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Reports on the need for updated regulations for government approval of in vitro diagnostic devices. The two ways medical devices are marketed; The role of the United States Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) in ensuring medical devices are effective; Reasons why the FDA has problems in this area; Difficulty in monitoring all devices.

Competing Interests: Disclosure. The author declares no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The author is board certified in general pediatrics and neurodevelopmental disabilities. His clinical practice has been devoted exclusively to children with medical complexity in a pediatric outpatient complex care program since 2011 and a pediatric long-term care facility since 1999.

Background: The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high absolute neutrophil count [ANC], and low platelet count at baseline) benefited most from treatment with the antiviral remdesivir. It is unknown which patient characteristics are associated with benefit from treatment with the immunomodulator baricitinib., Objective: To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile., Design: Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04401579)., Setting: Sixty-seven trial sites in 8 countries., Participants: Adults hospitalized with COVID-19 ( n = 999; 85% U.S. participants)., Intervention: Baricitinib+remdesivir versus placebo+remdesivir., Measurements: Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories., Results: In the high-risk quartile, baricitinib+remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P = 0.020), decreased progression to IMV or death (HR, 0.57 [CI, 0.35 to 0.93]; P = 0.024), and improved recovery rate (HR, 1.53 [CI, 1.16 to 2.02]; P = 0.002) compared with placebo+remdesivir. After 5 days, participants receiving baricitinib+remdesivir had significantly larger increases in ALC and significantly larger decreases in ANC compared with control participants, with the largest effects observed in the high-risk quartile., Limitation: Secondary analysis of data collected before circulation of current SARS-CoV-2 variants., Conclusion: The ACTT risk profile identifies a subgroup of hospitalized patients who benefit most from baricitinib treatment and captures a patient phenotype of treatment response to an immunomodulator and an antiviral. Changes in ALC and ANC trajectory suggest a mechanism whereby an immunomodulator limits severe COVID-19., Primary Funding Source: National Institute of Allergy and Infectious Diseases., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2593.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined., Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots., Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets., Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease., Competing Interests: Potential conflicts of interest. N. J. reports salary support to his institution by Sagent Pharmaceuticals. D. I. has received clinical trial funding paid to her institution from Gilead Sciences. M. K. J. has received grant funding paid to her institution from Gilead Sciences. R. A. M. has received grants and research funding to his institution from Gilead Sciences, Pfizer, Sanofi, and GlaxoSmithKline (GSK). A. R. B. has received grant funding to her institution from Pfizer, Merck, and Cynavac, and has consulted for Janssen and GSK. A. L. has received research grant support to her institution from Gilead. R. G. has received research funding from Gilead Sciences and GSK. W. R. S. has received clinical trial funding paid to his institution from Gilead Sciences. C. A. B. has received contracts and grants to her institution from Gilead Sciences. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

We performed anorectal testing in 18 cis-gender men who have sex with men with symptoms consistent with mpox virus (MPXV) infection. We found rectal MPXV DNA in 9/9 with and 7/9 without proctitis. Future study of anorectal testing is needed and may inform the diagnosis and pathogenesis of MPXV disease., Competing Interests: Potential conflicts of interest. P. F. R. reports grants or contracts from Merck, Finch, Summit, Artugen, Armata, Contrafect, and Janssen. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear., Objective: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial)., Design: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4])., Setting: 94 hospitals in 10 countries (86% U.S. participants)., Participants: Adults hospitalized with COVID-19., Intervention: SOC., Measurements: 28-day mortality and recovery., Results: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages., Limitation: Unmeasured confounding., Conclusion: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas., Primary Funding Source: National Institute of Allergy and Infectious Diseases.

