Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis.

BACKGROUND: The World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage. METHODS: We evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing. RESULTS: There was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective. CONCLUSION: Pooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin.

BACKGROUND: Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes. PATIENTS AND METHODS: We performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors. RESULTS: A total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings. CONCLUSION: Prior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.

Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer.

OBJECTIVES: To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease. PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan-Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42-0.88) and PFS (aHR 0.63, 95% CI 0.45-0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately. CONCLUSION: Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study's retrospective nature, lack of randomization, and possible selection and confounding biases.

Prevalence of neutralising antibodies against SARS-CoV-2 in acute infection and convalescence: A systematic review and meta-analysis.

BACKGROUND: Individuals infected with SARS-CoV-2 develop neutralising antibodies. We investigated the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how this proportion varies with selected covariates. METHODOLOGY/PRINCIPAL FINDINGS: This systematic review and meta-analysis examined the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how these proportions vary with selected covariates. Three models using the maximum likelihood method assessed these proportions by study group, covariates and individually extracted data (protocol CRD42020208913). A total of 983 reports were identified and 27 were included. The pooled (95%CI) proportion of individuals with neutralising antibodies was 85.3% (83.5-86.9) using the titre cut off >1:20 and 83.9% (82.2-85.6), 70.2% (68.1-72.5) and 54.2% (52.0-56.5) with titres >1:40, >1:80 and >1:160, respectively. These proportions were higher among patients with severe COVID-19 (e.g., titres >1:80, 84.8% [80.0-89.2], >1:160, 74.4% [67.5-79.7]) than those with mild presentation (56.7% [49.9-62.9] and 44.1% [37.3-50.6], respectively) and lowest among asymptomatic infections (28.6% [17.9-39.2] and 10.0% [3.7-20.1], respectively). IgG and neutralising antibody levels correlated poorly. CONCLUSIONS/SIGNIFICANCE: 85% of individuals with proven SARS-CoV-2 infection had detectable neutralising antibodies. This proportion varied with disease severity, study setting, time since infection and the method used to measure antibodies.

COVID-19 Mortality and Case-Fatality Rates in Sergipe State, Northeast Brazil, From April to June 2020.

Information on how coronavirus disease 2019 (COVID-19) mortality is related to population characteristics in low- and middle-income countries is still limited. We described the deaths from COVID-19 in Sergipe state, Northeast Brazil, from April 2 to June 27, 2020. For this purpose, we conducted a study composed of (i) a case series study of all deaths due to COVID-19 and (ii) a population-based study to verify the behavior of the mortality and case-fatality rates (CFR) related to COVID-19. Data from 605 deaths due to COVID-19 were used to describe the characteristics of individuals with the disease, as well as the differences in gender, age, and comorbidities. Additionally, population data were extracted to estimate the mortality and CFR by population stratum. We also performed an adjusted CFR analysis including a time lag of 14 days between the onset of symptoms and reporting deaths. Of the 605 patients included in this study, 321 (53.1%) were males and the median age was 67.0 years. Most patients (n = 447, 73.9%) who died from COVID-19 had at least one pre-existing clinical condition. The mortality rate was 29.3 deaths per 100,000 inhabitants and the crude CRF was 2.6% (95% CI 2.4-2.8). CFR was higher in males (3.1%, 95% CI 2.8-3.4; p < 0.001) and people aged ≥60 years (14.2%, 95% CI 13.0-15.6; p = 0.042). About 25% of patients died during the first 24-h post-hospital admission. The adjusted CFR for a 14-day time lag was ~2-fold higher than the crude CFR over the study period.

Systematic Review of Pooling Sputum as an Efficient Method for Xpert MTB/RIF Tuberculosis Testing during the COVID-19 Pandemic.

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes.

OBJECTIVES: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line). RESULTS: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively). CONCLUSION: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.

