Glyburide confers neuroprotection against age-related macular degeneration (AMD).

Glyburide, a sulfonylurea drug used to treat type 2 diabetes, boasts neuroprotective effects by targeting the sulfonylurea receptor 1 (SUR1) and associated ion channels in various cell types, including those in the central nervous system and the retina. Previously, we demonstrated that glyburide therapy improved retinal function and structure in a rat model of diabetic retinopathy. In the present study, we explore the application of glyburide in non-neovascular ("dry") age-related macular degeneration (AMD), another progressive disease characterized by oxidative stress-induced damage and neuroinflammation that trigger cell death in the retina. We show that glyburide administration to a human cone cell line confers protection against oxidative stress, inflammasome activation, and apoptosis. To corroborate our in vitro results, we also conducted a case-control study, controlling for AMD risk factors and other diabetes medications. It showed that glyburide use in patients reduces the odds of new-onset dry AMD. A positive dose-response relationship is observed from this analysis, in which higher cumulative doses of glyburide further reduce the odds of new-onset dry AMD. In the quest for novel therapies for AMD, glyburide emerges as a promising repurposable drug given its known safety profile. The results from this study provide insights into the multifaceted actions of glyburide and its potential as a neuroprotective agent for retinal diseases; however, further preclinical and clinical studies are needed to validate its therapeutic potential in the context of degenerative retinal disorders such as AMD.

Utilization and Timing of Cystoscopy for Hematuria Evaluation by Advanced Practice Providers and Urologists.

OBJECTIVE: To characterize differences between urologists and advanced practice providers (APPs) in the utilization of cystoscopy for hematuria. METHODS: We identified patients initially evaluated for hematuria by a urologist or urology APP between 2015 and 2020 in the MarketScan Research Databases. We determined whether they received a cystoscopy within 6 months of their urology visit and the number of days until cystoscopy. We used multivariable regression to analyze the association between these outcomes and whether the urology clinician was an advanced practice registered nurse (APRN), physician assistant (PA), or urologist. RESULTS: We identified 34,470 patients with microscopic hematuria and 17,328 patients with gross hematuria. Patients evaluated by urologists more often received a same-day cystoscopy than those evaluated by APPs (13% vs 5.8%). The odds that patients evaluated for microscopic and gross hematuria received a cystoscopy were 46.2% and 26.2% lower, respectively, if they were evaluated by an APRN vs a urologist. Patients seeing an APRN for microscopic and gross hematuria also waited approximately 7 and 14 days longer for their cystoscopy, respectively. No differences were observed for patients evaluated by PAs vs urologists. CONCLUSION: Patients evaluated for hematuria by an APRN were less likely to receive a cystoscopy and had a longer wait until the procedure compared to those evaluated by a urologist; however, no differences were observed between PAs and urologists. Better understanding APP integration into urology clinics is warranted.

The Association Between Metformin Use and New-Onset ICD Coding of Geographic Atrophy.

Purpose: Metformin has been suggested to protect against the development of age-related macular degeneration (AMD) in multiple observational studies. However, the association between metformin and geographic atrophy (GA), a debilitating subtype of AMD, has not been analyzed. Methods: We conducted a case-control study of patients ages 60 years and older with new-onset International Classification of Diseases (ICD) coding of GA in the Merative MarketScan Commercial and Medicare Databases between 2017 and 2021. Cases were matched with propensity scores estimated by age, region, hypertension, and Charlson Comorbidity Index to a control without GA of the same year. Exposure to metformin was assessed for cases and controls in the year prior to their index visit. Conditional multivariable logistic regression, adjusting for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals (CIs). This study design and analysis were repeated in a sample of patients without diabetes. Results: In the full sample, we identified 10,505 cases with GA and 10,502 matched controls without GA. In total, 1149 (10.9%) cases and 1277 (12.2%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 12% (95% CI, 0.79-0.99). In the sample of patients without diabetes, we identified 7611 cases with GA and 7608 matched controls without GA. Twenty-nine (0.4%) cases and 63 (0.8%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 47% (95% CI, 0.33-0.83). Conclusions: Metformin may hold promise as a noninvasive, alternative agent to prevent the development of GA. This finding is notable due to shortcomings in recently approved therapeutics for GA and metformin's overall ease of use and few adverse effects. Additional studies are required to explore our findings further and motivate a clinical trial.

The percentage of men counseled by urologists who received a vasectomy mildly increased after the publication of the AUA vasectomy guideline.

