Citations

Abstract The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

Abstract Background Long-term mortality after primary THA is lower than in the general population, but it is unknown whether this is also true after revision THA. Questions/Purposes We examined (1) long-term mortality according to reasons for revision after revision THA, and (2) relative mortality trends by age at surgery, years since surgery, and calendar year of surgery. Methods This retrospective study included 5417 revision THAs performed in 4532 patients at a tertiary center between 1969 and 2011. Revision THAs were grouped by surgical indication in three categories: periprosthetic joint infections (938; 17%); fractures (646; 12%); and loosening, bearing wear, or dislocation (3833; 71%). Patients were followed up until death or December 31, 2016. The observed number of deaths in the revision THA cohort was compared with the expected number of deaths using standardized mortality ratios (SMRs) and Poisson regression models. The expected number of deaths was calculated assuming that the study cohort had the same calendar year, age, and sex-specific mortality rates as the United States general population. Results The overall age- and sex-adjusted mortality was slightly higher than the general population mortality (SMR, 1.09; 95% CI, 1.05-1.13; p < 0.001). There were significant differences across the three surgical indication subgroups. Compared with the general population mortality, patients who underwent revision THA for infection (SMR, 1.35; 95% CI, 1.24-1.48; p < 0.001) and fractures (SMR, 1.23; 95% CI, 1.11-1.37; p < 0.001) had significantly increased risk of death. Patients who underwent revision THA for aseptic loosening, wear, or dislocation had a mortality risk similar to that of the general population (SMR, 1.01; 95% CI, 0.96-1.06; p = 0.647). The relative mortality risk was highest in younger patients and declined with increasing age at surgery. Although the relative mortality risk among patients with aseptic indications was lower than that of the general population during the first year of surgery, the risk increased with time and got worse than that of the general population after approximately 8 to 10 years after surgery. Relative mortality risk improved with time after revision THA for aseptic loosening, wear, or dislocation. Conclusions Shifting mortality patterns several years after surgery and the excess mortality after revision THA for periprosthetic joint infections and fractures reinforce the need for long-term followup, not only for implant survival but overall health of patients having THA. Level of Evidence Level III, therapeutic study

Background: The US Food and Drug Administration approved the use of sacubitril/valsartan in patients with heart failure with reduced ejection fraction in July 2015. We aimed to assess the adoption and prescription drug costs of sacubitril/valsartan in its first 18 months after Food and Drug Administration approval. Methods and Results: Using a large US insurance database, we identified privately insured and Medicare Advantage beneficiaries who filled a first prescription for sacubitril/valsartan between July 1, 2015, and December 31, 2016. We compared them to patients treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Outcomes included adoption, prescription drug costs, and 180-day adherence, defined as a proportion of days covered ≥80%. A total of 2244 patients initiated sacubitril/valsartan. Although the number of users increased over time, the proportion of heart failure with reduced ejection fraction patients taking sacubitril/valsartan remained low (<3%). Patients prescribed sacubitril/valsartan were younger, more often male, with less comorbidity than those taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Although a majority of prescription costs were covered by the health plan (mean, $328.37; median, $362.44 per 30-day prescription), out-of-pocket costs were still high (mean, $71.16; median, $40.27). By comparison, median out-of-pocket costs were $2 to $3 for lisinopril, losartan, carvedilol, and spironolactone. Overall, 59.1% of patients were adherent to sacubitril/valsartan. Refill patterns suggested that nearly half of nonadherent patients discontinued sacubitril/valsartan within 180 days of starting. Conclusions: Adoption of sacubitril/valsartan after Food and Drug Administration approval has been slow and may be associated with the high cost.

In carbon tetrachloride-induced liver cirrhosis, diminution of hepatic endothelial nitric oxide synthase (eNOS) activity may contribute to impaired hepatic vasodilation and portal hypertension. The mechanisms responsible for these events remain unknown; however, a role for the NOS-associated proteins caveolin and calmodulin has been postulated. The purpose of this study is to characterize the expression and cellular localization of the NOS inhibitory protein caveolin-1 in normal rat liver and to then examine the role of caveolin in conjunction with calmodulin in regulation of NOS activity in cholestatic portal hypertension. In normal liver, caveolin protein is expressed preferentially in nonparenchymal cells compared with hepatocytes as assessed by Western blot analysis of isolated cell preparations. Additionally, within the nonparenchymal cell populations, caveolin expression is detected within both liver endothelial cells and hepatic stellate cells. Next, studies were performed 4 wk after bile duct ligation (BDL), a model of portal hypertension characterized by prominent cholestasis, as evidenced by a significant increase in serum cholesterol in BDL animals. After BDL, caveolin protein levels from detergent-soluble liver lysates are significantly increased as assessed by Western blot analysis. Immunoperoxidase staining demonstrates that this increase is most prominent within sinusoids and venules. Additionally, caveolin-1 upregulation is associated with a significant reduction in NOS catalytic activity in BDL liver lysates, an event that is corrected with provision of excess calmodulin, a protein that competitively binds eNOS from caveolin. We conclude that, in cholestatic portal hypertension, caveolin may negatively regulate NOS activity in a manner that is reversible by excess calmodulin.