Characteristics and Outcomes of US Veterans With Immunocompromised Conditions at High Risk of SARS-CoV-2 Infection With or Without Receipt of Oral Antiviral Agents.

OBJECTIVES: Molnupiravir and nirmatrelvir-ritonavir were the first oral antiviral agents to demonstrate reduced hospitalization or death in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but patients with immunocompromised conditions were not well-represented. The objective of this study was to characterize and compare the clinical outcomes of US veterans with immunocompromised conditions prescribed oral antivirals with those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. METHODS: This was a retrospective, observational, nationwide propensity-matched analysis of US veterans with immunocompromised conditions who developed documented SARS-CoV-2 infection. The primary outcome was the composite of any hospitalization or death within 30 days of diagnosis. Secondary outcomes included 30-day comparative rates of (1) any hospitalization, (2) death, (3) intensive care requirement, and (4) subset analyses of outcomes by oral antiviral used and vaccination status. RESULTS: The composite primary outcome was significantly lower in patients receiving oral antiviral therapy compared with those who did not (23/390 [5.9%] vs 57/390 [14.6%]; odds ratio, 0.37; 95% confidence interval, .22-.61). This difference was driven largely by fewer deaths in the oral antiviral group (1/390 [0.3%] vs 19/390 [4.9%]; odds ratio, 0.05; 95% confidence interval, .007-.38). There was no significant difference in rate of intensive care requirement. The composite outcome was improved in vaccinated patients (completing the first series or first booster dose) who received oral antiviral agents compared with those who did not receive oral antiviral agents. Compared with those prescribed nirmatrelvir-ritonavir, patients given molnupiravir were older, had a higher incidence of cautions/contraindications, greater prevalence of tobacco use, and more cardiovascular complications. CONCLUSIONS: Use of molnupiravir or nirmatrelvir-ritonavir was associated with lower incidences of hospitalization or death within 30 days of diagnosis in US veterans with immunocompromised conditions, regardless of vaccination status. These findings support the use of either oral antiviral in this patient population.

Characteristics and outcomes of US Veterans at least 65 years of age at high risk of severe SARS-CoV-2 infection with or without receipt of oral antiviral agents.

OBJECTIVES: Molnupiravir and nirmatrelvir/ritonavir each became available in the United States (US) through the Food and Drug Administration (FDA) emergency use authorization (EUA) in December 2021 after their respective initial prospective randomized controlled trials demonstrated efficacy for patients with mild-to-moderate SARS-CoV-2 active infection considered to be at high risk for progression of disease and hospitalization. Although sufficiently powered for this wide group, the mean age for patients in these studies was only 43 and 46 years of age, respectively. We sought to compare outcomes of US Veterans 65 years and older who received either of these oral antivirals to those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. METHODS: The current project was a retrospective, observational, nationwide propensity-matched analysis comparing outcomes of US Veterans 65 years and older who received either of these oral antivirals to US Veterans 65 years and older who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. RESULTS: The composite primary outcome of admission or death within 30 days of diagnosis was reached less often in those receiving either molnupiravir or nirmatrelvir/ritonavir versus those that received no antiviral (65/1370 [4.75%] vs. 139/1370 [10.2%]; odds ratio 0.44, 95% confidence interval 0.32-0.60, p<0.0001). Baseline differences between Veterans selected for molnupiravir vs. nirmatrelvir/ritonavir therapy were noted, particularly in the number of concomitant medications with cautions or contraindications with nirmatrelvir/ritonavir. CONCLUSIONS: Our findings support the use of molnupiravir or nirmatrelvir/ritonavir in patients 65 years of age and older. Patients with higher medication caution and contraindication burdens to nirmatrelvir/ritonavir are selected for molnupiravir therapy, which in the absence of a prospective head-to-head trial, may limit any efforts to compare the effectiveness of the two drugs.

