To evaluate the ocular hypotensive efficacy and safety of razuprotafib, a novel Tie2 activator, when used as an adjunct to latanoprost in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Subjects with OAG or OHT and an unmedicated IOP from ≥22 mm Hg to <36 mm Hg were randomized to one of three treatment arms razuprotafib every day (QD) + latanoprost; razuprotafib twice daily (BID) + latanoprost; or latanoprost monotherapy. The primary endpoint was change in mean diurnal IOP from baseline at day 28.

A total of 194 subjects were randomized, and 193 (99.5%) completed the study. Razuprotafib BID + latanoprost resulted in a significantly larger reduction in diurnal IOP than latanoprost alone (7.95 ± 0.26 mmHg vs. 7.04 ± 0.26 mm Hg, P < 0.05). A smaller improvement was observed after 14 days of treatment (7.62 ± 0.26 mm Hg vs. 7.03 ± 0.26 mm Hg, P = 0.11). Razuprotafib QD dosing did not demonstrate additional IOP lowering compared to latanoprost alone. Conjunctival hyperemia on Day 28 increased by 1.1 units on the four-point Efron scale two hours post dose from a baseline value of 0.6 units, and decreased thereafter.

Topical ocular razuprotafib as an adjunct to latanoprost therapy was well tolerated and significantly reduced IOP in patients with OAG/OHT.

These data support the IOP lowering efficacy of targeting Tie2 activation in Schlemm’s canal in the relevant patient population.

These data support the IOP lowering efficacy of targeting Tie2 activation in Schlemm’s canal in the relevant patient population.

This study quantifies the mortality attributable to Candida bloodstream infections (BSI) in the modern era of echinocandins.

We conducted a retrospective cohort study of adult patients admitted to Barnes Jewish Hospital, a 1,368-bed tertiary care academic hospital, in Saint Louis, Missouri from 1/2/2012-4/30/2019. We identified 626 adult patients with Candida BSI that were frequency-matched with 6,269 control patients that had similar Candida BSI risk-factors. The 90-day all-cause mortality attributable to Candida BSI was calculated using three methods-propensity score matching, matching by inverse weighting of propensity score, and stratified analysis by quintile.

The 90-day crude mortality was 42.4% (269 patients) for Candida BSI cases and 17.1% (1,083 patients) for frequency-matched controls. Following propensity score-matching, the attributable risk difference for 90-day mortality was 28.4% with hazard ratio (HR) of 2.12 (95% CI, 1.98-2.25, p<0.001). In the stratified analysis, the risk for mortaensure timely, effective treatment.

Systemic drug reaction (SDR) is a major safety concern with weekly rifapentine-based treatment (3HP) for latent tuberculosis infection (LTBI). Identifying SDR predictors and at-risk subjects before treatment can improve cost-effectiveness of the LTBI program.

We prospectively recruited 187 cases receiving 3HP (44 SDRs and 143 non-SDRs). A pilot cohort (8 SDRs and 12 non-SDRs) was selected for generating whole-blood transcriptomic data. Through the incorporation of the hierarchical system biology model and therapy-biomarker pathway approach, candidate genes were selected and evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then, interpretable machine learning models presenting as SHapley Additive exPlanations (SHAP) values were applied for SDR risk prediction. Finally, an independent cohort was used to evaluate the performance of these predictive models.

Based on the whole-blood transcriptomic profile of the pilot cohort and the RT-qPCR results of 2 SDR and 3 non-SDR samples in training cohort, six genes were selected. According to SHAP values for model construction and validation, a 3-gene model for SDR risk prediction achieved a sensitivity and specificity of 0.972 and 0.947, respectively, under a universal cutoff value for the joint of the training (28 SDRs and 104 non-SDRs) and testing (8 SDRs and 27 non-SDRs) cohorts. It also worked well across different subgroups.

The prediction model for 3HP-related SDR serves as a guide for establishing a safe and personalized regimen to foster the implementation of the LTBI program. Additionally, it provides a potential translational value for future studies on drug-related hypersensitivity.

The prediction model for 3HP-related SDR serves as a guide for establishing a safe and personalized regimen to foster the implementation of the LTBI program. Additionally, it provides a potential translational value for future studies on drug-related hypersensitivity.

Intense interest exists in novel ω-3 formulations with high bioavailability to reduce blood triglyceride (TG) levels.

To determine the phase 3 efficacy and safety of a naturally derived krill oil with eicosapentaenoic acid and docosahexaenoic acid as both phospholipid esters (PLs) and free fatty acids (FFAs) (ω-3-PL/FFA [CaPre]), measured by fasting TG levels and other lipid parameters in severe hypertriglyceridemia.

This study pooled the results of 2 identical randomized, double-blind, placebo-controlled trials. TRILOGY 1 (Study of CaPre in Lowering Very High Triglycerides) enrolled participants at 71 US centers from January 23, 2018, to November 20, 2019; TRILOGY 2 enrolled participants at 93 US, Canadian, and Mexican centers from April 6, 2018, to January 9, 2020. Patients with fasting TG levels from 500 to 1500 mg/dL, with or without stable treatment with statins, fibrates, or other agents to lower cholesterol levels, were eligible to participate.

