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Anthony K Ma,1 Jun Hui Lee,1 Joshua L Warren,2 Christopher C Teng3 1Yale School of Medicine, New Haven, CT, USA; 2Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA; 3Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT, USACorrespondence: Christopher C TengDepartment of Ophthalmology and Visual Science, Yale School of Medicine, 40 Temple Street, Suite 1B, New Haven, CT, USATel +1 203-785-3366Fax +1 203-785-6220Email christopher.teng@yale.eduPurpose: To understand the distribution of trabeculectomies, glaucoma drainage implants (GDI) and micro-invasive glaucoma surgeries (MIGS) performed in the United States through geospatial mapping.Methods: We performed an observational cohort study to evaluate glaucoma surgeries in patients age ≥ 65. The most recently released data from Centers for Medicare Part B Carrier Summary Files were queried to determine the number of glaucoma surgeries performed per state during the year of 2017. We created choropleth maps, titled “GlaucoMap”, to characterize the rates of various surgeries performed across the United States, defined as the number of procedures performed per 10,000 individuals. A chi-squared analysis was further used to evaluate differences in surgical preferences across geographic region. Standardized residuals (SR) were calculated to determine regional influences on surgical distribution.Results: There were 174,788 glaucoma surgeries performed: 22,862 trabeculectomies (13.1%), 19,991 GDI (11.4%) and 131,935 (75.5%) MIGS. The Northeast had the highest trabeculectomy rate, GDI was highest in the Southeast and MIGS were highest in the Southwest. There was a statistically significant difference in proportional use of conventional surgeries versus MIGS across various regions in the United States (p < 0.0001). Given the high trabeculectomy and GDI rates and relatively low MIGS adoption in the Southeast, we observed a +7.03 SR for conventional surgeries and − 4.01 SR for MIGS. The Southwest and Western states had the highest MIGS rate and contributed +3.29 and +3.24 SR toward disproportional MIGS preference, respectively. The preference for conventional surgeries in the Northeast (SR = +2.93) and MIGS in the Midwest (SR = +0.99) also contribute to the overall differences in glaucoma surgeries across the United States.Conclusion: GlaucoMap is useful for visualizing the distribution of glaucoma surgeries in the United States. The heterogeneity in surgical preferences points to regional differences in glaucoma management.Keywords: glaucoma, MIGS, trabeculectomies, GDI, heatmaps

Cindi K Yim,1,2 Christopher C Teng,3 Joshua L Warren,4 James C Tsai,2 Nisha Chadha2 1USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; 2Department of Ophthalmology, Icahn School of Medicine at Mount Sinai/New York Eye and Ear Infirmary, Eye and Vision Research Institute, New York, NY, USA; 3Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT, USA; 4Department of Biostatistics, Yale University, New Haven, CT, USACorrespondence: Nisha ChadhaDepartment of Ophthalmology, Icahn School of Medicine at Mount Sinai, 17 E 102nd Street, 8th Floor West, New York, NY 10029, USATel +1 212-241-0949Fax +1 212-241-9994Email nisha.chadha@mssm.eduPurpose: The emergence of microinvasive glaucoma surgeries (MIGS) has expanded glaucoma management options. Resident experience with these novel procedures is unclear as no residency minimums exist for them, nor are they part of Accreditation Council for Graduate Medical Education (ACGME) procedure logs. The purpose of this study was to assess resident experience with MIGS in ACGME ophthalmology residency programs across the United States.Methods: This was a cross-sectional survey study of resident MIGS experience. A survey was mailed to program directors of ACGME-accredited ophthalmology residency programs (N = 118) in January 2017. Descriptive analyses were used to characterize the respondent demographics. Chi-square, paired t-tests, and McNemar’s tests were used to analyze the geographical distribution and frequency of MIGS experience.Results: A total of 30 out of 118 (25%) residency program directors across all geographic regions responded. Most incorporated both MIGS lecture (87%) and wet lab (73%) didactics into their curriculum. Only 27% felt that MIGS should be part of ACGME requirements. The most common MIGS taught were iStent (70%), endoscopic cyclophotocoagulation (50%), and trabectome (40%). Few residents had completed MIGS procedures as the primary surgeon by graduation. Eleven out of 30 program directors (37%) did not feel that the experience was adequate for independent practice.Conclusion: This study suggests that residents are exposed to some MIGS procedures during training, but program directors did not feel that the experience was adequate for independent practice. Further research is necessary to understand the barriers to integrating MIGS training into residency programs.Keywords: MIGS, ophthalmology education, resident education, surgical education

