Identifying Veterans Who Benefit From Nirmatrelvir-Ritonavir: A Target Trial Emulation.

BACKGROUND: Nirmatrelvir-ritonavir is recommended for persons at risk for severe coronavirus disease 2019 (COVID-19) but remains underutilized. Information on which eligible groups are likely to benefit from treatment is needed. METHODS: We conducted a target trial emulation study in the Veterans Health Administration comparing nirmatrelvir-ritonavir treated versus matched untreated veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from April 2022 through March 2023. We measured incidence of any hospitalization or all-cause mortality at 30 days. Outcomes were measured for the entire cohort, as well as among subgroups defined by 30-day risk of death or hospitalization, estimated using an ensemble risk prediction model. RESULTS: Participants were 87% male with median age 66 years and 16% unvaccinated. Compared with matched untreated participants, those treated with nirmatrelvir-ritonavir (n = 24 205) had a lower 30-day risk for hospitalization (1.80% vs 2.30%; risk difference [RD], -0.50% points [95% confidence interval {CI}: -.69 to -.35]) and death (0.11% vs 0.30%; RD, -0.20 [95% CI: -.24 to -.13]). The greatest reductions in combined hospitalization or death were observed in the highest risk quartile (RD -2.85 [95% CI: -3.94 to -1.76]), immunocompromised persons (RD -1.91 [95% CI: -3.09 to -.74]), and persons aged ≥75 years (RD -1.16 [95% CI: -1.73 to -.59]). No reductions were observed in the 2 lowest risk quartiles or persons younger than 65 years. CONCLUSIONS: Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death in older veterans, those at highest predicted risk for severe outcomes, and immunocompromised groups. Benefit was not observed in younger veterans or groups at lower predicted risk for hospitalization and death.

Effect of Cranberry Capsules on Bacteriuria Plus Pyuria Among Older Women in Nursing Homes: A Randomized Clinical Trial.

Importance: Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes. Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Objective: To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015). Interventions: Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants. Main Outcomes and Measures: Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration. Results: Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25). Conclusions and Relevance: Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year. Trial Registration: clinicaltrials.gov Identifier: NCT01691430.

A cluster-randomized controlled trial of a multicomponent intervention protocol for pneumonia prevention among nursing home elders.

BACKGROUND: Pneumonia remains an important public health problem among elderly nursing home residents. This clinical trial sought to determine if a multicomponent intervention protocol, including manual tooth/gum brushing plus 0.12% chlorhexidine oral rinse, twice per day, plus upright positioning during feeding, could reduce the incidence of radiographically documented pneumonia among nursing home residents, compared with usual care. METHODS: This cluster-randomized clinical trial was conducted in 36 nursing homes in Connecticut. Eligible residents >65 years with at least 1 of 2 modifiable risk factors for pneumonia (ie, impaired oral hygiene, swallowing difficulty) were enrolled. Nursing homes were randomized to the multicomponent intervention protocol or usual care. Participants were followed for up to 2.5 years for development of the primary outcome, a radiographically documented pneumonia, and secondary outcome, a lower respiratory tract infection (LRTI) without radiographic documentation. RESULTS: A total of 834 participants were enrolled: 434 to intervention and 400 to usual care. The trial was terminated for futility. The number of participants in the intervention vs control arms with first pneumonia was 119 (27.4%) vs 94 (23.5%), respectively, and with first LRTI, 125 (28.8%) vs 100 (25.0%), respectively. In a multivariable Cox regression model, the hazard ratio in the intervention vs control arms, respectively, was 1.12 (95% confidence interval [CI], .84-1.50; P = .44) for first pneumonia and 1.07 (95% CI, .79-1.46, P = .65) for first LRTI. CONCLUSIONS: The multicomponent intervention protocol did not significantly reduce the incidence of first radiographically confirmed pneumonia or LRTI compared with usual care in nursing home residents. CLINICAL TRIALS REGISTRATION: NCT00975780.

Development of a prediction model for 30-day COVID-19 hospitalization and death in a national cohort of Veterans Health Administration patients-March 2022-April 2023.

OBJECTIVE: The epidemiology of COVID-19 has substantially changed since its emergence given the availability of effective vaccines, circulation of different viral variants, and re-infections. We aimed to develop models to predict 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applications. METHODS: We used comprehensive electronic health records from a national cohort of patients in the Veterans Health Administration (VHA) who tested positive for SARS-CoV-2 between March 1, 2022, and March 31, 2023. Full models incorporated 84 predictors, including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to fit prediction models. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset. RESULTS: Models were trained and tested on 198,174 patients, of whom 8% were hospitalized or died within 30 days of testing positive. AUCs for the full models ranged from 0.80 (hospitalization) to 0.91 (death). Brier scores were close to 0, with the lowest error in the mortality model (Brier score: 0.01). All three models were well calibrated with calibration intercepts <0.23 and slopes <1.05. Parsimonious models performed comparably to full models. CONCLUSIONS: We developed prediction models that accurately estimate COVID-19 hospitalization and mortality risk following emergence of the Omicron variant and in the setting of COVID-19 vaccinations and antiviral treatments. These models may be used for risk stratification to inform COVID-19 treatment and to identify high-risk patients for inclusion in clinical trials.

Implementer report: ICD-10 code F44.5 review for functional seizure disorder.

