Do Patient Point of Entry and Medicaid Status Affect Quality Outcomes Following Total Knee Arthroplasty?

BACKGROUND: The effect of surgeon practice and patient care setting have not been studied in the Medicaid population undergoing total knee arthroplasty (TKA). This study aims to evaluate whether point of entry and Medicaid status affect outcomes following TKA. METHODS: The electronic medical record at our urban, academic, tertiary care hospital system was retrospectively reviewed for all primary, unilateral TKA during January 2016 and January 2018. Outpatient visits within the 6-month preoperative period categorized TKA recipients as either Hospital Ambulatory Clinic Centers patients with Medicaid insurance or private office patients with non-Medicaid insurers. RESULTS: There were 174 Medicaid patients and 317 non-Medicaid patients for 491 total patients. Medicaid patients were significantly younger (62.6 ± 1.6 vs 65.4 ± 1.1 years, P < .01), of "other' ethnicity (43.1% vs 25.6%, P < .01), and to be a current smoker (9.3% vs 6.6%, P = .02). There was no difference in gender, body mass index, and American Society of Anesthesiologists score. After controlling for patient factors, the Medicaid effect was insignificant for surgical time (exponentiated ß 0.93, 95% confidence interval [CI] 0.86-1.01, P = .076) and facility discharge (odds ratio 1.58, 95% CI 0.71-3.51, P = .262). Medicaid status had a significant effect on length of stay (LOS) (rate ratio 1.21, 95% CI 1.02-1.43, P = .026). CONCLUSION: Multivariable analysis controlling for patient factors demonstrated that Medicaid coverage had minimal effect on surgical time and facility discharge. Medicaid patients had significantly longer LOS by one-half day. These results indicate that comparable outcomes can be achieved for Medicaid patients following TKA provided that the surgeon and care setting are similar. However, increased care coordination and preoperative education may be necessary to normalize disparities in hospital LOS. LEVEL OF EVIDENCE: III, retrospective observational analysis.

Intracellular antiviral activity of low-dose ritonavir in boosted protease inhibitor regimens.

Protease inhibitors are largely used for the treatment of HIV infection in combination with other antiretroviral drugs. Their improved pharmacokinetic profiles can be achieved through the concomitant administration of low doses of ritonavir (RTV), a protease inhibitor currently used as a booster, increasing the exposure of companion drugs. Since ritonavir-boosted regimens are associated with long-term adverse events, cobicistat, a CYP3A4 inhibitor without antiviral activity, has been developed. Recently, high intracellular concentrations of ritonavir in lymphocytes and monocytes were reported even when ritonavir was administered at low doses, so we aimed to compare its theoretical antiviral activity with those of the associated protease inhibitors. Intracellular concentrations of ritonavir and different protease inhibitors were determined through the same method. Inhibitory constants were obtained from the literature. The study enrolled 103 patients receiving different boosted protease inhibitors, darunavir-ritonavir 600 and 100 mg twice daily and 800 and 100 mg once daily (n = 22 and 4, respectively), atazanavir-ritonavir 300 and 100 mg once daily (n = 40), lopinavir-ritonavir 400 and 100 mg twice daily (n = 21), or tipranavir-ritonavir 500 and 200 mg twice daily (n = 16). According to the observed concentrations, we calculated the ratios between the intracellular concentrations of ritonavir and those of the companion protease inhibitor and between the theoretical viral protease reaction speeds with each drug, with and without ritonavir. The median ratios were 4.04 and 0.63 for darunavir-ritonavir twice daily, 2.49 and 0.74 for darunavir-ritonavir once daily, 0.42 and 0.74 for atazanavir-ritonavir, 0.57 and 0.95 for lopinavir-ritonavir, and 0.19 and 0.84 for tipranavir-ritonavir, respectively. Therefore, the antiviral effect of ritonavir was less than that of the concomitant protease inhibitors but, importantly, mostly with darunavir. Thus, further in vitro and in vivo studies of the RTV antiviral effect are warranted.

Effective Interventions for Improving Functional Movement Screen Scores Among "High-Risk" Athletes: A Systematic Review.

