 patients, 1921 (39.6%) used exenatide with insulin. Comparing patients who continued insulin with exenatide with non-insulin-treated patients, mean (±s.e.) latest HbA1c and weight reduction (median 26 weeks) were 0.51 ± 0.06 versus 0.94 ± 0.04% (p < 0.001) and 5.8 ± 0.2 versus 5.5 ± 0.1 kg (p = 0.278). Insulin-treated patients had higher rates of exenatide discontinuation (31.0 vs. 13.9%, p < 0.001), hypoglycaemia (8.9 vs. 6.1%, p < 0.001), gastrointestinal side effects (28.4 vs. 25.0%, p = 0.008) and treatment dissatisfaction (20.8 vs. 5.7%, p < 0.001). However, 34.2% of the patients continuing insulin still achieved HbA1c reduction ≥1%. There was significant insulin discontinuation, dose reduction and greater sulphonylurea discontinuation among insulin-treated patients. CONCLUSIONS: Addition of exenatide to obese, insulin-treated patients can improve glycaemia and weight. Adverse events were statistically but probably not clinically significantly higher, but combination treatment was less well tolerated. Overall, exenatide was less effective in lowering HbA1c among insulin-treated patients, although significant number of insulin-treated patients still achieved significant HbA1c, weight and insulin reductions. Further research into identifying obese, insulin-treated patients who will tolerate and benefit from exenatide treatment is urgently needed.

For debate. Glucose variability and diabetes complication risk: we need to know the answer.

There is still a debate as to whether or not glucose variability contributes to diabetes complication risk. There is much in vitro laboratory evidence that glycaemic instability gives rise to increased production of reactive oxygen species and has a detrimental effect on endothelial dysfunction. While some in vivo studies have also shown similar findings in patients with or without diabetes, others have been unable to confirm any association. Furthermore, clinical studies which have sought to translate this possible risk into an increased likelihood of developing micro- or macrovascular complications have so far not demonstrated an effect. However, few of these trials were specifically designed to establish any influence of glucose fluctuations. This issue is now one of the largest remaining unanswered questions in diabetes. While this article focuses on the data which do not support a role for glucose variability in the development of complications, it also highlights the need for further studies to be performed which will definitively resolve the matter.

Platelet function following induced hypoglycaemia in type 2 diabetes.

AIM: Strict glycaemic control has been associated with an increased mortality rate in subjects with type 2 diabetes (T2DM). Here we examined platelet function immediately and 24hours following induced hypoglycaemia in people with type 2 diabetes compared to healthy age-matched controls. METHODS: Hyperinsulinaemic clamps reduced blood glucose to 2.8mmol/L (50mg/dl) for 1hour. Sampling at baseline; euglycaemia 5mmol/L (90mg/dl); hypoglycaemia; and at 24 post clamp were undertaken. Platelet function was measured by whole blood flow cytometry. RESULTS: 10 subjects with T2DM and 8 controls were recruited. Platelets from people with T2DM showed reduced sensitivity to prostacyclin (PGI2, 1nM) following hypoglycaemia. The ability of PGI2 to inhibit platelet activation was significantly impaired at 24hours compared to baseline in the T2DM group. Here, inhibition of fibrinogen binding was 29.5% (10.3-43.8) compared to 50.8% (36.8-61.1), (P<0.05), while inhibition of P-selectin expression was 32% (16.1-47.6) vs. 54.4% (42.5-67.5) (P<0.05). No significant changes in platelet function were noted in controls. CONCLUSION: Induced hypoglycaemia in T2DM enhances platelet hyperactivity through impaired sensitivity to prostacyclin at 24hours.

Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism - a randomised controlled study.

