Associations Between HIV and Severe Mpox in an Atlanta Cohort.

BACKGROUND: In the Southeastern United States, the 2022 mpox outbreak disproportionately impacted people who are black and people with HIV (PWH). METHODS: We analyzed a cohort of 395 individuals diagnosed with mpox across 3 health care systems in Atlanta, Georgia between 1 June 2022 and 7 October 2022. We present demographic and clinical characteristics and use multivariable logistic regression analyses to evaluate the association between HIV status and severe mpox (per the US Centers for Disease Control and Prevention definition) and, among PWH, the associations between CD4+ T-cell count and HIV load with severe mpox. RESULTS: Of 395 people diagnosed with mpox, 384 (97.2%) were cisgender men, 335 (84.8%) identified as black, and 324 (82.0%) were PWH. Of 257 PWH with a known HIV load, 90 (35.0%) had > 200 copies/mL. Severe mpox occurred in 77 (19.5%) individuals and there was 1 (0.3%) death. Tecovirimat was prescribed to 112 (28.4%) people, including 56 (72.7%) people with severe mpox. In the multivariable analysis of the total population, PWH had 2.52 times higher odds of severe mpox (95% confidence interval [CI], 1.01-6.27) compared with people without HIV. In the multivariable analysis of PWH, individuals with HIV load > 200 copies/mL had 2.10 (95% CI, 1.00-4.39) times higher odds of severe mpox than PWH who were virologically suppressed. Lower CD4+ T-cell count showed a significant univariate association with severe mpox but was not found to be significantly associated with severe mpox in multivariable analysis. CONCLUSIONS: PWH with nonsuppressed HIV loads had more mpox complications, hospitalizations, and protracted disease courses than people without HIV or PWH with suppressed viral loads. PWH with nonsuppressed HIV loads who are diagnosed with mpox warrant particularly aggressive monitoring and treatment.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Epidemiologic, Immunologic, and Virus Characteristics in Patients With Paired Severe Acute Respiratory Syndrome Coronavirus 2 Serology and Reverse-Transcription Polymerase Chain Reaction Testing.

BACKGROUND: The natural history and clinical progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can be better understood using combined serological and reverse-transcription polymerase chain reaction (RT-PCR) testing. METHODS: Nasopharyngeal swabs and serum were collected at a single time-point from patients at an urban, public hospital during August-November 2020 and tested for SARS-CoV-2 using RT-PCR, viral culture, and anti-spike pan-immunoglobulin antibody testing. Participant demographics and symptoms were collected through interview. The χ 2 and Fisher exact tests were used to identify associations between RT-PCR and serology results with presence of viable virus and frequency of symptoms. RESULTS: Among 592 participants, 129 (21.8%) had evidence of SARS-CoV-2 infection by RT-PCR or serology. Presence of SARS-CoV-2 antibodies was strongly associated with lack of viable virus (P = .016). COVID-19 symptom frequency was similar for patients testing RT-PCR positive/seronegative and patients testing RT-PCR positive/seropositive. Patients testing RT-PCR positive/seronegative reported headaches, fatigue, diarrhea, and vomiting at rates not statistically significantly different from those testing RT-PCR negative/seropositive. CONCLUSIONS: While patients testing SARS-CoV-2 seropositive were unlikely to test positive for viable virus and were therefore at low risk for forward transmission, coronavirus disease 2019 (COVID-19) symptoms were common. Paired SARS-CoV-2 RT-PCR and antibody testing provides more nuanced understanding of patients' COVID-19 status.

Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection.

