Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

Impact of the COVID-19 pandemic on trauma activations at a pediatric level 1 trauma center in New York.

BACKGROUND: The disruptive effects on society and medical systems due to the coronavirus disease 2019 (COVID-19) pandemic are substantial and far-reaching. The effect of the pandemic on the quantity and quality of pediatric traumas is unclear and has a direct bearing on how scarce hospital resources should be allocated in a pandemic situation. METHODS: A retrospective review of the trauma registry was performed for trauma activations in the years 2018 through 2020 during the months of March, April, and May. Demographic and injury specific datapoints were compared across calendar years. RESULTS: There were 111, 100, and 52 trauma activations during the study interval in 2018, 2019, and 2020, respectively. There were fewer highest severity level activations in 2020 compared to 2018 and 2019 (1 vs 5 and 9; p < 0.01). The median Injury Severity Score was 5 in 2020 compared to 4 in both 2018 and 2019 (p < 0.01). More patients went directly to the operating room in 2020 compared to prior years (21.2% vs 8% and 6.1%; p < 0.01). There were fewer discharges from the emergency department (ED) (12.1% vs 36.6% and 32.7%). No increase in the number of child abuse reports and investigations was noted. There was no difference in the proportion of blunt versus penetrating trauma between years (p = 0.57). No pedestrians were struck by automobiles in 2020 compared to 12 and 14 in 2018 and 2019. However, there were a greater proportion of injuries from falls during 2020 compared to prior years. CONCLUSIONS: There were fewer trauma activations during the peak of the COVID pandemic compared to prior years. Due to the decrease in trauma volume during the peak of the pandemic, hospital resources could potentially be reallocated toward areas of greater need. LEVEL OF EVIDENCE: IV; Retrospective cohort study using historical controls.

Outcomes of Initial Subtotal Colectomy for Pediatric Inflammatory Bowel Disease.

BACKGROUND: Subtotal colectomy with end ileostomy (STC-I) has been well established in the adult literature as an initial surgical treatment for refractory inflammatory bowel disease (IBD)-related colitis. However, in the pediatric population, the efficacy of this approach has been less well characterized, likely because of concerns regarding the advisability of leaving a diseased rectum in situ. Our aim was to examine the outcomes after STC-I for refractory IBD at our pediatric tertiary care center. METHODS: An institutional review board-approved retrospective review of patients aged 5-21 y who underwent operative treatment with initial STC-I for medically refractory IBD from January 2010 to August 2018. Only complications related to the STC-I were considered; complications subsequent to reconstruction are excluded from analysis. Early complications were defined as occurring within 60 d of STC-I. We performed descriptive statistics using the Fisher exact test and the Student t-test, as appropriate. RESULTS: Over the study period, 37 patients (aged 12.3 ± 4.2 y) underwent STC-I, with 73.0% performed laparoscopically. Patients were predominately male (51.4%) and Caucasian (48.6%). Thirty-one (83.8%) colectomies were performed for ulcerative colitis, two (5.4%) for Crohn disease, and four (10.8%) for indeterminate colitis. Nutritional status improved postcolectomy. Albumin levels of 3.3 ± 0.8 preoperatively increased to 4.3 ± 0.47 postoperatively (P < 0.001). Colonic bleeding was stopped by STC-I with increases in the hematocrit from 30.5 ± 6.8 preoperative to 38.9 ± 4.1 postoperatively (P < 0.001). Average time to discontinuation of IBD-related medications was 4 wk (n = 27). Forty-eight percent required outpatient rectal treatment for proctitis. Patients did well long term, with 67.5% reestablishing intestinal continuity at our institution. Average postoperative length of stay was shorter in the laparoscopic group compared with those undergoing open operations (5.1 ± 2.2 versus 6.9 ± 1.6 d, P = 0.03). Readmission rate at 30 d was 21.1%. Patients experiencing unplanned readmission or unplanned operations were similar between groups (30% versus 33.3%, P = 0.85 and 30% versus 18.5%, P = 0.45, respectively). Overall, 14 (37.8%) patients experienced a complication with many patients experiencing multiple complications. Early complications occurred in nine (24.3%) patients. Late complications also occurred in 24.3% of patients. There were four (10.8%) patients with five admissions for bowel obstruction, two of whom required operative intervention (5.4%). CONCLUSIONS: Use of STC-I as an initial procedure in the treatment of refractory IBD-related colitis in children is a safe and reasonable surgical approach that allows weaning from immunosuppressing mediations and stops colonic bleeding. Implementing a laparoscopic approach to subtotal colectomy provides further benefit by reducing postoperative length of stay.