This retrospective cohort study explored whether the publication of the vasectomy guideline by the American Urological Association in December 2012 increased the percentage of men counseled by urologists who received a vasectomy. We used commercial health insurance claims between 2010 and 2015 to identify the initial sterilization counseling visit for men aged 18-64 and whether each of them received a vasectomy within six months of that visit. A difference-in-differences analysis isolated the effect of the guideline on the percentage of men counseled by urologists who received a vasectomy, exploiting suspected variation in guideline exposure and adherence between urologists and non-urologists. In total, 226 012 men had an initial sterilization counseling visit, of which 182 204 (80.6%) were counseled by urologists and 43 808 (19.4%) were counseled by non-urologists. The percentage of men counseled by urologists who received a vasectomy mildly increased by 1.5% (p = 0.002) after the publication of the guideline. Therefore, the percentage of men who receive a vasectomy may in part be explained by practice guidelines and clinicians' willingness to consider the procedure, and future research should investigate how clinicians arrive at their decisions to recommend a vasectomy and whether a standardized counseling protocol would ensure consistency.

ASSOCIATION OF METFORMIN USE WITH RISK OF NEWLY ONSET NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEVELOPMENT.

PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD). METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed. RESULTS: Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g. CONCLUSION: Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.

INTERACTIONS OF METFORMIN AND OTHER MEDICATIONS IN REDUCING THE ODDS OF AGE-RELATED MACULAR DEGENERATION IN A COHORT OF PATIENTS WITH DIABETES.

PURPOSE: A previous study from our group demonstrated protective effects of the use of metformin in the odds of developing age-related macular degeneration (AMD). This is a subgroup analysis in a cohort of patients with diabetes to assess the interaction of metformin and other medications in protecting diabetic patients against developing AMD. METHODS: This is a case-control analysis using data from the Merative MarketScan Commercial and Medicare databases. Patients were 55 years and older with newly diagnosed AMD and matched to controls. We performed multivariable conditional logistic regressions, which adjusted for known risk factors of AMD and tested multiple interaction effects between metformin and 1) insulin, 2) sulfonylureas, 3) glitazones, 4) meglitinides, and 5) statins. RESULTS: The authors identified 81,262 diabetic cases and 79,497 diabetic controls. Metformin, insulin, and sulfonylureas demonstrated independent protective effects against AMD development. Sulfonylureas in combination with metformin demonstrated further decreased odds of AMD development compared with metformin alone. The other medication group (exenatide, sitagliptin, and pramlintide) slightly increased the odds of developing AMD when taken alone, but the combination with metformin alleviated this effect. CONCLUSION: The authors believe that their results bring them one step closer to finding an optimal effective hypoglycemic regimen that also protects against AMD development in diabetic patients.

Metformin Use and Age-Related Macular Degeneration in Patients Without Diabetes.

Importance: Metformin use may protect against the development of age-related macular degeneration (AMD) based on results from observational studies. However, its potential effectiveness among patients without diabetes remains unclear. Objective: To assess the association between metformin use and the development of AMD in patients without diabetes. Design, Setting, and Participants: This case-control study used data from 2006 to 2017 in the Merative MarketScan Research Database, a nationwide insurance claims database that includes between 27 and 57 million patients in the US with primary or Medicare supplemental health insurance. Cases with AMD and controls without AMD aged 55 years or older were matched 1:1 by year, age, anemia, hypertension, region, and Charlson Comorbidity Index score. Then, cases and matched controls without a diagnosis of diabetes were selected. In subgroup analyses, cases with dry AMD and their matched controls were identified to explore the association between metformin use and AMD staging in patients without diabetes. Data were analyzed between March and September 2023. Exposures: Exposure to metformin in the 2 years prior to the index date (ie, date of AMD diagnosis in cases and date of a randomly selected eye examination for controls) was assessed from the claims database and categorized into quartiles based on cumulative dose (1-270, 271-600, 601-1080, and >1080 g/2 y). Exposure to other antidiabetic medications was also noted. Main Outcomes and Measures: Odds of new-onset AMD development as assessed by multivariable conditional logistic regression after adjusting for known risk factors for AMD, including female sex, hyperlipidemia, smoking, and exposures to other antidiabetic medications. Asymptotic Cochran-Armitage tests for trend were also performed. Results: We identified 231 142 patients with any AMD (mean [SD] age, 75.1 [10.4] years; 140 172 females [60.6%]) and 232 879 matched controls without AMD (mean [SD] age, 74.9 [10.5] years; 133 670 females [57.4%]), none of whom had a diagnosis of diabetes. The sample included 144 147 cases with dry AMD that were matched to 144 530 controls. In all, 2268 (1.0%) cases and 3087 controls (1.3%) were exposed to metformin in the 2 years before their index visit. After data adjustment, exposure to any metformin was associated with reduced odds of any AMD development (adjusted odds ratio [AOR], 0.83; 95% CI, 0.74-0.87), specifically in the dosing quartiles of 1 to 270, 271 to 600, and 601 to 1080 g/2 y. Any metformin use was also associated with a reduced odds of developing dry AMD (AOR, 0.85; 95% CI, 0.79-0.92), specifically in the dosing quartiles of 1 to 270 and 271 to 600 g/2 y. Adjusted odds ratios for any AMD and dry AMD development did not differ across the dosing quartiles. Asymptotic Cochran-Armitage tests for trend revealed 2-sided P = .51 and P = .66 for the any and dry AMD samples, respectively. Conclusions and Relevance: In this case-control study of a population without a diagnosis of diabetes, metformin use was associated with reduced odds of developing AMD. This association does not appear to be dose dependent. These findings provide further impetus to study metformin's usefulness in protecting against AMD in prospective clinical trials.

