A Case of Neonatal Monkeypox Treated With Oral Tecovirimat.

Since the Monkeypox virus outbreak erupted in May 2022, infection has been reported across all ages. Few cases exist in the medical literature about Monkeypox infection in neonates, and little is known about its clinical manifestations, disease course, or side effects of available antiviral agents in this age group. In this report, we describe the case of a 10-day-old neonate from the southern United States who presented with fevers and generalized papulopustular rash. She was treated empirically as a febrile neonate but mpox infection was suspected early because of the characteristic exanthem and its similarity to her mother's rash that she had developed a few days before the patient's presentation. Oral tecovirimat was initiated on the third day of admission and mpox was later confirmed by polymerase chain reaction analysis. The patient tolerated oral tecovirimat well and experienced a favorable outcome without lasting effects of infection.

Separate But Not Equal? A Cross-Sectional Study of Segregation by Payor Mix in Academic Primary Care Clinics.

BACKGROUND: At some US Academic Health Centers (AHCs), patients with predominantly Medicaid insurance are seen in one clinic and patients with other insurance are seen in another. The extent of this practice and implications are unknown. OBJECTIVE: To estimate the proportion of AHCs that have at least two primary care internal medicine clinics that differ substantially in proportion of patients with Medicaid and to compare patient demographic, staffing, and operational features. PARTICIPANTS: General internal medicine chiefs and clinic directors at 40 randomly selected US AHCs plus the top 10 AHCs in terms of NIH funding. MAIN MEASURE: An AHC was classified as maintaining clinics that differed substantially in the proportion of patients with Medicaid if any two differed by ≥ 40% (absolute). Other criteria were used for pre-specified secondary analyses (e.g., ≥ 30%). KEY RESULTS: Thirty-nine of 50 AHCs (78%) participated. Four of 39 (10%; 95% CI, 3 to 24%) had two clinics differing by ≥ 40% in the proportion of patients with Medicaid, eight (21%; 95% CI, 9 to 36%) had clinics differing by ≥ 30%, and 15 (38%; 95% CI, 23 to 55%) had clinics differing by ≥ 20%. Clinics with more patients with Medicaid by any of the three criteria were more likely to employ resident physicians as providers of longitudinal care (with faculty supervision) and more likely to have patients who were Black or Hispanic. CONCLUSIONS: Some US AHCs maintain separate clinics defined by the proportion of patients with Medicaid. Clinics with a higher proportion of patients insured by Medicaid are more likely to employ residents (with faculty oversight), feature residents as providers of longitudinal care, and serve patients who are Black and Hispanic. Further research is needed to understand why some AHCs have primary care clinics distinguishable by insurance mix with the goal of ensuring that racism and discrimination are not root causes.

Combining SJ733, an oral ATP4 inhibitor of Plasmodium falciparum, with the pharmacokinetic enhancer cobicistat: An innovative approach in antimalarial drug development.

BACKGROUND: SJ733, a newly developed inhibitor of P. falciparum ATP4, has a favorable safety profile and rapid antiparasitic effect but insufficient duration to deliver a single-dose cure of malaria. We investigated the safety, tolerability, and pharmacokinetics of a multidose SJ733 regimen and a single-dose pharmacoboost approach using cobicistat to inhibit CYP3A4, thereby increasing exposure. METHODS: Two multidose unboosted cohorts (n = 9) (SJ733, 300 mg and 600 mg daily for 3 days) followed by three single-dose boosted cohorts combining SJ733 (n = 18) (75-, 300-, or 600-mg single dose) with cobicistat (150-mg single dose) as a pharmacokinetic booster were evaluated in healthy volunteers (ClinicalTrials.gov: NCT02661373). FINDINGS: All participants tolerated SJ733 well, with no serious adverse events (AEs), dose-limiting toxicity, or clinically significant electrocardiogram or laboratory test findings. All reported AEs were Grade 1, clinically insignificant, and considered unlikely or unrelated to SJ733. Compared to unboosted cohorts, the SJ733/cobicistat-boosted cohorts showed a median increase in area under the curve and maximum concentration of 3·9 × and 2·6 ×, respectively, and a median decrease in the ratio of the major CYP3A-produced metabolite SJ506 to parent drug of 4·6 × . Incorporating these data in a model of parasite dynamics indicated that a 3-day regimen of SJ733/cobicistat (600 mg/150 mg daily) relative to a single 600-mg dose ± cobicistat would increase parasite clearance from 106 to 1012 parasites/µL. INTERPRETATION: The multidose and pharmacoboosted approaches to delivering SJ733 were well-tolerated and significantly increased drug exposure and prediction of cure. This study supports the further development of SJ733 and demonstrates an innovative pharmacoboost approach for an antimalarial. FUNDING: Global Health Innovative Technology Fund, Medicines for Malaria Venture, National Institutes of Health, and American Lebanese Syrian Associated Charities.