Background: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19., Methods: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168., Findings: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012)., Interpretation: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered., Funding: National Institute of Allergy and Infectious Diseases., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the phase 3 BRIGHTE study in heavily treatment-experienced adults with multidrug-resistant HIV-1, fostemsavir plus optimized background therapy (OBT) resulted in sustained rates of virologic suppression through 96 weeks. HIV-1 RNA <40 copies/mL was achieved in 163/272 (60%) Randomized Cohort (RC) participants (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants (with 0 fully active antiretrovirals). Here we report genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC participants who met protocol-defined virologic failure (PDVF) criteria through Week 96. The incidence of PDVF was as expected in this difficult-to-treat patient population and, among RC participants, was comparable regardless of the presence of predefined gp120 amino acid substitutions that potentially influence phenotypic susceptibility to temsavir (S375H/I/M/N/T, M426L, M434I, M475I) or baseline temsavir 50% inhibitory concentration fold change (IC 50 FC). The incidence of PDVF was lower among participants with higher overall susceptibility score to newly used antiretrovirals (OSS-new), indicating that OSS-new may be a preferred predictor of virologic outcome in heavily treatment-experienced individuals. Predefined gp120 substitutions, most commonly M426L or S375N, were emergent on treatment in 24/50 (48%) RC and 33/44 (75%) NRC participants with PDVF, with related increases in temsavir IC 50 FC. In BRIGHTE, PDVF was not consistently associated with treatment-emergent genotypic or phenotypic changes in susceptibility to temsavir or to antiretrovirals in the initial OBT. Further research will be needed to identify which factors are most likely to contribute to virologic failure in this heavily treatment-experienced population (ClinicalTrials.gov, NCT02362503).

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Heavily treatment-experienced (HTE) people living with HIV-1 (PLWH) have limited viable antiretroviral regimens available because of multidrug resistance and safety concerns. The first-in-class HIV-1 attachment inhibitor fostemsavir demonstrated efficacy and safety in HTE participants in the ongoing phase III BRIGHTE trial., Objectives: We describe patient-reported outcomes (PROs) through week 48., Methods: Eligible participants for whom their current regimen was failing were assigned to the randomized cohort (RC; one to two fully active agents remaining) or the nonrandomized cohort (NRC; no fully active agents remaining). PRO assessments included the EQ-5D-3L, EQ-VAS, and Functional Assessment of HIV Infection (FAHI) instruments., Results: Both cohorts achieved increases in EQ-5D-3L US- and UK-referenced utility score from baseline at week 24. Mean visual analog scale (VAS) scores in the RC and NRC increased from baseline by 8.7 (95% CI 6.2-11.2) and 5.6 points (95% CI 1.5-9.7) at week 24 and increased from baseline by 9.8 (95% CI 7.0-12.6) and 4.9 points (95% CI 0.6-9.2) at week 48, respectively. Mean increases in FAHI total score from baseline to weeks 24 and 48 in the RC were 6.9 (95% CI 4.2-9.7) and 5.8 (95% CI 2.7-9.0), respectively, whereas mean increases in physical and emotional well-being subscale scores were 2.7 (95% CI 1.9-3.6) and 2.4 (95% CI 1.3-3.4) and 3.2 (95% CI 2.2-4.2) and 2.6 (95% CI 1.6-3.7), respectively, with little to no change in other subscales., Conclusions: Improvements in major domains of the EQ-VAS and FAHI through week 48, combined with efficacy and safety results, support the use of fostemsavir for HTE PLWH., Trial Registration Number and Date: NCT02362503; February 13, 2015., (© 2021. The Author(s).)

Background: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19., Methods: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475., Findings: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group., Interpretation: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo., Funding: The National Institute of Allergy and Infectious Diseases (USA)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Disparities remain in HIV viral load (VL) suppression between people living with HIV (PLWH) who use cocaine and those who do not. It is not known how cannabis use affects VL suppression in PLWH who use cocaine. We evaluated the relationship between cannabis use and VL suppression among PLWH who use cocaine. We conducted a secondary data analysis of 119 baseline interviews from a randomized controlled trial in the Bronx, NY (6/2012 to 1/2017). Participants were adult PLWH prescribed antiretrovirals for ≥16 weeks, who endorsed imperfect antiretroviral adherence and used cocaine in the past 30-days. In bivariate and multivariable regression analyses, we examined how cannabis use, is associated with VL suppression among PLWH who use cocaine. Participants were a mean age of 50 years; most were male (64%) and non-Hispanic black (55%). Participants with VL suppression used cocaine less frequently than those with no VL suppression ( p  < 0.01); cannabis use was not significantly different. In regression analysis, compared with no use, daily/near-daily cannabis use was associated with VL suppression (aOR = 4.2, 95% CI: 1.1-16.6, p  < 0.05). Less-frequent cannabis use was not associated with VL suppression. Further investigation is needed to understand how cannabis use impacts HIV outcomes among PLWH who use cocaine.