Type 2 diabetes (T2DM) is associated with increased risk of fractures. Soy supplementation has been shown to have a beneficial effect on bone turnover markers (BTM) in postmenopausal women. However, the effect of soy supplementation on BTM in T2DM and particularly in men is unclear. We performed an analysis of a randomized double blind parallel study of 200 men with T2DM treated with soy, either with or without isoflavones. Outcome measures were type I collagen crosslinked beta C-telopeptide (ßCTX), and type 1 procollagen-N-propeptide (P1NP). The men, with a total testosterone <12 nmol/L, were treated with 15 g soy protein containing 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily for three months. There was a 15% reduction in ßCTX after three months of SPI compared to SP supplementation. There was no significant difference in P1NP with either SPI or SP supplementation. There was a significant linear correlation between the reduction in ßCTX in the SPI group with the reduction in HbA1c (r2 = 0.42; p = 0.04) and HOMA-IR (r2 = 0.54; p = 0.02). Our study indicates that there was a significant reduction in bone resorption following 3 months of SPI supplementation that correlated with an improvement of glycemic control in men with T2DM.

Predicting peak oxygen uptake from 6-min walk test performance in male patients with left ventricular systolic dysfunction.

BACKGROUND: In patients with left ventricular systolic dysfunction (LVSD), peak oxygen uptake (pVO2) has strong predictive power for mortality, and can be used to guide management. However, many patients cannot tolerate standard test protocols. The 6-min walk test (6-MWT) is often used to estimate functional capacity due to its simplicity, cost effectiveness and familiarity to patients with LVSD. The relationship between 6-MWT performance and pVO2 is not certain, but if closely related could allow substitution of an expensive and cumbersome test for a cheaper and more familiar one. METHODS AND RESULTS: 120 male patients with LVSD (LVEF <40%; (mean+/-S.D.) age 68+/-13 years; BMI 28+/-5) performed, in random order, a maximal incremental treadmill exercise test with metabolic gas exchange measurements to derive peak oxygen consumption (pVO2 = 19.8+/-5.8 mL.kg(-1).min(-1)), and a standardised 6-MWT (308+/-142 m; r = 0.44; P = 0.00001). In multivariate models including demographic data, resting blood pressure and heart rate, spirometry, routine blood samples, and walk distance, five variables were independently predictive of peak oxygen consumption. pVO2 = 11.92 + (1.48 x FEV1 (L)) + (1.12 x haemoglobin (g dl(-1))) + (0.016 x distance walked (m)) - (0.33 x BMI) - (0.11 x age (years)). This equation accounted for 48% of the variation in pVO2. CONCLUSIONS: Using these five simple variables, peak oxygen consumption can be estimated with moderate accuracy. In clinical practice, however, when an estimate of peak oxygen consumption is required, incremental exercise testing with metabolic gas exchange measurements cannot be avoided in male patients with LVSD. Further work is needed to assess the relation between estimated pVO2 and outcome.

Clinical determinants of poor six-minute walk test performance in patients with left ventricular systolic dysfunction and no major structural heart disease.

BACKGROUND: The clinical determinants of six-minute walk test (6-MWT) performance in patients with left ventricular systolic dysfunction (LVSD) have rarely been investigated, and it is not clear whether they differ from patients referred for the assessment of symptoms of heart failure who do not have major structural heart disease (MSHD). METHODS AND RESULTS: 571 patients with LVSD enrolled in a chronic disease management programme (79% male; mean age 71+/-10 years; BMI 28+/-5) completed a 6-MWT with a mean distance 337+/-103 m. 688 patients referred with suspected heart failure but in whom MSHD was excluded (49% male; mean age 70+/-11 years; BMI 28+/-6) had a mean 6-MWT distance of 391+/-106 m (P<0.001 compared to patients with LVSD). Relationships with walking distance were determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs) for walking300 m. In patients with LVSD, predictors of poor walking distance (or=75 years (OR=4.0, 95% CI=2.4-6.4); low BMI (<20) (OR=3.4, 95% CI=1.6-7.3); anaemia (OR=2.8, 95% CI=1.8-4.2); resting heart rate>80 beats x min(-1) (OR=2.2, 95% CI=1.3-3.5); and being female (OR=2.0, 95% CI=1.3-3.0). Serum creatinine and NT-proBNP showed dose-response effects, as did self-perceived feelings of depression and anxiety. Determinants of 6-MWT in patients without MSHD were similar including age>or=75 years (OR=6.0, 95% CI=3.4-10.4), anaemia (OR=2.8, 95% CI=1.6-4.9), resting HR>80 beats x min(-1) (OR=2.5, 95% CI=1.4-4.4) and being female (OR=1.6, 95% CI=1.9-2.4). NT-proBNP and self-perceived feelings of depression and anxiety also showed dose-response effects. CONCLUSION: The determinants of poor 6-MWT performance depend on physical-cardiovascular and non-cardiovascular, and psychological factors. Clinical predictors for poor walking performance are similar for patients with LVSD and without MSHD.

