Evaluating county-level spatial prevalence and clustering of medicare beneficiaries in Mississippi

Objective

This study seeks to examine how the extent of socioeconomic deprivation, racial and ethnic isolation, and health disadvantage differ among Medicare beneficiaries in Mississippi. Methods: Geographical information system (GIS) mappings are used in conjunction with cluster analysis to examine patterns of disparities in disease distribution, healthcare utilization and socioeconomic well-being among different counties in Mississippi.

Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure infections

Ceftaroline, the bioactive metabolite of ceftaroline fosamil (previously PPI-0903, TAK-599), is a broad-spectrum cephalosporin with potent in vitro activity against multidrug-resistant gram-positive aerobic pathogens, including methicillin-resistant Staphylococcus aureus. A randomized, observer-blinded study to evaluate the safety and efficacy of ceftaroline versus standard therapy in treating complicated skin and skin structure infections (cSSSI) was performed. Adults with cSSSI, including at least one systemic marker of inflammation, were randomized (2:1) to receive intravenous (i.v.) ceftaroline (600 mg every 12 h) or i.v. vancomycin (1 g every 12 h) with or without adjunctive i.v. aztreonam (1 g every 8 h) for 7 to 14 days. The primary outcome measure was the clinical cure rate at a test-of-cure (TOC) visit 8 to 14 days after treatment. Secondary outcomes included the microbiological success rate (eradication or presumed eradication) at TOC and the clinical relapse rate 21 to 28 days following treatment. Of 100 subjects enrolled, 88 were clinically evaluable; the clinical cure rate was 96.7% (59/61) for ceftaroline versus 88.9% (24/27) for standard therapy. Among the microbiologically evaluable subjects (i.e., clinically evaluable and having had at least one susceptible pathogen isolated at baseline), the microbiological success rate was 95.2% (40/42) for ceftaroline versus 85.7% (18/21) for standard therapy. Relapse occurred in one subject in each group (ceftaroline, 1.8%; standard therapy, 4.3%). Ceftaroline exhibited a very favorable safety and tolerability profile, consistent with that of marketed cephalosporins. Most adverse events from ceftaroline were mild and not related to treatment. Ceftaroline holds promise as a new therapy for treatment of cSSSI and other serious polymicrobial infections.     

Ending neglect: providing effective childhood tuberculosis training for health care workers in Tanzania

Setting: Health care facilities in Dar es Salaam, Pwani, and Arusha, Tanzania.Objective: To assess health care worker (HCW) knowledge and practices 1 year after specialized training in childhood tuberculosis (TB).Design: Using a standardized survey, we interviewed a convenience sample of HCWs providing both general and specialized care to children.Results: We interviewed 117 HCWs in TB clinics, maternal and child health clinics, human immunodeficiency virus (HIV) clinics, out-patient departments, and pediatric in-patient wards at 12 facilities. A total of 81 HCWs (62% of nurses, 74% of clinicians) reported having attended the national childhood TB training course. Most HCWs responded correctly to questions on childhood TB diagnosis, treatment, and TB-HIV co-management, regardless of training history. Most HCWs reported that they routinely obtain chest radiographs, HIV testing, and a TB contact history when evaluating children for TB. Less than half of HCWs reported routinely obtaining sputum for mycobacterial culture or performing a tuberculin skin test. Three times as many trained as untrained HCWs reported having ever prescribed isoniazid preventive therapy (IPT) to a child (P < 0.05).Conclusion: In general, levels of childhood TB knowledge were high and practices were in accordance with national guidance. Specific gaps in diagnosis, treatment and use of IPT were identified for future focused training.     

Synthesis,characterization, and monoamine transporter activity of the new psychoactive substance 3′,4′‐methylenedioxy‐4‐methylaminorex (MDMAR)