Background: HIV-infected people who use drugs (PWUD) have poor HIV outcomes. Few studies tested interventions to improve HIV outcomes among PWUD. Abstinence-reinforcing contingency management (CM) reduces drug use and could also improve HIV outcomes., Methods: From 2012-2017, we conducted a randomized controlled trial testing whether a 16-week abstinence-reinforcing CM intervention improved HIV viral load (VL) among HIV-infected adults using opioids or cocaine. In the CM intervention, drug-free urines led to escalating value of vouchers ($2.50-$80/voucher, $1320 total maximum). In intention-to-treat mixed-effects linear and logistic regression analyses, we examined whether the CM intervention improved log 10 VL (primary outcome), abstinence and antiretroviral adherence (secondary outcomes)., Results: Thirty-seven participants were randomized to the CM intervention and 36 to control. Median age was 49.2 years; most were male (61.6%) and non-Hispanic black (46.6%). In CM (vs. control) participants, mean reduction in log 10 VL was greater (-0.16 log 10 VL copies/mL per 4-week period; 95% CI: -0.29 to -0.03, p < 0.05). Over 16 weeks, CM participants had a mean reduction of 0.64 copies/mL in log 10 VL greater than control participants. The CM intervention was not significantly associated with abstinence or adherence., Conclusions: This is the first study to demonstrate improvements in HIV VL via an abstinence-reinforcing CM intervention. Because the CM intervention did not significantly affect abstinence or adherence, the mechanism of its effect is unclear. To end the HIV epidemic, innovative strategies must address individuals with poor HIV outcomes. Abstinence-reinforcing CM may be one potential strategy to improve HIV outcomes among a select group of PWUD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

: media-1vid110.1542/5852348672001PEDS-VA&#95;2017-3562 Video Abstract BACKGROUND AND OBJECTIVES: Multidisciplinary care teams may improve health and control total cost for children with medical complexity (CMC). We aim to quantify the time required to perform nonreimbursed care coordination activities by a multidisciplinary care coordination program for CMC and to estimate the direct salary costs of that time., Methods: From April 2013 to October 2015, program staff tracked time spent in practicably measured nonbilled care coordination efforts. Staff documented the discipline involved, the method used, and the target of the activity. Cost was estimated by multiplying the time spent by the typical salary of the type of personnel performing the activity., Results: Staff logged 53 148 unique nonbilled care coordination activities for 208 CMC. Dietitians accounted for 26% of total time, physicians and nurse practitioners 24%, registered nurses 29%, and social workers 21% (1.8, 2.3, 1.2, and 1.4 hours per CMC per month per full-time provider, respectively). Median time spent in nonreimbursed care coordination was 2.3 hours per child per month (interquartile range 0.8-6.8). Enrollees required substantially greater time in their first program month than thereafter (median 6.7 vs 2.1 hours per CMC per month). Based on 2015 national salary data, the adjusted median estimated cost of documented activities ranged from $145 to $210 per CMC per month., Conclusions: In this multidisciplinary model, care coordination for CMC required substantial staff time, even without accounting for all activities, particularly in the first month of program enrollment. Continued advocacy is warranted for the reimbursement of care coordination activities for CMC., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: Medical tourism is increasingly popular for elective cosmetic surgical procedures. However, medical tourism has been accompanied by reports of post-surgical infections due to rapidly growing mycobacteria (RGM). The authors' experience working with patients with RGM infections who have returned to the USA after traveling abroad for cosmetic surgical procedures is described here., Methods: Patients who developed RGM infections after undergoing cosmetic surgeries abroad and who presented at the Montefiore Medical Center (Bronx, New York, USA) between August 2015 and June 2016 were identified. A review of patient medical records was performed., Results: Four patients who presented with culture-proven RGM infections at the sites of recent cosmetic procedures were identified. All patients were treated with a combination of antibiotics and aggressive surgical treatment., Conclusions: This case series of RGM infections following recent cosmetic surgeries abroad highlights the risks of medical tourism. Close monitoring of affected patients by surgical and infectious disease specialties is necessary, as aggressive surgical debridement combined with appropriate antibiotic regimens is needed to achieve cure. Given the increasing reports of post-surgical RGM infections, consultants should have a low threshold for suspecting RGM, as rapid diagnosis may accelerate the initiation of targeted treatment and minimize morbidity., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Osteoporosis is a significant clinical problem in persons with moderate to severe cerebral palsy (CP), causing fractures with minimal trauma. Over the past decade, most studies examining osteoporosis and CP have been cross-sectional in nature, focused exclusively on children and adolescents and only involving one evaluation of bone mineral density (BMD). The purpose of this study was to assess BMD in a group including adults with CP, and changes in each individual's BMD over a 5- to 6-year period., Method: The study group included 40 residents of a long-term care facility aged 6 to 26 years at the time of their initial evaluation. Twenty-one patients (52.5%) were male, 35 (88%) were white, and 38 (95%) were in Gross Motor Function Classification System level V. BMD was assessed by dual-energy X-ray absorptiometry on the right and left distal femurs for three distinct regions of interest., Results: Five residents had a fracture that occurred during the study period; this represented a fracture rate of 2.1% per year in the study group. Longitudinally, annualized change in the median BMD was 0.7% to 1.0% per year in the different regions of the distal femur, but ranged widely among the study group, with both increases and decreases in BMD. Increase in BMD over time was negatively correlated with age and positively correlated with change in weight., Interpretation: Changes in BMD over time in profoundly involved persons with CP can range widely, which is important to recognize when evaluating potential interventions to improve BMD. Age and changes in body weight appear the most relevant factors., (© 2015 Mac Keith Press.)

