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Background: Evidence regarding effectiveness of BNT162b2 mRNA COVID-19 vaccine against Omicron in Latin America is limited. We estimated BNT162b2 effectiveness against symptomatic COVID-19 in Brazil when Omicron was predominant., Methods: This prospective test-negative, case-control study was conducted in Toledo, Brazil, following a mass COVID-19 vaccination with BNT162b2. Patients were included if they were aged ≥12 years, sought care for acute respiratory symptoms in the public health system between November 3, 2021 and June 20, 2022, and were tested for SARS-CoV-2 using RT-PCR. In the primary analysis, we determined the effectiveness of two doses of BNT162b2 against symptomatic COVID-19., Results: A total of 4,574 were enrolled; of these, 1,758 patients (586 cases and 1,172 controls) were included in the primary analysis. Mean age was 27.7 years, 53.8 % were women, and 90.1 % had a Charlson comorbidity index of zero. Omicron accounted for >97 % of all identified SARS-CoV-2 variants, with BA.1 and BA.2 accounting for 84.3 % and 12.6 %, respectively. Overall adjusted estimate of two-dose vaccine effectiveness against symptomatic COVID-19 was 46.7 % (95 %CI, 19.9 %-64.6 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 94 days (IQR, 60-139 days). Effectiveness waned from 77.7 % at 7-29 days after receipt of a second dose to <30 % (non-significant) after ≥120 days., Conclusion: In a relatively young and healthy Brazilian population, two doses of BNT162b2 provided protection against symptomatic Omicron infection. However, this protection waned significantly over time, underscoring the need for boosting with variant-adapted vaccines in this population prior to waves of disease activity., Trial Registration Number: ClinicalTrials.gov number, NCT05052307 (https://clinicaltrials.gov/ct2/show/NCT05052307)., Competing Interests: Declaration of Competing Interest Rosa reports honoraria fee related to investigator activities from Pfizer, and research grants from Pfizer and Brazilian Ministry of Health. Falavigna reports honoraria fee related to investigator activities from Pfizer, consulting fees from Sanofi, Ultragenyx,Novartis, Alnylam, PTC and JCR, and honoraria for lectures from Janssen, Abbvie, Sanofi, Roche, Pfizer and Novartis. Manfio, Araujo, Cohen, Barbosa, Paula de Souza, Silva, Sganzerla, da Silva, Ferreira, Rodrigues, Maltempi de Souza de Souza, Oliveira, Gradia, Brandalize, Royer, and Luiz report honoraria fee for working in this study from Hospital Moinhos de Vento. Valluri, Srivastava, Julião, Melone, Allen, Kyaw, Spinardi, Castillo, and McLaughlin are Pfizer empolyees. Kucharski, and Pedrotti have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies., Methods: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined., Findings: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions., Interpretation: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors., Competing Interests: Declaration of Competing Interest Avraham Karasik has received research grants and consulting fees from Boehringer Ingelheim; research grants from Astra Zeneca; research grants, consulting fees, and speaker fees from Novo Nordisk. Daisuke Yabe has received consulting/lecture fees from Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Company Limited, and grants from Arkray Inc., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim, Ono Pharmaceutical Co. Ltd., Taisho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, and Terumo Corporation. Dae Jung Kim has received grants support from Boehringer Ingelheim, AstraZeneca, Sanofi-Aventis Korea, Jeil Pharmaceutical, and Chong Kun Dang, speaker fees from Boehringer-Ingelheim, Novo Nordisk, Boryung, Hanmi, Novartis, Donga ST, Celltrion, AstraZeneca, and Dong Wha Pharmaceuticals. Wayne HH Sheu has been an advisor and/or speaker for AstraZeneca, Bayer HealthCare, Boehringer Ingelheim Pharmaceuticals, Daiichi-Sankyo, Eli Lilly and Company, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Sanofi-Aventis, Takeda Pharmaceutical Company. Kamlesh Khunti has acted as a consultant, speaker or received consultation/lecture grants for investigator-initiated studies for Astra Zeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer. Francesco Zaccardi has received speaker fees from Boehringer Ingelheim and Napp Pharmaceuticals. Thomas Nyström has received unrestricted