Association Between Arthrogryposis and Mortality in Infants With Congenital Zika Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND: Intrauterine Zika virus infection is associated with neurological disorders and other problems, including such as impaired visual and hearing function and orthopedic abnormalities, including arthrogryposis. We systematically investigated the prevalence of arthrogryposis in infants with congenital Zika syndrome and the respective risk of mortality. METHODS: We conducted a systematic review and meta-analysis of reports published in PubMed, Web of Science, SCOPUS, and World Health Organization Global Index Medicus databases, using the keywords Zika virus and arthrogryposis and related terms. RESULTS: After screening titles and abstracts, a total of four studies were included. Arthrogryposis was not associated with increased risk for fetal demise (risk ratio, 3.33; 95% confidence interval, 0.73 to 15.26). However, arthrogryposis was associated with a 13-fold increased risk of mortality in neonates with congenital Zika syndrome (risk ratio, 13.11; 95% confidence interval, 3.74 to 45.92) than neonates with congenital Zika syndrome but without arthrogryposis. CONCLUSIONS: Neonates with both congenital Zika syndrome and arthrogryposis had higher morbidity and mortality risks, making it necessary to implement protocols for the early identification of neuromuscular changes and appropriate management of patients.

Spatiotemporal clustering, social vulnerability and risk of congenital syphilis in northeast Brazil: an ecological study.

BACKGROUND: To investigate the spatial distribution of congenital syphilis (CS) and its association to social vulnerability indexes in northeast Brazil. METHODS: This was an ecological study referring to all cases of CS and CS deaths recorded in the northeast region of Brazil from 2008 to 2015. Data were obtained from three Brazilian information systems. We examined statistical correlations between CS indicators by state and municipality and their socioeconomic and social vulnerability characteristics. We used Bayesian empirical local models to identify fluctuations of the indicators. Spatial statistical tests were used to identify spatial clusters and the municipalities at high risk of CS. RESULTS: The incidence of CS ranged from 2.1 cases/1000 live births (LB) in 2008 to 6.9/1000 LB in 2015, with an annual increase of 19.9% (p < 0.001). The mortality coefficient of CS ranged from 2.9/1000 LB in 2008 to 6.5/1000 LB in 2015, resulting in an annual increase of 15.1% (p < 0.001). Nine spatial clusters were identified. Cases of congenital syphilis occurred in well-defined spatiotemporal clusters and in areas with high levels of social vulnerability. CONCLUSIONS: CS incidence is associated with social vulnerability. CS control programmes should target spatial clusters and populations with high levels of social vulnerability.

Prolonged Fecal Shedding of SARS-CoV-2 in Pediatric Patients: A Quantitative Evidence Synthesis.

The aim of the study was to investigate differences in viral shedding in respiratory and fecal samples from children with novel coronavirus disease 19. We searched PubMed, SCOPUS, Embase, and Web of Science databases to identify pediatric studies comparing the pattern of fecal and respiratory shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Summary estimates were calculated using random-effects models. Four studies reporting data from 36 children were included. A higher proportion of children had viral shedding in stools after 14 days of symptoms onset compared to respiratory samples (risk ratio = 3.2, 95% confidence interval 1.2-8.9, I2 = 51%). Viral RNA shedding was longer in fecal samples with a mean difference of approximately 9 days (mean difference = 8.6, 95% confidence interval 1.7-15.4, I2 = 77%) compared with respiratory samples. SARS-CoV-2 shedding seems to be present in feces for a longer time than in the respiratory tract of children. Although fecal SARS-CoV-2 presence in feces do not confirm its transmissibility, the high and fast spread of the novel coronavirus disease 19 worldwide indicate other transmission routes are also plausible.

Preservation of Forensic Evidence by Nurses in a Prehospital Emergency Care Service in Brazil.

Violence is a growing public health problem worldwide. Nurses increasingly must perform forensic procedures with the responsibility to collect, document, preserve, and store evidence that may be used in the investigation of a violent crime. However, few nurses receive education in forensic evidence collection as part of their training. This study aimed to evaluate the relationship between nurses' knowledge and performance of forensic evidence procedures. This is a descriptive survey study of nurses working in a prehospital emergency care service in Aracaju, Brazil. A 32-question survey related to forensic evidence knowledge and procedures was completed by 128 nurses. Descriptive statistics and Kendall's Tau-b were used to describe the sample and evaluate correlations. Results revealed an overall linear relationship between knowledge and performance of forensic evidence procedures (r = .69). The strongest correlation was between knowledge and documentation (r = .71). Weaker correlations were demonstrated between knowledge and evidence collection (r = .47), evidence preservation (r = .47), and overall evidence procedure execution (r = .53). Forensic nursing knowledge is related to forensic evidence procedure performance. Although the study showed that nurses agreed forensic evidence procedures are important for criminal investigations, most reported they were unprepared to carry out these procedures. The need for additional training and adherence to established institutional protocols are identified as contributing factors.

Preservation of forensic traces by health professionals in a hospital in Northeast Brazil.