Background: The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose., Methods: VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24., Results: Mean change in HIV-1 RNA at day 8 was -1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily., Conclusions: DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus., Clinical Trials Registration: www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574)., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Evidence suggests that sexual problems are common among people living with HIV and may be related to sexual risk taking and treatment adherence. This study explored the extent to which sexual problems experienced by people with HIV are addressed in primary care as well as how primary care responses to sexual problems are experienced by patients. Structured interviews were conducted with 60 patients at an urban HIV clinic. The average age of the participants (37 male, 23 female) was 45.8 years (SD = 7.9). Sexual problems were common. The most common sexual problem experienced in the past year was a lack of interest in sex (53.3 % reported) and the least common problem was painful intercourse (reported by 20 %). There were no gender differences in reports of sexual problems, except that painful intercourse was more frequently reported by women than men. Relatively few individuals who experienced sexual problems had discussed them with their provider, but these individuals were generally pleased with the counseling they had received and could identify several factors that facilitated a positive patient-provider interaction. Those who offer primary care services to people with HIV should be aware of sexual problems their patients may be experiencing and should feel confident in their ability to successfully address these problems. Providers may need additional training in order to adequately address sexual problems among people with HIV in primary care settings.

Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) is a rapid and accurate method of identifying microorganisms. Throughout Europe, it is already in routine use but has not yet been widely implemented in the United States, pending FDA approval. Here, we describe two medically complex patients at a large tertiary-care academic medical center with recurring bacteremias caused by distinct but related species. Bacterial identifications were initially obtained using the Vitek-2 system with the GPI card for Enterococcus and the API system for staphylococci. Initial results misled clinicians as to the source and proper management of these patients. Retrospective investigation with MALDI-TOF MS clarified the diagnosis by identifying a single microorganism as the pathogen in each case. To our knowledge, this is one of the first reports in the United States demonstrating the use of MALDI-TOF MS to facilitate the clinical diagnosis in patients with recurrent bacteremias of unclear source.

There is no consensus on optimal screening for anal cancer (AC) in HIV+ women. Seven hundred fifteen unique asymptomatic women in a high-prevalence HIV+ community were screened for AC with anal cytology and triage to high-resolution anoscopy after routine screening was implemented in a large urban hospital system. Of these, 75 (10.5%) had an abnormal anal cytology and 29 (38.7%) of those with an abnormality had high-grade anal intraepithelial neoplasia (AIN). Women with poorly controlled HIV were significantly more likely to have high-grade AIN (P = 0.03). Given the high rate of AIN in screened HIV-infected women, routine AC screening in all HIV-infected women should be strongly considered.

