Reminders, but not monetary incentives, increase COVID-19 booster uptake.

Despite substantially decreasing the risk of hospitalization and death from COVID-19, COVID-19 booster vaccination rates remain low around the world. A key question for public health agencies is how to increase booster vaccination rates, particularly among high-risk groups. We conducted a large preregistered randomized controlled trial (with 57,893 study subjects) in a county health system in northern California to test the impact of personal reminder messages and small financial incentives of $25 on booster vaccination rates. We found that reminders increased booster vaccination rates within 2 wk by 0.86 percentage points (P = 0.000) or nearly 33% off the control mean of 2.65%. Monetary incentives had no additional impact on vaccination rates. The results highlight the potential of low-cost targeted messages, but not small financial incentives, to increase booster vaccination rates.

Prevalence and Epidemiology of Mycoplasma genitalium in a Pacific-Region Military Population.

BACKGROUND: Mycoplasma genitalium is an important emerging sexually transmitted pathogen commonly causing urethritis in men, cervicitis, and pelvic inflammatory disease in women with potential of infertility. Accumulating evidence identifies the prevalence of M. genitalium similar to long recognized pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae. The purpose of this study was to establish the prevalence and epidemiology of M. genitalium in a mid-Pacific military population. METHODS: A prospective analysis was conducted from routine specimens collected as standard of care for sexually transmitted infection (STI) testing at Tripler Army Medical Center on Oahu, HI. The prevalence of M. genitalium was determined using the Aptima M. genitalium assay, a transcription-mediated amplification test. A multivariate analysis was performed to assess the associations for this infection with other STIs and demographic factors. RESULTS: A total of 1876 specimens were tested in a 6-month period including 6 sample types from 1158 females and 718 males. Subject ages ranged from 18 to 76 years, with a median of 24 years (interquartile range, 21-29 years). The prevalence of M. genitalium was 8.8% overall (n = 165), 7.1% in females and 11.6% in males. Coinfection with M. genitalium occurred with another sexually-transmitted pathogen in 43 patients (18.3%), with C. trachomatis as the most common organism (n = 38). CONCLUSIONS: These data contribute to the evidence base for M. genitalium and STI screening in an active-duty military.

Physician Agency and Patient Survival.

We investigate the role of physician agency in determining health care supply and patient outcomes. We show that an increase in health care supply due to a change in private physician incentives has a theoretically ambiguous impact on patient welfare. The increase can reflect either induced demand for ineffective care or a reduction in prior rationing of effective care. Furthermore, physician market structure matters in determining the welfare effects of changes in private physician incentives. We then analyze a change to Medicare fees that caused physicians to increase their provision of chemotherapy. We find that this increase in treatment improved patient survival, extending median life expectancy for lung cancer patients by about 18%. Consistent with the model, we find that while the treatment response was larger in less concentrated markets, survival improvements were larger in more concentrated markets.

Structural and functional studies of gpX of Escherichia coli phage P2 reveal a widespread role for LysM domains in the baseplates of contractile-tailed phages.

A variety of bacterial pathogenicity determinants, including the type VI secretion system and the virulence cassettes from Photorhabdus and Serratia, share an evolutionary origin with contractile-tailed myophages. The well-characterized Escherichia coli phage P2 provides an excellent system for studies related to these systems, as its protein composition appears to represent the "minimal" myophage tail. In this study, we used nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of gpX, a 68-residue tail baseplate protein. Although the sequence and structure of gpX are similar to those of LysM domains, which are a large family associated with peptidoglycan binding, we did not detect a peptidoglycan-binding activity for gpX. However, bioinformatic analysis revealed that half of all myophages, including all that possess phage T4-like baseplates, encode a tail protein with a LysM-like domain, emphasizing a widespread role for this domain in baseplate function. While phage P2 gpX comprises only a single LysM domain, many myophages display LysM domain fusions with other tail proteins, such as the DNA circulation protein found in Mu-like phages and gp53 of T4-like phages. Electron microscopy of P2 phage particles with an incorporated gpX-maltose binding protein fusion revealed that gpX is located at the top of the baseplate, near the junction of the baseplate and tail tube. gpW, the orthologue of phage T4 gp25, was also found to localize to this region. A general colocalization of LysM-like domains and gpW homologues in diverse phages is supported by our bioinformatic analysis.