Within 8 weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no clear clinical correlates or validated biomarkers that can predict recurrence during primary infection. This study demonstrated the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence. Forty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Samples of serum and a novel matrix from circulating plasmablasts called "medium-enriched for newly synthesized antibodies" (MENSA) were collected during weeks 1, 2, and 4. Antibodies specific for 10 C. difficile antigens were measured in each sample. Among the 46 C. difficile-infected patients, 9 (19.5%) experienced recurrence within 8 weeks of primary infection. Among the 37 nonrecurrent patients, 23 (62%; 23/37) had anti-C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred early (within the first 12 days post-symptom onset), including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (51%; 19/37). In contrast, none (0%; 0/9) of the patients who subsequently recurred after hospitalization produced antibodies specific for any of the three C. difficile toxin antigens. Thus, patients with a negative early MENSA response against all three C. difficile toxin antigens had a 19-fold greater relative risk of recurrence. MENSA and serum levels of immunoglobulin A (IgA) and/or IgG antibodies for three C. difficile toxins have prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence thereby providing a biomarker of protection from recurrent CDI. Patients who are positive by this immunoassay are unlikely to suffer a recurrence. Early identification of patients at risk for recurrence by negative MENSA creates opportunities for targeted prophylactic strategies that can reduce the incidence, cost, and morbidity due to recurrent CDI.

Loss of Smell and Taste Among Healthcare Personnel Screened for Coronavirus 2019.

Among 283 symptomatic healthcare personnel (HCP) tested for SARS-CoV-2, 51 (18%) were positive. Among those 51 HCP, self reported loss of smell and taste were present in 51% and 52.9%, respectively, with either present in 60.8%. These symptoms had high specificity (93% each, 96% for either) for a positive SARS-CoV-2 test.

Effects of Patient Characteristics on Diagnostic Performance of Self-Collected Samples for SARS-CoV-2 Testing.

We evaluated the performance of self-collected anterior nasal swab (ANS) and saliva samples compared with healthcare worker-collected nasopharyngeal swab specimens used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used the same PCR diagnostic panel to test all self-collected and healthcare worker-collected samples from participants at a public hospital in Atlanta, Georgia, USA. Among 1,076 participants, 51.9% were men, 57.1% were >50 years of age, 81.2% were Black (non-Hispanic), and 74.9% reported >1 chronic medical condition. In total, 8.0% tested positive for SARS-CoV-2. Compared with nasopharyngeal swab samples, ANS samples had a sensitivity of 59% and saliva samples a sensitivity of 68%. Among participants tested 3-7 days after symptom onset, ANS samples had a sensitivity of 80% and saliva samples a sensitivity of 85%. Sensitivity varied by specimen type and patient characteristics. These findings can help physicians interpret PCR results for SARS-CoV-2.

Clinical Implications of Multiplex Pathogen Panels for the Diagnosis of Acute Viral Gastroenteritis.

Acute gastroenteritis remains a significant cause of morbidity and mortality in both high- and low-resource settings. The development of nucleic acid-based testing has demonstrated that viruses are a common, yet often undetected, cause of acute gastroenteritis. The development of multiplex pathogen PCR panels makes it possible to detect these viral pathogens with greater sensitivity and rapidity than with previous methods. At present, there is insufficient evidence to recommend the routine use of these panels for the average patient with acute gastroenteritis. However, there are specific scenarios and patient populations, such as epidemiology/outbreak surveillance, antimicrobial stewardship, and the care of immunocompromised patients, where these tests could be clinically useful today. Further research on the effect of these syndromic panels on provider antibiotic prescribing behavior and patient length of stay will be necessary to know their ultimate role in clinical practice.

Effect of infant feeding practices on iron status in a cohort study of Bolivian infants.

