Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration: A Nonrandomized Controlled Trial.

Importance: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable. Objective: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD. Design, Setting, and Participants: This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023. Intervention: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years. Main Outcomes and Measures: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase. Results: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 µm per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants). Conclusions and Relevance: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

Impact of cascade reporting of antimicrobial susceptibility on fluoroquinolone and meropenem consumption at a Veterans' Affairs medical center.

OBJECTIVE: To determine whether cascade reporting is associated with a change in meropenem and fluoroquinolone consumption. DESIGN: A quasi-experimental study was conducted using an interrupted time series to compare antimicrobial consumption before and after the implementation of cascade reporting. SETTING: A 399-bed, tertiary-care, Veterans' Affairs medical center. PARTICIPANTS: Antimicrobial consumption data across 8 inpatient units were extracted from the Center for Disease Control and Prevention (CDC) National Health Safety Network (NHSN) antimicrobial use (AU) module from April 2017 through March 2019, reported as antimicrobial days of therapy (DOT) per 1,000 days present (DP). INTERVENTION: Cascade reporting is a strategy of reporting antimicrobial susceptibility test results in which secondary agents are only reported if an organism is resistant to primary, narrow-spectrum agents. A multidisciplinary team developed cascade reporting algorithms for gram-negative bacteria based on local antibiogram and infectious diseases practice guidelines, aimed at restricting the use of fluoroquinolones and carbapenems. The algorithms were implemented in March 2018. RESULTS: Following the implementation of cascade reporting, mean monthly meropenem (P =.005) and piperacillin/tazobactam (P = .002) consumption decreased and cefepime consumption increased (P < .001). Ciprofloxacin consumption decreased by 2.16 DOT per 1,000 DP per month (SE, 0.25; P < .001). Clostridioides difficile rates did not significantly change. CONCLUSION: Ciprofloxacin consumption significantly decreased after the implementation of cascade reporting. Mean meropenem consumption decreased after cascade reporting was implemented, but we observed no significant change in the slope of consumption. cascade reporting may be a useful strategy to optimize antimicrobial prescribing.

Physical Therapy Use, Costs, and Value for Latent Classes of Good vs Poor Outcome in Patients Who Catastrophize About Their Pain Prior to Knee Arthroplasty.

OBJECTIVE: To examine use, costs, and value of physical therapy (PT) among subgroups. DESIGN: We conducted an observational study of data from a randomized trial of a pain coping skills intervention. Good and poor outcome subgroups were determined based on Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain and Physical Function scores. The use and costs of PT care as well as changes in WOMAC Pain and Physical Function scores over 4 time periods during a 1-year follow-up were reported. We compared the number of PT visits, total PT costs, and cost per 1-unit improvement in WOMAC scores for the 2 latent subgroups. SETTING: Five academic medical centers. PARTICIPANTS: Patients who catastrophized about their pain prior to knee arthroplasty (N=384). INTERVENTIONS: Pain coping skills training, arthritis education, and usual care. MAIN OUTCOME MEASURES: The WOMAC Pain Scale was the primary outcome. RESULTS: The value of PT was lower and the cost of PT was higher for poor vs good outcome subgroups beginning 2 months after knee arthroplasty. For example, during the 2- to 6-month period, participants in the poor outcome subgroup incurred a PT cost of $5181.22 per 1-unit improvement in WOMAC Pain compared with $437.87 per 1-unit improvement in WOMAC Pain for the good outcome subgroup (P<.001). From the 6- to 12-month period, WOMAC scores worsened for the poor outcome subgroup, indicating no benefit from PT. CONCLUSIONS: Patients in 2 latent classes demonstrated clinically important differences in value of PT. Future research should identify rehabilitation-based interventions that reduce utilization and enhance effectiveness for patients at high risk for poor outcome.

Changes in Metronidazole and Vancomycin Utilization for Nonsevere Clostridioides difficile Infection Among Institutions Caring for Children.

Clostridioides difficile infection guidelines were published in final format on April 1, 2018. Among 4962 and 3545 C. difficile infection cases in children the year before and after publication, oral metronidazole use decreased from 63.0% to 44.3% (P < 0.001) and oral vancomycin use increased from 27.3% to 47.7% (P < 0.001). Quarterly metronidazole utilization decreased postguidelines among 117 institutions, incidence rate ratios 0.86 (95% confidence intervals: 0.78-0.96).

