Cardio-renal-metabolic disease in primary care setting.

In the primary care setting providers have more tools available than ever before to impact positively obesity, diabetes, and their complications, such as renal and cardiac diseases. It is important to recognise what is available for treatment taking into account diabetes heterogeneity. For those who develop type 2 diabetes (T2DM), effective treatments are available that for the first time have shown a benefit in reducing mortality and macrovascular complications, in addition to the well-established benefits of glucose control in reducing microvascular complications. Some of the newer medications for treating hyperglycaemia have also a positive impact in reducing heart failure (HF). Technological advances have also contributed to improving the quality of care in patients with diabetes. The use of technology, such as continuous glucose monitoring systems (CGM), has improved significantly glucose and glycated haemoglobin A1c (HbA1c) values, while limiting the frequency of hypoglycaemia. Other technological support derives from the use of predictive algorithms that need to be refined to help predict those subjects who are at great risk of developing the disease and/or its complications, or who may require care by other specialists. In this review we also provide recommendations for the optimal use of the new medications; sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like peptide-receptor agonists 1 (GLP1RA) in the primary care setting considering the relevance of these drugs for the management of T2DM also in its early stage.

Ecological security assessment at different spatial scales in central Yunnan Province, China.

Healthy ecosystems are the basis of social and economic development. It is of great significance to conduct ecological security assessments in rapidly urbanization areas. Based on the driving forces, pressure, state, impact, and response (DPSIR) model, five years (1995, 2000, 2005, 2010 and 2015) of remote sensing images, social and economic statistics, and field survey data were used to establish an ecological security assessment index system. The ecological security assessment of central Yunnan Province (CYP) urban agglomeration was conducted at the 1 km × 1 km pixel scale and at the county scale based on the multilevel weighted comprehensive index method. The results showed that: (1) With 2005 as the turning point, the ecological security situation in CYP first decreased and then increased. (2) The ecological security at the county scale was mainly categorized as unsafe. At the pixel scale, ecologically unsafe and relatively unsafe areas were mainly distributed in central, northern, and western CYP. (3) The ecological security deterioration and strengthened spatial distribution differences were caused by habitat fragmentation, different physical geographical conditions, and population agglomeration. These results can provide a basis for the coordination and sustainability of economic development and environmental protection in urban agglomerations with rapid urbanization.

Detection of Genetic Alterations in Oral Squamous Cell Carcinoma Using Multiplex LigationDependent Probe Amplification (MLPA)

@#Deletions and amplifications of genes often occur during multistep progression from oral precancer, seen as oral epithelial dysplasia (OED) to cancerous stage. These genetic alterations could be used as markers to aid in detection of oral squamous cell carcinomas (OSCC). This study explored the use of multiplex ligation-dependent probe amplification (MLPA) technique in detecting OSCC and OED specific genetic alterations. MLPA was used to detect gains and losses of 106 genes in DNA extracted from frozen tissue samples of 10 OSCC and 10 noncancer patients. Two biopsies of OED were analyzed to explore the alterations in oral potentially malignant disorders. There were significant differences (p<0.001) in the number of alterations in OSCC and dysplasia compared to non-cancer samples respectively. The most frequently altered genes in OSCC were PTP4A3, RECQL4, ATM, and KLK3 (60%). Five genes (MYC, SLA, TNFRSF1A, MESDC1, MIF) were altered in 50% of OSCC samples. These nine genes were specific to OSCC samples (p<0.05). Some genes, including MYB, MET, CASP2, SLA and PTEN occurred in 50% of OED samples. MLPA was able to detect genetic alterations, that are present only in the OSCC samples and showed potential to be used as an adjunctive tool in early diagnosis of OSCC.

