Combined rotation scarf and Akin osteotomies for hallux valgus: a patient focussed 9 year follow up of 50 patients

<p>Abstract</p> <p>Background</p> <p>The Cochrane review of hallux valgus surgery has disputed the scientific validity of hallux valgus research. Scoring systems and surrogate measures such as x-ray angles are commonly reported at just one year post operatively but these are of dubious relevance to the patient. In this study we extended the follow up to a minimum of 8 years and sought to address patient specific concerns with hallux valgus surgery. The long term follow up also allowed a comprehensive review of the complications associated with the combined rotation scarf and Akin osteotomies.</p> <p>Methods</p> <p>Between 1996 and 1999, 101 patients underwent rotation scarf and Akin osteotomies for the treatment of hallux valgus. All patients were contacted and asked to participate in this study. 50 female participants were available allowing review of 73 procedures. The average follow up was over 9 years and the average age at the time of surgery was 57. The participants were physically examined and interviewed.</p> <p>Results</p> <p>Post-operatively, in 86% of the participants there were no footwear restrictions. Stiffness of the first metatarsophalangeal joint was reported in 8% (6 feet); 10% were unhappy with the cosmetic appearance of their feet, 3 feet had hallux varus, and 2 feet had recurrent hallux valgus. There were no foot-related activity restrictions in 92% of the group. Metatarsalgia occurred in 4% (3 feet). 96% were better than before surgery and 88% were completely satisfied with their post-operative result. Hallux varus was the greatest single cause of dissatisfaction. The most common adverse event in the study was internal fixation irritation. Hallux valgus surgery is not without risk and these findings could be useful in the informed consent process.</p> <p>Conclusions</p> <p>When combined the rotation scarf and Akin osteotomies are an effective treatment for hallux valgus that achieves good long-term correction with a low incidence of recurrence, footwear restriction or metatarsalgia. The nature of the osteotomies allows early return to normal shoes and activity without the need for postoperative immobilisation in a plaster cast.</p

Does self monitoring of blood glucose as opposed to urinalysis provide additional benefit in patients newly diagnosed with type 2 diabetes receiving structured education? The DESMOND SMBG randomised controlled trial protocol

BackgroundThe benefit of self-monitoring of blood glucose (SMBG) in people with type 2 diabetes on diet or oral agents other than sulphonylureas remains uncertain. Trials of interventions incorporating education about self-monitoring of blood glucose have reported mixed results. A recent systematic review concluded that SMBG was not cost-effective. However, what was unclear was whether a cheaper method of self-monitoring (such as urine glucose monitoring) could produce comparable benefit and patient acceptability for less cost.Methods/DesignThe DESMOND SMBG trial is comparing two monitoring strategies (blood glucose monitoring and urine testing) over 18 months when incorporated into a comprehensive self-management structured education programme. It is a multi-site cluster randomised controlled trial, conducted across 8 sites (7 primary care trusts) in England, UK involving individuals with newly diagnosed Type 2 diabetes.The trial has 80% power to demonstrate equivalence in mean HbA1c (the primary end-point) at 18 months of within &plusmn; 0.5% assuming 20% drop out and 20% non-consent. Secondary end-points include blood pressure, lipids, body weight and psychosocial measures as well as a qualitative sub-study.Practices were randomised to one of two arms: participants attend a DESMOND programme incorporating a module on self-monitoring of either urine or blood glucose. The programme is delivered by accredited educators who received specific training about equipoise. Biomedical data are collected and psychosocial scales completed at baseline, and 6, 12, and 18 months post programme. Qualitative research with participants and educators will explore views and experiences of the trial and preferences for methods of monitoring.DiscussionThe DESMOND SMBG trial is designed to provide evidence to inform the debate about the value of self-monitoring of blood glucose in people with newly diagnosed type 2 diabetes. Strengths include a setting in primary care, a cluster design, a health economic analysis, a comparison of different methods of monitoring while controlling for other components of training within the context of a quality assured structured education programme and a qualitative sub-study

Are ethnic disparities in HbA1c levels explained by mental wellbeing? Analysis of population-based data from the Health Survey for England