Impact of the Centers for Medicare and Medicaid Services Sepsis Core Measure on Antibiotic Use.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) implemented a core measure sepsis (SEP-1) bundle in 2015. One element was initiation of broad-spectrum antibiotics within 3 hours of diagnosis. The policy has the potential to increase antibiotic use and Clostridioides difficile infection (CDI). We evaluated the impact of SEP-1 implementation on broad-spectrum antibiotic use and CDI occurrence rates. METHODS: Monthly adult antibiotic data for 4 antibiotic categories (surgical prophylaxis, broad-spectrum for community-acquired infections, broad-spectrum for hospital-onset/multidrug-resistant [MDR] organisms, and anti-methicillin-resistant Staphylococcus aureus [MRSA]) from 111 hospitals participating in the Clinical Data Base Resource Manager were evaluated in periods before (October 2014-September 2015) and after (October 2015-June 2017) policy implementation. Interrupted time series analyses, using negative binomial regression, evaluated changes in antibiotic category use and CDI rates. RESULTS: At the hospital level, there was an immediate increase in the level of broad-spectrum agents for hospital-onset/MDR organisms (+2.3%, P = .0375) as well as a long-term increase in trend (+0.4% per month, P = .0273). There was also an immediate increase in level of overall antibiotic use (+1.4%, P = .0293). CDI rates unexpectedly decreased at the time of SEP-1 implementation. When analyses were limited to patients with sepsis, there was a significant level increase in use of all antibiotic categories at the time of SEP-1 implementation. CONCLUSIONS: SEP-1 implementation was associated with immediate and long-term increases in broad-spectrum hospital-onset/MDR organism antibiotics. Antimicrobial stewardship programs should evaluate sepsis treatment for opportunities to de-escalate broad therapy as indicated.

Associations Between Physical Therapy Visits and Pain and Physical Function After Knee Arthroplasty: A Cross-Lagged Panel Analysis of People Who Catastrophize About Pain Prior to Surgery.

OBJECTIVE: Physical therapy visit number and timing following knee arthroplasty (KA) are variable in daily practice. The extent to which the number and timing of physical therapy visits are associated with current and future pain and function-and, alternatively, whether pain and function are associated with the number of future physical therapy visits following KA-are unknown. The purpose of this study was to determine temporal and reciprocal associations between the number of physical therapy visits and future pain and function in people with KA. METHODS: A cross-lagged panel design was applied to a secondary analysis of data from a randomized clinical trial of patients with pain catastrophizing. The 326 participants underwent KA and completed at least 7 of 9 health care diaries over the year following surgery. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales were completed preoperatively and multiple times during follow-up. Separate cross-lagged panel analyses were conducted for WOMAC pain and physical function. RESULTS: From surgery to 2 months postsurgery, reciprocal associations were generally not found between physical therapy visit number and future pain or function. From 2 to 6 months postsurgery, a greater number of physical therapy weekly visits were associated with higher (worse) 6-month pain and function. Higher (worse) WOMAC pain at 2 and 6 months led to more visits from 2 to 6 and 6 to 12 months, respectively. CONCLUSIONS: Higher pain scores 2 months postsurgery were associated with higher physical therapy use in the 2 to 6 months following surgery. However, patients with increased physical therapy use from 2 to 6 months had significantly higher pain scores 6 months postsurgery. Those patients with persistent pain 6 months postsurgery were higher users of physical therapy 6 to 12 months postsurgery. This reciprocal positive association between pain and physical therapy during this time period suggests minimal benefit of physical therapy despite an increased physical therapy use for patients with higher pain. IMPACT: This is the first study to determine the association between the number and timing of physical therapy visits and current and future pain and function. Based on the results, physical therapy might not be a cost-effective strategy to treat patients with persistent pain following KA.

Impact of Suction-Assisted Laryngoscopy and Airway Decontamination Technique on Intubation Quality Metrics in a Helicopter Emergency Medical Service: An Educational Intervention.