Nisha Chadha,1,2 Joshua L Warren,3 Ji Liu,2 James C Tsai,1 Christopher C Teng2 1Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York Eye and Ear, Eye and Vision Research Institute, NY 10029, USA; 2Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA; 3Department of Biostatistics, Yale University, New Haven, CT 06510, USA Purpose: This study evaluated US resident and fellow glaucoma surgical experience over a 7- and 8-year period, respectively.Methods: US ophthalmology resident glaucoma case logs from 2009 to 2016 and glaucoma fellow case logs from 2008 to 2016 were reviewed. The number of total, average, median, and minimum cases, along with percentile data for filtering surgery, shunting surgery, and novel procedures were analyzed for year-to-year trends.Results: Among residents training from 2009 to 2016, there was a decline in the average number of primary filtering surgeries by 20%, from 6.0±5.0 to 4.8±4.0 cases, with a concurrent increase in average primary glaucoma drainage implant (GDI) surgeries by 40%, from 4.5±4.0 to 6.3±5.0 cases, which represented an increase of 6.5% per year, P

Background: Both the United States and Canada offer government-financed health insurance for the elderly, but few studies have compared care at the end of life for cancer patients between the two systems.Methods: We identified care for non-small cell lung cancer (NSCLC) patients who died of cancer at age 65 years and older during 1999-2003. Patients were identified from US Surveillance, Epidemiology, and End Results (SEER)-Medicare data (N = 13,533) and the Ontario Cancer Registry (N = 8100). Health claims during the last 5 months of life identified chemotherapy and emergency room use, hospitalizations, and supportive care. We estimated rates per person-months (PM) for short-term survivors (died <6 months after diagnosis) and longer-term survivors (died ≥6 months after diagnosis), adjusting for demographic differences. To test whether monthly rates in Ontario were statistically significantly different from the United States, standardized differences were computed, and a 99% confidence interval (CI) was constructed to account for the multiple tests performed. All statistical tests were two-sided.Results: Rates of chemotherapy use were statistically significantly higher for SEER-Medicare patients than Ontario patients in every month before death (short-term survivors at 5 months before death: SEER-Medicare, 33.2 patients per 100 PM vs Ontario, 9.5 per 100 PM, rate difference = 23.7 per 100 PM, 99% CI = 18.3 to 29.1 per 100 PM, P < .001; longer-term survivors at 5 months before death: SEER-Medicare, 24.4 patients per 100 PM vs Ontario, 14.5 per 100 PM, rate difference = 9.9 per 100 PM, 99% CI = 7.7 to 12.1 per 100 PM, P <. 001). During the last 30 days of life, fewer SEER-Medicare than Ontario patients were hospitalized (short-term survivors, 49.9 vs 78.6 patients per 100 PM, rate difference = 28.6 per 100 PM, 95% CI = 22.9 to 34.4 per 100 PM, P <. 001; longer-term survivors, 44.1 vs 67.1 patients per 100 PM, rate difference = 23.0 per 100 PM, 95% CI = 18.5 to 27.5 per 100 PM, P < .001).Conclusions: NSCLC patients in both Ontario and the United States used extensive end-of-life care. Limited availability of hospice care in Ontario and differing attitudes between the United States and Ontario regarding end-of-life care may explain the differences in practice patterns. [ABSTRACT FROM AUTHOR]

BACKGROUND:: Identifying appropriate comorbidity data sources is a key consideration in health services and outcomes research. OBJECTIVE:: Using cancer patients as an example, we compared comorbid conditions identified: 1) on the discharge facesheet versus full hospital medical record and 2) in the hospital record versus Medicare claims, both precancer diagnosis and associated with a cancer treatment-related index hospitalization. METHODS:: We used data from 1995 Surveillance, Epidemiology and End Results patterns of care studies for 1382 patients. Comorbid conditions were ascertained from the hospital record associated with the most definitive cancer treatment and Medicare claims. We calculated the prevalence for and assessed concordances among 12 conditions derived from the hospital record facesheet; full hospital record; Medicare claims precancer diagnosis, with and without a rule-out algorithm applied; and Medicare claims associated with an index hospitalization. RESULTS:: The proportion of patients with one or more comorbid conditions varied by data source, from 21% for the facesheet to 85% for prediagnosis Medicare claims without the rule-out algorithm. Condition prevalences were substantially lower for the facesheet compared with the full hospital record. For prediagnosis Medicare claims, condition prevalences were more than 1.7 times greater in the absence of an algorithm to screen for rule-out diagnoses. Measures assessing concordance between the full hospital record and prediagnosis Medicare claims (rule-out algorithm applied) showed modest agreement. CONCLUSIONS:: The hospital record and Medicare claims are complementary data sources for identifying comorbid conditions. Comorbidity is greatly underascertained when derived only from the facesheet of the hospital record. Investigators using Part B Medicare claims to measure comorbidity should remove conditions that are listed for purposes of generating bills but are not true comorbidities. [ABSTRACT FROM AUTHOR]