Driving ability reported by neovascular age-related macular degeneration patients after treatment with ranibizumab.

OBJECTIVES: To determine the impact of ranibizumab on driving status, driving ability perception, and having 20/40 vision or better in patients with choroidal neovascularization resulting from age-related macular degeneration (AMD). DESIGN: Phase III, multicenter, randomized clinical trials (Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration [MARINA] and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration [ANCHOR]). PARTICIPANTS: One thousand one hundred twenty-six patients with choroidal neovascularization resulting from AMD. METHODS: Participants were assigned randomly to sham (n=238), 0.3-mg ranibizumab monthly injections (n=238), or 0.5-mg ranibizumab monthly injections (n=240) for 24 months (MARINA), or were randomized to verteporfin photodynamic therapy (PDT; n=143), 0.3-mg ranibizumab monthly injections (n=140), or 0.5-mg ranibizumab monthly injections (n=140) for 24 months (ANCHOR). MAIN OUTCOME MEASURES: Self-reported driving status and driving ability perception were assessed as exploratory outcomes at baseline through 24 months after baseline using the 25-item National Eye Institute Visual Function Questionnaire. Best-corrected visual acuity in each eye was assessed monthly through 24 months. RESULTS: At baseline, 68.6% of patients in the MARINA trial and 62.7% of patients in the ANCHOR trial reported driving. Among patients driving at baseline in the MARINA trial 2 years after randomization, 67.2% (95% confidence interval [CI], 59.2-75.2) of sham patients and 78.4% (95% CI, 71.8-85.0) of 0.5-mg patients reported that they were still driving. Among patients driving at baseline in the ANCHOR trial at 2 years after randomization, 71.6% (95% CI, 60.8-82.4) of PDT patients and 91.4% (95% CI, 85.3-97.5) of 0.5-mg patients were still driving. Also in the ANCHOR trial, ranibizumab-treated patients who were not driving at baseline seemed more likely to drive by months 12 and 24 than PDT patients. Perception of driving ability was correlated with improvement in visual acuity (VA) in the better-seeing eye at 12 and 24 months (R2=0.17 and R2=0.20 at 12 and 24 months, respectively [P<0.001], in the MARINA trial; R2=0.13 and R2=0.14, respectively [P<0.001], in the ANCHOR trial). Visual acuity in one or both eyes 2 years after randomization was more likely to be 20/40 or better in the ranibizumab-treated groups. CONCLUSIONS: These results suggest that patients with neovascular AMD treated with ranibizumab are more likely to report driving ability and have vision of at least 20/40 than patients given sham treatment or PDT. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Clinical Features Associated with Acute Elevated Intraocular Pressure After Intravitreal Anti-VEGF Injections.

Purpose: To study the effects of intravitreal injection (IVI) of anti-VEGF (vascular endothelial growth factor) agents on intraocular pressure (IOP) and find associations with acute pressure spikes. Methods: This was a three-month, prospective study of patients receiving outpatient IVI of anti-VEGF agents for diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) at the Acuity Eye Group Medical Centers. IOP was measured pre- and post-injection at 10-minute intervals up to 50 minutes after injection with a handheld tonometer. Patients with an IOP greater than 35 mmHg at 30 minutes received an anterior chamber paracentesis (ACP), while patients below 35 mmHg were monitored without intervention. Results: A total of 617 patients (51% female, 49% male) received IVI for DR (n = 199), AMD (n = 355), and RVO (n = 63). ACP was performed in 17 patients. Average pre-injection IOP was 16 ± 4 compared to 24 ± 7 mmHg for the non-ACP vs ACP group, respectively (mean ± standard deviation), p < 0.0001. IOP returned to baseline in 98% of patients at 50 minutes. A diagnosis of glaucoma and glaucoma suspect was more prevalent in the ACP group compared to the non-ACP group, 82.3% vs 14.2% and 17.6% vs 9.0%, respectively, p < 0.0001 and p > 0.05. Patients with a pre-injection IOP >25 mmHg and a history of glaucoma had a 58.3% rate of ACP. A 31-gauge needle had a higher mean increase in IOP from baseline compared to 30-gauge needle, p < 0.0001. Conclusion: IOP spikes are most significant in the first 10 minutes after IVI but typically resolve within the first hour. However, utilizing a smaller 31-gauge IVI in patients with a glaucoma history and pre-injection IOP >25 mmHg may be associated with significant IOP spikes lasting longer than 30 minutes.