Aims: It is unclear how ethnic differences in HbA1c levels are affected by individual variations in mental wellbeing. Thus, the aim of this study was to assess the extent to which HbA1c disparities between Caucasian and South Asian adults are mediated by various aspects of positive psychological functioning. Methods: Data from the 2014 Health Survey for England was analysed using bootstrapping methods. A total of 3894 UK residents with HbA1c data were eligible to participate. Mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-Being Scale. To reduce bias BMI, blood pressure, diabetes status, and other factors were treated as covariates. Results: Ethnicity directly predicted blood sugar control (unadjusted coefficient -2.15; 95% CI -3.64, -0.67), with Caucasians generating lower average HbA1c levels (37.68 mmol/mol (5.6%)) compared to South Asians (39.87 mmol/mol (5.8%)). This association was mediated by positive mental wellbeing, specifically concerning perceived vigour (unadjusted effect 0.30; 95% CI 0.13, 0.58): South Asians felt more energetic than Caucasians (unadjusted coefficient -0.32; 95% CI -0.49, -0.16), and greater perceived energy predicted lower HbA1c levels (unadjusted coefficient -0.92; 95% CI -1.29, -0.55). This mediator effect accounted for just over 14% of the HbA1c variance, and was negated after adjusting for BMI. Conclusions: Caucasian experience better HbA1c levels compared with their South Asian counterparts. However, this association is partly confounded by individual differences in perceived energy levels, which is implicated in better glycaemic control, and appears to serve a protective function in South Asians

The value of episodic, intensive blood glucose monitoring in non-insulin treated persons with type 2 diabetes: Design of the Structured Testing Program (STeP) Study, a cluster-randomised, clinical trial [NCT00674986]

<p>Abstract</p> <p>Background</p> <p>The value and utility of self-monitoring of blood glucose (SMBG) in non-insulin treated T2DM has yet to be clearly determined. Findings from studies in this population have been inconsistent, due mainly to design differences and limitations, including the prescribed frequency and timing of SMBG, role of the patient and physician in responding to SMBG results, inclusion criteria that may contribute to untoward floor effects, subject compliance, and cross-arm contamination. We have designed an SMBG intervention study that attempts to address these issues.</p> <p>Methods/design</p> <p>The Structured Testing Program (STeP) study is a 12-month, cluster-randomised, multi-centre clinical trial to evaluate whether poorly controlled (HbA1c ≥ 7.5%), non-insulin treated T2DM patients will benefit from a comprehensive, integrated physician/patient intervention using structured SMBG in US primary care practices. Thirty-four practices will be recruited and randomly assigned to an active control group (ACG) that receives enhanced usual care or to an enhanced usual care group plus structured SMBG (STG). A total of 504 patients will be enrolled; eligible patients at each site will be randomly selected using a defined protocol. Anticipated attrition of 20% will yield a sample size of at least 204 per arm, which will provide a 90% power to detect a difference of at least 0.5% in change from baseline in HbA1c values, assuming a common standard deviation of 1.5%. Differences in timing and degree of treatment intensification, cost effectiveness, and changes in patient self-management behaviours, mood, and quality of life (QOL) over time will also be assessed. Analysis of change in HbA1c and other dependent variables over time will be performed using both intent-to-treat and per protocol analyses. Trial results will be available in 2010.</p> <p>Discussion</p> <p>The intervention and trial design builds upon previous research by emphasizing appropriate and collaborative use of SMBG by both patients and physicians. Utilization of per protocol and intent-to-treat analyses facilitates a comprehensive assessment of the intervention. Use of practice site cluster-randomisation reduces the potential for intervention contamination, and inclusion criteria (HbA1c ≥ 7.5%) reduces the possibility of floor effects. Inclusion of multiple dependent variables allows us to assess the broader impact of the intervention, including changes in patient and physician attitudes and behaviours.</p> <p>Trial Registration</p> <p>Current Controlled Trials NCT00674986.</p

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Coronary Artery Disease.

BACKGROUND: The Placebo-controlled Trial of Percutaneous Coronary Intervention for the Relief of Stable Angina (ORBITA-2) provided evidence for the role of percutaneous coronary intervention (PCI) for angina relief in stable coronary artery disease (CAD). Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are often used to guide PCI, however their ability to predict placebo-controlled angina improvement is unknown. METHODS: Participants with angina, ischemia, and stable CAD were enrolled and antianginal medications were stopped. Participants reported angina episodes daily for 2 weeks using the ORBITA-app. At the research angiogram, FFR and iFR were measured. After sedation and auditory isolation, participants were randomized to PCI or placebo, before entering a 12-week blinded follow-up phase with daily angina reporting. The ability of FFR and iFR, analyzed as continuous variables, to predict the placebo-controlled effect of PCI, was tested using Bayesian proportional odds modelling. RESULTS: Invasive physiology data were available in 279 patients (140 PCI and 139 placebo). The median (IQR) age was 65 years (59.0 to 70.5) and 223 (79.9%) were male. Median FFR was 0.60 (0.46 to 0.73) and median iFR was 0.76 (0.50 to 0.86). The lower the FFR or iFR, the greater the placebo-controlled improvement with PCI across all endpoints. There was strong evidence that a patient with an FFR at the lower quartile would have a greater placebo-controlled improvement in angina symptom score with PCI than a patient at the upper quartile (FFR 0.46 vs. 0.73: OR 2.01, 95% CrI 1.79 to 2.26, Pr(Interaction)>99.9%). Similarly, there was strong evidence that a patient with an iFR at the lower quartile would have a greater placebo controlled improvement in angina symptom score with PCI than a patient with an iFR at the upper quartile (iFR 0.50 vs. 0.86: OR 2.13, 95% CrI 1.87 to 2.45, Pr(Interaction) >99.9%). The relationship between benefit and physiology was seen in both Rose angina and Rose nonangina. CONCLUSIONS: Physiological stenosis severity, as measured by FFR and iFR, predicts placebo-controlled angina relief from PCI. Invasive coronary physiology can be used to target PCI to those patients who are most likely to experience benefit