BACKGROUND: Iron deficiency (ID) is the most common micronutrient deficiency worldwide, with potentially severe consequences on child neurodevelopment. Though exclusive breastfeeding (EBF) is recommended for 6 months, breast milk has low iron content. This study aimed to estimate the effect of the length of EBF on iron status at 6 - 8 months of age among a cohort of Bolivian infants. METHODS: Mother-infant pairs were recruited from 2 hospitals in El Alto, Bolivia, and followed from one through 6 - 8 months of age. Singleton infants > 34 weeks gestational age, iron-sufficient at baseline, and completing blood draws at 2 and 6 - 8 months of age were eligible for inclusion (N = 270). Ferritin was corrected for the effect of inflammation. ID was defined as inflammation-corrected ferritin < 12 µg/L, and anemia was defined as altitude-corrected hemoglobin < 11 g/dL; IDA was defined as ID plus anemia. The effect of length of EBF (infant received only breast milk with no other liquids or solids, categorized as < 4, 4 - 6, and > 6 months) was assessed for ID, IDA, and anemia (logistic regression) and ferritin (Fer) and hemoglobin (Hb, linear regression). RESULTS: Low iron status was common among infants at 6 - 8 months: 56% of infants were ID, 76% were anemic, and 46% had IDA. EBF of 4 months and above was significantly associated with ID as compared with EBF <  4 months (4 - 6 months: OR 2.0 [1.1 - 3.4]; > 6 months: 3.3 [1.0 - 12.3]), but not with IDA (4 - 6 months: OR 1.4 [0.8 - 2.4]; > 6 months: 2.2 [0.7 - 7.4]), or anemia (4 - 6 months: OR 1.4 [0.7 - 2.5]; > 6 months: 1.5 [0.7 - 7.2]). Fer and Hb concentrations were significantly lower with increasing months of EBF. CONCLUSIONS: Results suggest a relationship between prolonged EBF and ID, but are not sufficient to support changes to current breastfeeding recommendations. More research is needed in diverse populations, including exploration of early interventions to address infant IDA.

Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with Isoniazid-Resistant Tuberculosis in Atlanta, Georgia.

BACKGROUND: Although isoniazid-resistant tuberculosis is more common than multidrug-resistant tuberculosis, it has been much less studied. We examined the impact of isoniazid resistance and treatment regimen, including use of a fluoroquinolone, on clinical outcomes. METHODS: A retrospective cohort study among patients with sputum culture-positive tuberculosis was performed. Early fluoroquinolone (FQ) use was defined as receiving ≥5 doses during the first month of treatment. The primary outcome was time to sputum culture conversion (tSCC). A multivariate proportional hazards model was used to determine the association of isoniazid resistance with tSCC. RESULTS: Among 236 patients with pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39), and isoniazid resistance was not associated with tSCC in multivariate analysis (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P = .05); however, it was not significantly associated with tSCC in univariate analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid-resistant tuberculosis were treated with regimens containing rifampin, pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191 (83%) patients were cured. There was no difference in initial treatment outcomes; however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3) occurred among patients with isoniazid-resistant tuberculosis. CONCLUSIONS: There was no significant association with isoniazid resistance and tSCC or initial treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a high cure rate, the cases of recurrence and acquired drug resistance are concerning and highlight the need for longer-term follow-up studies.

Using a monitoring and evaluation framework to improve study efficiency and quality during a prospective cohort study in infants receiving rotavirus vaccination in El Alto, Bolivia: the Infant Nutrition, Inflammation, and Diarrheal Illness (NIDI) study.

BACKGROUND: Implementing rigorous epidemiologic studies in low-resource settings involves challenges in participant recruitment and follow-up (e.g., mobile populations, distrust), biological sample collection (e.g., cold-chain, laboratory equipment scarcity) and data collection (e.g., literacy, staff training, and infrastructure). This article describes the use of a monitoring and evaluation (M&E) framework to improve study efficiency and quality during participant engagement, and biological sample and data collection in a longitudinal cohort study of Bolivian infants. METHODS: The study occurred between 2013 and 2015 in El Alto, Bolivia, a high-altitude, urban, low-resource community. The study's M&E framework included indicators for participant engagement (e.g., recruitment, retention, safety), biological sample (e.g., stool and blood), and data (e.g., anthropometry, questionnaires) collection and quality. Monitoring indicators were measured regularly throughout the study and used for course correction, communication, and staff retraining. RESULTS: Participant engagement indicators suggested that enrollment objectives were met (461 infants), but 15% loss-to-follow-up resulted in only 364 infants completing the study. Over the course of the study, there were four study-related adverse events (minor swelling and bruising related to a blood draw) and five severe adverse events (infant deaths) not related to study participation. Biological sample indicators demonstrated two blood samples collected from 95% (333 of 350 required) infants and stool collected for 61% of reported infant diarrhea episodes. Anthropometry data quality indicators were extremely high (median SDs for weight-for-length, length-for-age and weight-for-age z-scores 1.01, 0.98, and 1.03, respectively), likely due to extensive training, standardization, and monitoring efforts. CONCLUSIONS: Conducting human subjects research studies in low-resource settings often presents unique logistical difficulties, and collecting high-quality data is often a challenge. Investing in comprehensive M&E is important to improve participant recruitment, retention and safety, and sample and data quality. The M&E framework from this study can be applied to other longitudinal studies.