Stem cell therapy for retinal disease.

PURPOSE OF REVIEW: Stem cell therapy holds great promise for the treatment of retinal diseases. This review summarizes recent advances in stem cell biology, outlines ongoing clinical trials and details the obstacles that must be overcome for stem cell therapy to be a viable treatment for retinal disease. RECENT FINDINGS: Stem cells can now be directed to specific retinal cell fates with high yields and acceptable purity for clinical trials. New stem cell sources have been discovered including induced pluripotent stem cells that can be derived from adult tissues then differentiated into multiple retinal cell types. The initial results of clinical trials of subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelium cells in patients with Stargardt's macular dystrophy and dry age-related macular degeneration showed preliminary safety and possible visual acuity benefits. A phase I trial of intravitreally injected autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy demonstrated no evidence of toxicity with possible visual acuity benefits but no structural or functional changes. Ongoing trials are examining the trophic effects of undifferentiated umbilical cells for the treatment of geographic atrophy in age-related macular degeneration. SUMMARY: Stem cell therapy is a promising treatment under active investigation in multiple retinal diseases. Ongoing clinical trials should yield further insights into the potential for stem cell-based retinal therapies.

Can financial incentives and other nudges increase COVID-19 vaccinations among the vaccine hesitant? A randomized trial.

Despite rapid initial uptake, COVID-19 vaccinations in the United States stalled within a few months of widespread rollout in 2021. In response, many state and local governments, employers and health systems used public health messaging, financial incentives and creative scheduling tools to increase vaccine uptake. Although these approaches drew on evidence from influenza and other vaccination efforts, they were largely untested in the context of SARS-CoV-2. In mid-2021, months after vaccines were widely available, we evaluated vaccination intentions and vaccine uptake using a randomized control trial. To do this, we recruited unvaccinated members of a Medicaid managed care plan in California (n = 2,701) and randomly assigned them to different public health messages, $10 or $50 financial incentives for vaccination, a simple vaccination appointment scheduler, or control. While messages increased vaccination intentions, none of the interventions increased vaccination rates. Estimates for financial incentives rule out even relatively small increases in vaccination rates. Small financial incentives and other behavioral nudges do not meaningfully increase COVID-19 vaccination rates amongst the vaccine hesitant.

Recovery of a catalase-negative Staphylococcus epidermidis strain in blood and urine cultures from a patient with pyelonephritis.

This report describes a 60-year-old patient with bilateral nephrolithiasis. A catalase-negative Staphylococcus epidermidis strain was recovered from both urine and blood cultures. Although rare, isolates of catalase-negative Staphylococcus spp., including Staphylococcus aureus, have been reported. Here, we describe the first report of a catalase-negative S. epidermidis strain.

Racial and Ethnic Disparities in SARS-CoV-2 Testing and COVID-19 Outcomes in a Medicaid Managed Care Cohort.