Health-Related Quality of Life among Patients with Oral Potentially Malignant Disorder and Oral Cancer in Malaysia

ABSTRACT@#Presently there is a lack of health-related quality of life (HRQOL) measure and its corresponding utility values for oral cancer and oral potentially malignant disorders (OPMD). This limits patient-centered outcomes for cost-effectiveness evaluations. The study aimed to determine post-treatment HRQOL of patients and ascertained differences between OPMD, early and late-stage oral cancer. A cross-sectional survey was conducted among patients in oral maxillofacial specialist clinics in two public tertiary hospitals. Consented participants were required to complete the EQ-5D-5L questionnaire with the EQ Visual Analogue System (VAS). Kruskal-Wallis test was used to explore differences in values between stages. Multiple linear regression was used to explore factors that influenced the HRQOL. A total of 50 OPMD and 52 oral cancer patients were surveyed. The mean EQ-5D-5L health utility values was 0.842 (n = 50, SD = 0.139), 0.822 (n = 10, SD = 0.150) and 0.626 (n = 42, SD = 0.310) for OPMD, early- and late-stage cancer, respectively. The mean values of the EQ-5D-5L index and EQ-VAS scale showed significant differences between groups and between early- and late-stage cancer with good discriminative properties. Results of the multiple linear regression indicated that ethnicity, income, residency, diagnosis, and treatment modality were able to significantly account for 25% of EQ-5D-5L utility values, F(10,91) = 3.83, p < 0.001, R2 = 0.360. Indian ethnicity, rural location, income less than RM4,360, late-stage cancer, and multi-modal therapies were all predictors of poorer HRQOL. This study evidenced disease severity and treatment modality to greatly impact the HRQOL of patients, in addition to socio-demographic factors such as ethnicity and income.

COVID-19 mitigation for high-risk populations in Springfield Massachusetts USA: a health systems approach.

BACKGROUND: Numerous reports have demonstrated the disproportionate impact that COVID-19 has had on vulnerable populations. Our purpose is to describe our health care system's response to this impact. METHODS: We convened a Workgroup with the goal to mitigate the impact of COVID-19 on the most medically vulnerable people in Springfield, Massachusetts, USA, particularly those with significant social needs. We did this through (1) identifying vulnerable patients in high-need geographic areas, (2) developing and implementing a needs assessment/outreach tool tailored to meet cultural, linguistic and religious backgrounds, (3) surveying pharmacies for access to medication delivery, (4) gathering information about sources of food delivery, groceries and/or prepared food, (5) gathering information about means of travel, and (6) assessing need for testing. We then combined these six elements into a patient-oriented branch and a community outreach/engagement branch. CONCLUSIONS: Our highly intentional and methodical approach to patient and community outreach with a strong geographic component has led to fruitful efforts in COVID-19 mitigation. Our patient-level outreach engages our health centers' clinical teams, particularly community health workers, and is providing the direct benefit of material and service resources for our at-risk patients and their families. Our community efforts leveraged existing relationships and created new partnerships that continue to inform us-healthcare entities, healthcare employees, and clinical teams-so that we can grow and learn in order to authentically build trust and engagement.

A new risk and issue management system to improve productivity, quality, and compliance in clinical trials.

OBJECTIVE: We present a new system to track, manage, and report on all risks and issues encountered during a clinical trial. MATERIALS AND METHODS: Our solution utilizes JIRA, a popular issue and project tracking tool for software development, augmented by third-party and custom-built plugins to provide the additional functionality missing from the core product. RESULTS: The new system integrates all issue types under a single tracking tool and offers a range of capabilities, including configurable issue management workflows, seamless integration with other clinical systems, extensive history, reporting, and trending, and an intuitive web interface. DISCUSSION AND CONCLUSION: By preserving the linkage between risks, issues, actions, decisions, and outcomes, the system allows study teams to assess the impact and effectiveness of their risk management strategies and present a coherent account of how the trial was conducted. Since the tool was put in production, we have observed an increase in the number of reported issues and a decrease in the median issue resolution time which, along with the positive user feedback, point to marked improvements in quality, transparency, productivity, and teamwork.

High rates of severe hypoglycemia among African American patients with diabetes: the surveillance, prevention, and Management of Diabetes Mellitus (SUPREME-DM) network.