Background: Black-white disparities exist in receipt of recommended medical care, including colorectal cancer treatment. This retrospective cohort study examines the degree to which health systems (e.g., physician, hospital) factors explain black-white disparities in colon cancer care.Methods: Data from the Surveillance, Epidemiology, and End Results program; Medicare claims; the American Medical Association Masterfile; and hospital surveys were linked to examine chemotherapy receipt after stage III colon cancer resection among 5294 elderly (> or = 66 years of age) black and white Medicare-insured patients. Logistic regression analysis was used to identify factors associated with black-white differences in chemotherapy use. All statistical tests were two-sided.Results: Black and white patients were equally likely to consult with a medical oncologist, but among patients who had such a consultation, black patients were less likely than white patients (59.3% versus 70.4%, difference = 10.9%, 95% confidence interval [CI] = 5.1% to 16.4%, P < .001) to receive chemotherapy. This black-white disparity was highest among patients aged 66-70 years (black patients 65.7%, white patients 86.3%, difference = 20.6%, 95% CI = 10.7% to 30.4%, P < .001) and decreased with age. The disparity among patients aged 66-70 years also remained statistically significant in the regression analysis. Overall, patient, physician, hospital, and environmental factors accounted for approximately 50% of the disparity in chemotherapy receipt among patients aged 66-70 years; surgical length of stay and neighborhood socioeconomic status accounted for approximately 27% of the disparity in this age group, and health systems factors accounted for 12%.Conclusions: Black and white Medicare-insured colon cancer patients have an equal opportunity to learn about adjuvant chemotherapy from a medical oncologist but do not receive chemotherapy equally. Little disparity was explained by health systems; more was explained by illness severity, social support, and environment. Further qualitative research is needed to understand the factors that influence the lower receipt of chemotherapy by black patients. [ABSTRACT FROM AUTHOR]

Background: Nonmedical costs of care, such as patient time associated with travel to, waiting for, and seeking medical care, are rarely measured systematically with population-based data.Objectives: The purpose of this study was to estimate patient time costs associated with colorectal cancer care.Methods: We identified categories of key medical services for colorectal cancer care and then estimated patient time associated with each service category using data from national surveys. To estimate average service frequencies for each service category, we used a nested case control design and SEER-Medicare data. Estimates were calculated by phase of care for cases and controls, using data from 1995 to 1998. Average service frequencies were then combined with estimates of patient time for each category of service, and the value of patient time assigned. Net patient time costs were calculated for each service category, summarized by phase of care, and compared with previously reported net direct costs of colorectal cancer care.Results: Net patient time costs for the 3 phases of colorectal cancer care averaged dollar 4592 (95% confidence interval [CI] dollar 4427-4757) over the 12 months of the initial phase, dollar 2788 (95% CI dollar 2614-2963) over the 12 months of the terminal phase, and dollar 25 (95% CI: dollar 23-26) per month in the continuing phase of care. Hospitalizations accounted for more than two thirds of these estimates. Patient time costs were 19.3% of direct medical costs in the initial phase, 15.8% in the continuing phase, and 36.8% in the terminal phase of care.Conclusions: Patient time costs are an important component of the costs of colorectal cancer care. Application of this method to other tumor sites and inclusion of other components of the costs of medical care will be important in delineating the economic burden of cancer in the United States. [ABSTRACT FROM AUTHOR]

Objective: To investigate racial differences in posttreatment bowel surveillance after colorectal cancer surgery in a large population of Medicare patients.Data Sources: We used a large population-based dataset: Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data.Study Design: This is a retrospective cohort study. We analyzed data from 44,768 non-Hispanic white, 2,921 black, and 4,416 patients from other racial/ethnic groups, aged 65 and older at diagnosis, who had a diagnosis of local or regional colorectal cancer between 1986 and 1996, and were followed through December 31, 1998. Cox Proportional Hazards models were used to investigate the relation of race and receipt of posttreatment bowel surveillance.Data Collection: Sociodemographic, hospital, and clinical characteristics were collected at the time of diagnosis for all members of the cohort. Surgery and bowel surveillance with colonoscopy, sigmoidoscopy, and barium enema were obtained from Medicare claims using ICD-9-CM and CPT-4 codes.Principal Findings: The chance of surveillance within 18 months of surgery was 57 percent, 48 percent, and 45 percent for non-Hispanic whites, blacks, and others, respectively. After adjusting for sociodemographic, hospital, and clinical characteristics, blacks were 25 percent less likely than whites to receive surveillance if diagnosed between 1991 and 1996 (RR = 0.75, 95 percent CI = 0.70-0.81).Conclusions: Elderly blacks were less likely than non-Hispanic whites to receive posttreatment bowel surveillance and this result was not explained by measured racial differences in sociodemographic, hospital, and clinical characteristics. More research is needed to explore the influences of patient- and provider-level factors on racial differences in posttreatment bowel surveillance. [ABSTRACT FROM AUTHOR]