Modelling 5-year functional outcome in a major traumatic injury survivor cohort.

AIM: To estimate associations between possible predictors of functional disability outcome at 5 years in a working adult population cohort of survivors of major traumatic injury and to develop a prognostic model of outcome. DESIGN: Population based retrospective cohort study. POPULATION: Persons who had experienced major traumatic injury (Injury Seventy Score >15) in the area of the former Yorkshire Regional Health Authority during the period 30 September 1988 to 1 October 1989 and who survived for 5 years (average 5.3 years). METHODS: The same interviewer saw each survivor at their home and used the OPCS Adult Disability Schedule to ascertain levels of functional disability. Disability scores for each survivor were then combined in accordance with the OPCS guidance to calculate a level of disability between 0 (no disability) to 10 (maximum disability). The OPCS level was then dichotomised with a cut-point at 4/5. Possible predictor and confounding variables from pre-injury, injury and post-injury periods were modelled in a logistic regression to identify those that predicted outcome level. Two reduced models were developed to allow early prognosis of late outcome. RESULTS: The full model correctly classified 91% of observed outcomes. Inpatient length of stay OR 1.031 (95% CI 1.014,1.048) per day predicted poorer 5-year outcome; Glasgow Coma Score OR 0.790(0.629,0.992) per 1 point increase; stay in Intensive Care Unit OR 0.931 (0.877,0.987) per day; attainment of degree-level education OR 0.014 (0.000,0.707); single civil status OR 0.110 (0.013,0.908); being taken initially to a hospital with a neurosurgical facility OR 0.064(0.010,0.420); being in paid work during the 2 weeks before index injury OR 0.093(0.009,0.969) predicted better 5-year disability outcome. Two reduced models were constructed that included a simple set of variables, one of these models excluded any rehabilitation variables but still correctly classified 85% of the observed outcomes. CONCLUSION: As well as level of traumatic brain injury (TBI) and total inpatient stay, Pre-injury educational attainment and employment, civil status, immediate care in a hospital with a neurosurgical facility and stay in an Intensive Care Unit determined 5-year outcome. It is possible to efficiently predict outcome at an early stage. Previous work on predictors of disablement have suffered from large selection and attrition biases.

Frequency and natural history of subdural haemorrhages in babies and relation to obstetric factors.

BACKGROUND: Subdural haematomas are thought to be uncommon in babies born at term. This view is mainly based on findings in symptomatic neonates and babies in whom subdural haemorrhages are detected fortuitously. We aimed to establish the frequency of subdural haemorrhages in asymptomatic term neonates; to study the natural history of such subdural haematomas; and to ascertain which obstetric factors, if any, are associated with presence of subdural haematoma. METHODS: We did a prospective study in babies who were born in the Jessop wing of the Central Sheffield University Hospitals between March, 2001, and November, 2002. We scanned neonates with a 0.2 T magnetic resonance machine. FINDINGS: 111 babies underwent MRI in this study. 49 were born by normal vertex delivery without instrumentation, 25 by caesarean section, four with forceps, 13 ventouse, 18 failed ventouse leading to forceps, one failed ventouse leading to caesarean section, and one failed forceps leading to caesarean section. Nine babies had subdural haemorrhages: three were normal vaginal deliveries (risk 6.1%), five were delivered by forceps after an attempted ventouse delivery (27.8%), and one had a traumatic ventouse delivery (7.7%). All babies with subdural haemorrhage were assessed clinically but no intervention was needed. All were rescanned at 4 weeks and haematomas had completely resolved. INTERPRETATION: Presence of unilateral and bilateral subdural haemorrhage is not necessarily indicative of excessive birth trauma.