Randomization (2.51.0) to ω-3-PL/FFA, 4 g/d, vs pl5% [95% CI, -34.5% to -4.6%]; P = .08 for interaction) and with lower (less than median) baseline blood eicosapentaenoic acid plus docosahexaenoic acid levels (-19.5% [95% CI, -33.8% to -5.3%]; P = .08 for interaction). ω-3-PL/FFA was well tolerated, with a safety profile similar to that of placebo.

This study found that ω-3 -PL/FFA, a novel krill oil-derived ω-3 formulation, reduced TG levels and was safe and well tolerated in patients with severe hypertriglyceridemia.

ClinicalTrials.gov Identifiers NCT03398005 and NCT03361501.

ClinicalTrials.gov Identifiers NCT03398005 and NCT03361501.

In the US, live donor (LD) kidney transplant rates have decreased in pediatric recipients. Pediatric patients with kidney failure will likely need more than 1 kidney transplant during their lifetime, but the optimal sequence of transplant (ie, deceased donor [DD] followed by LD or vice versa) is not known.

To determine whether pediatric recipients should first receive a DD allograft followed by an LD allograft (DD-LD sequence) or an LD allograft followed by a DD allograft (LD-DD sequence).

This decision analytical model examined US pediatric patients with kidney failure included in the US Renal Data System 2019 Report who were waiting for a kidney transplant, received a transplant, or experienced graft failure.

Kidney transplant sequences of LD-DD vs DD-LD.

Difference in projected life-years between the 2 sequence options.

Among patients included in the analysis, the LD-DD sequence provided more net life-years in those 5 years of age (1.82 [95% CI, 0.87-2.77]) and 20 years of age (2.23 [95% CI, 1.for retransplant and future availability of an LD transplant, the LD-DD sequence is likely the better option. This strategy of an LD transplant first would not only benefit pediatric recipients but allow DD kidneys to be used by others who do not have an LD option.

These findings suggest that the decreased use of LD kidney transplants in pediatric recipients during the past 2 decades should be scrutinized. Given the uncertainty of future recipient eligibility for retransplant and future availability of an LD transplant, the LD-DD sequence is likely the better option. This strategy of an LD transplant first would not only benefit pediatric recipients but allow DD kidneys to be used by others who do not have an LD option.

Cardiometabolic and other risk factors could render patients with gout more likely to undergo lower extremity amputation (LEA).

To examine the rate of and factors associated with LEA in patients with gout.

In this matched cohort study using national administrative data, multivariable Cox proportional hazards regression models were used to examine the associations of gout with LEA. In analyses limited to patients with gout, attributes of serum urate control and treatment with urate-lowering therapy were examined as factors associated with LEA. This study included patients who used US Department of Veterans Affairs services from January 1, 2000, to July 31, 2015. Patients with gout were identified using diagnostic codes and matched with up to 10 controls by age, sex, and year of benefit enrollment. Data analysis was performed from January 26, 2021, to September 3, 2021.

Gout classification served as the primary independent variable of interest. In analyses limited to patients with gout, factors associatutation may be preventable in some patients.

Hospital consolidations have been shown not to improve quality on average.

To assess a full-integration approach to hospital mergers based on quality metrics in a safety net hospital acquired by an urban academic health system.

This quality improvement study analyzed outcomes for all nonpsychiatric, nonrehabilitation, non-newborn patients discharged between September 1, 2010, and August 31, 2019, at a US safety net hospital that was acquired by an urban academic health system in January 2016. Interrupted time series and statistical process control analyses were used to assess the main outcomes and measures. Data sources included the hospital’s electronic health record, Centers for Medicare & Medicaid Services Hospital Compare, and nursing quality reports.

A full-integration approach to the merger that included (1) early administrative and clinical leadership integration with the academic health system; (2) rapid transition to the academic health system electronic health record; (3) local ownershipes after accounting for baseline trends. There were fewer central line infections per 1000 catheter days, fewer catheter-associated urinary tract infections per 1000 discharges, and a higher likelihood of patients recommending the hospital or ranking it 9 or 10.

In this quality improvement study, a hospital merger with a full-integration approach to consolidation was found to be associated with improvement in quality outcomes.

In this quality improvement study, a hospital merger with a full-integration approach to consolidation was found to be associated with improvement in quality outcomes.

Weight-for-height z score (WHZ) is a standard indicator of children’s nutritional status even though it does not fully reflect body fat.

To examine the combined association of WHZ and body fat with early development in the East Asia and Pacific region.

Children from the East Asia-Pacific Early Child Development Scales validation study, with full data available regarding their nutritional status and outcomes, were included in this cross-sectional analysis. In brief, a multilevel stratified random sampling was used to select representative samples from each participating country in the study. WHZ and body fat were independently trichotomized using established references and were combined to form a 9-category exposure variable. Data collection was performed between 2012 and 2014, and the analyses were conducted in June 2021.

The binary outcome variable of not being developmentally on track (hereafter referred to as poor development) was defined as a score less than the 25th percentile in the following domains cognitive, language, socioemotional, motor development, and total development score.