To examine the effectiveness of the recombinant zoster vaccine (RZV) for preventing herpes zoster ophthalmicus (HZO) in the general United States population.
Retrospective, observational cohort ...study.
Individuals enrolled in the OptumLabs Data Warehouse (OLDW; OptumLabs, Cambridge, MA) who were age eligible for herpes zoster (HZ) vaccination (≥50 years of age) from 2018 through 2019. The OLDW is a longitudinal, de-identified administrative claims and electronic health record database of patients in the United States with commercial insurance, Medicare Part D, or Medicare Advantage METHODS: Patients were required to have 365 days or more of continuous enrollment to be eligible. Those with a diagnosis code of HZ or an immunocompromising condition within 1 year before study inclusion were excluded. Vaccination with the RZV was ascertained by Current Procedural Terminology codes, and HZO was ascertained by International Classification of Diseases, Tenth Revision, codes. Cox proportional hazards regression models were used to estimate the hazard ratio of HZO associated with RZV, and inverse-probability weighting was used to control for confounding. Vaccine effectiveness was calculated from hazard ratios.
Incidence of HZO in vaccinated versus unvaccinated person-times and vaccine effectiveness were assessed.
From January 1, 2018, through December 31, 2019, a total of 4 842 579 individuals were included in this study. One hundred seventy-seven thousand two hundred eighty-nine (3.7%) received 2 valid doses of RZV. The incidence rate of HZO was 25.5 cases (95% confidence interval CI, 17.4-35.8 cases) per 100 000 person-years in the vaccinated group compared with 76.7 cases (95% CI, 74.7-78.7 cases) in the unvaccinated group. The overall adjusted effectiveness of RZV against HZO was 89.1% (95% CI, 82.9%-93.0%).
The effectiveness of RZV against HZO in individuals 50 years of age and older is high in a clinical setting. However, the low vaccination rate in this study highlights the public health need to increase HZV use. Ophthalmologists can play an important role in recommending vaccination to eligible patients.
As part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per ...million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI).
To estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California.
We created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained.
In the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to $48 billion. These had an incremental cost per QALY of $657,000 to $3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY.
Substantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks.
Over-prescribing of antibiotics is considered to result in increased morbidity and mortality from drug-resistant organisms. A resulting common wisdom is that it would be better for society if ...physicians would restrain their prescription of antibiotics. In this view, self-interest and societal interest are at odds, making antibiotic use a classic "tragedy of the commons".
We developed two mathematical models of transmission of antibiotic resistance, featuring de novo development of resistance and transmission of resistant organisms. We analyzed the decision to prescribe antibiotics as a mathematical game, by analyzing individual incentives and community outcomes.
A conflict of interest may indeed result, though not in all cases. Increased use of antibiotics by individuals benefits society under certain circumstances, despite the amplification of drug-resistant strains or organisms. In situations where increased use of antibiotics leads to less favorable outcomes for society, antibiotics may be harmful for the individual as well. For other scenarios, where a conflict between self-interest and society exists, restricting antibody use would benefit society. Thus, a case-by-case assessment of appropriate use of antibiotics may be warranted.
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.
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.
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.
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.
To study the relationship between cone spacing and density and clinical measures of visual function near the fovea.
High-resolution images of the photoreceptor mosaic were obtained with adaptive ...optics scanning laser ophthalmoscopy from 26 patients with inherited retinal degenerations. Cone spacing measures were made close to or at the foveal center (mean SD eccentricity, 0.02 0.03 degree; maximum eccentricity, 0.13 degree) and were converted to Z-scores, fraction of cones, and percentage-of-cones-below-average compared with normal values for each location (based on 37 age-similar visually normal eyes). Z-scores and percentage of cones below average were compared with best-corrected visual acuity (VA) and foveal sensitivity.
Visual acuity was significantly correlated with cone spacing (Spearman rank correlation ρ = -0.60, P = 0.003) and was preserved (≥ 80 letters), despite cone density measures that were 52% below normal. Foveal sensitivity showed significant correlation with cone spacing (ρ = -0.47, P = 0.017) and remained normal (≥ 35 decibels), despite density measures that were approximately 52% to 62% below normal.
Cone density was reduced by up to 62% below normal at or near the fovea in eyes with VA and sensitivity that remained within normal limits. Despite a significant correlation with foveal cone spacing, VA and sensitivity are insensitive indicators of the integrity of the foveal cone mosaic. Direct, objective measures of cone structure may be more sensitive indicators of disease severity than VA or foveal sensitivity in eyes with inherited retinal degenerations.