Inconsistency in Opioid Prescribing Practices After Pediatric Ambulatory Hernia Surgery.

INTRODUCTION: Nonmedical opioid use is a major public health problem. There is little standardization in opioid-prescribing practices for pediatric ambulatory surgery, which can result in patients being prescribed large quantities of opioids. We have evaluated the variability in postoperative pain medication given to pediatric patients following routine ambulatory pediatric surgical procedures. METHODS: Following IRB approval, pediatric patients undergoing umbilical hernia repair, inguinal hernia repair, hydrocelectomy, and orchiopexy from 2/1/2017 to 2/1/2018 at our tertiary care children's hospital were retrospectively reviewed. Data collected include operation, surgeon, resident or fellow involvement, utilization of preoperative analgesia, opioid prescription on discharge, and patient follow-up. RESULTS: Of 329 patients identified, opioids were prescribed on discharge to 37.4% of patients (66.3% of umbilical hernia repairs, 20.6% of laparoscopic inguinal hernia repairs, and 33.3% of open inguinal hernia repairs [including hydrocelectomies and orchiopexies]). For each procedure, there was large intrasurgeon and intersurgeon variability in the number of opioid doses prescribed. Opioid prescription ranged from 0 to 33 doses for umbilical hernia repairs, 0 to 24 doses for laparoscopic inguinal repairs, and 0 to 20 doses prescribed for open inguinal repairs, hydrocelectomies, and orchiopexies. Pediatric surgical fellows were less likely to discharge a patient with an opioid prescription than surgical resident prescribers (P < 0.01). In addition, surgical residents were more likely to prescribe more than twelve doses of opioids than pediatric surgical fellows (P < 0.01). Increasing patient age was associated with an increased likelihood of opioid prescription (P < 0.01). There were two phone calls and two clinic visits for pain control issues with equal numbers for those with and without opioid prescriptions. CONCLUSIONS: There is significant variation in opioid-prescribing practices after pediatric surgical procedures; increased awareness may help minimize this variability and reduce overprescribing. Training level has an impact on the frequency and quantity of opioids prescribed.

A randomized double-blind placebo-controlled trial of a multi-strain probiotic in treatment of symptomatic uncomplicated diverticular disease.

BACKGROUND: Diverticular disease is a significant burden on healthcare systems that is managed, surgically or medically, mainly as an emergency or acute condition. There are no standardized treatment recommendations for symptomatic uncomplicated disease. We hypothesized that a probiotic would reduce abdominal pain in such patients. METHODS: We conducted a single-center, double-blind, placebo-controlled trial of probiotic treatment (Symprove) in adult patients with moderate-to-severe chronic, non-acute symptomatic diverticular disease. 143 patients were randomized to receive 1 mL/kg/day of probiotic liquid (N = 72) or placebo (N = 71) daily for 3 months. The primary endpoint was abdominal pain severity. Secondary endpoints consisted of the change in the frequency of eight abdominal symptoms and the level of intestinal inflammation (fecal calprotectin). RESULTS: 120 patients completed the trial. Abdominal pain score, the primary end point, decreased in both groups, but no significant difference between the groups was found (P = 0.11). In relation to placebo, the probiotic significantly decreased the frequency of four of the eight secondary endpoints: constipation, diarrhea, mucorrhea, and back pain (P < 0.04). No significant differences were found in frequency of abdominal pain, PR bleeding, dysuria, and bloating. CONCLUSIONS: Multi-strain liquid probiotic did not improve abdominal pain scores significantly, but significantly improved the frequency of four other symptoms associated with chronic, non-acute symptomatic diverticular disease.