Early deterioration of iron status among a cohort of Bolivian infants.

Iron deficiency (ID) and iron deficiency anemia (IDA) are major contributors to infant and maternal morbidity worldwide. There is limited longitudinal data on iron status in young infants and on methods to adjust iron biomarkers for inflammation. We aimed to quantify the prevalence of inflammation-adjusted ID, anemia, and IDA over the first year in a cohort of Bolivian infants and their mothers. Healthy mother-infant dyads were recruited from two peri-urban hospitals. Infants provided three blood draws (2, 6-8, and 12-18 months; N = 160); mothers provided two blood draws (1 and 6-8 months postpartum [plus third anemia measurement at 12-18 months]; N = 250). Blood was analyzed for hemoglobin, ferritin, soluble transferrin receptor, C-reactive protein (CRP), and alpha(1)-acid glycoprotein (AGP). Iron biomarkers were adjusted for inflammation using CRP and AGP; hemoglobin cutoffs were adjusted for altitude. Inflammation (elevated CRP or AGP) was 17% among toddlers 12-18 months of age. ID (inflammation-adjusted ferritin) increased with age (<1%, 56%, and 79% at each blood draw), as did anemia and IDA (anemia: 70%, 76%, and 81%; IDA: <1%, 46%, and 68%). Maternal ID declined from the first to second assessment (39% vs. 27%). Inflammation-adjusted ID prevalence was up to 15 percentage points higher than unadjusted estimates. The high prevalence of ID, anemia, and IDA in this cohort of Bolivian infants beginning at 6-8 months of age suggests that early interventions may be necessary in vulnerable populations.

Polymicrobial ventriculitis involving Pseudomonas fulva.

Infections due to Pseudomonas fulva remain a rare but emerging concern. A case of ventriculitis due to Enterobacter cloacae and Pseudomonas fulva following placement of an external ventricular drain is described. Similar to other reports, the organism was initially misidentified as Pseudomonas putida. The infection was successfully treated with levofloxacin.

The economic burden of pediatric gastroenteritis to Bolivian families: a cross-sectional study of correlates of catastrophic cost and overall cost burden.

BACKGROUND: Worldwide, acute gastroenteritis causes substantial morbidity and mortality in children less than five years of age. In Bolivia, which has one of the lower GDPs in South America, 16% of child deaths can be attributed to diarrhea, and the costs associated with diarrhea can weigh heavily on patient families. To address this need, the study goal was to identify predictors of cost burden (diarrhea-related costs incurred as a percentage of annual income) and catastrophic cost (cost burden ≥ 1% of annual household income). METHODS: From 2007 to 2009, researchers interviewed caregivers (n = 1,107) of pediatric patients (<5 years old) seeking treatment for diarrhea in six Bolivian hospitals. Caregivers were surveyed on demographics, clinical symptoms, direct (e.g. medication, consult fees), and indirect (e.g. lost wages) costs. Multivariate regression models (n = 551) were used to assess relationships of covariates to the outcomes of cost burden (linear model) and catastrophic cost (logistic model). RESULTS: We determined that cost burden and catastrophic cost shared the same significant (p < 0.05) predictors. In the logistic model that also controlled for child sex, child age, household size, rural residence, transportations taken to the current visit, whether the child presented with complications, and whether this was the child's first episode of diarrhea, significant predictors of catastrophic cost included outpatient status (OR 0.16, 95% CI [0.07, 0.37]); seeking care at a private hospital (OR 4.12, 95% CI [2.30, 7.41]); having previously sought treatment for this diarrheal episode (OR 3.92, 95% CI [1.64, 9.35]); and the number of days the child had diarrhea prior to the current visit (OR 1.14, 95% CI [1.05, 1.24]). CONCLUSIONS: Our analysis highlights the economic impact of pediatric diarrhea from the familial perspective and provides insight into potential areas of intervention to reduce associated economic burden.