When people learn categories, the importance of the features and relations in the category representation reflects both their diagnosticity for classification and their relevance to the use of the category. In earlier work in which the influence of category use on the representation has been shown, only cases in which the features and relations were simple, observable, and very specific were examined. Learners may begin to understand the underlying similarities of category members by using the categories. In the four experiments presented here, learners applied a simple category-specific formula to category members. The test results showed that the learners had incorporated relations among features from this use, including cases in which the relations were abstract. This learning occurred even though the relations were actually not predictive of category membership but just perceived to be so as a function of the use. [ABSTRACT FROM AUTHOR]

Context: Few studies have compared patterns of care in health maintenance organization (HMO) and fee-for-service (FFS) settings.Objective: To examine breast cancer stage at diagnosis and, for those at an early stage, treatment patterns for elderly women in HMO and FFS settings.Design: Cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare enrollment records.Settings and Participants: Women aged 65 years or older residing in 11 geographic areas who were newly diagnosed as having breast cancer between 1988 and 1993.Main Outcome Measures: Standardized percentage of cases diagnosed at late stages for HMO vs FFS; standardized percentage of early-stage cases undergoing initial treatment with breast-conserving surgery (BCS); and, among BCS cases, standardized percentage receiving adjuvant radiation therapy. Standardization was achieved through logistic regression, controlling for patient demographics, cancer history, county of residence, year of diagnosis, and educational attainment at the census tract level. Analyses of treatment patterns were controlled for stage at diagnosis and tumor size.Results: The HMO enrollees were less likely to have breast cancer diagnosed at late stages than FFS patients (HMO, 7.6%; FFS, 10.8%; difference, -3.2% [95% confidence interval (CI), -4.2% to -2.2 %]). Among early-stage cases, the percentages undergoing BCS were similar in HMO and FFS settings overall (HMO, 38.4%; FFS, 36.8%; difference, 1.6% [95% CI, 0.0%-3.2%]); percentages varied markedly at the individual plan level. Among women undergoing BCS, HMO enrollees were significantly more likely to receive radiation therapy but, again, results varied by plan (HMO, 69.0%; FFS, 63.7%; difference, 5.3% [95% CI, 2.9%-7.7%]). In general, use of BCS and radiation therapy was substantially higher than that found in an earlier study examining cases diagnosed between 1985 and 1989.Conclusions: Treatment of early-stage breast cancer in HMOs often differs from local FFS patterns, but not in a consistent way. During the period of our study, elderly HMO enrollees did not appear to have systematic access problems with adjuvant radiation therapy following BCS compared with women in an FFS setting. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening is underutilized among those with lower socioeconomic status and in racial and ethnic minoritized populations who have been disproportionately impacted by COVID., Objective: To compare disparities in CRC screening before and after the onset of the COVID pandemic among privately insured individuals., Design: Retrospective cohort study using deidentified claims data from the USA between January 1, 2017, and December 31, 2022., Participants: Blue Cross Blue Shield beneficiaries aged 50-75 years with average risk of CRC., Main Measure(s): Mean screening use was compared by demographic and area-level socioeconomic factors between the periods preceding (January 1, 2017 to February 28, 2020) and following (July 1, 2020 to December 31, 2022) the onset of the COVID pandemic. Difference-in-differences analysis was used to evaluate changes in screening differences., Results: Our study included 21,724,223 beneficiaries. Compared to males, females had higher screening in both periods (p < 0.05), and this sex difference in screening increased 1.63% (95% confidence interval [CI]: 1.32%, 1.94%) following the onset of the pandemic. Compared to residents in areas with high socioeconomic status (SES), low SES area residents had lower screening (p < 0.001) during both periods. Furthermore, this difference grew 4.32% (95% CI, 3.76%, 4.88%) during the post-onset period. Metropolitan area residents had higher screening than non-metropolitan area residents during both periods (p < 0.001); however, this difference decreased 0.77% (95% CI, 0.34%, 1.20%) during the post-onset period. Among beneficiaries with high risk of CRC, the difference in screening based on social deprivation index and metropolitan area status increased 6.99% (95% CI, 5.77%, 8.20%) and 1.82% (95% CI, 0.88%, 2.74%), respectively., Conclusions: Among privately insured individuals, CRC screening after the COVID pandemic recovered unevenly based on sex, area-level socioeconomic measures, and metropolitan area status, with pre-pandemic disparities persisting and even worsening for some of the factors., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: In the United States (US), incidence of early age of onset colorectal cancer (EOCRC, diagnosed <50 years of age) has been increasing. Using a Bayesian analytic approach, we evaluated the association between county-level ecological factors and survival among individuals with EOCRC and identified hotspot and coldspot counties with unexplained low and high survival, respectively., Methods: Principal component (PC) analysis was used to reduce dimensionality of 36 county-level social, behavioral, and preventive factors from the Centers for Disease Control and Prevention data. Survival information was derived from the Surveillance, Epidemiology, and End Results Program data from January 1, 2000 to December 31, 2019. The association between the identified PCs and survival was evaluated using multivariable spatial generalized linear mixed models. Counties with residual low and high survival (i.e., unexplained by the PCs) were classified as hotspots and coldspots, respectively., Results: Four PCs were used to explain the spatial variability in 5-year survival among 75,215 individuals with EOCRC: PC1) poverty, chronic disease, health risk behaviors (β = -0.03, 95% credible interval (CrI): -0.04, -0.03); PC2) younger age, chronic disease-free, minority status (β = -0.01, 95% CrI: -0.02, 0.00); PC3) urban environment, preventive services (β = 0.02, 95% CrI: 0.00, 0.03); and PC4) older age (-0.04, 95% CrI: -0.06, -0.02). Among individuals with distant malignancies, the residual spatial variability remained high for two US counties: 1) Salt Lake County, UT residents experiencing 26.5% (95% CrI: 1.5%, 47.8%) lower odds of survival [hotspot], and 2) Riverside County, CA residents experiencing 37% (95% CrI: 7.97%, 78.8%) higher odds survival [coldspot] after adjustment for county-level factors., Conclusions: County-level ecological factors are strongly associated with survival among individuals with EOCRC. Yet there is some evidence of survival disparities among individuals with distant malignancies that remain unexplained by the included factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Siddique et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multicountry study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among children ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile., Methods: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000 to 2019, with 1 795 789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the postvaccination period, with other causes of death used as synthetic controls for unrelated temporal trends., Results: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among people aged ≥65 years in Chile., Discussion: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases., Competing Interests: Potential conflicts of interest . D. M. W. has received consulting fees from Pfizer, Merck, Affinivax, and Matrivax for work unrelated to this article; and is Principal Investigator on grants from Pfizer and Merck to Yale University for work unrelated to this article. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings., Objective: To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization., Design Setting and Participants: This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab-eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative., Exposure: Nirsevimab immunization, verified through state immunization registries., Main Outcomes and Measures: Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons., Results: The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible., Conclusions and Relevance: Nirsevimab provided substantial protection against RSV-related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program., Competing Interests: Competing interests: VEP was previously a member of the WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC). All other authors declare no conflicts of interest.