Growth in Newborn Circumcisions Performed by Pediatric Urologists and Advanced Practice Providers Between 2010 and 2021 in the United States.

OBJECTIVE: To characterize changes in the proportion of newborn circumcisions performed by pediatric urologists and advanced practiced providers (APPs) in the United States over the last decade. METHODS: The Merative MarketScan Commercial Database was queried for newborn circumcision private health insurance claims (Common Procedural Terminology 54150) between 2010 and 2021. Setting (inpatient/outpatient), US Census Bureau region, clinician specialty, and patient age (days) were determined for the full study time period, and by study year. Simple linear regression assessed growth in proportion of newborn circumcisions performed by pediatric urologists and APPs (nurse practitioner/physician assistant/midwife), over time. RESULTS: In total, 1,006,748 newborn circumcisions (59% inpatient) were identified; while most were performed by obstetricians (45%) or pediatricians (33%); APPs performed 0.9%, and pediatric urologists performed 0.7%. From 2010-2021, the proportion of newborn circumcisions performed by pediatric urologists increased from 0.3% to 2.0% and by APPs in from 0.5% to 2.9% (P < .001 for both). Growth for both pediatric urologists and APPs occurred APPs predominantly from 2016 to 2021. Trends in proportion of newborn circumcision performed by pediatricians was stable [31.5% (2010) and 32.5% (2021)], but decreased for obstetricians [48.8% (2014) and 38.1% (2021)]. CONCLUSION: The proportion of newborn circumcisions performed by pediatric urologists and APPs increased more than 6-fold between 2010 and 2021, though both specialties still perform a minority of newborn circumcisions. These data provide important baseline information for newborn circumcision workforce planning, including evaluating collaborative care models where pediatric urologists train APPs to perform circumcision.

Associations Between Autoimmune Disease and the Development of Age-Related Macular Degeneration.

Purpose: The pathogenesis of age-related macular degeneration (AMD) likely implicates the dysregulation of immune response pathways. Several studies demonstrate that the pathogenic elements of AMD resemble those of autoimmune diseases, yet the association between AMD development and most autoimmune diseases remain unexplored. Methods: We conducted a case-control analysis of patients ages 55 and older with new-onset International Classification of Diseases (ICD) coding of dry, wet, or unspecified AMD between 2005 and 2019 in the Merative MarketScan Commercial and Medicare Databases. The diagnosis of an autoimmune disease was defined by an outpatient or inpatient claim with a relevant ICD code in the 12 months before the index visit. Conditional multivariable logistic regression, adjusted for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals. Results: We identified 415,027 cases with new-onset ICD coding for AMD matched with propensity scores to 414,853 controls. In total, 16.1% of cases and 15.9% of controls were diagnosed with any autoimmune disease. The diagnosis of any autoimmune disease did not affect the odds of new-onset ICD coding for AMD in multivariable regression (OR = 1.01; 95% CI, 0.999-1.02). Discoid lupus erythematosus (OR = 1.29; 95% CI, 1.12-1.48), systemic lupus erythematosus (SLE) (OR = 1.21; 95% CI, 1.15-1.27), giant cell arteritis (OR = 1.19; 95% CI, 1.09-1.30), Sjogren's syndrome (OR = 1.17; 95% CI, 1.09-1.26), and Crohn's disease (OR = 1.13; 95% CI, 1.06-1.22) increased the odds of a new-onset ICD coding for AMD. Conclusions: Most autoimmune diseases do not affect the odds of developing AMD but several common autoimmune disorders such as SLE and Crohn's disease were associated with modestly increased odds of AMD. Further studies are needed to validate and investigate the underlying mechanisms of these associations.