INTRODUCTION: Socioeconomic differences may confound racial and ethnic differences in SARS-CoV-2 testing and COVID-19 outcomes. METHODS: A retrospective cohort study was conducted of racial/ethnic differences in SARS-CoV-2 testing and positive tests and COVID-19 hospitalizations and deaths among adults impaneled at a Northern California regional medical center and enrolled in the county Medicaid managed care plan (N=84,346) as of March 1, 2020. Logistic regressions adjusted for demographics, comorbidities, and neighborhood characteristics. RESULTS: Nearly 30% of enrollees were ever tested for SARS-CoV-2, and 4% tested positive. A total of 19.7 per 10,000 were hospitalized for and 9.4 per 10,000 died of COVID-19. Those identified as Asian, Black, or of other/unknown race had lower testing rates, whereas those identified as Latino had higher testing rates than Whites. Enrollees of Asian or other/unknown race had slightly higher odds of a positive test, and Latinos had much higher odds of a positive test (OR=3.77, 95% CI=3.41, 4.17) than Whites. The odds of hospitalization (OR=2.85, 95% CI=1.85, 4.40) and death (OR=4.75, 95% CI=2.23, 10.12) were higher for Latino than for White patients, even after adjusting for demographics, comorbidities, and neighborhood characteristics. CONCLUSIONS: In a Medicaid managed care population, where socioeconomic differences may be reduced, the odds of a positive SARS-CoV-2 test, COVID-19 hospitalization, and COVID-19 death were higher for Latino but not Black patients than for White patients. Racial/ethnic disparities depend on local context. The substantially higher risk facing Latinos should be a key consideration in California's strategies to mitigate disease transmission and harm.

Vision-related function after ranibizumab treatment by better- or worse-seeing eye: clinical trial results from MARINA and ANCHOR.

OBJECTIVE: To examine the effects of ranibizumab on the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) scores in neovascular age-related macular degeneration (AMD) according to whether the study eye was the better- or worse-seeing eye at baseline. DESIGN: Within 2 randomized, double-masked clinical trials (MARINA and ANCHOR), the NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. PARTICIPANTS: We included 646 MARINA and 379 ANCHOR patients. INTERVENTION: Patients were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or control (sham injections for MARINA; photodynamic therapy [PDT] with verteporfin for ANCHOR). MAIN OUTCOME MEASURES: Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: Across all treatment arms, 21% to 38% of enrolled eyes were the better-seeing eye. At the 24-month follow-up visit, mean change in composite scores with ranibizumab seemed to be better than control for both better-seeing eyes (8.4 [95% confidence interval (CI), 5.2-11.6], 7.5 [95% CI, 3.7-11.4], and -9.4 [95% CI, -12.5 to -6.3] for the 0.3-mg, 0.5-mg, and sham groups, respectively) and worse-seeing eyes (1.7 [95% CI, -1.1 to 4.4], 1.7 [95% CI, -0.7 to 4.1], and -5.4 [95% CI, -7.9 to -2.8] for the 0.3-mg, 0.5-mg, and sham groups, respectively) in MARINA, as well as the better-seeing eye in ANCHOR (11.3 [95% CI, 5.3-17.3], 13.3 [95% CI, 7.7-19.0], and -2.7 [95% CI, -9.0 to 3.7] for the 0.3-mg, 0.5-mg, and PDT groups, respectively). When the worse-seeing eye was treated in ANCHOR, such differences could not be detected at 24 months (1.3 [95% CI, -1.7 to 4.2], 2.6 [95% CI, -1.1 to 6.3], and 0.1 [95% CI, -3.5 to 3.7] for the 0.3-mg, 0.5-mg, and PDT groups, respectively). CONCLUSIONS: Analysis of patient perception of vision-related function in phase III trials evaluating ranibizumab for neovascular AMD demonstrates improved patient-reported outcomes regardless of whether the treated eye is the better- or worse-seeing eye at onset of treatment, and supports treatment of such lesions with ranibizumab, even those in the worse-seeing eye. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Safety and Efficacy of Subretinally Administered Palucorcel for Geographic Atrophy of Age-Related Macular Degeneration: Phase 2b Study.