Meta-analysis is a powerful analytic method for summarizing effect estimates across studies. However, conventional meta-analysis often assumes a linear exposure-outcome relationship and does not account for variability over the exposure ranges. In this work, we first used simulation techniques to illustrate that the linear-based meta-analytical approach may result in oversimplistic effect estimation based on three plausible non-linear exposure-outcome curves (S-shape, inverted U-shape, and M-shape). We showed that subgroup meta-analysis that stratifies on exposure levels can investigate non-linearity and identify the consistency of effect magnitudes in these simulated examples. Next, we examined the heterogeneity of effect estimates across exposure ranges in two published linear-based meta-analyses of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on changes in mean birth weight or risk of preterm birth. The re-analysis found some varying effect sizes and potential heterogeneity when restricting to different PFAS exposure ranges, but findings were sensitive to the cut-off choices used to rank the exposure levels. Finally, we discussed methodological challenges and recommendations for detecting and interpreting potential non-linear associations in meta-analysis. Using meta-analysis without accounting for exposure range could contribute to literature inconsistency for exposure-induced health effects and impede evidence-based policymaking. Therefore, investigating result heterogeneity by exposure range is recommended., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate the long-term natural history of ellipsoid zone (EZ) width in USH2A -retinopathy., Methods: EZ width measurements from optical coherence tomography were retrospectively obtained from 110 eyes of 55 participants with molecularly confirmed biallelic USH2A -retinopathy. We used a hierarchical Bayesian method to construct and compare different mathematical models describing the long-term decline of EZ width., Results: Compared with linear and quadratic models, exponential decline best represented the long-term loss of EZ width based on the deviance information criterion score. Log-transformed EZ width declined linearly over 30 years of inferred disease duration (median: 0.063 (IQR: 0.040-0.086) log (µm)/year). Compared with the raw EZ width decline rate, the log-transformed EZ width decline rate required 48% fewer patients to achieve an identically powered 1-year trial (38 vs 73 participants). Log EZ width decline rate was uncoupled from baseline EZ width (Spearman ρ=-0.18, p=0.06) and age (ρ=-0.10, p=0.31). Eyes with Usher syndrome exhibited earlier median onset ages of macular EZ width loss (18.8 (IQR: 13.1-24.7) vs 28.1 (IQR: 18.5-35.8) years, p<0.001) but comparable log EZ width decline rates (0.060 (IQR: 0.035-0.100) vs 0.065 (IQR: 0.050-0.079) log (µm)/year; p=0.42)., Conclusions: EZ width follows an exponential decline in USH2A -retinopathy. Compared with raw EZ width decline rate, log-transformed EZ width decline rate may be a superior endpoint for clinical trials. Syndromic eyes exhibit an earlier onset of macular EZ width loss but progress at comparable rates to non-syndromic eyes., Competing Interests: Competing interests: MH: None. JW: None. PO: None. JLD: funding support from Foundation Fighting Blindness (FFB) as Study Chair of Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study; co-chair, Executive Committee, FFB Consortium and Chair, FFB Scientific Advisory Board. MM: None. LVD: FFB Advisory Board; LambdaVision; Tissue Regeneration Sciences. LLS: None., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.