Relationship Between Standardized Test Scores and Board Certification Exams in a Combined Internal Medicine/Pediatrics Residency Program.

Background Combined Internal Medicine/Pediatrics (Med/Peds) residencies rely on categorical program data to predict pass rates for the American Board of Internal Medicine Certifying Exam (ABIM-CE) and the American Board of Pediatrics Certifying Exam (ABP-CE). There is insufficient literature describing what best predicts a Med/Peds resident passing board exams. In this study, we aimed to determine how standardized test scores predict performance on ABIM-CE and ABP-CE for Med/Peds residents. Methodology We analyzed prior exam scores for 91/96 (95%) residents in a Med/Peds program from 2008 to 2017. Scores from the United States Medical Licensing Examination (USMLE) Steps 1 and 2 Clinical Knowledge (CK) and In-Training Exams in Internal Medicine (ITE-IM) and Pediatrics (ITE-P) were analyzed with the corresponding ABIM-CE and ABP-CE first-time scores. Linear and logistic regression were applied to predict board scores/passage. Results USMLE 1 and 2 CK, ITE-IM, and ITE-P scores had a linear relationship with both ABIM-CE and ABP-CE scores. In the linear regression, adjusted R2 values showed low-to-moderate predictive ability (R2 = 0.11-0.35), with the highest predictor of ABIM-CE and ABP-CE being USMLE Step 1 (0.35) and Postgraduate Year 1 (PGY-1) ITE-IM (0.33), respectively. Logistic regression showed odds ratios of passing board certifications ranging from 1.05 to 1.53 per point increase on the prior exam score. The PGY-3 ITE-IM was the best predictor of passing both certifying exams. Conclusions In one Med/Peds program, USMLE Steps 1 and 2 and all ITE-IM and ITE-P scores predicted certifying exam scores and passage. This provides Med/Peds-specific data to allow individualized resident counseling and guide programmatic improvements targeted to board performance.

Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial.