BACKGROUND: Health professionals who work in emergency services must be prepared for the recognition, collection, storage, preservation and documentation of all physical traces related to injuries or crime, because failures in these processes may compromise any forensic analysis. We, therefore, investigated emergency health professionals' levels of knowledge about these processes and their abilities to implement them in practice during the care of victims of violence in an emergency unit of a specialized trauma hospital. METHODS: This was a survey to describe the knowledge of professionals working in the emergency department of the Sergipe Urgent Care Hospital (HUSE) in Sergipe state, Northeast Brazil about the preservation of forensic traces and their ability to implement the necessary related processes in practice. Their knowledge of the preservation of forensic materials and their abilities to implement the processes related to their preservation were assessed using the Portuguese version of the Questionnaire on the Preservation of Forensic Traces in Victim Assistance. RESULTS: A total of 144 health professionals completed the questionnaire, of whom 23 (16 %) were physicians, 33 (22.9 %) nurses and 88 (61.1 %) nursing technicians. Most physicians (15/65.2 %) reported knowing between 50 and 70 % of the required procedures, and the majority of nurses and nursing technicians knew less than 50 % (15/45.5 % and 72/81.8 %, respectively). Regarding their actual implementation, most physicians and nurses reported performing between 50 % and 70 % of the procedures (22/95.7 % and 15/45.5 %, respectively), while nursing technicians reported performing less than 50 % (55/62.5 %). CONCLUSION: Most professionals in the three professions (physician, nurse and nursing technician) knew less than 50 % of the required procedures for the documentation, collection and preservation of forensic traces, which explains the low implementation of most of the actions, particularly those related to the collection and preservation of traces.

Risk Factors for Physical Disability in Patients With Leprosy: A Systematic Review and Meta-analysis.

IMPORTANCE: The World Health Organization (WHO) 2016-2020 Global Leprosy Strategy aims to reinvigorate efforts to control leprosy and avert leprosy disability to less than 1 per million population. OBJECTIVE: To systematically identify clinical factors associated with physical disability in patients with leprosy. DATA SOURCE: Searches were conducted in Scopus, PubMed, and Web of Science databases to identify studies published from January 23, 1988, to May 23, 2018, using the keywords leprosy and physical disability and related terms. STUDY SELECTION: Studies that evaluated patients using the WHO leprosy disability grading system and reported the number of patients with and without disability by clinical characteristics were included. DATA EXTRACTION AND SYNTHESIS: The odds ratio (OR) was used as a measure of association between the clinical features and physical disability. Summary estimates were calculated using random-effects models. MAIN OUTCOMES AND MEASURES: The primary outcome was physical disability according to the WHO disability classification. The association between clinical features and physical disability was evaluated. RESULTS: The search identified 2447 reports. After screening titles and abstracts, 177 full-text articles were assessed for eligibility, and 32 studies were included in the systematic review; 24 of the 32 studies included sex information (39 571 patients), of whom 24 218 (61.2%) were male. Male patients with leprosy were more likely to have physical disability than female patients with leprosy (pooled OR, 1.66; 95% CI, 1.43-1.93; I2, 81.3%; P < .001). Persons with multibacillary leprosy were 4-fold more likely to have physical disability than those with paucibacillary leprosy (pooled OR, 4.32; 95% CI, 3.37-5.53; I2, 88.9%, P < .001). Patients having leprosy reactions were more likely to have disability (pooled OR, 2.43; 95% CI, 1.35-4.36; I2, 92.1%; P < .001). Patients with lepromatous leprosy experienced 5- to 12-fold higher odds of disability. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis confirms the association between the presence of physical disabilities and male sex, multibacillary leprosy, leprosy reactions, and lepromatous presentation. These findings can guide the development of targeted interventions for early identification of individuals at greater risk of developing physical disabilities and education campaigns to promote early consultation to institute treatment for leprosy reactions and prevent physical disability.

Association between histamine-2 receptor antagonists and adverse outcomes in neonates: A systematic review and meta-analysis.

