Reversal and Remission of T2DM - An Update for Practitioners.

Over the past 50 years, many countries around the world have faced an unchecked pandemic of obesity and type 2 diabetes (T2DM). As best practice treatment of T2DM has done very little to check its growth, the pandemic of diabesity now threatens to make health-care systems economically more difficult for governments and individuals to manage within their budgets. The conventional view has been that T2DM is irreversible and progressive. However, in 2016, the World Health Organization (WHO) global report on diabetes added for the first time a section on diabetes reversal and acknowledged that it could be achieved through a number of therapeutic approaches. Many studies indicate that diabetes reversal, and possibly even long-term remission, is achievable, belying the conventional view. However, T2DM reversal is not yet a standardized area of practice and some questions remain about long-term outcomes. Diabetes reversal through diet is not articulated or discussed as a first-line target (or even goal) of treatment by any internationally recognized guidelines, which are mostly silent on the topic beyond encouraging lifestyle interventions in general. This review paper examines all the sustainable, practical, and scalable approaches to T2DM reversal, highlighting the evidence base, and serves as an interim update for practitioners looking to fill the practical knowledge gap on this topic in conventional diabetes guidelines.

Can surgical skills be taught using technological advances online? A comparative study of online and face-to-face surgical skills training.

INTRODUCTION: Online teaching has rapidly emerged as a viable alternative to traditional face-to-face education. How to teach surgical skills in the online environment, however, has not yet been fully established nor evaluated. METHODS: An international 1-day online surgical skills course consisting of lectures, pre-recorded virtual workshops, live demonstrations and along with surgical skills teaching in breakout rooms was organised. Based on existing learning theories, new methods were developed to deliver skills teaching online. Simultaneously, traditional in-person surgical skills teaching was also conducted and used as a benchmark. Skills development was assessed by trained demonstrators and self-reported competency scores were compared between the online and face-to-face event. RESULTS: 553 delegates from 20 different countries attended the online course. Of these, 64 were trained in breakout rooms with a 1:5 demonstrator-to-delegate ratio whilst the remaining 489 delegates participated in didactic skills development sessions. In a separate face-to-face course, 20 delegates were trained with traditional methods. Demonstrators rated the competency of delegates for suturing, tendon repair and vascular anastomosis. There was no significant difference in the competency ratings of delegates receiving online teaching or face-to-face teaching (p = 0.253, p = 0.084, p = 1.00, respectively). The development of the same skills to "articulation" were not different between formats (p = 0.841, p = 0.792, p = 1.00, respectively). Post course self-rated competency scores improved for all technical skills (p < 0.001). Small group sessions, both online and face-to-face, received higher satisfaction ratings compared to large group sessions in terms of clarity of instructions, answers to questions and demonstrator feedback. Overall feedback on teaching quality, however, was equivalent across both groups. DISCUSSION: Online teaching of surgical skills for early training years is an appropriate alternative to face-to-face teaching.

Checking for model failure and for prior-data conflict with the constrained multinomial model.

Multinomial models can be difficult to use when constraints are placed on the probabilities. An exact model checking procedure for such models is developed based on a uniform prior on the full multinomial model. For inference, a nonuniform prior can be used and a consistency theorem is proved concerning a check for prior-data conflict with the chosen prior. Applications are presented and a new elicitation methodology is developed for multinomial models with ordered probabilities.

The patient safety practices of emergency medical teams in disaster zones: a systematic analysis.

INTRODUCTION: Disaster zone medical relief has been criticised for poor quality care, lack of standardisation and accountability. Traditional patient safety practices of emergency medical teams (EMTs) in disaster zones were not well understood. Improving the quality of healthcare in disaster zones has gained importance within global health policy. Ascertaining patient safety practices of EMTs in disaster zones may identify areas of practice that can be improved. METHODS: A systematic search of OvidSP, Embase and Medline databases; key journals of interest; key grey literature texts; the databases of the WHO, Médecins Sans Frontieres and the International Committee of the Red Cross; and Google Scholar was performed. Descriptive studies, case reports, case series, prospective trials and opinion pieces were included with no limitation on date or language of publication. RESULTS: There were 9685 records, evenly distributed between the peer-reviewed and grey literature. Of these, 30 studies and 9 grey literature texts met the inclusion criteria and underwent qualitative synthesis. From these articles, 302 patient safety statements were extracted. Thematic analysis categorised these statements into 84 themes (total frequency 632). The most frequent themes were limb injury (9%), medical records (5.4%), surgery decision-making (4.6%), medicines safety (4.4%) and protocol (4.4%). CONCLUSION: Patient safety practices of EMTs in disaster zones are weighted toward acute clinical care, particularly surgery. The management of non-communicable disease is under-represented. There is widespread recognition of the need to improve medical record-keeping. High-quality data and institutional level patient safety practices are lacking. There is no consensus on disaster zone-specific performance indicators. These deficiencies represent opportunities to improve patient safety in disaster zones.

Varying-coefficient semiparametric model averaging prediction.