BACKGROUND: The Functional Movement ScreenTM (FMSTM) is a tool designed to screen a series of movements that aids in the identification of compensatory fundamental movement patterns, functional limitations, and asymmetrical movement patterns. A previous systematic review and meta-analysis has shown that athletes with an FMSTM score <13-14 are considered "high-risk" and are more likely to be injured. There are discrepancies regarding the efficacy of physical intervention programs in improving FMSTM scores. PURPOSE: The aim of this systematic review was to assess the role of physical intervention programs in increasing functional movement in "high-risk" athletes as measured by the FMSTM. STUDY DESIGN: Systematic Review. METHODS: A computerized search was performed in 2019 according to PRISMA guidelines searching Embase, Science Direct, Ovid, and PubMed. The studies were assessed for quality and risk of bias using the Modified Downs and Black checklist. Participant demographics, intervention routines, and FMSTM scores were extracted from the included studies. RESULTS: Six studies met the inclusion criteria and demonstrated a fair methodological quality. Comparisons across all studies revealed significant improvement in FMSTM scores following implementation of a variety of physical intervention programs. These programs included those that utilized functional training, foot muscle strengthening, Pilates, core stability training, and resistance movements. Despite variations in the corrective exercises performed, the number of training sessions, and the length of the intervention program, all studies demonstrated an increase in the total FMSTM score following program implementation. CONCLUSION: The included intervention programs significantly improved total FMSTM scores in "high-risk" athletes. Despite variations in the corrective exercises (interventions) performed, the number of training sessions, and the length of the program, all studies demonstrated a significant increase in the total FMSTM score following program implementation.

Use of the United States Medical Licensing Examination Step-1 Score as a Screening Tool for Orthopaedic Surgery Away Rotations.

BACKGROUND: Orthopaedic surgery has become an increasingly competitive specialty for medical students applying to residency. Aside from residency interviews, away rotations are one of the only opportunities for residency programs to qualitatively evaluate an applicant. The purpose of this study was to determine if residency program directors (PDs) use a minimum United States Medical Licensing Examination (USMLE) Step-1 score as a screening tool for students applying for away rotations at their institution. METHODS: An anonymous 12-question survey about residency selection criteria and which criteria are used to select applicants for away rotations was distributed to PDs at U.S. allopathic orthopaedic surgery residency programs who are members of the Council of Orthopaedic Residency Directors (CORD). Questions included information on minimum USMLE Step-1 scores, the number of students who complete away rotations at the program each year, and how applicants are selected for rotations. RESULTS: Survey responses were received from 87 (58%) of 149 PDs. Seventy-one (82%) of these PDs reported that their program uses a minimum Step-1 score for residency applications, with the most common cutoff score being between 231 and 240 (as answered by 33 [46%] of 72 PDs). Twenty-seven (31%) of 87 PDs reported that if a student does not meet their residency minimum Step-1 score, he or she is not offered the opportunity to rotate at the program. Eleven (25%) of 44 PDs reported that they do not inform students when their score is below the program's minimum. CONCLUSIONS: A substantial proportion of orthopaedic surgery residency PDs use the USMLE Step-1 score as a screening tool for students interested in doing away rotations at their programs. If a student's Step-1 score does not meet the program's minimum, the majority of programs still will allow the student to rotate at their institution. Students should take this information into account when selecting away rotations in order to maximize their chances of matching into an orthopaedic surgery program.

Collapsing glomerulopathy in a child with LCHAD deficiency: a rare association.

Metabolic disorders, although rare, can involve multiple organ systems and have a varied presentation. Renal involvement has been reported in several metabolic disorders in the pediatric age group. We report a rare metabolic disorder, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, in a child who developed steroid-resistant nephrotic syndrome at the age of 5 years. Renal biopsy showed features of collapsing glomerulopathy. The child had progressive chronic kidney disease. Alternative immunosuppressants including tacrolimus failed to show any clinical improvement. There have been no reports of children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency developing steroid-resistant nephrotic syndrome and collapsing glomerulopathy. This case highlights the need to monitor renal function and proteinuria among this group of children.

UPLC-MS/MS method with automated on-line SPE for the isomer-specific quantification of the first-generation anti-HCV protease inhibitors in peripheral blood mononuclear cells.