Background: Heterogeneous outcome correlations across treatment arms and clusters have been increasingly acknowledged in cluster randomized trials with binary endpoints, where analytical methods have been developed to study such heterogeneity. However, cluster-specific outcome variances and correlations have yet to be studied for cluster randomized trials with continuous outcomes., Methods: This article proposes models fitted in the Bayesian setting with hierarchical variance structure to quantify heterogeneous variances across clusters and explain it with cluster-level covariates when the outcome is continuous. The models can also be extended to analyzing heterogeneous variances in individually randomized group treatment trials, with arm-specific cluster-level covariates, or in partially nested designs. Simulation studies are carried out to validate the performance of the newly introduced models across different settings., Results: Simulations showed that overall the newly introduced models have good performance, reporting low bias and approximately 95% coverage for the intraclass correlation coefficients and regression parameters in the variance model. When variances are heterogeneous, our proposed models had improved model fit over models with homogeneous variances. When used to analyze data from the Kerala Diabetes Prevention Program study, our models identified heterogeneous variances and intraclass correlation coefficients across clusters and examined cluster-level characteristics associated with such heterogeneity., Conclusion: We proposed new hierarchical Bayesian variance models to accommodate cluster-specific variances in cluster randomized trials. The newly developed methods inform the understanding of how an intervention strategy is implemented and disseminated differently across clusters and can help improve future trial design., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.L.W. has received consulting fees from Pfizer and Revelar Biotherapeutics, Inc. for work unrelated to the topics in this manuscript.

The human brain undergoes substantial developmental changes in the first five years of life. Particularly in the white matter, myelination of axons occurs near birth and continues at a rapid pace during the first 2 to 3 years. Diffusion MRI (dMRI) has revolutionized our understanding of developmental trajectories in white matter. However, the mm-resolution of in vivo techniques bears significant limitation in revealing the microstructure of the developing brain. Polarization sensitive optical coherence tomography (PSOCT) is a three-dimensional (3D) optical imaging technique that uses polarized light interferometry to target myelinated fiber tracts with micrometer resolution. Previous studies have shown that PSOCT contributes significantly to the elucidation of myelin content and quantification of fiber orientation in adult human brains. In this study, we utilized the PSOCT technique to study developing brains during the first 5 years of life in combination with ex vivo dMRI. The results showed that the optical properties of PSOCT quantitatively reveal the myelination process in young children. The imaging contrast of the optic axis orientation is a sensitive measure of fiber orientations in largely unmyelinated brains as young as 3-months-old. The micrometer resolution of PSOCT provides substantially enriched information about complex fiber networks and complements submillimeter dMRI. This new optical tool offers great potential to reveal the white matter structures in normal neurodevelopment and developmental disorders in unprecedented detail.