PURPOSE: To evaluate safety and successful use of a novel subretinal delivery system and suprachoroidal surgical approach and safety and activity of human umbilical tissue-derived cells (palucorcel) via a novel delivery system in patients with geographic atrophy (GA). DESIGN: Multicenter, open-label phase 2b study. PARTICIPANTS: Participants were 55 to 90 years with GA secondary to age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) of 20/80 to 20/800. Exclusion criteria included neovascular AMD in the intervention eye, glaucoma with intraocular pressure of 25 mmHg or more, or other significant ophthalmologic conditions. METHODS: Participants received a subretinal injection of palucorcel, 3.0 × 105 cells in 50 µl, using the custom-designed delivery system and surgical procedure. MAIN OUTCOME MEASURES: Safety assessments included treatment-emergent adverse events (AEs), immunologic assessments, and ophthalmologic evaluations. Efficacy was evaluated as change in mean number of BCVA letters from baseline, proportion of participants gaining 15 BCVA letters or more, and growth rate of GA lesions at 12 months. RESULTS: Surgery and palucorcel administration were performed in 21 participants at 8 sites by 8 different surgeons. At baseline, median total area of GA was 13.4 mm2 and median BCVA was 43 letters in the intervention eye. Eye-related AEs occurred in 76% of participants (16/21), including conjunctival hemorrhage (n = 5), retinal hemorrhage (n = 4), and vitreous floaters (n = 4). Most AEs were mild and resolved within 1 month. No serious AEs, no retinal detachment or perforation, and no significant changes in intraocular pressure occurred. At month 12, mean change in BCVA from baseline was -5.9 letters correct (standard deviation, 13.0 letters correct) in the intervention eye and -3.7 letters correct (standard deviation, 9.0 letters correct) in the fellow eye. No participants showed improvement of 15 letters or more in the intervention eye, and 3 participants lost more than 15 letters by month 1. No apparent effect of treatment was observed. CONCLUSIONS: Palucorcel was delivered successfully to the targeted subretinal site using a novel delivery system and suprachoroidal approach for most participants; however, improvement in GA area, retardation of growth, or visual acuity were not demonstrated.

Short-term effectiveness of intravitreal bevacizumab versus ranibizumab injections for patients with neovascular age-related macular degeneration.

PURPOSE: To compare the effectiveness of three consecutive intravitreal injections of bevacizumab (Avastin) and ranibizumab (Lucentis) in patients with treatment-naïve neovascular age-related macular degeneration. METHODS: This is a retrospective comparative study of qualifying consecutively treated patients (n = 176) with new-onset subfoveal choroidal neovascularization presenting at 6 retina referral centers. Patients were treated with 3 consecutive monthly injections of ranibizumab (0.5 mg) or 3 injections of bevacizumab every 6 weeks (1.25 mg) as determined by physician and patient preference. Ophthalmologic evaluations included monthly visual acuity measurements, ocular examinations, and optical coherence tomography imaging at each visit. RESULTS: A 29.2% reduction in the mean central foveal thickness measurement through optical coherence tomography was found in the ranibizumab-treated patients versus a 20.9% reduction in the bevacizumab-treated patients (P

Battle for the thermostat: Gender and the effect of temperature on cognitive performance.

This paper studies differences in the effect of temperature on cognitive performance by gender in a large controlled lab experiment (N = 543). We study performance in math, verbal and cognitive reflection tasks and find that the effects of temperature vary significantly across men and women. At higher temperatures, women perform better on a math and verbal task while the reverse effect is observed for men. The increase in female performance in response to higher temperature is significantly larger and more precisely estimated than the corresponding decrease in male performance. In contrast to math and verbal tasks, temperature has no impact on a measure of cognitive reflection for either gender. Our findings suggest that gender mixed workplaces may be able to increase productivity by setting the thermostat higher than current standards.

Rank-ordered multifractal spectrum for intermittent fluctuations.

The hallmark of nonlinear complexity phenomena in magnetohydrodynamic and plasma turbulence as well as all natural sciences is the appearance of intermittent fluctuating events. We introduce here a unique procedure that is both physically explicable and quantitatively accurate in deciphering the multifractal characteristics of intermittency. The generic character of the procedure provides a natural connection between the suggested spectrum based on rank order and the idea of one-parameter scaling for monofractals. We demonstrate the utility of this method using results obtained from a large scale two-dimensional magnetohydrodynamic simulation mimicking solar wind turbulence.

Idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN): new observations and a proposed staging system.

PURPOSE: To review the clinical features, disease progression, and effects of treatment on idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN). DESIGN: Retrospective interventional case series. PARTICIPANTS: Ten patients with IRVAN originally reported in 1995 and 12 additional patients identified since the original series. INTERVENTION: Patients in the series had testing that may have included fluorescein angiography, indocyanine green angiography, and systemic evaluation. Treatments included panretinal laser photocoagulation, cryotherapy, vitrectomy surgery, and injection of periocular or intravitreal steroids. MAIN OUTCOME MEASURES: Initial visual acuity (VA), initial stage at diagnosis, clinical course, surgical intervention, final VA, and complications of disease. RESULTS: A total of 44 eyes of 22 patients were studied; 9 eyes had reached stage 1 or 2 disease at last follow-up, 17 had reached stage 3, and 12 had reached stage 4 or 5. At the time of last follow-up, 14 eyes had maintained 20/20 vision, 15 had between 20/40 and 20/200 vision, and 9 had 20/300 vision or worse. Later stages of retinal ischemia are associated with worse VA. Thirty-two of 38 followed eyes were treated. Twenty-five were treated initially with panretinal laser photocoagulation. The clinical course of each eye after initiation of panretinal laser photocoagulation was evaluated with respect to the final VA and stage of ischemic retinopathy at the initiation of treatment. Panretinal laser photocoagulation was initiated in 3 eyes at stage 2, 16 at stage 3, 5 at stage 4, and 1 at stage 5. Seven eyes underwent grid laser retinal photocoagulation of the macula for macular edema. CONCLUSIONS: Idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis is an isolated retinal vascular disease that can progress rapidly to severe vision loss due to ischemic sequelae despite treatment with panretinal laser photocoagulation. Based on our review of the largest cohort of IRVAN patients, early panretinal laser photocoagulation should be considered when angiographic evidence of widespread retinal nonperfusion is present, and before (or shortly after) the development of neovascularization. A functional staging system is proposed to improve treatment paradigms.

Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial.

OBJECTIVE: To examine the effects of ranibizumab on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with neovascular age-related macular degeneration (AMD). DESIGN: In MARINA, a randomized, double-masked clinical trial, 716 patients with AMD with recent disease progression and minimally classic or occult with no classic lesion component were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or sham injections. The NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. Main Outcome Measure Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: At 12 months, ranibizumab-treated patients (0.3 mg [n = 238] and 0.5 mg [n = 240]) had mean improvements in NEI VFQ-25 composite scores of +5.2 (95% confidence interval [CI], 3.5 to 6.9) and +5.6 (95% CI, 3.9 to 7.4), respectively; sham-injected patients (n = 238) had a mean decline of -2.8 (95% CI, -4.6 to -1.1; P < .001 vs each dose). Ranibizumab-treated patients were more likely to improve in near activities, distance activities, and vision-specific dependency through 24 months. CONCLUSIONS: In MARINA, ranibizumab-treated patients were more likely than sham-treated patients to report visual function improvements at 12 and 24 months. APPLICATION TO CLINICAL PRACTICE: Treatment of neovascular AMD with ranibizumab can improve patient-reported visual function in a meaningful way compared with sham treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056836.

Going to Pot? The Impact of Dispensary Closures on Crime.

Jurisdictions that sanction medical or, more recently, recreational marijuana use often allow retail sales at dispensaries. Dispensaries are controversial as many believe they contribute to local crime. To assess this claim, we analyze the short-term mass closing of hundreds of medical marijuana dispensaries in Los Angeles. Contrary to popular wisdom, we find an immediate increase in crime around dispensaries ordered to close relative to those allowed to remain open. The increase is specific to the type of crime most plausibly deterred by bystanders, and is correlated with neighborhood walkability. We find a similar pattern of results for temporary restaurant closures due to health code violations. A likely common mechanism is that "eyes upon the street" deter some types of crime.