HCV infection affects over 170 million people worldwide. The current standard for treatment of genotype 1 infection is the association of the first generation protease inhibitors boceprevir or telaprevir to ribavirin and peginterferon α. Although the response rate has been improved with these new drugs, some pharmacokinetic/pharmacodinamic issues emerged in the past years. To date, some analytical methods are available for the quantification of these drugs in plasma; however, the real active concentrations of the two drugs are those in hepatocytes. Being the withdrawal of hepatocytes too invasive, in this work we aimed to develop and validate a chromatographic method coupled with tandem mass spectrometry capable of quantifying boceprevir and telaprevir isomers in peripheral blood mononuclear cells, used as an "in-vivo" cellular model of compartmentalization. The method used an on-line solid phase extraction protocol based on the new OSM(®) platform and was fully validated following FDA guidelines. This method showed mean intra- and inter-day inaccuracy and imprecision both lower than 15%, high and stable recovery and contained matrix effect, with a run time of 6min, comprehensive of SPE extraction. The method was then applied on 35 real samples from patients treated with boceprevir or telaprevir, with good analytical performances, thus assessing its eligibility for a possible future routine use. Peculiar pharmacokinetic data have been observed, suggesting the usefulness of investigating intracellular pharmacokinetics of these drugs. Further studies will be required to test the correlation of intracellular concentrations with effectiveness and toxicity of triple therapy.

Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics.

Boceprevir (BOC) is a directly-acting antiviral agent for the treatment of hepatitis C virus genotype 1 (HCV-1) infection. It is a mixture of two stereoisomers, the inactive R and the active S isomers. No data have previously been published on BOC intracellular accumulation. In this study, BOC isomer concentrations in peripheral blood mononuclear cells (PBMCs) and plasma were determined. The influence of various single nucleotide polymorphisms (SNPs) on plasma and intracellular drug exposure at Week 4 of triple therapy were also evaluated. Plasma and intracellular BOC concentrations were determined at the end of the dosing interval (C(trough)) using a UPLC-MS/MS validated method. Allelic discrimination was performed through real-time PCR. Median plasma concentrations were 65.97 ng/mL for the S isomer and 36.31 ng/mL for the R isomer; the median S/R plasma concentration ratio was 1.66. The median PBMC concentration was 2285.88 ng/mL for the S isomer; the R isomer was undetectable within PBMCs. The median S isomer PBMC/plasma concentration ratio was 28.59. A significant positive correlation was found between plasma and PBMC S isomer concentrations. ABCB1 1236, SLC28A2 124 and IL28B rs12979860 SNPs were associated with the S isomer PBMC/plasma concentration ratio. In regression models, S isomer plasma levels and FokI polymorphism were able to predict S isomer intracellular exposure, whereas SNPs in AKR1, BCRP1 and SLC28A2 predicted the S isomer PBMC/plasma concentration ratio. No similar data regarding BOC pharmacogenetics and pharmacokinetics have been published previously. This study adds a novel and useful overview of the pharmacological properties of this drug.

Telaprevir-S isomer enhances ribavirin exposure and the ribavirin-related haemolytic anaemia in a concentration-dependent manner.

The standard-of-care for the treatment of genotype-1 chronic hepatitis C is based on the combination of direct acting antivirals, such as boceprevir and telaprevir, with ribavirin and pegylated-interferon alfa. These triple regimens give a higher response rate than dual therapy, but on the other hand show a more than 10% higher rate of anaemia. Not enough focus has been given to the interaction between telaprevir and RBV. In this work, we aimed to study and deepen this relationship by comparing ribavirin plasma and intra-erythrocytic concentrations at one month of triple and dual therapy (17 vs. 119 patients). Moreover, we determined telaprevir isomers concentrations and tested them for correlation with ribavirin concentrations and haemoglobin loss at one month of treatment. Finally, all drugs concentration data were tested for their correlation with the renal function during treatment. The comparisons of ribavirin concentration and toxicity data were repeated on a sub-group of 9 patients who had been treated 1 year before with dual therapy and then re-treated with triple therapy. The observed ribavirin plasma and intra-erythrocytic concentrations in triple therapy were significantly higher compared to dual therapy, both in whole group and sub-group comparison. Ribavirin concentrations were significantly correlated to the haemoglobin loss and telaprevir-S isomer concentrations (r(2)=0.317 P(value)=0.023 and r(2)=0.388 P(value)=0.008, respectively). Renal function had a significant decrease from the baseline value, but was not significantly correlated with drugs concentrations. These results highlight for the first time that, in the context of triple therapy with telaprevir, ribavirin exposure is related to the telaprevir-S isomer plasma concentration. We conclude that the addition of telaprevir to the dual therapy increases ribavirin exposure and haemoglobin loss: this effect could probably be managed through the therapeutic drug monitoring of ribavirin and telaprevir-S concentrations.