Evaluation of a residential nutrition rehabilitation center in rural Bolivia: short-term effectiveness and follow-up results.

BACKGROUND: Nutrition rehabilitation centers (NRCs) have shown mixed results in reducing morbidity and mortality among undernourished children in the developing world. Follow-up on children after leaving these programs remains undocumented. OBJECTIVE: To assess the nutritional improvement of children attending the Centro de Rehabilitación Infantil Nutricional (CRIN), a residential NRC in rural Bolivia, from entrance to exit and to a household follow-up visit 1 month to 6 years later, and to identify factors associated with nutritional improvement. METHODS: A retrospective analysis was conducted of clinical records collected by CRIN staff from 135 children under 3 years of age attending CRIN in rural Cochabamba, Bolivia, from 2003 to 2009, and of clinical records of household follow-up measurements on a subset of 26 children that were taken between 1 month and 6 years postexit. Nutritional status was evaluated by calculating z-scores for weight-for-height (WHZ), weight-for-age (WAZ), and height-for-age (HAZ). Children with z-scores < -2 were considered to be wasted, underweight, or stunted, respectively. RESULTS: The prevalence of wasting decreased significantly, while the prevalence of stunting did not change significantly between entrance and exit from the program. From entrance to exit, the mean changes in WHZ (0.79) and WAZ (1.08) were statistically significant, while the mean change in HAZ (-0.02) was not significant. Linear regression analysis suggested that nutritional status and diarrhea at entrance had the greatest effect on WHZ and HAZ changes between entrance and exit. Children maintained their nutritional gains from the program between exit and follow-up and showed statistically significant improvement in WAZ (but not HAZ). CONCLUSIONS: CRIN is effective at rehabilitating nutritional deficits associated with wasting, but not those associated with stunting.

The impact of implementation of rapid blood culture identification panels on antimicrobial optimization: a retrospective cohort study.

Objective: Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. Design: Retrospective cohort study. Methods: From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents. Additional analysis investigated the impact of the availability of antimicrobial stewardship program support. This study was conducted at Grady Health System, a large metropolitan safety-net hospital in the southeastern United States. Results: A total of 253 blood cultures were included in this study (153 BCID and 100 standard). Blood culture identification use was associated with a reduction in median time to optimal antimicrobial therapy (43.4 vs 72.1 h, P < .001) and median time to de-escalation of anti-MRSA agents (27.7 vs 46.7 h, P = .006), and a trend towards reduction of median time to de-escalation of anti-pseudomonal agents (38.8 vs 54.8 h, P = .07). These reductions persisted when controlling for patient age, sex, intensive care unit status, Charlson Comorbidity Index, and antimicrobial stewardship program availability. Conclusions: Despite restricted use and lack of 24/7 antimicrobial stewardship program availability, BCID panel utilization was associated with earlier initiation of optimal therapy and pathogen identification with subsequent de-escalation of broad-spectrum antimicrobials, as compared to standard antimicrobial techniques. This suggests the potential for benefit from adopting novel diagnostic technologies outside of idealized fully-resourced settings.

