Analyzing treatment aggressiveness and identifying high‐risk patients in diabetic foot ulcer return to care

Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all‐cause 30‐day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30‐day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011–2012. All‐cause 30‐day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high‐risk for readmission can improve counseling and treatment strategies for this fragile patient population.     

Neurons in superficial trigeminal subnucleus caudalis responsive to oral cooling, menthol, and other irritant stimuli

The recent discoveries of cold-sensitive transient receptor potential (TRP) channels prompted us to investigate the responses of neurons in trigeminal subnucleus caudalis (Vc) to intraoral cooling and agonists of TRPM8 and TRPA1. Single units responsive to lingual cooling were recorded in superficial laminae of Vc in thiopental-anesthetized rats. All units responded to noxious heat and 88% responded to menthol. Responses increased with menthol concentration from 0.1 to 1% (6.4-64 mM) and plateaued at 10% (640 mM). Noxious cold-evoked responses were significantly enhanced after menthol in a concentration-dependent manner. Constant-flow application of 1% menthol elicited a phasic discharge that adapted over 2-8 min and significantly enhanced subsequent cold-evoked but not heat-evoked responses; vehicle (10% ethanol) was ineffective. Reapplication of menthol 15 min later elicited a significantly reduced response (self-desensitization). Vc units were similarly excited phasically by 1% menthol dissolved in 40% ethanol. The 40% ethanol briefly excited Vc units during the first minute and reduced subsequent responses to noxious heat and cold while exhibiting neither self-desensitization nor cross-desensitization to menthol. Menthol cross-desensitized Vc responses to 40% ethanol. Most menthol-responsive units also responded to the TRPA1 agonists cinnamaldehyde and mustard oil, and the TRPV1 agonist capsaicin. Units in superficial Vc receive convergent input from primary afferents that express TRPM8, TRPA1, and/or TRPV1 channels, either directly or indirectly via intersubnuclear pathways. The convergent nature of these units suggests a general role in signaling noxious stimuli.     

Dietary Supplement Use in a Large,Representative Sample of the US Armed Forces

Background

Dietary supplement (DS) use is prevalent among the US Armed Forces personnel, but representative cross-service comparisons and characteristics of personnel using DSs are limited.

Deep Convolutional Neural Network Analysis of Flow Imaging Microscopy Data to Classify Subvisible Particles in Protein Formulations

Flow-imaging microscopy (FIM) is commonly used to characterize subvisible particles in therapeutic protein formulations. Although pharmaceutical companies often collect large repositories of FIM images of protein therapeutic products, current state-of-the-art methods for analyzing these images rely on low-dimensional lists of “morphological features” to characterize particles that ignore much of the information encoded in the existing image databases. Deep convolutional neural networks (sometimes referred to as “CNNs or ConvNets”) have demonstrated the ability to extract predictive information from raw macroscopic image data without requiring the selection or specification of “morphological features” in a variety of tasks. However, the inherent heterogeneity of protein therapeutics and optical phenomena associated with subvisible FIM particle measurements introduces new challenges regarding the application of ConvNets to FIM image analysis. We demonstrate a supervised learning technique leveraging ConvNets to extract information from raw images in order to predict the process conditions or stress states (freeze-thawing, mechanical shaking, etc.) that produced a variety of different protein particles. We demonstrate that our new classifier, in combination with a “data pooling” strategy, can nearly perfectly differentiate between protein formulations in a variety of scenarios of relevance to protein therapeutics quality control and process monitoring using as few as 20 particles imaged via FIM.     

Dermatotoxicology of sulfur mustard: Historical perspectives from World War I

Sulfur mustard has been used as a chemical warfare agent for the past century. After its introduction by the Germans in World War I, investigators quickly began studying its impact on the human body including its deleterious effects on skin. This review focuses on two groups in particular who conducted experiments from 1917 to 1918: the United States Army at the American University Experiment Station Laboratories and Torald Sollmann at Western Reserve University. Through this work, these researchers proved far ahead of their time by anticipating dermatologic phenomena not described in the literature until later in the twentieth century. These include regional variation of percutaneous penetration, effect of vehicle on penetration and predicting immunologic contact urticaria. The work conducted by these researchers set the groundwork for much of twentieth century dermatotoxicology.     

Decaffeinated green and black tea polyphenols decrease weight gain and alter microbiome populations and function in diet-induced obese mice

Purpose

Decaffeinated green tea (GT) and black tea (BT) polyphenols inhibit weight gain in mice fed an obesogenic diet. Since the intestinal microflora is an important contributor to obesity, it was the objective of this study to determine whether the intestinal microflora plays a role in the anti-obesogenic effect of GT and BT.

Methods

C57BL/6J mice were fed a high-fat/high-sucrose diet (HF/HS, 32% energy from fat; 25% energy from sucrose) or the same diet supplemented with 0.25% GTP or BTP or a low-fat/high-sucrose (LF/HS, 10.6% energy from fat, 25% energy from sucrose) diet for 4 weeks. Bacterial composition was assessed by MiSeq sequencing of the 16S rRNA gene.

Results

GTP and BTP diets resulted in a decrease of cecum Firmicutes and increase in Bacteroidetes. The relative proportions of Blautia, Bryantella, Collinsella, Lactobacillus, Marvinbryantia, Turicibacter, Barnesiella, and Parabacteroides were significantly correlated with weight loss induced by tea extracts. BTP increased the relative proportion of Pseudobutyrivibrio and intestinal formation of short-chain fatty acids (SCFA) analyzed by gas chromatography. Cecum propionic acid content was significantly correlated with the relative proportion of Pseudobutyrivibrio. GTP and BTP induced a significant increase in hepatic 5′adenosylmonophosphate-activated protein kinase (AMPK) phosphorylation by 70 and 289%, respectively (P < 0.05) determined by Western blot.

Conclusion

In summary, both BTP and GTP induced weight loss in association with alteration of the microbiota and increased hepatic AMPK phosphorylation. We hypothesize that BTP increased pAMPK through increased intestinal SCFA production, while GTPs increased hepatic AMPK through GTP present in the liver.

     

Measures of clustering and heterogeneity in multilevel Poisson regression analyses of rates/count data

Multilevel data occur frequently in many research areas like health services research and epidemiology. A suitable way to analyze such data is through the use of multilevel regression models. These models incorporate cluster‐specific random effects that allow one to partition the total variation in the outcome into between‐cluster variation and between‐individual variation. The magnitude of the effect of clustering provides a measure of the general contextual effect. When outcomes are binary or time‐to‐event in nature, the general contextual effect can be quantified by measures of heterogeneity like the median odds ratio or the median hazard ratio, respectively, which can be calculated from a multilevel regression model. Outcomes that are integer counts denoting the number of times that an event occurred are common in epidemiological and medical research. The median (incidence) rate ratio in multilevel Poisson regression for counts that corresponds to the median odds ratio or median hazard ratio for binary or time‐to‐event outcomes respectively is relatively unknown and is rarely used. The median rate ratio is the median relative change in the rate of the occurrence of the event when comparing identical subjects from 2 randomly selected different clusters that are ordered by rate. We also describe how the variance partition coefficient, which denotes the proportion of the variation in the outcome that is attributable to between‐cluster differences, can be computed with count outcomes. We illustrate the application and interpretation of these measures in a case study analyzing the rate of hospital readmission in patients discharged from hospital with a diagnosis of heart failure.