BACKGROUND: The use of histamine-2 receptor antagonists (H2RA) in neonates is still debated because of possible risk of infection, necrotizing enterocolitis (NEC) and increased mortality. AIM: To review whether the use of H2RA in neonates admitted to neonatal intensive care units (NICU) is associated with infection, NEC or mortality. MATERIALS AND METHOD: We performed a systematic search in PubMed, Web of Science and SCOPUS databases using the terms "histamine-2 receptor antagonists", "infection", "necrotizing enterocolitis", "mortality", "neonates" and related terms to identify studies published up to April 30, 2017. We included studies conducted in hospitalized neonates and exposed to H2RA. The primary outcomes were infection, NEC and mortality. We included reports of infections with clinical signs and positive culture, and NEC according to Bell stages (stage ≥II) based on standardised clinical and radiologic criteria. Among 1,144 studies identified, 10 fulfilled the selection criteria. Information extracted included study design, sample size and number of participants, along with the outcomes of interest. We conducted a meta-analysis of adjusted data and pooled estimates of infection, NEC and mortality are reported as odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: Ten studies were analysed. There were substantial associations between H2RA and infection (pooled OR: 2.09; 95%CI: 1.35-3.24; P = 0.001) and NEC (pooled OR: 2.81, 95%CI: 1.19-6.64; P = 0.02) but not with the mortality risk (pooled OR: 1.76; 95%CI: 0.50-6.16; P: 0.38). CONCLUSION: Current evidence suggests that H2RA is associated with an increased risk of infection and NEC, but not with mortality in neonates admitted to NICU. The use of H2RA in neonates must be stringently considered when necessary.

Rotavirus Genotypes Circulating in Brazil Before and After the National Rotavirus Vaccine Program: A Review.

BACKGROUND: Rotavirus vaccines created the opportunity to control diarrhea in children. We describe the rotavirus genotypes before and after the rotavirus vaccine introduction in Brazil. METHODS: We reviewed the distribution of rotavirus genotypes in Brazil before and after vaccine introduction by searching publication. RESULTS: Eighty-six studies reported 6884 (15.2%) rotavirus episodes among 45,305 children. Rotavirus caused 22.4% and 11.6% of cases before and after vaccine introduction. G1P[8], G9P[8] and G2P[4] heterotypic strains were most common before and after vaccine introduction. CONCLUSIONS: The vaccines may have selected heterotypic strains in this highly vaccinated population.

Case Report: Microcephaly in Twins due to the Zika Virus.

Recent studies have demonstrated an association between congenital Zika virus (ZIKV) infection and microcephaly; however, to date, there have been no reports on the consequences of ZIKV infection on fetuses in twin pregnancies. Herein, we reported on the first case of a monochorionic diamniotic (MCDA) twin pregnancy having ZIKV-related microcephaly. Our findings suggested that, in an MCDA twin pregnancy, the ZIKV may cause infection in both fetuses, resulting in severe abnormalities in the central nervous system due to neural cell destruction and the disruption of the normal development processes of the brain. This case report and other similar twin cases may help to understand the pathogenesis and to confirm the etiology of ZIKV as a teratogenic microorganism.

Use of ranitidine is associated with infections in newborns hospitalized in a neonatal intensive care unit: a cohort study.

BACKGROUND: The inhibition of gastric acid secretion with ranitidine is frequently prescribed off-label to newborns admitted to neonatal intensive care units (NICU). Some studies show that the use of inhibitors of gastric acid secretion (IGAS) may predispose to infections and necrotising enterocolitis (NEC), but there are few data to confirm this association. This study aimed to compare the rates of neonatal infections and NEC among preterm infants (<37 weeks gestation) hospitalised in a NICU exposed or not to treatment with ranitidine. METHODS: A retrospective cohort study was conducted with all consecutive preterm newborns admitted to a NICU between August-2014 and October-2015. The rates of infection, NEC, and death of newborns exposed or not to ranitidine were recorded. RESULTS: A total of 300 newborns were enrolled, of which 115 had received ranitidine and 185 had not. The two groups were similar with regard to the main demographic and clinical characteristics. Forty-eight (41.7%) of the 115 infants exposed to ranitidine and 49 (26.5%) of the 185 infants not exposed were infected (RR = 1.6, 95%CI 1.1-2.2, p = 0.006). The late onset (>48 h) blood culture positive infection rate was higher in the group exposed to ranitidine than in the untreated group (13.0% vs. 3.8%, p = 0.001). There was no significant association between the use of ranitidine and NEC (Bell stage >II) (p = 0.36). The mortality rate risk was 4-fold higher in infants receiving ranitidine (16.5% vs. 8.6%, p < 0.001). CONCLUSION: Ranitidine use in neonates was associated with an increased risk of infections and mortality, but not with NEC.