A Feasibility Study of a Remotely-Delivered Mindfulness-Based Training for Adolescents During the COVID-19 Pandemic.

Social distancing, home confinement, economic challenges, and COVID-19-related illness and deaths during the COVID-19 pandemic can significantly affect mental health in youth. One promising approach to reduce anxiety and depression in adolescents is the neuroscience-based mindfulness intervention Training for Awareness, Resilience, and Action (TARA). The objective of this individually randomized waitlist-controlled trial (RCT) was (1) to test the feasibility of TARA, delivered partially over Zoom, and (2) to assess changes in the emotional wellbeing in healthy adolescents between the ages of 14-18 years old during the COVID-19 pandemic. METHODS: Twenty-one healthy adolescents were randomized to the TARA intervention or to the waitlist control group in February 2020, just before the start of the pandemic. The TARA group intervention was delivered in person for the first five sessions and remotely over Zoom for the remaining seven sessions due to the pandemic. The participants' acceptability of TARA was assessed weekly using the Child Session Rating Scale (CSRS). The primary outcome was the emotional wellbeing measured using emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ) pre/post-TARA. We also explored weekly changes in TARA participants' wellbeing using the Child Outcome Rating Scale (CORS). RESULTS: The overall session rating in TARA participants improved after the switch to Zoom (Cohen's d = 1.2, p = 0.008). The results of the two-way ANOVA showed no statistically significant difference in the change of the SDQ emotional symptoms during the 12 weeks between the TARA group and waitlist-control group (timepoint × group interaction: F = 0.77, p = 0.38). The exploratory analysis using the CORS in the TARA participants showed a significant improvement in their functioning over the weeks of training. CONCLUSION: Our results support the feasibility of TARA delivered over Zoom. While our primary outcome did not provide support for the improvement of the emotional wellbeing with TARA compared to a passive control group, our exploratory analysis in the intervention group indicated an improved functioning over the weeks of TARA training. The important general positive impact of this study lies in the possibility of offering a neuroscience-based mindfulness intervention remotely to youth living in remote areas and for all youth during pandemic times.

Implication of Trends in Timing of Dialysis Initiation for Incidence of End-stage Kidney Disease.

Importance: In the last 2 decades, there have been notable changes in the level of estimated glomerular filtration rate (eGFR) at which patients initiate long-term dialysis in the US and around the world. How changes over time in the likelihood of dialysis initiation at any given eGFR level in at-risk patients are associated with the population burden of end-stage kidney disease (ESKD) has not been not well defined. Objective: To examine temporal trends in long-term dialysis initiation by level of eGFR and to quantify how these patterns are associated with the number of patients with ESKD. Design, Setting, and Participants: Retrospective cohort study analyzing data obtained from a large, integrated health care delivery system in Northern California from 2001 to 2018 in successive 3-year intervals. Included individuals, ranging in number from as few as 983 122 (2001-2003) to as many as 1 844 317 (2016-2018), were adult members with 1 or more outpatient serum creatinine levels determined in the prior year. Main Outcomes and Measures: One-year risk of initiating long-term dialysis stratified by eGFR levels. Multivariable logistic regression was performed to assess temporal trends in each 3-year cohort with adjustment for age, sex, race, and diabetes status. The potential change in dialysis initiation in the final cohort (2016-2018) was estimated using the relative difference between the standardized risks in the initial cohort (2001-2003) and the final cohort. Results: In the initial 3-year cohort, the mean (SD) age was 55.4 (16.3) years, 55.0% were women, and the prevalence of diabetes was 14.9%. These characteristics, as well as the distribution of index eGFR, were stable across the study period. The likelihood of receiving dialysis at eGFR levels of 10 to 24 mL/min/1.73 m2 generally increased over time. For example, the 1-year odds of initiating dialysis increased for every 3-year interval by 5.2% (adjusted odds ratio, 1.052; 95% CI, 1.004-1.102) among adults with an index eGFR of 20 to 24 mL/min/1.73 m2, by 6.6% (adjusted odds ratio, 1.066; 95% CI, 1.007-1.130) among adults with an eGFR of 16 to 17 mL/min/1.73 m2, and by 5.3% (adjusted odds ratio, 1.053; 95% CI, 1.008-1.100) among adults with an eGFR of 10 to 13 mL/min/1.73 m2, adjusting for age, sex, race, and diabetes. The incidence of new cases of ESKD was estimated to have potentially been 16% (95% CI, 13%-18%) lower if there were no changes in system-level practice patterns or other factors besides timing of initiating long-term dialysis from the initial 3-year interval (2001-2003) to the final interval (2016-2018) assessed in this study. Conclusions and Relevance: The present results underscore the importance the timing of initiating long-term dialysis has on the size of the population of individuals with ESKD.