Context: Current reports on human immunodeficiency virus (HIV) pain are limited to epidemiological data on neuropathic pain in HIV and most studies were conducted before the availability of highly active antiretroviral therapy. Complex pain was reported to be highly prevalent and associated with advanced disease., Objectives: The authors conducted a retrospective review of the medical records of 81 patients from the Center for Positive Living (CPL) at Montefiore Medical Center who were newly referred to a pain management program in 2006 to identify the potential benefits of integrating a pain management team into the care of persons living with HIV and etiologies of pain., Methods: A standardized chart abstraction tool was used to capture clinical data. Data related to health service utilization and viral outcomes were obtained from the clinical information systems., Results: The most common pain diagnoses were multiple syndromes, degenerative disc disease or spinal stenosis, and neuropathy. There was a decrease in emergency room utilization in the 12 months following an initial pain management appointment (p < 0.0001) and an increase in use of primary care (p = 0.0017). The use of adjuvant medications increased after intake into the pain clinic (p < 0.0001). Having an opioid dose in excess of 200 mg/d oral morphine equivalents and maintenance of each palliative care and infectious disease clinic appointment were inversely associated with viral loads in excess of 75 copies: odds ratio (OR) = 0.21 (95% confidence interval/CI], 0.11-0.44), OR = 0.77 (95% CI, 0.68-0.86), and 0.94 (95% CI, 0.93-0.99), respectively., Conclusions: The decrease in emergency room visits and increase in use of adjuvant analgesics and compliance with primary care and nonmedication approaches for the management of pain in the 12 months subsequent to initial palliative/pain clinic appointments highlight potential improved quality of care associated with the integration of a pain management team into the primary care of persons living with HIV disease.

Aging, HIV infection, and antiretroviral therapy have been associated with increasing rates of chronic comorbidities in patients with HIV. Urban minority populations in particular are affected by both the HIV/AIDS and chronic disease epidemics. Our objectives were to estimate the prevalence of and risk factors for hypertension, dyslipidemia, and diabetes among HIV-infected adults in the Bronx and describe comorbidity-related treatment outcomes. This was a cross-sectional study of 854 HIV-positive adults receiving care at 11 clinics which provide HIV primary care services; clinics were affiliated with a large urban academic medical center. Data on blood pressure (BP), cholesterol, and glycemic control were collected through standardized chart review of outpatient medical records. We found prevalence rates of 26%, 48%, and 13% for hypertension, dyslipidemia, and diabetes, respectively. Older age, obesity, family history, and current protease inhibitor use were consistently associated with comorbidity. Diabetes treatment goals were achieved less often than BP and lipid goals, and concurrent diabetes was a significant predictor for BP and lipid control. In conclusion, major cardiovascular-related comorbidities are prevalent among HIV-positive adults in the Bronx, especially older and obese individuals. Differences exist in comorbidity-related treatment outcomes, especially for patients with concurrent diabetes. Because cardiovascular risk is modifiable, effective treatment of related comorbidities may improve morbidity and mortality in HIV-infected patients.

Background: Follicular dendritic cell (FDC) sarcoma is an uncommon neoplasm occurring not only in lymph nodes but also in extranodal sites. Because of an increasing number of case reports, awareness of this tumor has grown. The nature of the disease and its relation to other diseases, treatment, prognosis and immunochemistry findings are being actively studied. So far, only a limited number of cytology cases describing the fine needle aspiration (FNA) biopsy findings of FDC sarcoma have been reported., Case: A 47-year-old man had a history of hypertension and human immunodeficiency virus (HIV) infection treated with antiretroviral therapy. He developed a slowly growing, nontender right neck mass over the course of 3 years. FNA revealed sheets and thick syncytial clusters of bland cells with pale cytoplasm and indistinct cell borders, round to oval nuclei with fine or vesicular chromatin, and small nucleoli. The mass was subsequently excised. A diagnosis of FDC sarcoma was made based on the histologic appearance and the marker studies. Conclusion The diagnosis ofFDC sarcoma in FNA can be suspected if a pathologist is aware of its characteristic features. Research studies have demonstrated the presence of HIV-related FDC hyperplasia. It is likely that HIV infection may have played a role in tumor formation in this patient. (Acta

Pharmacy refill adherence has become an increasingly important measure of adherence to antiretroviral medications. It offers a simple, inexpensive, and valid method for measuring adherence. Over the past year, there have been several published developments in the use of pharmacy refill data to measure adherence. Given the utility of this adherence measurement, it is likely that pharmacy refill will be the method of choice for measuring antiretroviral adherence in an increasing number of clinical and research settings.

