Insulin initiation and intensification in patients with T2DM for the primary care physician

Type 2 diabetes mellitus (T2DM) is characterized by both insulin resistance and inadequate insulin secretion. All patients with the disease require treatment to achieve and maintain the target glycosylated hemoglobin (A1C) level of 6.5%–7%. Pharmacological management of T2DM typically begins with the introduction of oral medications, and the majority of patients require exogenous insulin therapy at some point in time. Primary care physicians play an essential role in the management of T2DM since they often initiate insulin therapy and intensify regimens over time as needed. Although insulin therapy is prescribed on an individualized basis, treatment usually begins with basal insulin added to a background therapy of oral agents. Prandial insulin injections may be added if glycemic targets are not achieved. Treatments may be intensified over time using patient-friendly titration algorithms. The goal of insulin intensification within the primary care setting is to minimize patients’ exposure to chronic hyperglycemia and weight gain, and reduce patients’ risk of hypoglycemia, while achieving individualized fasting, postprandial, and A1C targets. Simplified treatment protocols and insulin delivery devices allow physicians to become efficient prescribers of insulin intensification within the primary care arena

Uncovering undetected hypoglycemic events

Hypoglycemia is the rate-limiting factor that often prevents patients with diabetes from safely and effectively achieving their glycemic goals. Recent studies have reported that severe hypoglycemia is associated with a significant increase in the adjusted risks of major macrovascular events, major microvascular events, and mortality. Minor hypoglycemic episodes can also have serious implications for patient health, psychological well being, and adherence to treatment regimens. Hypoglycemic events can impact the health economics of the patient, their employer, and third-party payers. Insulin treatment is a key predictor of hypoglycemia, with one large population-based study reporting an overall prevalence of 7.1% (type 1 diabetes mellitus) and 7.3% (type 2 diabetes mellitus) in insulin-treated patients, compared with 0.8% in patients with type 2 diabetes treated with an oral sulfonylurea. Patients with type 1 diabetes typically experience symptomatic hypoglycemia on average twice weekly and severe hypoglycemia once annually. The progressive loss of islet cell function in patients with type 2 diabetes results in a higher risk of both symptomatic and unrecognized hypoglycemia over time. Patients with diabetes who become hypoglycemic are also more susceptible to developing defective counter-regulation, also known as hypoglycemia awareness autonomic failure, which is life-threatening and must be aggressively addressed. In patients unable to recognize hypoglycemia symptoms, frequent home monitoring or use of continuous glucose sensors are critical. Primary care physicians play a key role in the prevention and management of hypoglycemia in patients with diabetes, particularly in those requiring intensive insulin therapy, yet physicians are often unaware of the multitude of consequences of hypoglycemia or how to deal with them. Careful monitoring, adherence to guidelines, and use of optimal treatment combinations are all important steps toward improving care in patients with diabetes. The most important goals are for primary care physicians to recognize that every patient treated with antihyperglycemic medications is at risk of iatrogenic hypoglycemia and to ask patients about hypoglycemia at every visit

Promoting VCU Community Solutions

This promotional project focuses on VCU Community Solutions — the new interdisciplinary initiative for education, research, and service. Since this initiative demonstrates the synergy that students, faculty, and community members can create by working together, the promotional video captures their perspectives. Through interviews and footage of community programs, the video shows how VCU Community Solutions engages university and community partners in addressing critical social issues — creating more imovative approaches by working together

Juvenile Probation Officers Call for a New Response to Teen Drug and Alcohol Use and Dependency

Shares lessons learned from RWJF's Reclaiming Futures initiative from a juvenile justice practitioner's perspective. Discusses the need to reform the system's treatment services, the challenges faced at the ten project sites, and recommendations

Neural Process Reconstruction from Sparse User Scribbles

We present a novel semi-automatic method for segmenting neural processes in large, highly anisotropic EM (electron microscopy) image stacks. Our method takes advantage of sparse scribble annotations provided by the user to guide a 3D variational segmentation model, thereby allowing our method to globally optimally enforce 3D geometric constraints on the segmentation. Moreover, we leverage a novel algorithm for propagating segmentation constraints through the image stack via optimal volumetric pathways, thereby allowing our method to compute highly accurate 3D segmentations from very sparse user input. We evaluate our method by reconstructing 16 neural processes in a 1024×1024×50 nanometer-scale EM image stack of a mouse hippocampus. We demonstrate that, on average, our method is 68% more accurate than previous state-of-the-art semi-automatic methods.Engineering and Applied Science

Determinants of vaccination coverage and consequences for rabies control in Bali, Indonesia