The recent occurrence of deaths associated with the psychostimulant cis‐4,4′‐dimethylaminorex (4,4′‐DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4‐methylenedioxy‐4‐methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis‐ and trans‐MDMAR followed by extensive characterization by chromatographic, spectroscopic, mass spectrometric platforms and crystal structure analysis. MDMAR obtained from an online vendor was subsequently identified as predominantly the cis‐isomer (90%). Exposure of the cis‐isomer to the mobile phase conditions (acetonitrile/water 1:1 with 0.1% formic acid) employed for high performance liquid chromatography analysis showed an artificially induced conversion to the trans‐isomer, which was not observed when characterized by gas chromatography. Monoamine release activities of both MDMAR isomers were compared with the non‐selective monoamine releasing agent (+)‐3,4‐methylenedioxymethamphetamine (MDMA) as a standard reference compound. For additional comparison, both cis‐ and trans‐4,4′‐DMAR, were assessed under identical conditions. cis‐MDMAR, trans‐MDMAR, cis‐4,4′‐DMAR and trans‐4,4′‐DMAR were more potent than MDMA in their ability to function as efficacious substrate‐type releasers at the dopamine (DAT) and norepinephrine (NET) transporters in rat brain tissue. While cis‐4,4′‐DMAR, cis‐MDMAR and trans‐MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), trans‐4,4′‐DMAR acted as a fully efficacious uptake blocker. Currently, little information is available about the presence of MDMAR on the market but the high potency of ring‐substituted methylaminorex analogues at all three monoamine transporters investigated here might be relevant when assessing the potential for serious side‐effects after high dose exposure. Copyright © 2014 John Wiley & Sons, Ltd.     

A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism

Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the absorption of sodium through the highly selective, amiloride-sensitive epithelial sodium channel (ENaC) made of three homologous subunits (α, β, and γ). In human, autosomal recessive mutations of α, β, or γENaC subunits cause pseudohypoaldosteronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldosterone, hyponatremia, life-threatening hyperkaliemia, and metabolic acidosis. In the mouse, inactivation of αENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype. Transgenic expression of αENaC driven by a cytomegalovirus promoter in αENaC(−/−) knockout mice [αENaC(−/−)Tg] rescued the perinatal lethal pulmonary phenotype and partially restored Na⁺ transport in renal, colonic, and pulmonary epithelia. At days 5–9, however, αENaC(−/−)Tg mice showed clinical features of severe PHA-1 with metabolic acidosis, urinary salt-wasting, growth retardation, and 50% mortality. Adult αENaC(−/−)Tg survivors exhibited a compensated PHA-1 with normal acid/base and electrolyte values but 6-fold elevation of plasma aldosterone compared with wild-type littermate controls. We conclude that partial restoration of ENaC-mediated Na⁺ absorption in this transgenic mouse results in a mouse model for PHA-1.     

Discriminant scorecard for diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia

Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention.     

Diagnostic criteria for computer-aided electrocardiographic 15-lead system. Evaluation using 12 leads and Frank orthogonal leads with vector display.

The criteria for the diagnosis of myocardial infarction and ischaemic heart disease by an automated 15-lead computer-aided electrocardiographic system were examined using electrocardiograms of 543 patients. Errors in the electrocardiographic diagnosis were evaluated for each lead system (Frank orthogonal 3-lead, 12-lead, and hybrid 15-lead) using clinical and catheterization data for definitive diagnosis before review of the electrocardiograms and their reports. The effects of combinations of these diagnoses and additional ventricular conduction defects were also studied. Myocardial infarction and left ventricular hypertrophy were more reliably diagnosed using 3-lead and 12-lead systems together than with either system alone. The most sensitive criteria for anterior infarction were a Q/R ratio in Z less than 0-1 and loss of the first 20 ms of anterior forces in the horizontal and sagittal planes of the vectorcardiogram. However, false positive results were frequent, particularly in association with left ventricular hypertrophy, non-specific intraventricular conduction defects, and left bundle branch system block. Our V lead criteria were more specific whether or not these associated conditions were present. No single criterion with an acceptable false positive rate could be found to be sensitive for inferior infarction in all situations. Our most sensitive criteria were those based on the limb leads, and the presence of superior forces for the first 30 ms in the frontal plane of the vectorcardiogram, but these were better in combination. Limb lead criteria were the most specific. False positive results for inferior infarction were more frequent in the presence of left ventricular hypertrophy or ventricular conduction defects other than left anterior hemiblock. ST and T wave abnormalities were more apparent in the 12 leads than in the orthogonal leads. Specificity and sensitivity of criteria were poor, and specificity was decreased and sensitivity was not significantly improved by combining 3-lead with 12-lead criteria. Because of frequent measurement errors of ST, T, and also Q waves by the computer programme, in practice we have achieved increased sensitivity in the diagnosis of ischaemia and infarction with the combination of 3-lead and 12-lead systems. It is concluded that errors of diagnosis by a computer-aided system can be reduced by using multiple leads and that both 12-lead and orthogonal 3-lead systems are necessary for optimal computer diagnosis of left ventricular hypertrophy, myocardial infarction, and ischaemia.