OBJECTIVE: The study aimed to measure the validity of International Classification of Diseases, 10th Edition (ICD-10) code F44.5 for functional seizure disorder (FSD) in the Veterans Affairs Connecticut Healthcare System electronic health record (VA EHR). METHODS: The study used an informatics search tool, a natural language processing algorithm and a chart review to validate FSD coding. RESULTS: The positive predictive value (PPV) for code F44.5 was calculated to be 44%. DISCUSSION: ICD-10 introduced a specific code for FSD to improve coding validity. However, results revealed a meager (44%) PPV for code F44.5. Evaluation of the low diagnostic precision of FSD identified inconsistencies in the ICD-10 and VA EHR systems. CONCLUSION: Information system improvements may increase the precision of diagnostic coding by clinicians. Specifically, the EHR problem list should include commonly used diagnostic codes and an appropriately curated ICD-10 term list for 'seizure disorder,' and a single ICD code for FSD should be classified under neurology and psychiatry.

Suicide and Seizures: A National Cohort Study in Veterans.

OBJECTIVE: The increased rate of suicide associated with epilepsy has been described, but no studies have reported the rates of suicide and suicide-related behavior (SRB) associated with psychogenic nonepileptic seizures (PNESs). METHODS: This retrospective cohort study analyzed data from October 2002 to October 2017 within Veterans Health Administration services. Of 801,734 veterans, 0.09% had PNES, 1.37% had epilepsy, and 98.5% had no documented seizures. Veterans coded for completed suicide, suicide attempts, and suicidal ideation were identified from electronic health records. The primary measure was the suicide-specific standardized mortality ratio (SMR) based on the number of suicide deaths and CDC national suicide mortality database. A Poisson regression was used to calculate the relative risk (RR) of suicide across groups. RESULTS: A total of 1,870 veterans (mean age [SD] 33.76 [7.81] years) completed suicide. Veterans with PNES (RR = 1.75, 95% confidence interval [CI] 0.84-4.24) and veterans with epilepsy (RR = 2.19, 95% CI 2.10-2.28) had a higher risk of suicide compared with the general veteran population. Veterans with PNES or epilepsy had a higher risk of suicide and SRB if they had comorbid alcohol abuse, illicit drug abuse, major depression, posttraumatic stress disorder, and use of psychotropic medications. Conversely, those who were married or attained higher education were at a decreased risk. The SMR for completed suicide for PNES, epilepsy, and the comparison group was 2.65 (95% CI 1.95-5.52), 2.04 (95% CI 1.60-2.55), and 0.70 (95% CI 0.67-0.74), respectively. CONCLUSIONS: Veterans with seizures (both psychogenic and epileptic) are at a greater risk of death by suicide and SRB than the comparison group. These findings suggest that although the pathophysiology of PNES and epilepsy is different, the negative impact of seizures is evident in the psychosocial outcomes in both groups.

Managing Functional Neurological Disorders: Protocol of a Cohort Study on Psychogenic Non-Epileptic Seizures Study.

BACKGROUND: Functional neurological disorders (FNDs) are neurological symptoms that cannot be explained by an underlying neurological lesion or other medical illness and that do not have clear neuropathological correlates. Psychogenic non-epileptic seizures (PNES) are a common and highly disabling form of FND, characterized by paroxysmal episodes of involuntary movements and altered consciousness that can appear clinically similar to epileptic seizures. PNES are unique among FNDs in that they are diagnosed by video electroencephalographic (VEEG), a well-established biomarker for the disorder. The course of illness and response to treatment of PNES remain controversial. This study aims to describe the epidemiology of PNES in the Department of Veterans Affairs Healthcare System (VA), evaluate outcomes of veterans offered different treatments, and compare models of care for PNES. METHODS: This electronic health record (EHR) cohort study utilizes an informatics search tool and a natural language processing algorithm to identify cases of PNES nationally. We will use VA inpatient, outpatient, pharmacy, and chart abstraction data across all 170 medical centers to identify cases in fiscal years 2002-2018. Outcome measurements such as seizure frequency, emergency room visits, hospital admissions, suicide-related behavior, and the utilization of psychotherapy prior to and after PNES diagnosis will be used to assess the effectiveness of models of care. DISCUSSION: This study will describe the risk factors and course of treatment of a large cohort of people with PNES. Since PNES are cared for by a variety of different modalities, treatment orientations, and models of care, effectiveness outcomes such as seizure outcomes and utilization of emergency visits for seizures will be assessed. Outcome measurements such as seizure frequency, emergency room visits, hospital admissions, suicide-related behavior, and psychotherapy prior to and after PNES diagnosis will be used to assess the effectiveness of models of care.

Informatics tools to improve clinical research study implementation.

BACKGROUND: There are numerous potential sources of problems when performing complex clinical research trials. These issues are compounded when studies are multi-site and multiple personnel from different sites are responsible for varying actions from case report form design to primary data collection and data entry. METHODS: We describe an approach that emphasizes the use of a variety of informatics tools that can facilitate study coordination, training, data checks and early identification and correction of faulty procedures and data problems. The paper focuses on informatics tools that can help in case report form design, procedures and training and data management. CONCLUSION: Informatics tools can be used to facilitate study coordination and implementation of clinical research trials.