AIMS: Seven-year surveillance study (2005-2011) to evaluate race/ethnic differences in the trends in rates of severe hypoglycemia (SH) in a population of insured, at-risk adults with diabetes. METHODS: SH events were identified via any primary or principal diagnosis from emergency department or inpatient encounters among African American, Asian, Latino and White adult diabetes patients treated with insulin or secretagogues (Sulfonylureas or Meglitinides), receiving care from integrated healthcare delivery systems across the United States. We calculated age- and sex-standardized annual SH rates and average annual percent change (AAPC) in SH rates. RESULTS: Annual SH rates ranged from 1.8% to 2.1% during this 7-year observation period (2,200,471 person-years). African Americans had consistently higher SH rates compared with Whites, while Latinos and Asians had consistently lower rates compared with Whites in each of the 7 years (all p < 0.01). The trend increased significantly only among African Americans (AAPC = +4.3%; 95% CI: +2.1, +6.5%); in the other groups, the AAPC was not significantly different from zero. CONCLUSIONS: Surveillance efforts should monitor the racial/ethnic-specific rates. The factors underlying substantially higher rates of hypoglycemia in African Americans should be evaluated. Clinically and culturally-appropriate strategies to reduce the risk of SH need to be developed and tested.

Telemedicine Can Replace the Neurologist on a Mobile Stroke Unit.

BACKGROUND AND PURPOSE: The BEST-MSU study (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit) is a comparative effectiveness trial in patients randomized to mobile stroke unit or standard management. A substudy tested interrater agreement for tissue-type plasminogen activator eligibility between a telemedicine vascular neurologist and onboard vascular neurologist. METHODS: On scene, both the telemedicine vascular neurologist and onboard vascular neurologist independently evaluated the patient, documenting their tissue-type plasminogen activator treatment decision, National Institutes of Health Stroke Scale score, and computed tomographic interpretation. Agreement was determined using Cohen κ statistic. Telemedicine-related technical failures that impeded remote assessment were recorded. RESULTS: Simultaneous and independent telemedicine vascular neurologist and onboard vascular neurologist assessment was attempted in 174 patients. In 4 patients (2%), the telemedicine vascular neurologist could not make a decision because of technical problems. The telemedicine vascular neurologist agreed with the onboard vascular neurologist on 88% of evaluations (κ=0.73). CONCLUSIONS: Remote telemedicine vascular neurologist assessment is reliable and accurate, supporting either telemedicine vascular neurologist or onboard vascular neurologist assessment on our mobile stroke unit. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02190500.

Hemicraniectomy versus Conservative Treatment in Large Hemispheric Ischemic Stroke Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several small trials have inconclusively evaluated the effect of hemicraniectomy in reducing death and disability in acute ischemic stroke patients with large hemispheric infarctions. We compared the effects of hemicraniectomy on death and disability with conservative treatment in patients with large hemispheric infarctions. METHODS: We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using random-effects models from 7 randomized trials that compared hemicraniectomy with conservative treatment in acute ischemic stroke patients. The primary end point was a favorable outcome defined by modified Rankin Scale grades of 0 (no symptoms), 1 (no significant disability), 2 (slight disability), and 3 (moderate disability) at 6-12 months post randomization. RESULTS: Of the 341 total subjects randomized, the proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to hemicraniectomy than among those randomized to conservative treatment (OR 2.04, 95% CI 1.03-4.03, P = .04). Survival was also significantly greater among those randomized to hemicraniectomy (OR 5.56, 95% CI 3.40-9.08, P < .001) than among those randomized to conservative treatment. There was a trend toward higher odds of favorable outcome among those randomized to hemicraniectomy than among those randomized to conservative treatment in trials that permitted recruitment of patients aged 60 years or older (303 subjects analyzed; OR 1.87, 95% CI .91-3.86, P = .09). CONCLUSIONS: Compared with conservative treatment, the odds of achieving a favorable outcome at 6 months is approximately 2-folds higher with hemicraniectomy in patients with large hemispheric infarctions.

One-Pot Synthesis of Highly Substituted Nicotinic Acid Derivatives Based on a Formylation Strategy of Enamino Keto Esters.

A facile one-pot synthesis of 4-chloro or 4-bromonicotinic acid esters with optional 2- and 2,5-disubstitution on the pyridine ring has been developed from easily accessible enamino keto esters by a formylation followed by in situ intramolecular cyclization strategy under optimized Vilsmeier reaction conditions. The effect of the substituents on the ß-carbon and the nature of the keto functionality were explored in detail to understand the mechanism of pyridine ring formation under the described conditions.

Effect of Intensive Blood Pressure Lowering on Incident Atrial Fibrillation and P-Wave Indices in the ACCORD Blood Pressure Trial.