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

BACKGROUND: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. METHODS: Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. RESULTS: Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. CONCLUSIONS: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

Treatment Outcomes for Patients with Extensively Drug-Resistant Tuberculosis, KwaZulu-Natal and Eastern Cape Provinces, South Africa.

We analyzed data for a retrospective cohort of patients treated for extensively drug-resistant tuberculosis in 2 provinces in South Africa and compared predictors of treatment outcome in HIV-positive patients who received or had not received antiretroviral drugs with those for HIV-negative patients. Overall, 220 (62.0%) of 355 patients were HIV positive. After 2 years, 34 (10.3%) of 330 patients with a known HIV status and known outcome had a favorable outcome. Multivariate analysis showed that predictors of favorable outcome were negative results for acid-fast bacilli by sputum microscopy at start of treatment and weight >50 kg. HIV-positive patients were more likely to have an unfavorable outcome. The strongest predictor of unfavorable outcome was weight <50 kg. Overall outcomes were poor. HIV status was not a predictor of favorable outcome, but HIV-positive patients were more likely to have an unfavorable outcome. These results underscore the need for timely and adequate treatment for tuberculosis and HIV infection.

Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.

Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens.

Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study.

BACKGROUND: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen. METHODS AND FINDINGS: We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse. CONCLUSIONS: MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.

Nonsteroidal anti-inflammatory drugs and exacerbations of inflammatory bowel disease.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesics for treatment of variety of pain and inflammatory conditions. Their effects on the gastrointestinal tract are well described, but their possible propensity to cause clinical relapse in patients with inflammatory bowel disease (IBD) remains somewhat unclear. AIM: We reviewed case reports, case-control and cohort studies, as well as clinical trials of NSAIDs in patients with quiescent IBD in order to better assess the magnitude and type of effect. RESULTS: The published literature on this subject is of mixed quality and many of the studies are open to criticism. The majority of patients with IBD tolerate these medications, while in the sole clinical trial of NSAIDs 20% experienced a clinical and laboratory documented relapse of disease, within 7-10 days of NSAID ingestion. The data on cyclooxygenase (COX)-2-selective anti-inflammatory analgesic are somewhat unclear, but nimesulide, celecoxib and etoricoxib do not appear to be associated with relapse of disease. CONCLUSION: Conventional NSAIDs may cause clinical relapse in about 20% of patients with quiescent IBD, which may be due to dual inhibition of the COX enzymes. Certain COX-2-selective NSAIDs appear to be safe.

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.

BACKGROUND: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. METHODS: To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. CONCLUSIONS: Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.

Treatment outcomes for extensively drug-resistant tuberculosis and HIV co-infection.

High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3-9 drugs); 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) withdrew from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome.

Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study.

BACKGROUND: The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries. METHODS: From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis. FINDINGS: Among 1278 patients, 43·7% showed resistance to at least one second-line drug, 20·0% to at least one second-line injectable drug, and 12·9% to at least one fluoroquinolone. 6·7% of patients had XDR tuberculosis (range across study sites 0·8-15·2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries. INTERPRETATION: Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies. FUNDING: US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare.

Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study.

BACKGROUND: Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes. METHODS: In a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion. FINDINGS: 195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0.13). Treatment with moxifloxacin (hazard ratio 0.11, 95% CI 0.01-0.82; p=0.03), previous culture-proven multidrug-resistant tuberculosis (5.21, 1.93-14.1; p=0.001), and number of drugs used in a regimen (0.59, 0.45-0.78, p<0.0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0.38, 0.18-0.80; p=0.01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment. INTERPRETATION: In South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity. FUNDING: South African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership.

High incidence of hospital admissions with multidrug-resistant and extensively drug-resistant tuberculosis among South African health care workers.