Experience With a Subretinal Cell-based Therapy in Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration.

PURPOSE: To evaluate the safety and tolerability of and clinical response to a single, subretinal dose of human umbilical tissue-derived cells (palucorcel [CNTO-2476]) in the eyes of adults aged ≥50 years with bilateral geographic atrophy (GA) secondary to age-related macular degeneration (AMD). DESIGN: Phase 1/2a, multicenter, open-label, dose-escalation, fellow-eye-controlled study. METHODS: In the phase 1 portion, eyes were assigned to receive a single, subretinal dose of palucorcel (ranging from 6.0 × 104 to 5.6 × 105 viable cells). In the phase 2a portion, eyes were assigned to one of 2 palucorcel doses (6.0 × 104 or 3.0 × 105 cells) determined during the phase 1 portion. The intervention eye was the eye with worse baseline visual acuity. RESULTS: A total of 35 eligible subjects underwent at least a partial surgical procedure. Palucorcel was administered in 33 eyes. Overall, 17.1% (6/35) of subjects experienced retinal detachments and 37.1% (13/35) experienced retinal perforations. No episodes of immune rejection or tumor formation were observed. At 1 year, ≥10- and ≥15-letter gains in best-corrected visual acuity were observed in 34.5% (10/29) and 24.1% (7/29) of eyes receiving palucorcel, respectively, and in 3.3% (1/30; for both) of fellow eyes. CONCLUSIONS: The subretinal delivery procedure in this study was associated with a high rate of retinal perforations (n = 13) and retinal detachments (n = 6). When cells were sequestered in the subretinal space, palucorcel was well tolerated and may be associated with improvements in visual acuity. Larger randomized controlled studies are required to confirm these results. Future studies would require a modified surgical approach.

Outcomes of 140 consecutive cases of 25-gauge transconjunctival surgery for posterior segment disease.

PURPOSE: To evaluate the safety and efficacy of 25-gauge instrumentation for a variety of vitreoretinal conditions on previously nonvitrectomized eyes. DESIGN: Single-center, retrospective, interventional case series. PARTICIPANTS: One-hundred forty eyes of 140 patients were evaluated at the Doheny Retina Institute from July 2002 to July 2003. INTERVENTION: All patients underwent surgical procedures using the Millennium 25-gauge Transconjunctival Standard Vitrectomy system. Twenty eyes (14.3%) underwent procedures without vitrectomy. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), intraocular pressure, surgical time, postoperative inflammation, complications, and number of sutured sites. RESULTS: No intraoperative complications were noted. No cases required conversion to 20-gauge machines. Ten cases (7.1%) involved single-site sclerotomy suture placement due to bleb formation at the conclusion of the procedure, but 5 of these entry sites were enlarged to facilitate larger instrumentation for tissue manipulation. Median VA improved from 20/250 (logarithm of the minimum angle of resolution, 1.08+/-0.47) preoperatively to 20/60 (0.47+/-0.30) (P<0.0001) at final visit. Mean follow-up was 33.8+/-9.7 weeks, and all eyes were observed for a minimum of 12 weeks. Mean total surgical time was 17.4+/-6.9 minutes. Intraocular pressures remained stable throughout the postoperative course. Five eyes (3.8%) presented on day 1 with shallow choroidal detachments, but all resolved by day 7, and none required volume infusion during the postoperative period. All but one of these cases was within the first 50 procedures performed. No detectable inflammation was noted in any eyes by 4 weeks postoperatively. No case of retinal detachment or endophthalmitis was recorded. CONCLUSIONS: Transconjunctival surgery using 25-gauge instrumentation may hasten postoperative recovery by decreasing overall surgical time and postoperative inflammation. Procedures requiring minimal intraocular manipulation did not require sutures and, thus, may be better suited for this surgical modality.