BACKGROUND: There are no proven strategies to prevent atrial fibrillation (AF) in patients with type 2 diabetes (T2DM). We compared standard blood pressure (BP) lowering vs. intensive BP lowering in reducing incidence of AF or P-wave indices (PWI-ECG markers of left atrial abnormality that are considered intermediate phenotypes of AF) in patients with T2DM. METHODS: We analyzed data from the ACCORD BP trial-a randomized controlled nonblinded trial (2001-2009) which randomized patients with T2DM and systolic BP (SBP) 130-180mm Hg on ≤3 antihypertensive medications aged 40-79 years with cardiovascular disease (CVD) or aged 55-79 years with subclinical CVD or ≥2 CVD risk factors to standard BP lowering (SBP <140mm Hg) vs. intensive BP lowering (SBP <120mm Hg). The primary outcome was a composite of incident AF and PWI. RESULTS: Data from 3,087 participants (mean age, 62.2 years; women, 48.2%; non-White, 39.2%) were analyzed. During a mean follow-up of 4.4 years, the primary outcome occurred in 1,063 participants (incidence rate, 84.5 per 1,000 person-years in the standard-therapy group vs. 73.9 per 1,000 person-years in the intensive-therapy group). The adjusted hazard ratios (95% confidence intervals) of intensive-therapy group for the primary outcome and for incident PWI alone were 0.87 (0.77-0.98), P = 0.02 and 0.87 (0.76-0.98), P = 0.02, respectively. The effect of intensive therapy on the incidence of AF alone did not reach statistical significance. CONCLUSIONS: In patients with T2DM, intensive BP lowering reduces the incidence of the composite outcome of AF and PWI, suggesting a potential benefit from stringent BP control in patients with T2DM. clinical trials registration Trial Number NCT00000620.

Medication Adherence Does Not Explain Black-White Differences in Cardiometabolic Risk Factor Control among Insured Patients with Diabetes.

BACKGROUND: Among patients with diabetes, racial differences in cardiometabolic risk factor control are common. The extent to which differences in medication adherence contribute to such disparities is not known. We examined whether medication adherence, controlling for treatment intensification, could explain differences in risk factor control between black and white patients with diabetes. METHODS: We identified three cohorts of black and white patients treated with oral medications and who had poor risk factor control at baseline (2009): those with glycated hemoglobin (HbA1c) >8 % (n = 37,873), low-density lipoprotein cholesterol (LDL-C) >100 mg/dl (n = 27,954), and systolic blood pressure (SBP) >130 mm Hg (n = 63,641). Subjects included insured adults with diabetes who were receiving care in one of nine U.S. integrated health systems comprising the SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) consortium. Baseline and follow-up risk factor control, sociodemographic, and clinical characteristics were obtained from electronic health records. Pharmacy-dispensing data were used to estimate medication adherence (i.e., medication refill adherence [MRA]) and treatment intensification (i.e., dose increase or addition of new medication class) between baseline and follow-up. County-level income and educational attainment were estimated via geocoding. Logistic regression models were used to test the association between race and follow-up risk factor control. Models were specified with and without medication adherence to evaluate its role as a mediator. RESULTS: We observed poorer medication adherence among black patients than white patients (p < 0.01): 50.6 % of blacks versus 39.7 % of whites were not highly adherent (i.e., MRA <80 %) to HbA1c oral medication(s); 58.4 % of blacks and 46.7 % of whites were not highly adherent to lipid medication(s); and 33.4 % of blacks and 23.7 % of whites were not highly adherent to BP medication(s). Across all cardiometabolic risk factors, blacks were significantly less likely to achieve control (p < 0.01): 41.5 % of blacks and 45.8 % of whites achieved HbA1c <8 %; 52.6 % of blacks and 60.8 % of whites achieved LDL-C <100; and 45.7 % of blacks and 53.6 % of whites achieved SBP <130. Adjusting for medication adherence/treatment intensification did not alter these patterns or model fit statistics. CONCLUSIONS: Medication adherence failed to explain observed racial differences in the achievement of HbA1c, LDL-C, and SBP control among insured patients with diabetes.

Severe Hypoglycemia Requiring Medical Intervention in a Large Cohort of Adults With Diabetes Receiving Care in U.S. Integrated Health Care Delivery Systems: 2005-2011.