Renin-Angiotensin System Blockade after Acute Kidney Injury (AKI) and Risk of Recurrent AKI.

BACKGROUND AND OBJECTIVES: How to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a cohort study of 10,242 members of an integrated health care delivery system in Northern California who experienced AKI and survived a hospitalization between January 1, 2006 and December 31, 2013. All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior. New receipt and time-updated exposure of ACE-Is/ARBs was identified on the basis of dispensed prescriptions found in outpatient health plan pharmacy databases. The main outcome of interest was subsequent episode of hospitalized AKI after discharge from an initial index hospitalization complicated by AKI. Recurrent AKI episode was defined using acute changes in serum creatinine concentrations. Marginal structural models were used to adjust for baseline and potential time-dependent confounders. RESULTS: Forty-seven percent of the study population had a documented eGFR<60 ml/min per 1.73 m2 or documented proteinuria before hospitalization. With a median of 3 (interquartile range, 1-5) years of follow-up, 1853 (18%) patients initiated use of ACE-Is/ARBs and 2124 (21%) patients experienced recurrent AKI. Crude rate of recurrent AKI was 6.1 (95% confidence interval [95% CI], 5.9 to 6.4) per 100 person-years off ACE-Is/ARBs and 5.7 (95% CI, 4.9 to 6.5) per 100 person-years on ACE-Is/ARBs. In marginal structural causal inference models that adjusted for baseline and potential time-dependent confounders, exposure to ACE-I/ARB use was not associated with higher incidence of recurrent AKI (adjusted odds ratio, 0.71; 95% CI, 0.45 to 1.12). CONCLUSIONS: In this study of AKI survivors without heart failure, new use of ACE-I/ARB therapy was not independently associated with increased risk of recurrent hospitalized AKI.

HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate is used to prevent the sexual acquisition of HIV in groups at high risk such as transgender women. We used data from the iPrEx study to assess PrEP efficacy, effectiveness, and adherence in transgender women. METHODS: The iPrEx trial was a randomised controlled trial of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate compared with placebo in men who have sex with men (MSM) and transgender women, followed by an open-label extension. Drug concentrations were measured in blood by liquid chromatography and tandem mass spectroscopy. We did unplanned exploratory analyses to investigate differences in PrEP outcomes among transgender women and between transgender women and MSM. FINDINGS: Of the 2499 participants enrolled in the randomised controlled trial, 29 (1%) identified as women, 296 (12%) identified as trans, 14 (1%) identified as men but reported use of feminising hormones, such that 339 (14%) reported one or more characteristics and are classified as transgender women for the purpose of this study. Compared with MSM, transgender women more frequently reported transactional sex, receptive anal intercourse without a condom, or more than five partners in the past 3 months. Among transgender women, there were 11 HIV infections in the PrEP group and ten in the placebo group (hazard ratio 1·1, 95% CI 0·5-2·7). In the PrEP group, drug was detected in none of the transgender women at the seroconversion visit, six (18%) of 33 seronegative transgender women (p=0·31), and 58 (52%) of 111 seronegative MSM (p<0·0001). PrEP use was not linked to behavioural indicators of HIV risk among transgender women, whereas MSM at highest risk were more adherent. INTERPRETATION: PrEP seems to be effective in preventing HIV acquisition in transgender women when taken, but there seem to be barriers to adherence, particularly among those at the most risk. Studies of PrEP use in transgender women populations should be designed and tailored specifically for this population, rather than adapted from or subsumed into studies of MSM. FUNDING: US National Institutes of Health and the Bill & Melinda Gates Foundation.

Early addition of topical corticosteroids in the treatment of bacterial keratitis.