grants from AstraZeneca and NovoNordisk and has been a national advisor of Abbot, Amgen, Novo Nordisk, Sanofi-Aventis, Eli Lilly, MSD, and Boehringer Ingelheim. Leo Niskanen has received speaker and consulting fees from Boehringer Ingelheim, MSD, AstraZeneca, and Sanofi, research grant to the institution, consulting fees, and speaker fees from Novo Nordisk. Majken Linnemann Jensen, Fabian Hoti, Riho Klement are employees of IQVIA and contracted by Boehringer Ingelheim to conduct the analyses. Soulmaz Fazeli Farsani, Anouk Déruaz-Luyet are employees of Boehringer Ingelheim International GmbH. Moe H Kyaw was employee of Boehringer Ingelheim. Lisette Koeneman is employee of Eli Lilly & Company and owns stock of Eli Lilly & Company. Dorte Vistisen has received research grants from Bayer A/S, Sanofi, Novo Nordisk A/S, and Boehringer Ingelheim. She holds shares in Novo Nordisk A/S. Sigrun Halvorsen has received speaker fees from Sanofi, Novartis, Boehringer Ingelheim, Bayer, Pfizer, and Bristol-Myers Squibb. Gisle Langslet has received consulting/lecture fees from Amgen, Sanofi, and Boehringer Ingelheim. Elisabetta Patorno has received a research grant from Boehringer Ingelheim. Julio Núñez reports personal fees from AstraZeneca, Novartis, Boehringer-Ingelheim, Eli Lilly, Rovi, Novo Nordisk, and Vifor Pharma (outside the submitted work). Stefanie Lanzinger, Reinhard W Holl, Elise Chia-Hui Tan, Cheli Melzer-Cohen, Kyong Hwa, Bendix Carstensen: None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil's health system. This study aimed to examine clinical characteristics, overall vaccine uptake, and to assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period., Methods: A nationwide retrospective study was conducted using various Brazilian databases including, COVID-19 related databases, public health systems, and other surveillance/demographic datasets. Individuals with positive COVID-19 test results between January 1 2022 and April 30 2022, during Omicron BA.1/BA.2 wave, were identified. Patients' demographics, vaccine uptake, HCRU and corresponding costs were described by age groups., Results: A total of 8,160,715 (3.80%) COVID-19 cases were identified in the study cohort, ranging from 2.43% in <5 years to 62.05% in 19-49 years. The uptake of partial (Dose 1) or full immunization (Dose 2) was less than 0.1% in children aged <5 years, whereas in individuals ≥ 19 years, it exceeded 89.78% for Dose 1 and 84.07% for Dose 2. Overall booster vaccine uptake was 38.06%, which was significantly higher among individuals aged ≥ 65 years, surpassing 74.79%. Regardless of vaccination status, 87.2% cases were symptomatic, and 1.48% were hospitalized due to acute COVID-19 (<5 years: 2.33%, 5-11 years: 0.99%, 12-18 years: 0.32%, 19-49 years: 0.40%; 50-64 years: 1.50%, 65-74 years: 5.43%, and ≥ 75 years: 17.89%). Among the hospitalized patients ( n  = 120,450), 32.57% were admitted to ICU, of whom 31,283 (79.75%) individuals required mechanical ventilation (MV) support. The average cost per day in normal ward and ICU without MV in public/general hospital settings was $104.36 and $302.81, respectively. While average cost per day in normal ward and ICU with MV was $75.91 and $301.22 respectively., Conclusions: This study quantified the burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has continuously evolved, requiring the development of adapted vaccines. This study estimated the impact of the introduction and increased coverage of an Omicron-adapted bivalent booster vaccine in Thailand., Research Design and Methods: The outcomes of booster vaccination with an Omicron-adapted bivalent vaccine versus no booster vaccination were estimated using a combined cohort Markov decision tree model. The population was stratified into high- and standard-risk subpopulations. Using age-specific inputs informed by published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations., Results: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 97,596 cases 36,578 hospitalizations, 903 deaths, THB 3,119 million in direct medical costs, and THB 10,589 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (95%), hospitalizations (512%), infections (782%), direct costs (550%), and indirect costs (687%) compared to the base case., Conclusions: Broader vaccination with an Omicron-adapted bivalent booster vaccine could have significant public health and economic benefits in Thailand.