BACKGROUND: (+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans. METHODS: The phase 1a was a single-centre, dose-escalation, first-in-human study of SJ733 allowing modifications to dose increments and dose-cohort size on the basis of safety and pharmacokinetic results. The phase 1a took place at St Jude Children's Research Hospital and at the University of Tennessee Clinical Research Center (Memphis, TN, USA). Enrolment in more than one non-consecutive dose cohort was allowed with at least 14 days required between doses. Participants were fasted in seven dose cohorts and fed in one 600 mg dose cohort. Single ascending doses of SJ733 (75, 150, 300, 600, 900, or 1200 mg) were administered to participants, who were followed up for 14 days after SJ733 dosing. Phase 1a primary endpoints were safety, tolerability, and pharmacokinetics of SJ733, and identification of an SJ733 dose to test in the induced blood-stage malaria model. The phase 1b was a single-centre, open-label, volunteer infection study using the induced blood-stage malaria model in which fasted participants were intravenously infected with blood-stage P falciparum and subsequently treated with a single dose of SJ733. Phase 1b took place at Q-Pharm (Herston, QLD, Australia) and was initiated only after phase 1a showed that exposure exceeding the threshold minimum exposure could be safely achieved in humans. Participants were inoculated on day 0 with P falciparum-infected human erythrocytes (around 2800 parasites in the 150 mg dose cohort and around 2300 parasites in the 600 mg dose cohort), and parasitaemia was monitored before malaria inoculation, after inoculation, immediately before SJ733 dosing, and then post-dose. Participants were treated with SJ733 within 24 h of reaching 5000 parasites per mL or at a clinical score higher than 6. Phase 1b primary endpoints were calculation of a parasite reduction ratio (PRR48) and parasite clearance half-life, and safety and tolerability of SJ733 (incidence, severity, and drug-relatedness of adverse events). In both phases of the trial, SJ733 hydrochloride salt was formulated as a powder blend in capsules containing 75 mg or 300 mg for oral administration. Healthy men and women (of non-childbearing potential) aged 18-55 years were eligible for both studies. Both studies are registered with ClinicalTrials.gov (NCT02661373 for the phase 1a and NCT02867059 for the phase 1b). FINDINGS: In the phase 1a, 23 healthy participants were enrolled and received one to three non-consecutive doses of SJ733 between March 14 and Dec 7, 2016. SJ733 was safe and well tolerated at all doses and in fasted and fed conditions. 119 adverse events were recorded: 54 (45%) were unrelated, 63 (53%) unlikely to be related, and two (2%) possibly related to SJ733. In the phase 1b, 17 malaria-naive, healthy participants were enrolled. Seven participants in the 150 mg dose cohort were inoculated and dosed with SJ733. Eight participants in the 600 mg dose cohort were inoculated, but two participants could not be dosed with SJ733. Two additional participants were subsequently inoculated and dosed with SJ733. SJ733 exposure increased proportional to the dose through to the 600 mg dose, then was saturable at higher doses. Fasted participants receiving 600 mg exceeded the target area under the concentration curve extrapolated to infinity (AUC0-∞) of 13 000 µg × h/L (median AUC0-∞ 24 283 [IQR 16 135-31 311] µg × h/L, median terminal half-life 17·4 h [IQR 16·1-24·0], and median timepoint at which peak plasma concentration is reached 1·0 h [0·6-1·3]), and this dose was tested in the phase 1b. All 15 participants dosed with SJ733 had at least one adverse event. Of the 172 adverse events recorded, 128 (74%) were mild. The only adverse event attributed to SJ733 was mild bilateral foot paraesthesia that lasted 3·75 h and resolved spontaneously. The most common adverse events were related to malaria. Based on parasite clearance half-life, the derived log10PRR48 and corresponding parasite clearance half-lives were 2·2 (95% CI 2·0-2·5) and 6·47 h (95% CI 5·88-7·18) for 150 mg, and 4·1 (3·7-4·4) and 3·56 h (3·29-3·88) for 600 mg. INTERPRETATION: The favourable pharmacokinetic, tolerability, and safety profile of SJ733, and rapid antiparasitic effect support its development as a fast-acting component of combination antimalarial therapy. FUNDING: Global Health Innovative Technology Fund, Medicines for Malaria Venture, and the American Lebanese Syrian Associated Charities.

HIV Health Care Transition Readiness: Embracing the Opportunity and Challenge.

Because of effective treatment and prolonged survival, thousands of young adult people living with HIV will need to transfer their health care to adult care providers. However, many lack basic essential skills and are not prepared for this transition. Many providers do not assess transition readiness on a regular basis. Validated transition readiness assessment tools can help providers guide interventions based on identified skill and knowledge deficits. Our purpose was to describe the impact of incorporating a validated Transition Readiness Assessment Questionnaire (TRAQ) into clinical practice. A retrospective chart review of 48 patients with HIV, ages 22-24 years, showed that the use of the TRAQ significantly affected provider interventions in the area of medication management (odds ratio: 0.02). Overall, the use of the TRAQ did not increase clinical interventions; however, it enabled providers to identify knowledge or skill deficits not previously addressed and to plan future clinical interventions to meet individual patient needs.