Maintaining high vaccination coverage is key to successful rabies control, but mass dog vaccination can be challenging and population turnover erodes coverage. Declines in rabies incidence following successive island-wide vaccination campaigns in Bali suggest that prospects for controlling and ultimately eliminating rabies are good. Rabies, however, has continued to circulate at low levels. In the push to eliminate rabies from Bali, high coverage needs to be maintained across all areas of the island. We carried out door-to-door (DTD) questionnaire surveys (n = 10,352 dog-owning households) and photographic mark–recapture surveys (536 line transects, 2,597 observations of free-roaming dogs) in 2011–2012 to estimate dog population sizes and assess rabies vaccination coverage and dog demographic characteristics in Bali, Indonesia. The median number of dogs per subvillage unit (banjar) was 43 (range 0–307) for owned dogs estimated from the DTD survey and 17 (range 0–83) for unconfined dogs (including both owned and unowned) from transects. Vaccination coverage of owned dogs was significantly higher in adults (91.4%) compared to juveniles (<1 year, 43.9%), likely due to insufficient targeting of pups and from puppies born subsequent to vaccination campaigns. Juveniles had a 10–70 times greater risk of not being vaccinated in urban, suburban, and rural areas [combined odds ratios (ORs): 9.9–71.1, 95% CI: 8.6–96.0]. Free-roaming owned dogs were also 2–3 times more likely to be not vaccinated compared to those confined (combined Ors: 1.9–3.6, 95% CI: 1.4–5.4), with more dogs being confined in urban (71.2%) than in suburban (16.1%) and rural areas (8.0%). Vaccination coverage estimates from transects were also much lower (30.9%) than household surveys (83.6%), possibly due to loss of collars used to identify the vaccination status of free-roaming dogs, but these unconfined dogs may also include dogs that were unowned or more difficult to vaccinate. Overall, coverage levels were high in the owned dog population, but for future campaigns in Bali to have the highest chance of eliminating rabies, concerted effort should be made to vaccinate free-roaming dogs particularly in suburban and rural areas, with advertising to ensure that owners vaccinate pups. Long-lasting, cheap, and quick methods are needed to mark vaccinated animals and reassure communities of the reach of vaccination campaigns

A life in progress: motion and emotion in the autobiography of Robert M. La Follette

This article is a study of a La Follette’s Autobiography, the autobiography of the leading Wisconsin progressive Robert M. La Follette, which was published serially in 1911 and, in book form, in 1913. Rather than focusing, as have other historians, on which parts of La Follette’s account are accurate and can therefore be trusted, it explains instead why and how this major autobiography was conceived and written. The article shows that the autobiography was the product of a sustained, complex, and often fraught series of collaborations among La Follette’s family, friends, and political allies, and in the process illuminates the importance of affective ties as well as political ambition and commitment in bringing the project to fruition. In the world of progressive reform, it argues, personal and political experiences were inseparable

Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors

In Lao People's Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villages, 895 humans and 647 pigs were sampled and serologically tested for zoonotic pathogens including: hepatitis E virus (HEV), Japanese encephalitis virus (JEV) and Trichinella spiralis; In addition, human sera were tested for Taenia spp. and cysticercosis. Seroprevalence of zoonotic pathogens in humans was high for HEV (Luang Prabang: 48.6%, Savannakhet: 77.7%) and T. spiralis (Luang Prabang: 59.0%, Savannakhet: 40.5%), and lower for JEV (around 5%), Taenia spp. (around 3%) and cysticercosis (Luang Prabang: 6.1, Savannakhet 1.5%). Multiple correspondence analysis and hierarchical clustering of principal components was performed on descriptive data of human hygiene practices, contact with pigs and consumption of pork products. Three clusters were identified: Cluster 1 had low pig contact and good hygiene practices, but had higher risk of T. spiralis. Most people in cluster 2 were involved in pig slaughter (83.7%), handled raw meat or offal (99.4%) and consumed raw pigs' blood (76.4%). Compared to cluster 1, cluster 2 had increased odds of testing seropositive for HEV and JEV. Cluster 3 had the lowest sanitation access and had the highest risk of HEV, cysticercosis and Taenia spp. Farmers which kept their pigs tethered (as opposed to penned) and disposed of manure in water sources had 0.85 (95% CI: 0.18 to 0.91) and 2.39 (95% CI: 1.07 to 5.34) times the odds of having pigs test seropositive for HEV, respectively. The results have been used to identify entry-points for intervention and management strategies to reduce disease exposure in humans and pigs, informing control activities in a cysticercosis hyper-endemic village

The Dementia Care Study (D-Care): Recruitment Strategies and Demographic Characteristics of Participants in a Pragmatic Randomized Trial of Dementia Care

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare. METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients. RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), 58.4% were women, and 8.8% were Hispanic/Latino, and 11.9% were Black/African American. Caregivers were mostly children of the PLWD (46.5%) or spouses/partners (45.2%), 75.8% were women, 9.4% were Hispanic/Latino, and 11.6% were Black/African American. DISCUSSION: Health systems can successfully enroll diverse dyads in a pragmatic clinical trial

Cortical-Bone Fragility - Insights from sFRP4 Deficiency in Pyle's Disease

BACKGROUND Cortical-bone fragility is a common feature in osteoporosis that is linked to non - vertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments. METHODS We evaluated four patients with Pyle’s disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger se - quencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture. RESULTS In all affected patients, we found biallelic truncating mutations in SFR P4 , the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4 , like persons with Pyle’s disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treat - ment of Sfrp4- deficient mice with a soluble Bmp2 receptor (RAP-661) or with anti - bodies to sclerostin corrected the cortical-bone defect. CONCLUSIONS Our study showed that Pyle’s disease was caused by a deficiency of sFRP4, that cortical- bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross-regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss Na - tional Foundation and the National Institutes of Health.