Background: Coronavirus disease 2019 (COVID-19) case numbers have increased following the emergence of the Omicron variant. This study estimated the impact of introducing and increasing the coverage of an Omicron-adapted bivalent booster vaccine in Malaysia., Research Design and Methods: A combined cohort Markov decision tree model was used to compare booster vaccination with an Omicron-adapted bivalent COVID-19 vaccine versus no booster vaccination in Malaysia. The model utilized age-specific data from January 2021 to March 2022 derived from published sources. The outcomes of interest included case numbers, hospitalizations, deaths, medical costs, and productivity losses. The population was stratified into high-risk and standard-risk subpopulations, and the study evaluated the benefits of increased coverage in different age and risk groups., Results: Vaccinating only high-risk individuals and those aged ≥ 65 years was estimated to avert 274,313 cases, 33229 hospitalizations, 2,434 deaths, Malaysian ringgit (MYR) 576 million in direct medical costs, and MYR 579 million in indirect costs. Expanding vaccination coverage in the standard-risk population to 75% was estimated to avert more deaths (31%), hospitalizations (155%), infections (206%), direct costs (206%), and indirect costs (281%)., Conclusions: These findings support broader population Omicron-adapted bivalent booster vaccination in Malaysia with potential for significant health and economic gains.

Background: The diagnosis of bacterial meningitis (BM) is problematic in young infants, as clinical features may be nonspecific or even absent. Cerebrospinal fluid (CSF) analysis usually confirms the diagnosis, but the CSF parameters can be normal also in culture-proven BM. Our objective was to identify the clinical and CSF indices, that quickly and without laboratory likely lead to the diagnosis of confirmed of probable BM in young infants in Angola., Methods: We conducted a prospective, observational, single-site study from February 2016 to October 2017 in the Pediatric Hospital of Luanda. All assessed infants showed symptoms and signs compatible of BM or neonatal sepsis and were <90 days of age., Results: Of the 1088 infants, 212 (19%) showed bacteria in CSF, while 88 (8%) had probable BM. Independent clinical indicators of BM were not-clear CSF, seizures, weight <2500 g and illness >7 days. In infants with BM, CSF leukocytes were >10 × 106/L in 46%, CSF glucose <25 mg/dL in 43% and CSF protein >120 mg/dL in 58%. All measured parameters were in normal range in 25% of patients. In 515 infants with normal CSF parameters, bacteria were found in 74 (14%). In these infants, illness >7 days, weight <2500 g and malnutrition increased the probability of BM., Conclusions: Our study confirms and underlines the problems in diagnosing BM in young infants. While the CSF parameters were normal in 25% of infants, the easily recognizable unclear appearance of CSF was the single strongest predictor of BM., Competing Interests: T.P. and S.U. report grants from the Paediatric Research Foundation, and T.P. from the Päivikki and Sakari Sohlberg Foundation, Helsinki, Finland. M.H.K. was employee of Sanofi Pasteur during the implementation of the study. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Yearly, about two million infants die during the first 28 days of life. Most of these deaths occur in sub-Saharan Africa and a third of those are caused by severe infections. The early identification of infants at risk of death is important when trying to prevent poor outcomes., Objective: The aim of this study was to identify risk factors for death among young infants with possible serious bacterial infection (pSBI) at hospital admission., Methods: This prospective, observational, single-site, descriptive study forms part of a larger study on bacterial meningitis in infants <90 days of age admitted to the Pediatric Hospital of Luanda, the capital of Angola, from February 1, 2016 to October 23, 2017. Infants with pSBI, a known outcome, and a final diagnosis were included., Results: Of 574 young infants with pSBI, 115 (20%) died in hospital. An altered level of consciousness, absence of spontaneous movements, dyspnea, CSF that is not clear, low CSF glucose, high CSF protein, heart rate over the median, and seizures were identified as risk factors for death in the univariate analysis. In the multivariate analysis, only heart rate over the median and seizures were independent predictors of death., Conclusions: Easily