IMPORTANCE: Scarring from bacterial keratitis remains a leading cause of visual loss. OBJECTIVE: To determine whether topical corticosteroids are beneficial as an adjunctive therapy for bacterial keratitis if given early in the course of infection. DESIGN, SETTING, AND PARTICIPANTS: The Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial that overall found no effect of adding topical corticosteroids to topical moxifloxacin hydrochloride in bacterial keratitis. Here, we assess the timing of administration of corticosteroids in a subgroup analysis of the SCUT. We define earlier administration of corticosteroids (vs placebo) as addition after 2 to 3 days of topical antibiotics and later as addition after 4 or more days of topical antibiotics. MAIN OUTCOMES AND MEASURES: We assess the effect of topical corticosteroids (vs placebo) on 3-month best spectacle-corrected visual acuity in patients who received corticosteroids or placebo earlier vs later. Further analyses were performed for subgroups of patients with non-Nocardia keratitis and those with no topical antibiotic use before enrollment. RESULTS: Patients treated with topical corticosteroids as adjunctive therapy within 2 to 3 days of antibiotic therapy had approximately 1-line better visual acuity at 3 months than did those given placebo (-0.11 logMAR; 95% CI, -0.20 to -0.02 logMAR; P = .01). In patients who had 4 or more days of antibiotic therapy before corticosteroid treatment, the effect was not significant; patients given corticosteroids had 1-line worse visual acuity at 3 months compared with those in the placebo group (0.10 logMAR; 95% CI, -0.02 to 0.23 logMAR; P = .14). Patients with non-Nocardia keratitis and those having no topical antibiotic use before the SCUT enrollment showed significant improvement in best spectacle-corrected visual acuity at 3 months if corticosteroids were administered earlier rather than later. CONCLUSIONS AND RELEVANCE: There may be a benefit with adjunctive topical corticosteroids if application occurs earlier in the course of bacterial corneal ulcers.

Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis.

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. DESIGN AND METHODS: The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy. RESULTS: There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy. CONCLUSIONS: In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.

The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial.

PURPOSE: To determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes. DESIGN: Randomized, placebo-controlled, double-masked clinical trial. METHODS: This multicenter trial compared 1.0% prednisolone sodium phosphate to placebo in the treatment of bacterial keratitis among 500 patients with culture-positive ulcers receiving 48 hours of moxifloxacin before randomization. The primary endpoint was 3 months from enrollment, and 399 patients were evaluated at 12 months. The outcomes examined were best spectacle-corrected visual acuity (BSCVA) and scar size at 12 months. Based on previous results, regression models with adjustments for baseline status and/or causative organism were used for analysis. RESULTS: No significant differences in clinical outcomes by treatment group were seen with the prespecified regression models (BSCVA: -0.04 logMAR, 95% CI, -0.12 to 0.05, P = .39; scar size: 0.03 mm, 95% CI, -0.12 to 0.18, P = .69). A regression model including a Nocardia-treatment arm interaction found corticosteroid use associated with a mean 1-line improvement in BSCVA at 12 months among patients with non-Nocardia ulcers (-0.10 logMAR, 95% CI, -0.19 to -0.02, P = .02). No significant difference was observed in 12-month BSCVA for Nocardia ulcers (0.18 logMAR, 95% CI, -0.04 to 0.41, P = .16). Corticosteroids were associated with larger mean scar size at 12 months among Nocardia ulcers (0.47 mm, 95% CI, 0.06-0.88, P = .02) and no significant difference was identified by treatment for scar size for non-Nocardia ulcers (-0.06 mm, 95% CI, -0.21 to 0.10, P = .46). CONCLUSIONS: Adjunctive topical corticosteroid therapy may be associated with improved long-term clinical outcomes in bacterial corneal ulcers not caused by Nocardia species.

Moxifloxacin susceptibility mediates the relationship between causative organism and clinical outcome in bacterial keratitis.