OBJECTIVE: Appropriate glycemic control is fundamental to diabetes care, but aggressive glucose targets and intensive therapy may unintentionally increase episodes of hypoglycemia. We quantified the burden of severe hypoglycemia requiring medical intervention in a well-defined population of insured individuals with diabetes receiving care in integrated health care delivery systems across the U.S. RESEARCH DESIGN AND METHODS: This observational cohort study included 917,440 adults with diabetes receiving care during 2005 to 2011 at participating SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) network sites. Severe hypoglycemia rates were based on any occurrence of hypoglycemia-related ICD-9 codes from emergency department or inpatient medical encounters and reported overall and by age, sex, comorbidity status, antecedent A1C level, and medication use. RESULTS: Annual rates of severe hypoglycemia ranged from 1.4 to 1.6 events per 100 person-years. Rates of severe hypoglycemia were higher among those with older age, chronic kidney disease, congestive heart failure, cardiovascular disease, depression, and higher A1C levels, and in users of insulin, insulin secretagogues, or ß-blockers (P < 0.001 for all). Changes in severe hypoglycemia occurrence over time were not clinically significant in the cohort as a whole but were observed in subgroups of individuals with chronic kidney disease, congestive heart failure, and cardiovascular disease. CONCLUSIONS: Risk of severe hypoglycemia in clinical settings is considerably higher in identifiable patient subgroups than in randomized controlled trials. Strategies that reduce the risk of hypoglycemia in high-risk patients are needed.

Antimicrobial Prophylaxis in Instrumented Spinal Fusion Surgery: A Comparative Analysis of 24-Hour and 72-Hour Dosages

STUDY DESIGN: Prospective study. PURPOSE: To compare the efficacy of 24-hour and 72-hour antibiotic prophylaxis in preventing surgical site infections (SSIs). OVERVIEW OF LITERATURE: Antimicrobial prophylaxis in surgical practice has become a universally accepted protocol for minimizing postoperative complications related to infections. Although prophylaxis is an accepted practice, a debate exists with regard to the antibiotic type and its administration duration for various surgical procedures. METHODS: Our institute is a tertiary care hospital with more than 100 spinal surgeries per year for various spine disorders in the department of orthopedics. We conducted this prospective study in our department from June 2012 to January 2015. A total of 326 patients were enrolled in this study, with 156 patients in the 72-hour antibiotic prophylaxis group (group A) and 170 patients in the 24-hour group (group B). Cefazolin was the antibiotic used in both groups. Two surgeons were involved in conducting all the spinal procedures. Our study compared SSIs among patients undergoing instrumented spinal fusion. RESULTS: The overall rate of SSIs was 1.8% with no statistical difference between the two groups. CONCLUSIONS: The 24-hour antimicrobial prophylaxis is as effective as the 72-hour dosage in instrumented spinal fusion surgery.

Design, Synthesis, and Pharmacological Evaluation of 5,6-Disubstituted Pyridin-2(1H)-one Derivatives as Phosphodiesterase 10A (PDE10A) Antagonists.

We report the design and synthesis of novel 5,6-diarylated pyridin-2(1H)-one derivatives as pharmacophoric PDE10A inhibitors. This highly potent molecular scaffold was developed from an inactive diarylpyridine-2-amine derivative 3b by extensive and systematic analogue synthesis and SAR analysis. Further optimization of the scaffold resulted in identification of pyridin-2(1H)-one 18b as a lead compound with good potency (IC50 = 1.6 nM) and selectivity (>6000-fold) over other related PDEs but with a poor pharmacokinetic profile. Careful metabolite profiling of 18b revealed that poor systemic exposure in rats (Cmax = 44 ng/mL; AUC0-t = 359 ng · h/mL) at 10 mg/kg was due to the formation of O-glucuronide conjugate by phase 2 metabolism. The structure of the glucuronide metabolite was confirmed by retention time and LC-MS/MS fragmentation matching with the synthetic glucuronide 26. The problem of low exposure of 18b was effectively addressed by its conversion to an acetate prodrug 25b, which upon oral dosing resulted in an improved pharmacokinetic profile (Cmax = 359 ng.h/mL; AUC0-t = 2436 ng.h/mL) and a desirable brain to plasma ratio of 1.2. The prodrug 25b showed good efficacy in selected rodent models of psychosis.