Medication errors remain an important cause of patient morbidity and mortality. Although all medications have the potential to induce unwanted adverse effects, data on the actual incidence and overall severity of preventable adverse drug reactions remains unknown. An Institute of Medicine report (Institute of Medicine. Preventing medication errors: Quality chasm series. Washington DC, National Academies Press. 2007-06-15) estimated that 1.5 million preventable adverse drug events occur annually in the US and that from 44,000 to 98,000 individuals die in hospitals annually from preventable medication errors. The types of medication errors of clinical relevance leading to moderate to severe outcomes are unfortunately numerous. Such errors would include wrong drug, wrong dose / wrong dose interval and represent the more serious form of a medication error. Institutionalized patients and those patients cared for in long-term care facilities appear to be at heightened risk for a medication error. These patients often receive multiple medications and suffer from variable degrees of cognitive impairment which complicates or negates patient-caregiver communication, one of the most important means to prevent medication errors. Moreover, the increasing financial constraints placed upon treatment facilities encourage the use of generic, rather than name brand medications by their pharmacy provider. While the use of bioequivalent generic medications is completely appropriate and can be very cost-effective, generic drug manufacturers are less often manufacturing their generic medications to look like the name brand drug. Rather, more and more generic medications are plain appearing with no resemblance whatsoever to the name brand product. This difference in drug appearance between the generic and the brand name product as well as differences in drug appearance between different generic drug manufacturers for the same medication represents another, important means by which patients may experience moderate to serious consequences from a medication error. We report such an experience where a patient in a long-term care facility received multi-day, excessive dosing of glipizide rather than her anti-spasticity medication, baclofen.

A 16-year-old varicella-seronegative resident at a chronic care facility received varicella vaccine; 15 days later he developed severe varicella. Subsequently, a 13-year-old resident and a 39-year-old health care worker developed mild varicella. We demonstrate that vaccine-strain virus was transmitted to both persons, and that transmission included at least 2 variant vaccine strains.

Objective: The goal of this study was to determine the validity and utility of a pharmacy-based time-to-refill measure of antiretroviral therapy adherence., Methods: We performed an observational cohort study of 110 HIV-infected subjects on a stable, highly active antiretroviral regimen for at least 3 months at a Veterans' Affairs Medical Center in Philadelphia, Pennsylvania., Results: The viral load decreased by 0.12 log c/mL (95% confidence interval [CI] 0.01-0.23 log c/mL) for each 10% increase in pharmacy-based time-to-refill defined adherence as compared with 0.05 log c/mL (95% CI -0.14-0.25 log c/mL) for the self-reported adherence measure. Thus, only the refill-defined measure was statistically significantly associated with viral load change. When adherence was classified as good (> or = 85%) versus poor (<85%), both measures demonstrated a significant difference in outcome between groups. Yet, in individuals self-reporting 100% adherence, those classified as good adherers using the pharmacy-based measure had greater viral load reductions than poor adherers (2.4 log c/mL [interquartile range 1.4-3.4] vs. 1.5 log c/mL [interquartile range 0.8-2.4, P=.03)., Conclusions: The pharmacy-based technique is a valid measure of antiretroviral therapy adherence. Because it provides clinically relevant information in subjects who self-report 100% adherence, it should be incorporated into clinical practice and adherence research.

Background: There are few data on the rate of compliance with universal precautions among pediatricians. We hypothesized that compliance in pediatrics would be poor because of the intrinsic difficulties in performing invasive procedures in small subjects., Design: Prospective, observational study., Setting: Tertiary care children's hospital., Study Participants: A convenience sample of pediatric house staff., Main Outcome Measures: Pediatric house staff members were observed while performing invasive procedures. Procedure type, number of attempts required, and patient's age and diagnosis were recorded. Degree of compliance with universal precautions was judged by means of Centers for Disease Control and Prevention guidelines. Comparisons between the compliant and noncompliant groups were analyzed by chi2 and 2-tailed t test., Results: A total of 128 procedures performed by 43 house officers, 4 advanced medical students, and 3 chief residents or fellows were observed. Sixty-nine (53.9%) of the 128 procedures were performed correctly according to universal precaution guidelines. Rate of compliance did not appear to be influenced by small patient size, as judged by the lack of association with the age of the patient (mean+/-SD, 4.8+/-5.7 years among those in whom universal precautions were properly used vs 4.9+/-5.4 years among patients in whom precaution guidelines were breached; P=.96). Moreover, the number of attempts required in compliant procedures (1.31+/-0.53) was almost identical to that in noncompliant procedures (1.28+/-0.49; P=.73). Additionally, compliance did not improve with advanced level of training., Conclusions: Failure of compliance among pediatricians has no apparent association with procedure difficulty, and compliance rates continue to be poor through the course of pediatric training. These findings underline the need for effective education concerning universal precautions throughout pediatric residency, and they suggest that such efforts will not be precluded by obstacles intrinsic to performing invasive procedures on young subjects.