Background: High ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukaemia is the most common malignancy in children, the incidence is increasing, and in the USA disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia., Methods: We used data from California birth records (children born from Jan 1, 1982, to Dec 31, 2015) and California Cancer Registry (those diagnosed with childhood cancer in California from Jan 1, 1988, to Dec 31, 2015) to identify acute lymphoblastic leukaemia cases diagnosed in infants and children aged 14 years and younger and controls matched by sex, race, ethnicity, and date of last menstrual period. Ambient temperatures were estimated on a 1-km grid. The association between ambient temperature and acute lymphoblastic leukaemia was evaluated per gestational week, restricted to May-September, adjusting for confounders. Bayesian meta-regression was applied to identify critical exposure windows. For sensitivity analyses, we evaluated a 90-day pre-pregnancy period (assuming no direct effect before pregnancy), adjusted for relative humidity and particulate matter less than 2·5 microns in aerodynamic diameter, and constructed an alternatively matched dataset for exposure contrast by seasonality., Findings: 6849 cases of childhood acute lymphoblastic leukaemia were identified and, of these, 6258 had sufficient data for study inclusion. We also included 307 579 matched controls. Most of the study population were male (174 693 [55·7%] of the 313 837 included in the study) and of Latino ethnicity (174 906 [55·7%]). The peak association between ambient temperature and risk of acute lymphoblastic leukaemia was observed in gestational week 8, where a 5°C increase was associated with an odds ratio of 1·07 (95% CI 1·04-1·11). A slightly larger effect was seen among Latino children (OR 1·09 [95% CI 1·04-1·14]) than non-Latino White children (OR 1·05 [1·00-1·11]). The sensitivity analyses supported the results of the main analysis., Interpretation: Our findings suggest an association between high ambient temperature in early pregnancy and risk of childhood acute lymphoblastic leukaemia. Further replication and investigation of mechanistic pathways might inform mitigation strategies., Funding: Yale Center on Climate Change and Health, The National Center for Advancing Translational Science, National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Importance: Heat waves are increasing in frequency, intensity, and duration and may be acutely associated with pregnancy outcomes., Objective: To examine changes in daily rates of preterm and early-term birth after heat waves in a 25-year nationwide study., Design, Setting, and Participants: This cohort study of singleton births used birth records from 1993 to 2017 from the 50 most populous US metropolitan statistical areas (MSAs). The study included 53 million births, covering 52.8% of US births over the period. Data were analyzed between October 2022 and March 2023 at the National Center for Health Statistics., Exposures: Daily temperature data from Daymet at 1-km2 resolution were averaged over each MSA using population weighting. Heat waves were defined in the 4 days (lag, 0-3 days) or 7 days (lag, 0-6 days) preceding birth., Main Outcomes and Measures: Daily counts of preterm birth (28 to <37 weeks), early-term birth (37 to <39 weeks), and ongoing pregnancies in each gestational week on each day were enumerated in each MSA. Rate ratios for heat wave metrics were obtained from time-series models restricted to the warm season (May to September) adjusting for MSA, year, day of season, and day of week, and offset by pregnancies at risk., Results: There were 53 154 816 eligible births in the 50 MSAs from 1993 to 2017; 2 153 609 preterm births and 5 795 313 early-term births occurring in the warm season were analyzed. A total of 30.0% of mothers were younger than 25 years, 53.8% were 25 to 34 years, and 16.3% were 35 years or older. Heat waves were positively associated with daily rates of preterm and early-term births, showing a dose-response association with heat wave duration and temperatures and stronger associations in the more acute 4-day window. After 4 consecutive days of mean temperatures exceeding the local 97.5th percentile, the rate ratio for preterm birth was 1.02 (95% CI, 1.00-1.03), and the rate ratio for early-term birth was 1.01 (95% CI, 1.01-1.02). For the same exposure, among those who were 29 years of age or younger, had a high school education or less, and belonged to a racial or ethnic minority group, the rate ratios were 1.04 (95% CI, 1.02-1.06) for preterm birth and 1.03 (95% CI, 1.02-1.05) for early-term birth. Results were robust to alternative heat wave definitions, excluding medically induced deliveries, and alternative statistical model specifications., Conclusions and Relevance: In this cohort study, preterm and early-term birth rates increased after heat waves, particularly among socioeconomically disadvantaged subgroups. Extreme heat events have implications for perinatal health.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region., (© 2024. The Author(s).)

Incorporating historical data into a current data analysis can improve estimation of parameters shared across both datasets and increase the power to detect associations of interest while reducing the time and cost of new data collection. Several methods for prior distribution elicitation have been introduced to allow for the data-driven borrowing of historical information within a Bayesian analysis of the current data. We propose scaled Gaussian kernel density estimation (SGKDE) prior distributions as potentially more flexible alternatives. SGKDE priors directly use posterior samples collected from a historical data analysis to approximate probability density functions, whose variances depend on the degree of similarity between the historical and current datasets, which are used as prior distributions in the current data analysis. We compare the performances of the SGKDE priors with some existing approaches using a simulation study. Data from a recently completed phase III clinical trial of a maternal vaccine for respiratory syncytial virus are used to further explore the properties of SGKDE priors when designing a new clinical trial while incorporating historical data. Overall, both studies suggest that the new approach results in improved parameter estimation and power in the current data analysis compared to the considered existing methods., (© 2024 John Wiley & Sons Ltd.)