Forecasting and predictive inference are fundamental data analysis tasks. Most studies employ parametric approaches making strong assumptions about the data generating process. On the other hand, while nonparametric models are applied, it is sometimes found in situations involving low signal to noise ratios or large numbers of covariates that their performance is unsatisfactory. We propose a new varying-coefficient semiparametric model averaging prediction (VC-SMAP) approach to analyze large data sets with abundant covariates. Performance of the procedure is investigated with numerical examples. Even though model averaging has been extensively investigated in the literature, very few authors have considered averaging a set of semiparametric models. Our proposed model averaging approach provides more flexibility than parametric methods, while being more stable and easily implemented than fully multivariate nonparametric varying-coefficient models. We supply numerical evidence to justify the effectiveness of our methodology.

Management of infected femoral artery pseudoaneurysm repair: rectus abdominis flap as second-line management after sartorius flap failure.

BACKGROUND: The incidence of infected femoral artery pseudoaneurysms is likely to increase with increasing numbers of femoral artery interventions. METHODS: Case report and review of literature. RESULTS: We present a case of dehiscence of a vein patch repair of an infected femoral pseutoaneurysm treated with ligation of vessels and coverage by rectus abdominis muscle flap. CONCLUSION: We consider the use of this flap as a good second line option for the coverage of exposed femoral vessels, in the presence of sepsis, particularly when the external iliac artery has been ligated.

A stepwise likelihood ratio test procedure for rare variant selection in case-control studies.

There is much recent interest in finding rare genetic variants associated with various diseases. Owing to the scarcity of rare mutations, single-variant analyses often lack power. To enable pooling of information across variants, we use a random effect formulation within a retrospective modeling framework that respects the retrospective data collecting mechanism of case-control studies. More concretely, we model the control allele frequencies of the variants as random effects, and the systematic differences between the case and control frequencies as fixed effects, resulting in a mixed model. The use of Poisson approximation and gamma-distributed random effects results in a generalized negative binomial distribution for the joint distribution of the control and case frequencies. Variants are selected by conducting stepwise likelihood ratio tests. The superiority of the proposed method over two existing variant selection methods is demonstrated in a simulation study. The effects of non-gamma random effects and correlated variants are also found to be not too detrimental in the simulation study. When the proposed procedure is applied to identify rare variants associated with obesity, it identifies one additional variant not picked up by existing methods.

Unsuspected iatrogenic vertebral artery cannulation with a dialysis catheter.

Internal jugular vein cannulation is a common clinical procedure but not without risks including inadvertent artery puncture. The incidence of vertebral artery puncture during internal jugular vein cannulation is unclear but is thought to be much less than carotid artery involvement. Here, we describe an unsuspected case of vertebral artery cannulation with a Vas Cath dialysis catheter which was used for hemofiltration before the inadvertent artery cannulation was discovered later during open surgical retrieval.

Spatial analysis of ambulance response times related to prehospital cardiac arrests in the city-state of Singapore.

OBJECTIVES: The main objective of this study was to establish the spatial variation in ambulance response times for out-of-hospital cardiac arrests (OHCAs) in the city-state of Singapore. The secondary objective involved studying the relationships between various covariates, such as traffic condition and time and day of collapse, and ambulance response times. METHODS: The study design was observational and ecological in nature. Data on OHCAs were collected from a nationally representative database for the period October 2001 to October 2004. We used the conditional autoregressive (CAR) model to analyze the data. Within the Bayesian framework of analysis, we used a Weibull regression model that took into account spatial random effects. The regression model was used to study the independent effects of each covariate. RESULTS: Our results showed that there was spatial heterogeneity in the ambulance response times in Singapore. Generally, areas in the far outskirts (suburbs), such as Boon Lay (in the west) and Sembawang (in the north), fared badly in terms of ambulance response times. This improved when adjusted for key covariates, including distance from the nearest fire station. Ambulance response time was also associated with better traffic conditions, weekend OHCAs, distance from the nearest fire station, and OHCAs occurring during nonpeak driving hours. For instance, the hazard ratio for good ambulance response time was 2.35 (95% credible interval [CI] 1.97-2.81) when traffic conditions were light and 1.72 (95% CI 1.51-1.97) when traffic conditions were moderate, as compared with heavy traffic. CONCLUSIONS: We found a clear spatial gradient for ambulance response times, with far-outlying areas' exhibiting poorer response times. Our study highlights the utility of this novel approach, which may be helpful for planning emergency medical services and public emergency responses.

Spatial variation and geographic-demographic determinants of out-of-hospital cardiac arrests in the city-state of Singapore.