OBJECTIVE: Suction-assisted laryngoscopy and airway decontamination (SALAD) was created to assist with the decontamination of a massively soiled airway. This study aims to investigate the usefulness of SALAD training to prehospital emergency providers to improve their ability to intubate a massively contaminated airway. METHODS: This was a prospective study conducted as a before and after teaching intervention. Participants were made up of prehospital providers who were present at regularly scheduled training sessions and were asked to intubate a high-fidelity mannequin simulating large-volume emesis before and after SALAD instruction. They were subsequently tested on 3-month skill retention. Twenty subjects participated in all stages of the study and were included in the analysis. RESULTS: The median time to successful intubation for all study participants before instruction was 60.5 seconds (interquartile range [IQR] = 44.0-84.0); post-training was 43.0 seconds (IQR = 38.0-57.5); and at the 3-month follow-up, it was 29.5 seconds (IQR = 24.5-39.0). The greatest improvement was seen on subgroup analysis of the slowest 50th percentile where the median time before instruction was 84.0 seconds (IQR = 68.0-96.0); post-instruction was 41.5 seconds (IQR = 36.0-65.0); and at the 3-month follow-up, it was 29.5 seconds (IQR = 25.0-39.0). CONCLUSION: The implementation of the SALAD technique through a structured educational intervention improved time to intubation and the total number of attempts.

California Healthy Places Index: Frames Matter.

INTRODUCTION: We describe the California Healthy Places Index (HPI) and its performance relative to other indexes for measuring community well-being at the census-tract level. The HPI arose from a need identified by health departments and community organizations for an index rooted in the social determinants of health for place-based policy making and program targeting. The index was geographically granular, validated against life expectancy at birth, and linked to policy actions. MATERIALS AND METHODS: Guided by literature, public health experts, and a positive asset frame, we developed a composite index of community well-being for California from publicly available census-tract data on place-based factors linked to health. The 25 HPI indicators spanned 8 domains; weights were derived from their empirical association with tract-level life expectancy using weighted quantile sums methods. RESULTS: The HPI's domains were aligned with the social determinants of health and policy action areas of economic resources, education, housing, transportation, clean environment, neighborhood conditions, social resources, and health care access. The overall HPI score was the sum of weighted domain scores, of which economy and education were highly influential (50% of total weights). The HPI was strongly associated with life expectancy at birth (r = 0.58). Compared with the HPI, a pollution-oriented index did not capture one-third of the most disadvantaged quartile of census tracts (representing 3 million Californians). Overlap of the HPI's most disadvantaged quartile of census tracts was greater for indexes of economic deprivation. We visualized the HPI percentile ranking as a web-based mapping tool that presented the HPI at multiple geographies and that linked indicators to an action-oriented policy guide. PRACTICE IMPLICATIONS: The framing of indexes and specifications such as domain weighting have substantial consequences for prioritizing disadvantaged populations. The HPI provides a model for tools and new methods that help prioritize investments and identify multisectoral opportunities for policy action.

The Social Determinants of Health and the Decline in U.S. Life Expectancy: Implications for Appalachia.

For the past century, life expectancy in industrialized countries has increased, and the U.S. has shared in that progress. However, beginning in the 1980s, advances in U.S. life expectancy began to lose pace with peer countries. By 1998, U.S. life expectancy had fallen below the average for Organisation for Economic Cooperation and Development nations. U.S. life expectancy peaked in 2014 and has been decreasing for three consecutive years, a trend not been seen since the influenza pandemic a century ago. Put simply, U.S. health is in decline.

Spatial analysis of the relative risk of suicide for Virginia counties incorporating uncertainty of variable estimates.

PURPOSE: This research aimed to identify significantly elevated areas of risk for suicide in Virginia adjusting for risk factors and risk factor uncertainty. METHODS: We fit three Bayesian hierarchical spatial models for relative risk of suicide adjusting for risk factors and considering different random effects. We compared models with and without incorporating parameter estimates' margin of error (MOE) from the American Community Survey and identified counties with significantly elevated risk and highly significantly elevated risk for suicide. RESULTS: Incorporating MOEs and using a mixing parameter between unstructured and spatially structured random effects achieved the best model fit. Fifty-two counties had significantly elevated risk and 18 had highly significantly elevated risk of suicide. Models without MOEs underestimated relative risk and over-identified counties with elevated risk. CONCLUSIONS: Accounting for uncertainty in parameter estimates achieved better model fit. Efficient allocation of resources for suicide prevention can be attained by targeting clusters of counties with elevated risk.