BACKGROUND: Nosocomial transmission has been described in extensively drug-resistant tuberculosis (XDR-TB) and HIV co-infected patients in South Africa. However, little is known about the rates of drug-resistant tuberculosis among health care workers in countries with high tuberculosis and HIV burden. OBJECTIVE: To estimate rates of multidrug-resistant tuberculosis (MDR-TB) and XDR-TB hospitalizations among health care workers in KwaZulu-Natal, South Africa. DESIGN: Retrospective study of patients with drug-resistant tuberculosis who were admitted from 2003 to 2008 for the initiation of drug-resistant tuberculosis therapy. SETTING: A public tuberculosis referral hospital in KwaZulu-Natal, South Africa. PARTICIPANTS: 231 health care workers and 4151 non-health care workers admitted for initiation of MDR-TB or XDR-TB treatment. MEASUREMENTS: Hospital admission rates and hospital admission incidence rate ratios. RESULTS: Estimated incidence of MDR-TB hospitalization was 64.8 per 100,000 health care workers versus 11.9 per 100,000 non-health care workers (incidence rate ratio, 5.46 [95% CI, 4.75 to 6.28]). Estimated incidence of XDR-TB hospitalizations was 7.2 per 100,000 health care workers versus 1.1 per 100,000 non-health care workers (incidence rate ratio, 6.69 [CI, 4.38 to 10.20]). A higher percentage of health care workers than non-health care workers with MDR-TB or XDR-TB were women (78% vs. 47%; P < 0.001), and health care workers were less likely to report previous tuberculosis treatment (41% vs. 92%; P < 0.001). HIV infection did not differ between health care workers and non-health care workers (55% vs. 57%); however, among HIV-infected patients, a higher percentage of health care workers were receiving antiretroviral medications (63% vs. 47%; P < 0.001). LIMITATION: The study had an observational retrospective design, is subject to referral bias, and had no information on type of health care work or duration of occupational exposure to tuberculosis. CONCLUSION: Health care workers in this HIV-endemic area were substantially more likely to be hospitalized with either MDR-TB or XDR-TB than were non-health care workers. The increased risk may be explained by occupational exposure, underlining the urgent need for tuberculosis infection-control programs.

Usefulness of Elevated Troponin to Predict Death in Patients With COVID-19 and Myocardial Injury.

Elevations in troponin levels have been shown to predict mortality in patients with coronavirus disease 2019 (COVID-19). The role of inflammation in myocardial injury remains unclear. We sought to determine the association of elevated troponin with mortality in a large, ethnically diverse population of patients hospitalized with COVID-19, and to determine the association of elevated inflammatory markers with increased troponin levels. We reviewed all patients admitted at our health system with COVID-19 from March 1 to April 27, 2020, who had a troponin assessment within 48 hours of admission. We used logistic regression to calculate odds ratios (ORs) for mortality during hospitalization, controlling for demographics, co-morbidities, and markers of inflammation. Of 11,159 patients hospitalized with COVID-19, 6,247 had a troponin assessment within 48 hours. Of these, 4,426 (71%) patients had normal, 919 (15%) had mildly elevated, and 902 (14%) had severely elevated troponin. Acute phase and inflammatory markers were significantly elevated in patients with mildly and severely elevated troponin compared with normal troponin. Patients with elevated troponin had significantly increased odds of death for mildly elevated compared with normal troponin (adjusted OR, 2.06; 95% confidence interval, 1.68 to 2.53; p < 0.001) and for severely elevated compared with normal troponin (OR, 4.51; 95% confidence interval, 3.66 to 5.54; p < 0.001) independently of elevation in inflammatory markers. In conclusion, patients hospitalized with COVID-19 and elevated troponin had markedly increased mortality compared with patients with normal troponin levels. This risk was independent of cardiovascular co-morbidities and elevated markers of inflammation.

Presentation, patterns and predictive value of baseline liver tests on outcomes in COVID-19 patients without chronic liver disease.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is known to cause abnormal hepatic enzymes. The long term consequences of such elevations are uncertain. AIM: To assessed the prevalence and prognostic value of initial liver enzymes in a large cohort of COVID-19 patients. METHODS: We reviewed electronic medical records of 10614 COVID-19 patients without known chronic liver disease who were admitted to our health system from March 1, 2020, to April 30, 2020. We analyzed baseline demographics and liver chemistries. The primary outcome was in-hospital mortality, and the secondary outcome was a composite of in-hospital mortality or need for mechanical ventilation. RESULTS: Subjects with abnormal liver tests had increased risks of mortality and composite outcome when compared to patients with normal measurements on unadjusted analysis and after adjustment for demographic factors. CONCLUSION: In our diverse patient population, liver enzyme abnormalities are associated with increased mortality and the need for mechanical ventilation in subjects without chronic liver disease. Cholestasis patients are at the greatest risk for poor outcomes.

