Evaluating the prognostic performance of bedside tests used for peripheral arterial disease diagnosis in the prediction of diabetic foot ulcer healing.

INTRODUCTION: Diabetic foot ulceration (DFU) is a common and challenging complication of diabetes. Risk stratification can guide further management. We aim to evaluate the prognostic performance of bedside tests used for peripheral arterial disease (PAD) diagnosis to predict DFU healing. RESEARCH DESIGN AND METHODS: Testing for Arterial Disease in Diabetes (TrEAD) was a prospective observational study comparing the diagnostic performance of commonly used tests for PAD diagnosis. We performed a secondary analysis assessing whether these could predict DFU healing. Follow-up was performed prospectively for 12 months. The primary outcome was sensitivity for predicting ulcer healing. Secondary endpoints were specificity, predictive values, and likelihood ratios for ulcer healing. RESULTS: 123 of TrEAD participants with DFU were included. In 12 months, 52.8% of ulcers healed. The best negative diagnostic likelihood ratio (NDLR) was observed for the podiatry ankle duplex scan (PAD-scan) monophasic or biphasic with adverse features(NDLR 0.35, 95% CI 0.14-0.90). The highest positive likelihood ratios were observed for toe brachial pressure index of ≤0.2 (positive diagnostic likelihood ratio (PDLR) 7.67, 95% CI 0.91-64.84) and transcutaneous pressure of oxygen of ≤20 mm Hg (PDLR 2.68, 95% CI 0.54-13.25). Cox proportional hazards modeling demonstrated significantly greater probabilities of healing with triphasic waveforms (HR=2.54, 95% CI 1.23-5.3, p=0.012) and biphasic waveforms with non-adverse features (HR=13.67, 95% CI 4.78-39.1, p<0.001) on PAD-scan. CONCLUSIONS: No single test performed well enough to be used in isolation as a prognostic marker for the prediction of DFU healing. TRIAL REGISTRATION NUMBER: NCT04058626.

Visuospatial orientation: Differential effects of head and body positions.

To orientate in space, the brain must integrate sensory information that encodes the position of the body with the visual cues from the surrounding environment. In this process, the extent of reliance on visual information is known as the visual dependence. Here, we asked whether the relative positions of the head and body can modulate such visual dependence (VD). We used the effect of optokinetic stimulation (30°/s) on subjective visual vertical (SVV) to quantify VD as the average optokinetic-induced SVV bias in clockwise and counter-clockwise directions. The VD bias was measured in eight subjects with a head-on-body tilt (HBT) where only the head was tilted on the body, and also with a whole-body tilt (WBT) where the head and body were tilted together. The VD bias with HBT of 20° was in the same direction of the head tilt position (left tilt VD -1.35 ± 0.1.2°; right VD 1.60 ± 0.9°), whereas the VD bias with WBT of 20° was in a direction away from the body tilt position (left tilt VD 2.5 ± 1.1°; right tilt VD -2.1 ± 0.9°). These findings show differential effects of relative head and body positions on visual cue integration, a process which could facilitate optimal interaction with the surrounding environment for spatial orientation.

Intermittent fasting for the prevention of cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. Lifestyle changes are at the forefront of preventing the disease. This includes advice such as increasing physical activity and having a healthy balanced diet to reduce risk factors. Intermittent fasting (IF) is a popular dietary plan involving restricting caloric intake to certain days in the week such as alternate day fasting and periodic fasting, and restricting intake to a number of hours in a given day, otherwise known as time-restricted feeding. IF is being researched for its benefits and many randomised controlled trials have looked at its benefits in preventing CVD. OBJECTIVES: To determine the role of IF in preventing and reducing the risk of CVD in people with or without prior documented CVD. SEARCH METHODS: We conducted our search on 12 December 2019; we searched CENTRAL, MEDLINE and Embase. We also searched three trials registers and searched the reference lists of included papers. Systematic reviews were also viewed for additional studies. There was no language restriction applied. SELECTION CRITERIA: We included randomised controlled trials comparing IF to ad libitum feeding (eating at any time with no specific caloric restriction) or continuous energy restriction (CER). Participants had to be over the age of 18 and included those with and without cardiometabolic risk factors. Intermittent fasting was categorised into alternate-day fasting, modified alternate-day fasting, periodic fasting and time-restricted feeding. DATA COLLECTION AND ANALYSIS: Five review authors independently selected studies for inclusion and extraction. Primary outcomes included all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure. Secondary outcomes include the absolute change in body weight, and glucose. Furthermore, side effects such as headaches and changes to the quality of life were also noted. For continuous data, pooled mean differences (MD) (with 95% confidence intervals (CIs)) were calculated. We contacted trial authors to obtain missing data. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: Our search yielded 39,165 records after the removal of duplicates. From this, 26 studies met our criteria, and 18 were included in the pooled analysis. The 18 studies included 1125 participants and observed outcomes ranging from four weeks to six months. No studies included data on all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure at any point during follow-up. Of quantitatively analysed data, seven studies compared IF with ab libitum feeding, eight studies compared IF with CER, and three studies compared IF with both ad libitum feeding and CER. Outcomes were reported at short term (≤ 3 months) and medium term (> 3 months to 12 months) follow-up. Body weight was reduced with IF compared to ad libitum feeding in the short term (MD -2.88 kg, 95% CI -3.96 to -1.80; 224 participants; 7 studies; low-certainty evidence). We are uncertain of the effect of IF when compared to CER in the short term (MD -0.88 kg, 95% CI -1.76 to 0.00; 719 participants; 10 studies; very low-certainty evidence) and there may be no effect in the medium term (MD -0.56 kg, 95% CI -1.68 to 0.56; 279 participants; 4 studies; low-certainty evidence). We are uncertain about the effect of IF on glucose when compared to ad libitum feeding in the short term (MD -0.03 mmol/L, 95% CI -0.26 to 0.19; 95 participants; 3 studies; very-low-certainty of evidence) and when compared to CER  in the short term: MD -0.02 mmol/L, 95% CI -0.16 to 0.12; 582 participants; 9 studies; very low-certainty; medium term: MD 0.01, 95% CI -0.10 to 0.11; 279 participants; 4 studies; low-certainty evidence). The changes in body weight and glucose were not deemed to be clinically significant. Four studies reported data on side effects, with some participants complaining of mild headaches. One study reported on the quality of life using the RAND SF-36 score. There was a modest increase in the physical component summary score. AUTHORS' CONCLUSIONS: Intermittent fasting was seen to be superior to ad libitum feeding in reducing weight. However, this was not clinically significant. There was no significant clinical difference between IF and CER in improving cardiometabolic risk factors to reduce the risk of CVD. Further research is needed to understand the safety and risk-benefit analysis of IF in specific patient groups (e.g. patients with diabetes or eating disorders) as well as the effect on longer-term outcomes such as all-cause mortality and myocardial infarction.