STUDY OBJECTIVE: Our primary objective is to calculate the relative risk of cardiac arrests at the development guide plan (DGP) (equivalent to census tract) level in a city-state, Singapore, and examine its relationship with key area-level population characteristics. METHODS: This was an observational ecological study design. We calculated the relative risk as the ratio of the observed and population standardized expected counts of out-of-hospital cardiac arrests in Singapore, aggregated at DGP level. Data were collected from October 2001 to October 2004. We used conditional autoregressive spatial models to examine the predictors of increased risk at the DGP level. RESULTS: We found a spatial distribution of cardiac arrests, with an unexpected cluster caused by nonresident arrests occurring at the international airport. The risk of out-of-hospital cardiac arrest more than doubled, 2.35 (95% confidence interval [CI] 1.28 to 4.48), for each 5-point increase in the proportion of people aged 65 years and older. For each 5-point increase in the proportion of Chinese individuals living in a DGP, the risk of out-of-hospital cardiac arrest was reduced by a factor of 0.8 (95% CI 0.7 to 0.9). The risk of out-of-hospital cardiac arrest increased by 1.49-fold (95% CI 1.18 to 1.82) for every 5-point increase in the proportion of households with no family nucleus (live alone). When restricted to residential cases of out-of-hospital cardiac arrest, none of the variables remained significant, possibly because of small sample size. CONCLUSION: The risk of cardiac arrests could be related to the age and racial and family structure of DGPs in Singapore. This article models how such data can help to direct public health education, cardiopulmonary resuscitation training, and public access defibrillation programs in other health systems.

Ankle brachial pressure index (ABPI): An update for practitioners.

Peripheral vascular disease affects some 12%-14% of the general population, and the majority of people with the disease are asymptomatic. The ankle brachial pressure index (ABPI) test is widely used by a diverse range of practitioners (in the community and hospital setting) in order to screen asymptomatic patients, diagnose patients with clinical symptoms, and to monitor patients who have had radiological or surgical intervention. This paper explains the theoretical basis of the ABPI test, as well as the relevance of the common modifications of the test. It explores the background to the quoted normal ranges for the ABPI test. It reviews the large body of literature that has developed on the association between ABPI and cardiovascular risk, as well as ABPI as a predictor for cardiovascular morbidity and mortality, highlighting the evidence that can inform practice. The review looks critically at the limitations of the ABPI test, providing practitioners with an evidence-based update on the importance and challenges of standardizing ABPI methodology. This paper highlights the influence of the key technical aspects of the ABPI test that all practitioners need to consider in order to be able to make more reliable and informed management decisions based on ABPI findings.

Direct placement of a brachial plexus neural catheter for analgesia after traumatic upper limb amputation.

We report a case of traumatic upper limb injury that resulted in above elbow amputation. A multimodal approach was employed to optimize postoperative analgesia; this included continuous peripheral nerve blockade, initiated intraoperatively. Surgical access onto the axillary artery for proximal vascular control allowed placement of the nerve catheter under direct vision onto the brachial plexus. The pathophysiology of phantom pain is related to our case experience. This report highlights the complex challenge of controlling pain in combat casualties and promotes employment of multimodal analgesic strategies, including advanced regional anesthesia, in the military setting.

Intra- and inter-individual genetic differences in gene expression.

Genetic variation is known to influence the amount of mRNA produced by a gene. Because molecular machines control mRNA levels of multiple genes, we expect genetic variation in components of these machines would influence multiple genes in a similar fashion. We show that this assumption is correct by using correlation of mRNA levels measured from multiple tissues in mouse strain panels to detect shared genetic influences. These correlating groups of genes (CGGs) have collective properties that on average account for 52-79% of the variability of their constituent genes and can contain genes that encode functionally related proteins. We show that the genetic influences are essentially tissue-specific and, consequently, the same genetic variations in one animal may upregulate a CGG in one tissue but downregulate the CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. Thus, this class of genetic variation can result in complex inter- and intraindividual differences. This will create substantial challenges in humans, where multiple tissues are not readily available.

Meta-analysis and gene set enrichment relative to er status reveal elevated activity of MYC and E2F in the "basal" breast cancer subgroup.

BACKGROUND: Breast cancers lacking the estrogen receptor (ER) can be distinguished from other breast cancers on the basis of poor prognosis, high grade, distinctive histopathology and unique molecular signatures. These features further distinguish estrogen receptor negative (ER-) tumor subtypes, but targeted therapy is currently limited to tumors over-expressing the ErbB2 receptor. METHODOLOGY/PRINCIPAL FINDINGS: To uncover the pathways against which future therapies could be developed we undertook a meta-analysis of gene expression from five large microarray datasets relative to ER status. A measure of association with ER status was calculated for every Affymetrix HG-U133A probe set and the pathways that distinguished ER- tumors were defined by testing for enrichment of biologically defined gene sets using Gene Set Enrichment Analysis (GSEA). As expected, the expression of the direct transcriptional targets of the ER was muted in ER- tumors, but the expression of genes indirectly regulated by estrogen was enhanced. We also observed enrichment of independent MYC- and E2F-driven transcriptional programs. We used a cell model of estrogen and MYC action to define the interaction between estrogen and MYC transcriptional activity in breast cancer. We found that the basal subgroup of ER- breast cancer showed a strong MYC transcriptional response that reproduced the indirect estrogen response seen in estrogen receptor positive (ER+) breast cancer cells. CONCLUSIONS/SIGNIFICANCE: Increased transcriptional activity of MYC is a characteristic of basal breast cancers where it mimics a large part of an estrogen response in the absence of the ER, suggesting a mechanism by which these cancers achieve estrogen-independence and providing a potential therapeutic target for this poor prognosis sub group of breast cancer.