Industry Payments for Vibegron and Prescribing Patterns Among Urologic Clinicians.

This cross-sectional study compares the prescribing practices among urologists and advanced practice clinicians who received vs did not receive payment from drug manufacturers.

Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study.

Purpose: To investigate if metformin use is associated with decreased odds of developing new non-neovascular ("dry") age-related macular degeneration (AMD). Methods: Case-control study examining 194,135 cases with diagnoses of new-onset AMD between 2008 and 2017 and 193,990 matched controls in the Merative MarketScan Research Databases. The diabetic subgroup included 49,988 cases and 49,460 controls. Multivariable conditional logistic regressions identified the risks of exposures on the development of dry AMD. Main outcome measures were odds ratios (ORs) of developing dry AMD with metformin use. Results: In multivariable conditional logistic regression, any metformin use was associated with decreased odds of developing dry AMD (OR = 0.97; 95% confidence interval [CI], 0.95-0.99). This protective effect was noted for cumulative 2-year doses of metformin of 1 to 270 g (OR = 0.93; 95% CI, 0.90-0.97) and 271 to 600 g (OR = 0.92; 95% CI, 0.89-0.96). In a diabetic subgroup, metformin use below 601 g per 2 years decreased the odds of developing dry AMD (1-270 g: OR = 0.95; 95% CI, 0.91-0.99; 271-600 g: OR = 0.92; 95% CI, 0.89-0.96). Unlike in diabetic patients with diabetic retinopathy, diabetic patients without diabetic retinopathy had decreased odds of developing dry AMD with any metformin use (OR = 0.97; 95% CI, 0.94-0.998) and cumulative two-year doses of 1 to 270 g (OR 0.96; 95% CI, 0.91-0.998) and 271 to 600 g (OR = 0.92; 95% CI, 0.88-0.96). Conclusions: Metformin use was associated with decreased odds of developing dry AMD. The protective effect was observed for cumulative 2-year doses below 601 g. In diabetics, this association persisted, specifically in those without diabetic retinopathy. Therefore, metformin may be a strategy to prevent development of dry AMD.

Industry Payments to Urologists and Urologic Advanced Practice Providers in 2021.

OBJECTIVE: To compare industry payments from drug and medical device companies to urologists and urologic advanced practice providers (APPs) in 2021. METHODS: We used the 2020 Medicare Data on Provider Practice and Specialty file to identify single-specialty urology practices, defined as those where the majority of physicians were urologists. We then used the Open Payments Program Year 2021 data to summarize the value and number of industry payments to urologists and APPs, including nurse practitioners and physician assistants, in these practices. We calculated the total value and number of payments and median total value and number of payments per provider for urologists and urologic APPs. RESULTS: We identified 4418 urologists and 1099 APPs working in single-specialty urology practices in 2021 (Table 1). Of these, 3646 (87%) urologists received at least one industry payment, totaling $14,755,003 from 116,039 payments, and 954 urologic APPs (87%) received at least one industry payment, including 463 nurse practitioners (85%), totaling $401,283 from 13,035 payments, and 491 physician assistants (89%), totaling $543,429 from 14,626 payments. We observed significantly greater median total value and number of payments per provider for urologists ($620 and 24 payments) compared to urologic APPs ($473 and 21 payments; P < .001 and P = .017, respectively). CONCLUSION: A similar percentage of urologists and urologic APPs received industry payments in 2021. While urologists received a higher total number and total value of payments in 2021, urologic APPs were a common target of industry marketing payments.

Trends in the Vasectomy Rate Among Privately Insured Men Aged 18-64 in the United States Between 2014 and 2021.