To determine whether ocular trauma occurs more frequently in the summer months.
Retrospective, cross-sectional study.
The Nationwide Emergency Department Sample (NEDS) is a large, publicly available ...administrative database that provides nationally representative estimates of emergency department (ED) visits in the United States. Billing codes from NEDS from 2006 to 2013 were used to identify all cases of ocular trauma, and the United States decennial census was used to estimate the population at risk for visiting an ED. The main outcome measures were the seasonal and annual trends in the incidence of ED-diagnosed eye trauma.
Eye trauma was the primary diagnosis for an estimated 5 615 532 ED encounters over the 8-year study period. Those with an eye trauma encounter were predominantly male (66%) and under 60 years of age (91%). The most common ocular trauma presentations were superficial injury of eye and adnexa (101 ED-diagnosed cases per 100 000 population), extraocular foreign body (54 per 100 000 population), contusion of eye and adnexa (27 per 100 000 population), and ocular adnexal open wound (26 per 100 000 population). Each exhibited a statistically significant annual cycle, with a mean annual peak between May and July (P < .01 for each, Edwards test). Eye trauma visits decreased by an average of 4% per year over the study period, with a similar pattern of decline during each calendar month (incidence rate ratio 0.96, 95% confidence interval 0.94–0.98).
Eye trauma, although decreasing in incidence, is a seasonal condition. Prevention efforts would likely be most effective if implemented in the spring or summer months. Further study to identify other individual-level or regional-level factors that would most benefit from public health efforts is warranted.
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.
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.
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.
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).
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.
To evaluate foveal function in patients with inherited retinal degenerations (IRD) by measuring visual acuity (VA) after correction of higher-order aberrations.
Adaptive optics scanning laser ...ophthalmoscopy (AOSLO) was used to image cones in 4 healthy subjects and 15 patients with IRD. The 840-nm scanning laser delivered an "E" optotype to measure AOSLO-mediated VA (AOSLO-VA). Cone spacing was measured at the preferred retinal locus by two independent graders and the percentage of cones below the average density of 47 age-similar healthy subjects was computed. Cone spacing was correlated with best-corrected VA measured with the Early Treatment of Diabetic Retinopathy Study protocol (ETDRS-VA), AOSLO-VA, and foveal sensitivity.
ETDRS-VA significantly correlated with AOSLO-VA (ρ = 0.79, 95% confidence interval CI 0.5-0.9). Cone spacing correlated with AOSLO-VA (ρ = 0.54, 95% CI 0.02-0.7), and negatively correlated with ETDRS letters read (ρ = -0.64, 95% CI -0.8 to -0.2). AOSLO-VA remained ≥20/20 until cones decreased to 40.2% (CI 31.1-45.5) below normal. Similarly, ETDRS-VA remained ≥20/20 until cones were 42.0% (95% CI 36.5-46.1) below normal. Cone spacing z scores negatively correlated with foveal sensitivity (ρ = -0.79, 95% CI -0.9 to -0.4) and foveal sensitivity was ≥35 dB until cones were 43.1% (95% CI 39.3-46.6) below average.
VA and foveal cone spacing were weakly correlated until cones were reduced by 40% to 43% below normal. The relationship suggests that VA is an insensitive measure of foveal cone survival; cone spacing may be a more sensitive measure of cone loss.
Community-level interventions in cluster randomized controlled trials may alter the gut microbiome of individuals. The current method of estimating community diversities uses microbiome data obtained ...from multiple individual's specimens. Here we propose randomly pooling a number of microbiome samples from the same community into one sample before sequencing to estimate community-level microbiome diversity.
We design and analyze an experiment to compare community microbiome diversity (gamma-diversity) estimates derived from 16S rRNA gene sequencing of 1) individually sequenced specimens vs. 2) pooled specimens collected from a community. Pool sizes of 10, 20, and 40 are considered. We then compare the gamma-estimates using Pearson's correlation as well as using Bland and Altman agreement analysis for three established diversity indices including richness, Simpson's and Shannon's.
The gamma-diversity estimates are highly correlated, with most being statistically significant. All correlations between all three diversity estimates are significant in the 10-pooled data. Pools comprising 40 specimens are closest to the line of agreement, but all pooled samples and individual samples fall within the 95% limits of agreement.
Pooling microbiome samples before DNA amplification and metagenomics sequencing to estimate community-level diversity is a viable measure to consider in population-level association research studies.
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