recognizable clinical signs - tachycardia and seizures - may guide clinicians to identify infants at high risk of death due to severe bacterial infections in sub-Saharan Africa., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: To evaluate the effectiveness of empagliflozin in clinical practice in East Asia in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) East Asia study., Materials and Methods: Data were obtained from the Medical Data Vision database (Japan), National Health Insurance Service database (South Korea) and National Health Insurance database (Taiwan). Patients aged ≥ 18 years with type 2 diabetes initiating empagliflozin or a dipeptidyl peptidase-4 (DPP-4) inhibitor were 1:1 propensity score (PS) matched into sequentially built cohorts of new users naïve to both drug classes. This design reduces confounding due to switching treatments, time lag and immortal time biases. Outcomes included hospitalization for heart failure (HHF), end-stage renal disease (ESRD) and all-cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional models, controlling for > 130 baseline characteristics in each data source and pooled by random-effects meta-analysis., Results: Overall, 28 712 pairs of PS-matched patients were identified with mean follow-up of 5.7-6.8 months. Compared with DPP-4 inhibitors, the risk of HHF was reduced by 18% and all-cause mortality was reduced by 36% with empagliflozin (HR 0.82; 95% CI 0.71-0.94, and HR 0.64; 95% CI 0.50-0.81, respectively). Reductions were consistent across countries, and in patients with and without baseline cardiovascular disease. ESRD was also significantly reduced with empagliflozin versus DPP-4 inhibitors (HR 0.37; 95% CI 0.24-0.58)., Conclusions: Empagliflozin treatment was associated with reduced risk for HHF, all-cause mortality and ESRD compared with DPP-4 inhibitors in routine clinical practice in Japan, South Korea and Taiwan., (© 2020 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Despite effective antibiotics and vaccines, bacterial meningitis (BM) remains one of the leading causes of morbidity and mortality in young infants worldwide. Data from Africa on the aetiology and antibiotic susceptibility are scarce., Objective: To describe the aetiology of BM in Angolan infants <90 days of age., Methods: A prospective, observational, single-site study was conducted from February 2016 to October 2017 in the Paediatric Hospital of Luanda. All cerebrospinal fluid samples (CSF) from infants aged <90 days with suspected BM or neonatal sepsis were assessed. The local laboratory performed microscopy, chemistry, culture, and susceptibility testing. PCR for vaccine-preventable pathogens was performed in Johannesburg, South Africa., Results: Of the 1287 infants, 299 (23%) had confirmed or probable BM. Of the 212 (16%) identified bacterial isolates from CSF, the most common were Klebsiella spp (30 cases), Streptococcus pneumoniae (29 cases), Streptococcus agalactiae (20 cases), Escherichia coli (17 cases), and Staphylococcus aureus (11 cases). A fifth of pneumococci (3/14; 21%) showed decreased susceptibility to penicillin, whereas methicillin-resistant S. aureus (MRSA) was encountered in 4/11 cases (36%). Of the gram-negative isolates, 6/45 (13%) were resistant to gentamicin and 20/58 (34%) were resistant to third-generation cephalosporins. Twenty-four percent (33/135) of the BM cases were fatal, but this is likely an underestimation., Conclusions: BM was common among infants <90 days of age in Luanda. Gram-negative bacteria were predominant and were often resistant to commonly used antibiotics. Continued surveillance of the antibiogram is pivotal to detect potential changes without delay., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on the occurrence of first and subsequent otitis media (OM) episodes in early childhood is unclear. We compared the risk of OM episodes among children age <2 years before and after PCV13 introduction, accounting for the dependence between OM episodes., Methods: We identified consecutive annual (July-June) cohorts of Tennessee Medicaid-enrolled children (2006-2014) from birth through age 2 years. We identified OM episodes using coded diagnoses (we classified diagnoses <21 days apart as the same episode). We modeled adjusted hazard ratios (aHRs) for OM comparing 7-valent pneumococcal conjugate vaccine (PCV7)-era (2006-2010) and PCV13-era (2011-2014) birth cohorts, accounting for risk factors and dependence between first and subsequent episodes. Secondary analyses examined pressure equalization tube (PET) insertions and compared the risk of recurrent OM (≥3 episodes in 6 months or ≥4 episodes in 12 months) between PCV7- and PCV13-era birth cohorts., Results: We observed 618 968 OM episodes and 24 875 PET insertions among 368 063 children. OM and PET insertion rates increased during the PCV7 years and declined after PCV13 introduction. OM and PET insertion risks were lower in the 2013-2014 cohort compared with the 2009-2010 cohort (aHRs [95% confidence interval], 0.92 [.91-.93] and 0.76 [.72-.80], respectively). PCV13 introduction was associated with declines in the risk of first, subsequent, and recurrent OM., Conclusions: The transition from PCV7 to PCV13 was associated with a decline of OM among children aged <2 years due to a reduction in the risk of both the first and subsequent OM episodes., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To determine the carriage and the serogroup distribution of Neisseria meningitidis in military academy applicants in the Russian Federation., Design: This was a prospective, observational study of adults aged >18years from a military academy; applicants who had samples taken on arrival (Day 1), and applicants who had samples taken after passing exams (Day 30) and 60days after arrival. N. meningitidis serogrouping was determined by slide agglutination tests of isolates and real-time PCR., Results: Samples were provided by 671 applicants on Day 1 and 261 applicants on Day 30, with 232 of these also providing samples on Day 60. N. meningitidis was detected in 16.2% of samples from Day 1, 7.7% of samples from Day 30 and 15.9% of samples from Day 60. Serogroup composition was most diverse at Day 1, with serogroups B and W dominant (40% [17/43 isolates] and 9% [4/43], respectively; 30% [13/43] ungroupable); by Day 60, there was a low diversity, with 58% (14/24 isolates) serogroup W., Conclusions: While carriage of N. meningitidis in this study appeared stable, there was an increase in carriers of serogroup W in this population. Given recent increases in outbreaks attributed to serogroup W, further monitoring may be considered., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Guidelines recommend withholding clopidogrel 7 days before polypectomy to decrease bleeding risk, but these were written based on limited evidence. We investigated whether uninterrupted clopidogrel therapy increases the risk of delayed postpolypectomy bleeding in patients undergoing colonoscopy., Methods: We identified patients receiving clopidogrel for cardiovascular disease undergoing elective colonoscopies in Hong Kong from February 28, 2012 through April 11, 2018. Eligible patients were instructed to stop taking clopidogrel 7 days before colonoscopy. Then, they were randomly assigned to groups given clopidogrel (75 mg) or placebo daily until the morning of colonoscopy. All patients resumed their usual prescriptions of clopidogrel after colonoscopy. The primary end point was delayed postpolypectomy bleeding that required hospitalization or intervention up to 30 days after colonoscopy. Secondary end points were immediate postpolypectomy bleeding and serious cardio-thrombotic events for as long as 6 months after colonoscopy, according to Antithrombotic Trialists' criteria. All events were adjudicated by an independent masked committee., Results: In total, 387 patients underwent colonoscopy and 216 required polypectomies (106 patients in the clopidogrel group and 110 patients in the placebo group). The cumulative incidence of delayed postpolypectomy bleeding was 3.8% (95% confidence interval 1.4-9.7) in the clopidogrel group and 3.6% (95% confidence interval 1.4-9.4) in the placebo group (P = .945 by log-rank test). There were no significant differences in immediate postpolypectomy bleeding (8.5% vs 5.5%; P = .380) and cardio-thrombotic events (1.5% vs 2%; P = .713)., Conclusions: In a randomized controlled trial of clopidogrel users undergoing colonoscopy, a slightly larger proportion of patients continuing clopidogrel developed delayed and immediate postpolypectomy bleeding, although this difference was not statistically significant. ClinicalTrials.gov, number NCT01806090., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV)., Methods: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes., Results: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum., Conclusions: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines., (Copyright © 2018 The British Infection Association. All rights reserved.)

Background & Aims: There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy., Methods: We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 μg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline., Results: Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%-42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005)., Conclusions: In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Historically, semi-closed populations have had high rates of meningococcal carriage and have experienced recurrent outbreaks. As such, these high-risk groups are recommended for targeted vaccination in many countries., Methods: A systematic review of eight databases and Google Scholar forward citations was conducted to characterize serogroup-specific meningococcal carriage in university students, military personnel, and Hajj pilgrims from 2007 to 2016., Results: A total of 7014 records were identified and 22 studies were included. Overall carriage ranged from 0.0% to 27.4% in Hajj pilgrims, from 1.5% to 71.1% in university students, and from 4.2% to 15.2% in military personnel. Among serogroups A, B, C, W, X, and Y, serogroup B was most prevalent in Hajj pilgrims, B and Y in university students, and B, C, and Y in military personnel. 'Other' serogroups were more prevalent in university students than Hajj pilgrims or military personnel. Risk factors for carriage varied by setting. Among Hajj pilgrims, a high endemicity in the country of origin increased the risk of carriage, while smoking, male sex, and frequently attending parties increased the carriage risk for university students. Similarly, smoking increased the carriage risk for professional soldiers. Data gaps remain for many regions., Conclusions: Preventative vaccination policies for high-risk groups should be based on current disease data in individual countries, supplemented by carriage data. Meningococcal carriage studies and disease surveillance are critical for determining the local epidemiology, populations responsible for disease transmission, and the need for targeted vaccination., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The incidence of antithrombotic-associated gastrointestinal (GI) bleeding is increasing due to the growing advanced age population. There is consensus on ceasing anticoagulant and antiplatelet agents during an acute GI bleeding episode but clearer guidance is needed on resumption of these agents. This article reviews evidence for optimal management of antithrombotics in the setting of acute GI bleeding and highlights areas in which future studies are needed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding., Methods: For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660., Findings: Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months was 5·6% (95% CI 3·3-9·2) in the celecoxib group and 12·3% (8·8-17·1) in the naproxen group (p=0·008; crude hazard ratio 0·44, 95% CI 0·23-0·82; p=0·010). Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib group and 17 (7%) patients in the naproxen group had adverse events leading to discontinuation of treatment. No treatment-related deaths occurred during the study., Interpretation: In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety., Funding: The Research Grant Council of Hong Kong., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The dynamic evolution of the virus causing COVID-19 necessitates the development of adapted vaccines to protect against emerging variants., Research Design and Methods: A combined Markov-decision tree model estimated the outcomes of alternative vaccination strategies. The Saudi Arabian population was stratified into standard-risk and high-risk subpopulations, defined as either the population comprising individuals aged ≥ 65 years and individuals with at least one comorbidity. The model estimated the health and economic outcomes of vaccination based on age-specific inputs taken from published sources and national surveillance data., Results: The vaccination strategy targeting the elderly and high-risk subpopulation (was estimated to prevent 156,694 cases 12,800 hospitalizations, and 2,919 deaths and result in cost savings of SAR 1,239 million in direct costs and SAR 4,145 million in indirect costs. These gains increased with the vaccination strategies additionally targeting other subpopulations. Compared to the base case (aged ≥65 and those at high-risk), expanding vaccination coverage to 75% of the standard-risk population prevented more cases (323%), hospitalizations (154%), and deaths (60%) and increased the direct (232%) and indirect (270%) cost savings., Conclusions: The adoption of broad vaccination strategies using a vaccine adapted to the dominant variant in circulation would yield substantial benefits in Saudi Arabia.