OBJECTIVE: To update trends in the vasectomy rate among privately insured men aged 18-64 in the United States (U.S.) between 2014 and 2021. MATERIALS AND METHODS: We used commercial health insurance claims data between 2014 and 2021 to calculate the annual vasectomy rate in men aged 18-64 in the U.S. We performed these calculations nationally and by age group, marital status, maternal age of a wife, number of children, U.S. Census Bureau region, geography, geographical region, and state. We calculated the absolute and relative changes in these rates from 2014 to 2021 to study how much and how quickly they changed. RESULTS: The vasectomy rate among privately insured men aged 18-64 in the U.S. increased by 0.11%-a 26% change-from 2014 (0.427%) to 2021 (0.537%). The absolute changes were greatest in men with 3 or more children (0.489%), with 2 children (0.295%), with a wife not of advanced maternal age (0.276%), and aged 35-44 (0.243%). The relative changes were greatest in men with no children (61%), with a wife of advanced maternal age (40.8%), who were single (40.6%), and aged 18-24 (36.7%). In every region except the Northeast, the absolute and relative changes were greater in rural geographies compared to urban geographies. CONCLUSIONS: The vasectomy rate among privately insured men aged 18-64 in the U.S. increased between 2014 and 2021. Further investigation is needed to ensure demand for vasectomies may continue to be met.

Increasing Role of the Advanced Practice Provider in Men's Health Clinics: An Analysis of Medicare and Commercial Claims in the United States.

INTRODUCTION: As urological care delivery in the U.S. continues to evolve to meet patient needs, we aim to clarify the role of advanced practice providers for publicly and privately insured patients in the treatment of male urological conditions commonly encountered in men's health clinics. METHODS: Medicare and commercial insurance claims from the Physician/Supplier Procedure Summary and Merative MarketScan Commercial Database were queried for procedures submitted by advanced practice providers between 2010 and 2021. Common urological conditions were identified using Current Procedural Terminology codes and grouped into 4 categories: testicular hypofunction, erectile dysfunction and Peyronie's disease, benign prostatic hyperplasia, and scrotal pain. The proportion of procedures submitted by advanced practice providers was calculated for each year and category. RESULTS: From 2010 to 2021, the proportion of advanced practice provider-submitted service counts for each condition within the MarketScan group increased up to 5-fold, with benign prostatic hyperplasia representing the greatest growth. The proportion of advanced practice provider-submitted service counts within the Medicare group increased up to 8-fold, with erectile dysfunction/Peyronie's disease representing the greatest fold change. The proportion of claims submitted by advanced practice providers treating all 4 conditions was higher in 2021 than 2010 in both publicly and privately insured groups. CONCLUSIONS: The role of advanced practice providers in men's urological health is increasing for both privately and publicly insured patient populations. Advanced practice providers play a critical role in urological care and can help to improve access to men's health.

Outcomes of Hematuria Evaluation by Advanced Practice Providers and Urologists.

OBJECTIVE: To examine the quality and costs of care for patients evaluated for hematuria by urologic advanced practice providers (APPs) and urologists. The roles of APPs in urology are growing, but their clinical and financial outcomes compared to urologists are not well understood. METHODS: We conducted a retrospective cohort study of commercially insured patients using data from 2014 to 2020. We included adult beneficiaries with a diagnosis code for hematuria and an initial outpatient evaluation and management visit with a urologic APP or urologist. We assessed receipt of cystoscopy procedure, imaging study, bladder biopsy procedure, and bladder cancer diagnosis within 6 months of the initial visit. Secondary outcomes included the time until each of these outcomes occurred and the out-of-pocket spending and total payments. RESULTS: We identified 59,923 patients who were initially evaluated for hematuria. Visits with urologic nurse practitioners rather than urologists were associated with significantly lower odds of receiving cystoscopy procedures (odds ratio [OR] 0.93, 95% confidence interval [95% CI] 0.54-0.72, P < .001), imaging studies (OR 0.79, 95% CI 0.69-0.91, P < .001), and bladder biopsy procedures (OR 0.61, 95% CI 0.41-0.92, P = .02). Visits with urologic physician assistants were associated with 11% greater out-of-pocket payments (incident risk ratio 1.11, CI 1.01-1.22, P = .02) and 14% greater total payments (incident risk ratio 1.14, CI 1.04-1.25, P = .004). CONCLUSION: There are clinical and financial differences in hematuria care delivered by urologic APPs and urologists. The incorporation of APPs into urologic care warrants further study, and specialty-specific training for APPs should be considered.

Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). DESIGN: Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1-2) and case-control analysis in the Merative MarketScan Research Databases (#3). PARTICIPANTS: Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). METHODS: Eyes were divided into 2 groups (#1-2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100-300 mg, and approximately > 300 mg per day, #3). MAIN OUTCOME MEASURES: Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2-3) after adjusting for AMD risk factors. RESULTS: In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N = 84 088 control vs. 530 L-DOPA eyes, P = 0.006). In eyes with nonneovascular AMD (N = 42 081-203 155 control vs. 314-1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P = 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P = 0.024). In the MarketScan databases (N = 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75-0.97) and 23% (OR, 0.77; 95% CI, 0.67-0.87), respectively. CONCLUSIONS: Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Epidemiology of pediatric cartilage restoration procedures in the United States: insurance and geography play a role.