Early Tecovirimat Treatment for Mpox Disease Among People With HIV.

Importance: Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly PWH with low CD4+ T-cell counts or severe mpox clinical manifestations. Objective: To evaluate if PWH with mpox who were treated with tecovirimat within 7 days of symptom onset were less likely to have mpox disease progression. Design, Setting, and Participants: This cohort study included PWH diagnosed with mpox at 4 hospitals in Atlanta, Georgia, between June 1 and October 7, 2022. Patients were grouped according to whether they were treated with tecovirimat within 7 days of mpox symptom onset (early tecovirimat cohort) or they did not receive tecovirimat or received the drug 7 or more days after symptom onset (late or no tecovirimat cohort). Multivariable logistic regression models were used to identify factors associated with progression of mpox disease. The 2 cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared. Exposures: Treatment with tecovirimat within 7 days of mpox symptom onset. Main Outcome and Measures: Progression of mpox disease, defined as the development of at least 1 severe mpox criterion established by the US Centers for Disease Control and Prevention, after symptom day 7. Results: After propensity score matching, a total of 112 PWH were included in the analysis; 56 received tecovirimat within 7 days of mpox symptom onset (early tecovirimat group) and 56 were either treated later or did not receive tecovirimat (late or no tecovirimat group). In the early tecovirimat group, the median (IQR) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black individuals, and 10 (17.9%) were individuals of other races (American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or White) or unknown race. In the late or no tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black individuals, and 7 (12.5%) were individuals of other races or unknown race. Mpox disease progression occurred in 3 PWH (5.4%) in the early tecovirimat group and in 15 PWH (26.8%) in the late or no tecovirimat group (paired odds ratio, 13.00 [95% CI, 1.71-99.40]; P = .002). Conclusion and Relevance: Results of this cohort study support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is warranted to confirm these findings.

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design Setting and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast. Interventions: Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov ( NCT04885530 ).

The burden of pediatric diarrhea: a cross-sectional study of incurred costs and perceptions of cost among Bolivian families.

BACKGROUND: Worldwide, acute gastroenteritis represents an enormous public health threat to children under five years of age, causing one billion episodes and 1.9 to 3.2 million deaths per year. In Bolivia, which has one of the lower GDPs in South America, an estimated 15% of under-five deaths are caused by diarrhea. Bolivian caregiver expenses related to diarrhea are believed to be minimal, as citizens benefit from universal health insurance for children under five. The goals of this report were to describe total incurred costs and cost burden associated with caregivers seeking treatment for pediatric gastroenteritis, and to quantify relationships among costs, cost burden, treatment setting, and perceptions of costs. METHODS: From 2007 to 2009, researchers interviewed caregivers (n=1,107) of pediatric patients (<5 years of age) seeking treatment for diarrhea in sentinel hospitals participating in Bolivia's diarrheal surveillance program across three main geographic regions. Data collected included demographics, clinical symptoms, direct costs (e.g. medication, consult fees) and indirect costs (e.g. lost wages). RESULTS: Patient populations were similar across cities in terms of gender, duration of illness, and age, but familial income varied significantly (p<0.05) when stratified on appointment type. Direct, indirect, and total costs to families were significantly higher for inpatients as compared to outpatients of urban (p<0.001) and rural (p<0.05) residence. Consult fees and indirect costs made up a large proportion of total costs. Forty-five percent of patients' families paid ≥1% of their annual household income for this single diarrheal episode. The perception that cost was affecting family finances was more frequent among those with higher actual cost burden. CONCLUSIONS: This study demonstrated that indirect costs due to acute pediatric diarrhea were a large component of total incurred familial costs. Additionally, familial costs associated with a single diarrheal episode affected the actual and perceived financial situation of a large number of caregivers. These data serve as a baseline for societal diarrheal costs before and immediately following the implementation of the rotavirus vaccine and highlight the serious economic importance of a diarrheal episode to Bolivian caregivers.