The Epigenetic Trans-Silencing Effect in Drosophila Involves Maternally-Transmitted Small RNAs Whose Production Depends on the piRNA Pathway and HP1

BACKGROUND: The study of P transposable element repression in Drosophila melanogaster led to the discovery of the Trans-Silencing Effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences, "TAS") has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. Phenotypic and genetic analysis have shown that TSE exhibits variegation in ovaries, displays a maternal effect as well as epigenetic transmission through meiosis and involves heterochromatin (including HP1) and RNA silencing. PRINCIPAL FINDINGS: Here, we show that mutations in squash and zucchini, which are involved in the piwi-interacting RNA (piRNA) silencing pathway, strongly affect TSE. In addition, we carried out a molecular analysis of TSE and show that silencing is correlated to the accumulation of lacZ small RNAs in ovaries. Finally, we show that the production of these small RNAs is sensitive to mutations affecting squash and zucchini, as well as to the dose of HP1. CONCLUSIONS AND SIGNIFICANCE: Thus, our results indicate that the TSE represents a bona fide piRNA-based repression. In addition, the sensitivity of TSE to HP1 dose suggests that in Drosophila, as previously shown in Schizosaccharomyces pombe, a RNA silencing pathway can depend on heterochromatin components

Telomeric Trans-Silencing in Drosophila melanogaster: Tissue Specificity, Development and Functional Interactions between Non-Homologous Telomeres

BACKGROUND: The study of P element repression in Drosophila melanogaster led to the discovery of the telomeric Trans-Silencing Effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences, "TAS") has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. TSE can show variegation in ovaries, displays a maternal effect as well as an epigenetic transmission through meiosis and involves heterochromatin and RNA silencing pathways. PRINCIPAL FINDINGS: Here, we analyze phenotypic and genetic properties of TSE. We report that TSE does not occur in the soma at the adult stage, but appears restricted to the female germline. It is detectable during development at the third instar larvae where it presents the same tissue specificity and maternal effect as in adults. Transgenes located in TAS at the telomeres of the main chromosomes can be silencers which in each case show the maternal effect. Silencers located at non-homologous telomeres functionally interact since they stimulate each other via the maternally-transmitted component. All germinally-expressed euchromatic transgenes tested, located on all major chromosomes, were found to be repressed by a telomeric silencer: thus we detected no TSE escaper. The presence of the euchromatic target transgene is not necessary to establish the maternal inheritance of TSE, responsible for its epigenetic behavior. A single telomeric silencer locus can simultaneously repress two P-lacZ targets located on different chromosomal arms. CONCLUSIONS AND SIGNIFICANCE: Therefore TSE appears to be a widespread phenomenon which can involve different telomeres and work across the genome. It can explain the P cytotype establishment by telomeric P elements in natural Drosophila populations

Improving pulse crops as a source of protein, starch and micronutrients

Pulse crops have been known for a long time to have beneficial nutritional profiles for human diets but have been neglected in terms of cultivation, consumption and scientific research in many parts of the world. Broad dietary shifts will be required if anthropogenic climate change is to be mitigated in the future, and pulse crops should be an important component of this change by providing an environmentally sustainable source of protein, resistant starch and micronutrients. Further enhancement of the nutritional composition of pulse crops could benefit human health, helping to alleviate micronutrient deficiencies and reduce risk of chronic diseases such as type 2 diabetes. This paper reviews current knowledge regarding the nutritional content of pea (Pisum sativum L.) and faba bean (Vicia faba L.), two major UK pulse crops, and discusses the potential for their genetic improvement