The role of accountable care organizations in delivering value

The goal of Accountable Care Organizations is to improve patient outcomes while maximizing the value of the services provided. This will be achieved through the use of performance and quality measures that facilitate efficient, cost-effective, evidence-based care. By creating a network connecting primary care physicians, specialists, rehabilitation facilities and hospitals, patient care should be maximized while at the same time delivering appropriate value for those services provided. The Medicare Shared Savings Program will financially reward ACOs that meet performance standards while at the same time lowering costs. The orthopaedic surgeon can only benefit by understanding how to participate in and negotiate the complexities of these organizations.     

The physiology and toxicology of acute inhalation phosphine poisoning in conscious male rats

Phosphine (PH₃) is a toxidrome-spanning chemical that is widely used as an insecticide and rodenticide. Exposure to PH₃ causes a host of target organ and systemic effects, including oxidative stress, cardiopulmonary toxicity, seizure-like activity and overall metabolic disturbance. A custom dynamic inhalation gas exposure system was designed for the whole-body exposure of conscious male Sprague-Dawley rats (250–350?g) to PH₃. An integrated plethysmography system was used to collect respiratory parameters in real-time before, during and after PH₃ exposure. At several time points post-exposure, rats were euthanized, and various organs were removed and analyzed to assess organ and systemic effects. The 24?h post-exposure LCt₅₀, determined by probit analysis, was 23,270?ppm?×?min (32,345?mg?×?min/m³). PH₃ exposure affects both pulmonary and cardiac function. Unlike typical pulmonary toxicants, PH₃ induced net increases in respiration during exposure. Gross observations of the heart and lungs of exposed rats suggested pulmonary and cardiac tissue damage, but histopathological examination showed little to no observable pathologic changes in those organs. Gene expression studies indicated alterations in inflammatory processes, metabolic function and cell signaling, with particular focus in cardiac tissue. Transmission electron microscopy examination of cardiac tissue revealed ultrastructural damage to both tissue and mitochondria. Altogether, these data reveal that in untreated, un-anesthetized rats, PH₃ inhalation induces acute cardiorespiratory toxicity and injury, leading to death and that it is characterized by a steep dose-response curve. Continued use of our interdisciplinary approach will permit more effective identification of therapeutic windows and development of rational medical countermeasures and countermeasure strategies.     

Characterization of 10 polymorphic microsatellite loci for White-breasted mesites (Mesitornis variegata)

We characterized 10 specific microsatellite loci for White-breasted mesites (Mesitornis variegata), an endemic bird species from western Madagascar. Nine loci were in Hardy–Weinberg equilibrium, and we detected 4–10 alleles per locus (mean = 6.1). These primers will be used to study the mating system and social organization of White-breasted mesites and may have applications for the conservation of the few remaining populations of this vulnerable and still poorly studied species.     

Sexuality among Spanish adults with diabetes: A population-based case control study

ObjectivesTo describe and compare sexuality between subjects with diabetes with matched non-diabetic controls.MethodsPopulation based case control study using individual data from the Spanish National Sexual Health Survey. Diabetes status was self reported, we selected type 2 patients. We identified 461 diabetes sufferers. Two controls were matched by age, sex and sexual partner for each diabetic case.Sexuality measures included: sexual activity, importance of sex, satisfaction with partner, bothersome with one's sexual life and self-rated sexual health. Independent variables included: socio-demographics, physical health, chronic diseases and medications use.ResultsNo differences were found in “Sexually activity”, “Importance of sex” or “Bothersome” between those with and without diabetes. Dissatisfaction with partner was 25% in women with diabetes and 12.9% in non-diabetic controls (Adjusted-OR 1.82 95%CI 1.02–4.85).Diabetes sufferers reported sexual health as “fair/poor/very poor” more than their non-diabetic control, 58.1% vs. 45.1% for women (Adjusted-OR 1.74 95%CI 1.15–2.63) and 54.3% vs. 38% for men (Adjusted-OR 1.88 95%CI 1.29–2.75).Among diabetes sufferers “fair/poor/very poor” sexual health was associated with poorer physical health, not having a sexual partner and among men taking heart medications.ConclusionsWomen and men with diabetes have significantly worse sexuality measures than non diabetic controls.     

Incidence of urinary tract infection among patients with type 2 diabetes in the UK General Practice Research Database (GPRD)

The objective of this observational study was to quantify the incidence of urinary tract infections (UTI) among diabetes patients and compare this risk to patients without diabetes. Type 2 diabetes patients and a matched sample of patients without diabetes were identified from GPRD. Patients were followed for 1-year from their study index date until the first record of a UTI or a censored event. The incidence of UTI was 46.9 per 1000 person-years (95% confidence interval (CI) 45.8–48.1) among diabetes patients and 29.9 (95% CI 28.9–30.8) for patients without diabetes. Compared to the non-diabetes patients, the risk of UTI was 1.53 (95% CI 1.46–1.59) for all diabetes patients; and 2.08 (95% CI 1.93–2.24) for patients with previously diagnosed diabetes. In general practice, across gender and age, the risk of developing a UTI is higher for patients with type 2 diabetes compared to patients without diabetes.     

Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high‐performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR‐iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK‐EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter‐ and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR‐iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376‐383, 2012. © 2012 Wiley Periodicals, Inc.     

Prognostic impact of PD-1 and its ligands in renal cell carcinoma

Programmed death-1 receptor (PD-1) and programmed death-1 receptor-ligand (PD-L1) have been suggested to play a role as prognostic markers in clear cell renal cell carcinoma (ccRCC). The association between PD-L1 and prognosis seems to be more robust than for PD-1. Further, preliminary analyses suggest that neither PD-1 nor its ligands play a role as prognostic markers in non-clear cell RCC, while the prognostic role of PD-L2 in ccRCC as well as in non-clear cell RCC remains unclear.     

Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency.