Azithromycin to Reduce Mortality - An Adaptive Cluster-Randomized Trial.

BACKGROUND: Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested. METHODS: We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison. RESULTS: A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group. CONCLUSIONS: Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.).

Assessment of spillover of antimicrobial resistance to untreated children 7 to 12 years old after mass drug administration of azithromycin for child survival in Niger: a secondary analysis of the MORDOR cluster-randomized trial.

BACKGROUND: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs. METHODS: Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month timepoint adjusting for baseline prevalence. RESULTS: 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4% (95% CI -4.1% to 10.8%, P-value 0.37), -1.2% (95% CI -7.9% to 5.5%, P-value 0.72), and -3.3% (95% CI -9.5% to 2.8%, P-value 0.61), respectively. CONCLUSIONS: We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better understand the potential for spillover effects within these programs.

Association of weather variables with pathogens contributing to conjunctivitis worldwide.

PURPOSE: To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally. METHODS: Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus). RESULTS: 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95% CI: 0.46 to 0.82, P<0.001). Relative humidity (%) was associated with increased odds of RNA virus infections (OR=2.64, 95% CI: 1.51 to 4.61, P<0.001), and fungal infections (OR=2.35, 95% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95% CI: 0.25 to 0.71, P<0.001). Temperature (°C) was not associated with ocular infections for any pathogen type. CONCLUSIONS: This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases.

Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).

BACKGROUND: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. METHODS AND FINDINGS: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability. CONCLUSIONS: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored. TRIAL REGISTRATION: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

Ocular manifestations of mpox.

PURPOSE OF REVIEW: To highlight the clinical features of mpox with an emphasis on ocular manifestations and to review treatment options for this re-emerging infectious disease. RECENT FINDINGS: Ocular involvement of mpox varies by clade. The most recent 2022 outbreak appears to be associated with fewer conjunctivitis cases compared to previous outbreaks. However, the ocular findings occurring during this newly emerging clade can be visually threatening and include cases of keratitis, rapidly progressing scleritis, and necrotizing periorbital rashes. SUMMARY: Ocular mpox is an important clinical feature of systemic mpox virus (MPXV) infection. Heightened clinical suspicion allows for a timely diagnosis and the initiation of antiviral treatment, when appropriate. Randomized clinical trials for mpox systemic and ocular treatment efficacy are lacking. Prior clinical experience with smallpox and in-vitro mpox data support the use of systemic antivirals such as tecovirimat, cidofovir, brincidofovir and topical use of trifluridine in ocular mpox management, though treatment-resistant infection can occur and portend a poor prognosis.

Comparison of substernal and posterior mediastinal route of reconstruction after minimally invasive esophagectomy for esophageal cancer.

BACKGROUND: Substernal (ST) and posterior mediastinal (PM) routes are the two most common for reconstruction after esophagectomy with cervical anastomosis. Recent evidence showed similar outcomes between the routes; thus, the superior choice remained controversial. This study aimed to compare the short-term outcomes of the ST to the PM route for reconstruction after esophagectomy for esophageal cancer (EC). METHOD: This retrospective cohort study included 132 patients who underwent McKeown minimally invasive esophagectomy (MIE) with gastric conduit for EC between March 2015 and December 2022. Among these, 89 and 43 patients received the ST route and PM route for reconstruction, respectively. Short-term outcomes including operative characteristics, postoperative morbidity, and mortality were evaluated. RESULT: There was no conversion from ST to PM route. The ST group had longer operating time (375 min vs. 341 min). Oral feeding initiation, postoperative hospital stays, and overall complication rates were comparable in the two groups. The rate and severity of anastomotic leakage were similar between the groups. The ST group had a significantly lower incidence of postoperative ICU admission and pneumonia compared to the PM group (5.6% vs. 16.3% and 19.1% vs. 37.2%, respectively). Azygos vein bleeding, obstruction at feeding jejunostomy site, and conduit-trachea fistula were severe complications that only occurred in PM route. CONCLUSION: ST route was superior to PM route in term of postoperative ICU admission and pneumonia. This route may prevent severe complications that only occur in PM route. ST route can be favorable option for reconstruction after McKeown MIE for EC.

Use of Large Language Models to Assess the Likelihood of Epidemics From the Content of Tweets: Infodemiology Study.

BACKGROUND: Previous work suggests that Google searches could be useful in identifying conjunctivitis epidemics. Content-based assessment of social media content may provide additional value in serving as early indicators of conjunctivitis and other systemic infectious diseases. OBJECTIVE: We investigated whether large language models, specifically GPT-3.5 and GPT-4 (OpenAI), can provide probabilistic assessments of whether social media posts about conjunctivitis could indicate a regional outbreak. METHODS: A total of 12,194 conjunctivitis-related tweets were obtained using a targeted Boolean search in multiple languages from India, Guam (United States), Martinique (France), the Philippines, American Samoa (United States), Fiji, Costa Rica, Haiti, and the Bahamas, covering the time frame from January 1, 2012, to March 13, 2023. By providing these tweets via prompts to GPT-3.5 and GPT-4, we obtained probabilistic assessments that were validated by 2 human raters. We then calculated Pearson correlations of these time series with tweet volume and the occurrence of known outbreaks in these 9 locations, with time series bootstrap used to compute CIs. RESULTS: Probabilistic assessments derived from GPT-3.5 showed correlations of 0.60 (95% CI 0.47-0.70) and 0.53 (95% CI 0.40-0.65) with the 2 human raters, with higher results for GPT-4. The weekly averages of GPT-3.5 probabilities showed substantial correlations with weekly tweet volume for 44% (4/9) of the countries, with correlations ranging from 0.10 (95% CI 0.0-0.29) to 0.53 (95% CI 0.39-0.89), with larger correlations for GPT-4. More modest correlations were found for correlation with known epidemics, with substantial correlation only in American Samoa (0.40, 95% CI 0.16-0.81). CONCLUSIONS: These findings suggest that GPT prompting can efficiently assess the content of social media posts and indicate possible disease outbreaks to a degree of accuracy comparable to that of humans. Furthermore, we found that automated content analysis of tweets is related to tweet volume for conjunctivitis-related posts in some locations and to the occurrence of actual epidemics. Future work may improve the sensitivity and specificity of these methods for disease outbreak detection.

Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial.

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Isolated Ocular Mpox without Skin Lesions, United States.

We report a case of a 53-year-old HIV-negative patient in San Francisco, California, USA, with no classic mpox prodromal symptoms or skin lesions who experienced fulminant, vision-threatening scleritis, keratitis, and uveitis. Deep sequence analysis identified monkeypox virus RNA in the aqueous humor. We confirmed the virus on the cornea and sclera by PCR.

Seroepidemiology and Carriage of Diphtheria in Epidemic-Prone Area and Implications for Vaccination Policy, Vietnam.

In 2019, a community-based, cross-sectional carriage survey and a seroprevalence survey of 1,216 persons 1-55 years of age were conducted in rural Vietnam to investigate the mechanism of diphtheria outbreaks. Seroprevalence was further compared with that of an urban area that had no cases reported for the past decade. Carriage prevalence was 1.4%. The highest prevalence, 4.5%, was observed for children 1-5 years of age. Twenty-seven asymptomatic Coerynebacterium diphtheriae carriers were identified; 9 carriers had tox gene-bearing strains, and 3 had nontoxigenic tox gene-bearing strains. Child malnutrition was associated with low levels of diphtheria toxoid IgG, which might have subsequently increased child carriage prevalence. Different immunity patterns in the 2 populations suggested that the low immunity among children caused by low vaccination coverage increased transmission, resulting in symptomatic infections at school-going age, when vaccine-induced immunity waned most. A school-entry booster dose and improved infant vaccination coverage are recommended to control transmissions.

Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution.

BACKGROUND: Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear. METHODS: We investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months. RESULTS: Over the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa. CONCLUSIONS: Among villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).

Long-Term Outcomes of Open Versus Laparoscopic Distal Gastrectomy for T4a Gastric Cancer: A Propensity Score-Matched Cohort Study.

BACKGROUND: Laparoscopic gastrectomy for advanced gastric cancer (GC) has been applied more frequently worldwide but is still controversial for patients with serosal invasion (T4a). This study compared short- and long-term outcomes of laparoscopic distal radical gastrectomy (LDG) with open distal gastrectomy (ODG) for T4a GC. PATIENTS AND METHODS: We retrospectively studied 472 patients with T4a gastric adenocarcinoma in the lower or middle third of the stomach: 231 underwent LDG and 241 underwent ODG between 2013 and 2020. Short-term outcomes included operative characteristics and complications. Long-term outcomes included overall survival (OS) and disease-free survival (DFS). Propensity score-matched (PSM) analysis was used to adjust for imbalances in baseline characteristics between groups. RESULTS: The PSM strategy resulted in 294 patients (147 in each group). The LDG group had a significantly longer operating time (mean: 200 vs 190 min, p = 0.001) but reduced blood loss (mean: 50 vs 100 ml, p = 0.001). The LDG group had a higher rate of any postoperative complication (23.1% vs 12.2%, p = 0.021) but most were classified as grades I-II according to Clavien-Dindo classification. Grade III-V complications were similar between groups. Five-year OS was 69% versus 60% (p = 0.109) and 5-year DFS was 58% vs 53% (p = 0.3) in LDG and ODG groups, respectively. For tumor size < 5 cm, LDG was better in reduction of blood loss, postoperative hospital length of stay, and OS. CONCLUSIONS: LDG is feasible and safe for patients with T4a GC and is comparable to ODG regarding short- and long-term outcomes. Furthermore, LDG can be a favorable option for T4a GC smaller than 5 cm.

Case Series: Unbiased Deep Sequencing Analysis of Acute Infectious Conjunctivitis in an Ambulatory Eye Center in Berkeley, California.

SIGNIFICANCE: Acute infectious conjunctivitis poses significant challenges to eye care providers. It can be highly transmissible, and because etiology is often presumed, correct treatment and management can be difficult. This study uses unbiased deep sequencing to identify causative pathogens of infectious conjunctivitis, potentially allowing for improved approaches to diagnosis and management. PURPOSES: This study aimed to identify associated pathogens of acute infectious conjunctivitis in a single ambulatory eye care center. CASE REPORTS: This study included patients who presented to the University of California Berkeley eye center with signs and symptoms suggestive of infectious conjunctivitis. From December 2021 to July 2021, samples were collected from seven subjects (ages ranging from 18 to 38). Deep sequencing identified associated pathogens in five of seven samples, including human adenovirus D, Haemophilus influenzae , Chlamydia trachomatis , and human coronavirus 229E. CONCLUSIONS: Unbiased deep sequencing identified some unexpected pathogens in subjects with acute infectious conjunctivitis. Human adenovirus D was recovered from only one patient in this series. Although all samples were obtained during the COVID-19 pandemic, only one case of human coronavirus 229E and no SARS-CoV-2 were identified.

Culturally and Linguistically Diverse Gamblers of East Asian Descent in Australia: A Comprehensive Review of Current Evidence.

As a country with one of the highest per capita gambling losses per year in the world, and an evolving multicultural profile, Australia has become an important setting in which to examine the harms and benefits related to gambling. The Australian population includes people from East Asian cultural backgrounds who are a key demographic of interest for gambling operators planning to grow revenue. However, Australian gambling research has concentrated primarily on those belonging to the dominant cultural group. Most of the previous and limited number of studies to examine gambling among culturally and linguistically diverse (CALD) residents have focused on people of Chinese descent, and much of the literature is now becoming relatively old. This review examines the current evidence around cultural variations in gambling prevalence, motivations, beliefs, behaviours, and help service utilisation, focusing on gamblers with an East Asian cultural background. Numerous domains in which gambling motivations and behaviours vary across cultural groups are identified, and methodological considerations related to ethnographic gambling research are discussed. This review found that while barriers and predictors to help-seeking for CALD gamblers have been studied extensively, contemporary evidence of help service utilisation and effectiveness in Australia is lacking. Further research providing an accurate assessment of the impacts of gambling for CALD gamblers is needed to ensure that harm minimisation resources are effective for those most vulnerable to harm.

Surgical outcomes and quality of life assessment of esophagectomy for cancer with colon conduit via retrosternal route.

PURPOSE: Colon conduit is an alternative to a gastric conduit for esophagectomy in patients that stomach is not available. Surgical technique is complex and has a high risk of morbidities and mortality. Outcomes of patients are still lacking in the literature, thus aims of this study are to evaluate the safety, feasibility and long-term functional outcomes of patients who underwent esophagectomy for cancer with colon conduit via retrosternal route. METHODS: Twenty-six patients underwent operation between August 2016 and June 2021 for malignancies. Minimally invasive esophagectomy and laparotomy were performed in accordance with the 2017 Japan Esophageal Society's guidelines. Colonic interposition was used for esophageal replacement. Outcomes were technical success, complications assessed using Clavien-Dindo classification, and patient's quality of life (QOL) based on EORTC-QOL-OES18 questionnaire. RESULTS: Mean age was 56.0 ± 9.9 years and 21 patients (80.8%) were men. Mean operating time was 432 ± 66 min. Technical success was 100%. The average number of resected lymph nodes was 26 ± 14. Twelve patients (46.2%) experienced postoperative complications: 7/12 were classified as grade I-II, 3/12 as grade III, 1/12 as grade IV, and 1/12 as grade V (death). Patient's QOL improved during the follow-up period with median (25-75th percentiles) global EORTC-QOL-OES18 score was 29 (17-34); 13 (9-21), and 9 (6-16) at 3, 6, and 12 months, respectively. During the follow-up period, there were 4 late complications, 3 lymphatic recurrences, 5 distant metastases, and 6 deaths. CONCLUSIONS: Colon conduit via retrosternal route after esophagectomy is feasible, safe, and could provide acceptable long-term functional outcomes.