Background: Multidrug resistant tuberculosis (MDR-TB) represents a major public health concern in the Republic of Moldova, with an estimated 31% of new and 56% of previously treated TB cases having MDR disease in 2022. A recent genomic epidemiology study of incident TB occurring in 2018 and 2019 found that 92% of MDR-TB was the result of transmission. The MDR phenotype was concentrated among two M. tuberculosis (Mtb) lineages: L2.2.1 (Beijing) and L4.2.1 (Ural)., Methods: We developed and applied a hierarchical Bayesian multinominal logistic regression model to Mtb genomic, spatial, and epidemiological data collected from all individuals with diagnosed TB in Moldova in 2018 and 2019 to identify locations in which specific Mtb strains are being transmitted. We then used a logistic regression model to estimate locality-level factors associated with local transmission., Findings: We found differences in the spatial distribution and degree of local concentration of disease due to specific strains of Beijing and Ural lineage Mtb. Foci of transmission for four strains of Beijing lineage Mtb, predominantly of the MDR-TB phenotype, were located in several regions, but largely concentrated in Transnistria. In contrast, transmission of Ural lineage Mtb had less marked patterns of spatial aggregation, with a single strain (also of the MDR phenotype) spatially clustered in southern Transnistria. We found a 30% (95% credible interval 2%-80%) increase in odds of a locality being a transmission cluster for each increase of 100 persons per square kilometer, while higher local tuberculosis incidence and poverty were not associated with a locality being a transmission focus., Interpretation: Our results identified localities where specific Mtb transmission networks were concentrated and quantified the association between locality-level factors and focal transmission. This analysis revealed Transnistria as the primary area where specific Mtb strains (predominantly of the MDR-TB phenotype) were locally transmitted and suggests that targeted intensified case finding in this region may be an attractive policy option., Funding: Funding for this work was provided by the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health., Competing Interests: Declaration of interests All authors do not have conflicting interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: This study assessed the prevalence of specific major adverse financial events (AFEs)-bankruptcies, liens, and evictions-before a cancer diagnosis and their association with later-stage cancer at diagnosis., Methods: Patients age 20-69 years diagnosed with cancer during 2014-2015 were identified from the Seattle, Louisiana, and Georgia SEER population-based cancer registries. Registry data were linked with LexisNexis consumer data to identify patients with a history of court-documented AFEs before cancer diagnosis. The association of AFEs and later-stage cancer diagnoses (stages III/IV) was assessed using separate sex-specific multivariable logistic regression., Results: Among 101,649 patients with cancer linked to LexisNexis data, 36,791 (36.2%) had a major AFE reported before diagnosis. The mean and median timing of the AFE closest to diagnosis were 93 and 77 months, respectively. AFEs were most common among non-Hispanic Black, unmarried, and low-income patients. Individuals with previous AFEs were more likely to be diagnosed with later-stage cancer than individuals with no AFE (males-odds ratio [OR], 1.09 [95% CI, 1.03 to 1.14]; P < .001; females-OR, 1.18 [95% CI, 1.13 to 1.24]; P < .0001) after adjusting for age, race, marital status, income, registry, and cancer type. Associations between AFEs prediagnosis and later-stage disease did not vary by AFE timing., Conclusion: One third of newly diagnosed patients with cancer had a major AFE before their diagnosis. Patients with AFEs were more likely to have later-stage diagnosis, even accounting for traditional measures of socioeconomic status that influence the stage at diagnosis. The prevalence of prediagnosis AFEs underscores financial vulnerability of patients with cancer before their diagnosis, before any subsequent financial burden associated with cancer treatment.

Background: When a randomized controlled trial fails to demonstrate statistically significant efficacy against the primary endpoint, a potentially costly new trial would need to be conducted to receive licensure. Incorporating data from previous trials might allow for more efficient follow-up trials to demonstrate efficacy, speeding the availability of effective vaccines., Methods: Based on the outcomes from a failed trial of a maternal vaccine against respiratory syncytial virus (RSV), we simulated data for a new Bayesian group-sequential trial. We analyzed the data either ignoring data from the previous trial (i.e., weakly informative prior distributions) or using prior distributions incorporating the historical data into the analysis. We evaluated scenarios where efficacy in the new trial was the same, greater than, or less than that in the original trial. For each scenario, we evaluated the statistical power and type I error rate for estimating the vaccine effect following interim analyses., Results: When we used a stringent threshold to control the type I error rate, analyses incorporating historical data had a small advantage over trials that did not. If control of type I error is less important (e.g., in a postlicensure evaluation), the incorporation of historical data can provide a substantial boost in efficiency., Conclusions: Due to the need to control the type I error rate in trials used to license a vaccine, incorporating historical data provides little additional benefit in terms of stopping the trial early. However, these statistical approaches could be promising in evaluations that use real-world evidence following licensure., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Environmental epidemiologic studies routinely utilize aggregate health outcomes to estimate effects of short-term (eg, daily) exposures that are available at increasingly fine spatial resolutions. However, areal averages are typically used to derive population-level exposure, which cannot capture the spatial variation and individual heterogeneity in exposures that may occur within the spatial and temporal unit of interest (eg, within a day or ZIP code). We propose a general modeling approach to incorporate within-unit exposure heterogeneity in health analyses via exposure quantile functions. Furthermore, by viewing the exposure quantile function as a functional covariate, our approach provides additional flexibility in characterizing associations at different quantile levels. We apply the proposed approach to an analysis of air pollution and emergency department (ED) visits in Atlanta over 4 years. The analysis utilizes daily ZIP code-level distributions of personal exposures to 4 traffic-related ambient air pollutants simulated from the Stochastic Human Exposure and Dose Simulator. Our analyses find that effects of carbon monoxide on respiratory and cardiovascular disease ED visits are more pronounced with changes in lower quantiles of the population's exposure. Software for implement is provided in the R package nbRegQF., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Biometric Society.)