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.

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.

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.

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

[Figure: see text].

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.

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.

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.

Characteristics and risk factors associated with critical illness in pediatric COVID-19.

BACKGROUND: While much has been reported regarding the clinical course of COVID-19 in children, little is known regarding factors associated with organ dysfunction in pediatric COVID-19. We describe critical illness in pediatric patients with active COVID-19 and identify factors associated with PICU admission and organ dysfunction. This is a retrospective chart review of 77 pediatric patients age 1 day to 21 years admitted to two New York City pediatric hospitals within the Northwell Health system between February 1 and April 24, 2020 with PCR + SARS-CoV-2. Descriptive statistics were used to describe the hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. RESULTS: Forty-seven patients (61%) were admitted to the general pediatric floor and thirty (39%) to the PICU. The majority (97%, n = 75) survived to discharge, 1.3% (n = 1) remain admitted, and 1.3% (n = 1) died. Common indications for PICU admission included hypoxia (50%), hemodynamic instability (20%), diabetic ketoacidosis (6.7%), mediastinal mass (6.7%), apnea (6.7%), acute chest syndrome in sickle cell disease (6.7%), and cardiac dysfunction (6.7%). Of PICU patients, 46.7% experienced any significant organ dysfunction (pSOFA > = 2) during admission. Patients aged 12 years or greater were more likely to be admitted to a PICU compared to younger patients (p = 0.015). Presence of an underlying comorbidity was not associated with need for PICU admission (p = 0.227) or organ dysfunction (p = 0.87). Initial white blood cell count (WBC), platelet count, and ferritin were not associated with need for PICU admission. Initial C-reactive protein was associated with both need for PICU admission (p = 0.005) and presence of organ dysfunction (p = 0.001). Initial WBC and presenting thrombocytopenia were associated with organ dysfunction (p = 0.034 and p = 0.003, respectively). CONCLUSIONS: Age over 12 years and initial CRP were associated with need for PICU admission in COVID-19. Organ dysfunction was associated with elevated admission CRP, elevated WBC, and thrombocytopenia. These factors may be useful in determining risk for critical illness and organ dysfunction in pediatric COVID-19.

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.

Early Experience with Variant Two-Stage Approach in Surgical Management of Inflammatory Bowel Disease Colitis in the Pediatric Population.

Introduction: Multistaged surgical management of inflammatory bowel disease (IBD), culminating in ileal pouch-anal anastomosis (IPAA), can provide cure for refractory IBD symptoms while maintaining fecal continence. Surgical approaches to IPAA historically included a three-stage approach done by subtotal colectomy (STC) followed by IPAA with diversion. Recently, a variant two-stage approach without diversion at IPAA has become increasingly utilized, yet evidence of the efficacy of this approach is limited. Methods: Retrospective review of patients aged 5-21 years who underwent initial STC, followed by a total proctocolectomy with IPAA +/- diversion for medically refractory IBD from January 2010 to August 2018 (n = 25). Results: Majority of IPAA procedures were done laparoscopically (88.5%). Thirteen patients (52%) underwent two-stage variant IPAA. There were no differences in readmission rates (66.7% versus 53.8%, P = .5) or reoperation rates (50% versus 30.8%, P = .3) between groups. Forty percent of patients experienced a complication after IPAA. Complication rates were similar between two-stage and three-stage IPAA groups (38.5% versus 50%, P = .33). Complications within the two-stage group included anastomotic leak, pouchitis, wound infection, anastomotic stricture, and incarcerated hernia. Complications within the three-stage group included bloody ostomy output, dehydration, anastomotic stricture, small bowel obstruction, and pouch volvulus. Conclusions: Treatment of refractory IBD in children remains challenging, but STC followed by IPAA is an approach that provides symptom relief and preserves continence. Complication rates remained unchanged regardless of whether IPAA was conducted with or without diversion, demonstrating that the two-stage variant approach is a safe and feasible treatment that may reduce subsequent anesthesia exposure and trips to the operating room.

Modified open technique for laparoscopic gastrostomy tube placement results in more leakage post operatively than Seldinger technique.