PURPOSE: Bacterial keratitis is a sight-threatening infection of the cornea that is one of the leading causes of blindness globally. In this report, we analyze the role of moxifloxacin susceptibility in the relationship between causative organisms and clinical outcome in bacteria keratitis. METHODS: A mediation analysis is used to assess the role of moxifloxacin susceptibility in the relationship between causative organisms and clinical outcome in bacterial keratitis using data collected in a randomized, controlled trial. RESULTS: In the Steroids for Corneal Ulcers Trial (SCUT), 500 corneal infections were treated with topical moxifloxacin. The outcome of 3-week best spectacle-corrected visual acuity was significantly associated with an organism (Streptococcus pneumoniae, Pseudomonas aeruginosa, etc., P = 0.008). An indirect effects mediation model suggests that MIC accounted for approximately 13% (95% confidence interval, 3%-24%, P = 0.015) of the effect of the organism on 3-week visual acuity. CONCLUSIONS: Moxifloxacin mediates the relationship between causative organisms and clinical outcome in bacterial keratitis, and is likely on the causal pathway between the organism and outcome. (ClinicalTrials.gov number, NCT00324168.).

Relationship of in vitro susceptibility to moxifloxacin and in vivo clinical outcome in bacterial keratitis.

BACKGROUND: For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. METHODS: Data were collected as part of a National Eye Institute-funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. RESULTS: Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040-.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010-.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86-.97; P = .005). CONCLUSIONS: In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. CLINICAL TRIALS REGISTRATION: NCT00324168.

The steroids for corneal ulcers trial: study design and baseline characteristics.

OBJECTIVES: To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. METHODS: Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbiological results, and patient demographics, for patients enrolled in the trial. RESULTS: Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P = .04) and deeper infiltrates (P = .04) and were more likely to be localized centrally (P = .002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n = 366, 72%). CONCLUSIONS: The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00324168.

Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT).

OBJECTIVE: To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers. METHODS: Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization. MAIN OUTCOME MEASURES: The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation. RESULTS: Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (-0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, -0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, -0.31 to -0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (-0.37 to -0.04; P = .02). CONCLUSIONS: We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers. APPLICATION TO CLINICAL PRACTICE: Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00324168.

Neonatal watershed brain injury on magnetic resonance imaging correlates with verbal IQ at 4 years.

OBJECTIVE: We have previously described patterns of neonatal brain injury that correlate with global cognitive and motor outcomes. We now examine, in survivors of neonatal encephalopathy (presumed secondary to hypoxia-ischemia) without functional motor deficits, whether the severity and neuroanatomical involvement on neonatal MRI are associated with domain-specific cognitive outcomes, verbal and performance IQ, at 4 years of age. METHODS: In this prospective study, neonatal MRIs of 81 term infants with neonatal encephalopathy were scored for degree of injury in 2 common patterns: watershed distribution and basal ganglia distribution. Follow-up evaluation at 4 years of age by examiners blinded to clinical history and MRIs included a 5-point neuromotor score and the Wechsler Preschool and Primary Scale of Intelligence-Revised. In 64 subjects with no functional motor impairment, test of trend was used to examine the association of ordered watershed-distribution and basal ganglia-distribution MRI scores with mean verbal and performance IQ. RESULTS: Lower verbal and performance IQs were seen with increasing degree of injury on both watershed-distribution and basal ganglia-distribution scales in univariate analyses. When each MRI pattern score was adjusted for the other, only the association of decreasing verbal IQ with increasing watershed-distribution injury remained significant. A suggestion of decreasing verbal IQ with increasing basal ganglia-distribution injury was also seen in the multivariate model, whereas no association was seen between performance IQ and severity of injury in either MRI pattern. CONCLUSIONS: In survivors of neonatal encephalopathy without functional motor deficits at 4 years of age, an increasing severity of watershed-distribution injury is associated with more impaired language-related abilities.

Hematologic toxicity of high-dose iodine-131-metaiodobenzylguanidine therapy for advanced neuroblastoma.

PURPOSE: Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of (131)I-MIBG is myelosuppression, which might necessitate autologous hematopoietic stem-cell transplantation (AHSCT). The goal of this study was to determine risk factors for myelosuppression and the need for AHSCT after (131)I-MIBG treatment. PATIENTS AND METHODS: Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg (131)I-MIBG on a phase I/II protocol. The median whole-body radiation dose was 2.92 Gy. RESULTS: Almost all patients required at least one platelet (96%) or red cell (91%) transfusion and most patients (79%) developed neutropenia (< 0.5 x 10(3)/microL). Patients reached platelet nadir earlier than neutrophil nadir (P <.0001). Earlier platelet nadir correlated with bone marrow tumor, more extensive bone involvement, higher whole-body radiation dose, and longer time from diagnosis to (131)I-MIBG therapy (P