OBJECTIVES: The purpose of this study is to analyze the epidemiology of children and adolescents undergoing osteochondral autograft transplantation (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI) in the United States. METHODS: The Pediatric Health Information System, a national database consisting of 49 children's hospitals, was queried for all patients undergoing OAT, OCA, and ACI between 2012 and 2018. Demographic information was collected for each subject. United States Census guidelines were used to categorize hospitals geographically. Univariate analysis was followed by purposeful entry multivariate regression to adjust for confounding factors. RESULTS: A total of 809 subjects with a mean age of 15.4 ± 2.4 years were included in the analysis. Of these, 48.6% underwent OCA, 41.9% underwent OAT, and 9.5% underwent ACI. After adjusting for confounders in a multivariate model, ACI was 3.6 times more likely to be performed in patients with private insurance than those that were publicly insured (95% CI 1.6-8.0, p = 0.002). Furthermore, a patient in the Northeast was 33.1 times more likely to undergo ACI than in the West (95% CI 4.5-246.1, p = 0.001). OAT was performed most frequently in the West and Midwest (52.4% and 51.8% of the time, respectively; p < 0.001). CONCLUSION: In the United States, there is substantial variation in the procedures performed for cartilage restoration in children and adolescents. Though ACI is the least commonly selected operation overall, it is significantly more likely to be performed on patients with private insurance and those in the Northeast.

Association of metformin use with risk of newly onset neovascular age-related macular degeneration development.

PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD). METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched controls using the Merative™ Marketscan® Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic controls was also performed. RESULTS: Metformin use was associated with reduced odds ratio (OR) of developing nAMD (OR 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy (DR) -an effect that persisted after Bonferroni correction. In the diabetic cohort without DR, reduced OR was observed at 24-month cumulative doses of 1 to 300g, 301 to 630g, and 631 to 1080g. CONCLUSIONS: Metformin use was associated with reduced OR of nAMD, particularly in patients without DR. The protective effect was noted for 24-month cumulative doses below 1080g. Metformin may be a novel preventive strategy for nAMD.

Evaluation of Industry Payments to US Advanced Practice Clinicians in 2021.

Importance: Advanced practice clinicians (APCs) are a growing part of the US health care system, and their financial relationships with pharmaceutical and medical device companies have not been well studied. Objectives: To examine the value, frequency, and types of payments made to APCs and the association of state scope-of-practice laws with these payments. Design, Setting, and Participants: This cross-sectional study used 2021 Open Payments Program data to analyze payments from pharmaceutical or medical device companies to physicians or APCs between January 1 and December 31, 2021. Doctors of medicine and osteopathy were categorized as physicians, and nurse practitioners, physician assistants, clinical nurse specialists, certified registered nurse anesthetists, certified nurse midwives, and anesthesiologist assistants as APCs. Main Outcomes and Measures: The total value and total number of payments were calculated in aggregate and per clinician for each type of APC, all APCs, and physicians. These calculations were repeated by submitting manufacturer, form of payment, nature of payment, and state scope-of-practice law for nurse practitioners, physician assistants, and physicians. Results: A total of 412 000 physicians and 232 000 APCs collectively received $1.99 billion in payments from industry in 2021, of which APCs received $121 million (6.1%). The median total value of payments per clinician for physicians was $167 (IQR, $45-$712) and for APCs was $117 (IQR, $33-$357). The median total number of payments per clinician was equal for physicians and APCs (n = 4). The most common payments to APCs included food and beverage ($69 million [57.6%]), compensation for services other than consulting ($32 million [26.4%]), and consulting fees ($8 million [6.6%]). Advanced practice clinicians in states with the most restrictive scope-of-practice laws received 15.9% lower total value of payments than those in the least restrictive states (P = .002). Physician assistants received 7.6% (P = .005) higher value and 18.1% (P < .001) greater number of payments than nurse practitioners. Conclusions and Relevance: In this cross-sectional study, 232 000 APCs collectively received $121 million in industry payments in 2021. The frequency of industry interactions with APCs was similar to that for physicians, but the average value was lower. The greater value of payments to APCs who practice in states with the least restrictive scope-of-practice laws suggests that industry payments may be related to clinician autonomy.