Vaccine-Associated Measles Encephalitis in Immunocompromised Child, California, USA.

We report a fatal case of vaccine-associated measles encephalitis in an immunocompromised child in California, USA. The infection was confirmed by whole-genome RNA sequencing of measles virus from brain tissue. We observed biased matrix-gene hypermutation consistent with persistent measles virus central nervous system infection.

Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa.

BACKGROUND: The MORDOR I trial (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) showed that in Niger, mass administration of azithromycin twice a year for 2 years resulted in 18% lower postneonatal childhood mortality than administration of placebo. Whether this benefit could increase with each administration or wane owing to antibiotic resistance was unknown. METHODS: In the Niger component of the MORDOR I trial, we randomly assigned 594 communities to four twice-yearly distributions of either azithromycin or placebo to children 1 to 59 months of age. In MORDOR II, all these communities received two additional open-label azithromycin distributions. All-cause mortality was assessed twice yearly by census workers who were unaware of participants' original assignments. RESULTS: In the MORDOR II trial, the mean (±SD) azithromycin coverage was 91.3±7.2% in the communities that received twice-yearly azithromycin for the first time (i.e., had received placebo for 2 years in MORDOR I) and 92.0±6.6% in communities that received azithromycin for the third year (i.e., had received azithromycin for 2 years in MORDOR I). In MORDOR II, mortality was 24.0 per 1000 person-years (95% confidence interval [CI], 22.1 to 26.3) in communities that had originally received placebo in the first year and 23.3 per 1000 person-years (95% CI, 21.4 to 25.5) in those that had originally received azithromycin in the first year, with no significant difference between groups (P = 0.55). In communities that had originally received placebo, mortality decreased by 13.3% (95% CI, 5.8 to 20.2) when the communities received azithromycin (P = 0.007). In communities that had originally received azithromycin and continued receiving it for an additional year, the difference in mortality between the third year and the first 2 years was not significant (-3.6%; 95% CI, -12.3 to 4.5; P = 0.50). CONCLUSIONS: We found no evidence that the effect of mass administration of azithromycin on childhood mortality in Niger waned in the third year of treatment. Childhood mortality decreased when communities that had originally received placebo received azithromycin. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02047981.).

Outcomes of Uveitic Macular Edema in the First-line Antimetabolites as Steroid-Sparing Treatment Uveitis Trial.

PURPOSE: To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil. DESIGN: Subanalysis of a block-randomized, observer-masked, multicenter clinical trial. PARTICIPANTS: Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017. METHODS: Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group. MAIN OUTCOME MEASURES: Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity. RESULTS: Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 µm and 342 µm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 µm (interquartile range [IQR], -132.3 to 4.0) and 54 µm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 µm (IQR, -32.3 to -0.5) and 50 µm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92). CONCLUSIONS: Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema.

Biomarkers for primary open-angle glaucoma progression.

Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years, certain subgroups of POAG patients could progress over time even with treatment. This study is to identify aqueous humor (AH) biomarkers that may be associated with disease progression in POAG patients. Gene differential expression study of prospectively collected AH from patients with stable or progressive POAG. Metagenomic deep sequencing (MDS) was performed on the aqueous fluid of 20 patients with stable POAG and 20 patients with progressive POAG. Differential gene expression analysis was performed to identify host transcriptome signatures. A total of 21 transcripts were differentially expressed between groups. Differential transcripts identified by MDS. Twenty transcripts were up-regulated and 1 transcript was down-regulated in progressive POAG patients compared to stable patients. Of those, 11 transcripts were eye-related, and 5 transcripts were related to glaucomatous phenotypes (Fibronectin type III domain containing 3B (FNDC3B), Clusterin (CLU), Proprotein convertase subtilisin/kexin type 6 (PCSK6), Cadherin EGF LAG seven-pass G-type receptor 1 (Celsr1), and Rho guanine nucleotide exchange factor 4 (ARHGEF4)). Biomarkers associated with POAG progression can be identified from aqueous fluid. Identification of the biomarkers may improve glaucoma surveillance for progressive POAG.

Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial.

We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. Although the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs. CLINICAL TRIALS REGISTRATION: NCT02047981.