BACKGROUND: Laparoscopic gastrostomy tube (GT) placement is a common procedure and frequent cause of morbidity. Some surgeons perform a Seldinger technique (ST), while others perform a modified open technique (MOT). We hypothesized that the modified open technique would result in more complications. METHODS: A prospective study of primary GT placed 12/2016-06/2018, ensuring at least 6 months follow up. We assessed any episode of granulation tissue, troublesome leaking, tube dislodgment, and infection requiring antibiotic or drainage. RESULTS: 92 GT were placed, with 56 were placed as modified open (60.9%). 34 children (37.0%) developed granulation tissue, 18 children (19.6%) experienced tube dislodgment, and 6 children (6.5%) developed a site infection, with no difference depending on technique (P = 0.56, 0.29, and 0.76, respectively). Following ST, 2 children developed leakage (5.6%), whereas 15 children (26.8%) had leakage following the MOT (P = 0.01). CONCLUSION: MOT resulted in significantly more leaks. Other complications were similar between groups. Surgeons choosing MOT should be mindful of the size of gastrotomy at time of surgery, as this may result in increased complications.

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.

Emergency pediatric surgery: Comparing the economic burden in specialized versus nonspecialized children's centers.

BACKGROUND: The American College of Surgeons has developed a verification program for children's surgery centers. Highly specialized hospitals may be verified as Level I, while those with fewer dedicated resources as Level II or Level III, respectively. We hypothesized that more specialized children's centers would utilize more resources. STUDY DESIGN: We performed a retrospective study of the Maryland Health Services Cost Review Commission (HSCRC) database from 2009 to 2013. We assessed total charge, length of stay (LOS), and charge per day for all inpatients with an emergency pediatric surgery diagnosis, controlling for severity of illness (SOI). Using published resources, we assigned theoretical level designations to each hospital. RESULTS: Two hospitals would qualify as Level 1 hospitals, with 4593 total emergency pediatric surgery admissions (38.5%) over the five-year study period. Charges were significantly higher for children treated at Level I hospitals (all P<0.0001). Across all SOI, children at Level I hospitals had significantly longer LOS (all P<0.0001). CONCLUSION: Hospitals defined as Level II and Level III provided the majority of care and were able to do so with shorter hospitalizations and lower charges, regardless of SOI. As care shifts towards specialized centers, this charge differential may have significant impact on future health care costs. LEVEL OF EVIDENCE: Level III Cost Effectiveness Study.

The Right Way to Teach Left-Handed Residents: Strategies for Training by Right Handers.

PURPOSE: Left-handed (LH) residents remain underrepresented among surgical trainees, and there are few available data on how best to train them. The challenge is amplified when pairing a LH resident with a right-handed (RH) mentor. This report provides recommendations on how to improve the training of LH surgeons in a safe and effective manner. METHODS: A comprehensive literature review was performed using different databases and search engines to identify all articles relevant to the training of LH residents. RESULTS: A total of 40 articles highlighted the challenges for LH surgical residents and RH mentors. Our recommendations are based on the following 4 themes: identifying inherent differences in left vs. RH residents, providing guidance to RH mentors training LH residents, adapting the RH environment to the LH surgeon, and maximizing safety during training. CONCLUSION: An organized approach needs to be taken in training the LH resident. Changes should be instituted at program-wide and national levels to ensure that the training experience of the sinistral surgical resident is optimized.

Clinical and symptom scores are significantly correlated with fecal microbiota features in patients with symptomatic uncomplicated diverticular disease: a pilot study.

BACKGROUND: There is growing consensus that symptomatic uncomplicated diverticular disease is a chronic inflammatory condition, and that alterations in the fecal microbiota may contribute to its pathogenesis. OBJECTIVE: The aim of this study was to relate the fecal microbiota composition in symptomatic uncomplicated diverticular disease to measures of inflammation, symptoms, and history of previous acute diverticulitis. PARTICIPANTS AND METHODS: Fecal microbiota composition in 28 individuals with symptomatic uncomplicated diverticular disease was characterized by 16S RNA gene amplicon sequencing. Microbiota composition was related to clinical history, symptom and inflammation measures, and demographic variables. RESULTS: Previous acute diverticulitis was associated with higher relative abundance of Pseudobutyrivibrio, Bifidobacterium, Christensenellaceae family, and Mollicutes RF9 order (P=0.004, 0.006, 0.010, and 0.019, respectively), but not microbiota alpha or beta diversity. A higher bloating severity score was significantly correlated with a higher relative abundance of Ruminococcus (P=0.032), and significantly inversely correlated with the relative abundance of the Roseburia (P=0.002). Fecal calprotectin levels were positively correlated with alpha diversity (Shannon index, P=0.005) and the relative abundance of Lactobacillus (P=0.004). Pain score was positively correlated with the relative abundance of Cyanobacterium (adjusted P=0.032). CONCLUSION: Patient symptoms in symptomatic diverticular disease are significantly correlated with features of the fecal microbiota. Our findings suggest the potential utility of therapies that target intestinal microbiology, such as dietary prebiotic supplements.

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.

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination.

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.