Risk factors and outcomes for acute-on-chronic liver failure in COVID-19: a large multi-center observational cohort study.

OBJECTIVE: Coronavirus disease 2019 [COVID-19] infection in patients with chronic liver disease [CLD] may precipitate acute-on-chronic liver failure [ACLF]. In a large multi-center cohort of COVID-19-infected patients, we aim to analyze (1) the outcomes of patients with underlying CLD [with and without cirrhosis] and (2) the development and impact of ACLF on in-hospital mortality. DESIGN: We identified 192 adults with CLD from among 10,859 patients with confirmed COVID-19 infection (admitted to any of 12 hospitals in a New York health care system between March 1, 2020 and April 27, 2020). ACLF was defined using the EASL-CLIF Consortium definition. Patient follow-up was through April 30, 2020, or until the date of discharge, transfer, or death. RESULTS: Of the 84 patients with cirrhosis, 32 [38%] developed ACLF, with respiratory failure [39%] and renal failure [26%] being the most common. Hispanic/Latino ethnicity was particularly at higher risk of in-hospital mortality [adjusted HR 4.92, 95% 1.27-19.09, p < 0.02] in cirrhosis despite having lower risk of development of ACLF [HR 0.26, 95% CI 0.08-0.89, p = 0.03]. Hypertension on admission predicted development of ACLF [HR 3.46, 95% CI 1.12-10.75, p = 0.03]. In-hospital mortality was not different between CLD patients with or without cirrhosis [p = 0.24] but was higher in those with cirrhosis who developed ACLF [adjusted HR 9.06, 95% CI 2.63-31.12, p < 0.001] with a trend for increased mortality by grade of ACLF [p = 0.002]. There was no difference in in-hospital mortality between the CLD cohort compared to matched control without CLD (log rank, p = 0.98) and between the cirrhosis cohort compared to matched control without cirrhosis (log rank, p = 0.51). CONCLUSION: Development of ACLF is the main driver of increased in-hospital mortality in hospitalized patients with COVID-19 infection and cirrhosis.

Limiting hospital resources for acute appendicitis in children: Lessons learned from the U.S. epicenter of the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic resulted in the suspension of nonemergent surgeries throughout New York. Our tertiary care children's hospital pivoted towards a brief trial of intravenous (IV) antibiotic therapy in all patients in order to limit operating room (OR) utilization and avoid prolonged hospital stays. We describe our pandemic-based strategy for non-operative management (NOM) of appendicitis but with a limited duration of IV antibiotics. METHODS: We performed a retrospective study of children treated for acute appendicitis at our center from 3/31/2020 to 5/3/2020 during the peak of the New York pandemic. We compared appendicitis volume to similar months in prior years. We evaluated failure of NOM, length of stay, and compared characteristics of children we successfully treated with our expanded NOM protocol to previously published inclusion criteria for NOM. RESULTS: 45.5% of children (25/55) with acute appendicitis underwent NOM. Of the 30 who underwent surgery, 13 had complicated appendicitis while 17 had simple appendicitis. Three patients were COVID-positive, although none had respiratory symptoms. The majority of patients presenting with acute appendicitis (78.2%) did not meet previously published criteria for NOM. CONCLUSIONS: We treated a similar volume of children with acute appendicitis during the pandemic compared to prior years. We applied non-operative management to nearly half our patients, even as we expanded inclusion criteria for NOM to reduce OR utilization, but limited the duration of the antibiotic trial to avoid prolonged hospital stays. TYPE OF STUDY: Retrospective study. LEVEL OF EVIDENCE: IV.

The Association of Structural Inequities and Race With Out-of-Hospital Sudden Death During the COVID-19 Pandemic.

[Figure: see text].