Development of SARS-CoV-2 infection in patients with rheumatic conditions on hydroxychloroquine monotherapy vs. patients without rheumatic conditions: A retrospective, propensity-matched cohort study.

BACKGROUND: The primary purpose of the current study was to examine whether patients with rheumatologic conditions receiving only chronic hydroxychloroquine therapy for their disease are at less risk of developing SARS-CoV-2 infection than a comparative group of patients without rheumatologic conditions. METHODS: A retrospective, observational, nationwide stratified propensity analysis was conducted comparing patients only on chronic treatment with hydroxychloroquine for their rheumatologic condition to a random sample of patients without rheumatologic conditions and not receiving hydroxychloroquine, utilizing a Veterans Health Administration nationwide clinical administrative database. RESULTS: The 1-to-1 stratified propensity analysis was undertaken using a random sample of patients without rheumatoid conditions and not receiving hydroxychloroquine (n  33,081) and patients with rheumatoid conditions receiving hydroxychloroquine as the lone medication for their condition (n  6047). A total of 5,474 patients in each group were successfully matched. The incidence of documented SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (41/5,474 [0.749%] vs. 36/5,474 [0.658%], respectively, p = 0.57; Odds ratio [OR] 1.14, 95% confidence interval [CI] 0.73-1.79). There were no statistically-significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. Multivariate logistic regression to determine independent variables associated with the development of active SARS-CoV-2 infection failed to include receipt of hydroxychloroquine (OR 0.99, 95% CI 0.62-1.56). CONCLUSIONS: Hydroxychloroquine failed to demonstrate a preventative effect against SARS-CoV-2 infection in a large group of patients with rheumatologic conditions compared to patients without rheumatologic conditions.

Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study.

BACKGROUND: Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine. METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. A propensity score was calculated for each patient, and each patient who was receiving hydroxychloroquine was matched to two patients who were not receiving hydroxychloroquine (controls). The primary endpoint was the proportion of patients with PCR-confirmed SARS-CoV-2 infection among those receiving chronic hydroxychloroquine versus the propensity-matched patients not receiving chronic hydroxychloroquine between March 1 and June 30, 2020. Secondary outcomes were hospital admission associated with SARS-CoV-2 infection; intensive care requirement associated with SARS-CoV-2 infection; mortality associated with SARS-CoV-2 infection; and overall rates of any hospital admission and mortality (ie, all cause). Multivariate logistic regression analysis was done to determine independent variables for the development of active SARS-CoV-2 infection. FINDINGS: Between March 1 and June 30, 2020, 10 703 patients receiving hydroxychloroquine and 21 406 patients not receiving hydroxychloroquine were included in the primary analysis. The incidence of active SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (31 [0·3%] of 10 703 vs 78 [0·4%] of 21 406; odds ratio 0·79, 95% CI 0·52-1·20, p=0·27). There were no significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. For all patients in the study, overall mortality was lower in the hydroxychloroquine group than in the group of patients who did not receive hydroxychloroquine (odds ratio 0·70, 95% CI 0·55-0·89, p=0·0031). In multivariate logistic regression analysis, receipt of hydroxychloroquine was not associated with the development of active SARS-CoV-2 infection (odds ratio 0·79, 95% CI 0·51-1·42). INTERPRETATION: Hydroxychloroquine was not associated with a preventive effect against SARS-CoV-2 infection in a large group of patients with rheumatological conditions. FUNDING: None.

A Propensity-Matched Analysis Between Standard Versus Tapered Oral Vancomycin Courses for the Management of Recurrent Clostridium difficile Infection.

BACKGROUND: This study was conducted to compare clinical outcomes of oral vancomycin courses without taper versus oral vancomycin courses with taper for treatment of recurrent Clostridium difficile infection (CDI). METHODS: This investigation was a multicenter, retrospective, propensity score-matched analysis study using a Veterans Health Administration national clinical administrative database. Adult patients who were treated for recurrent CDI from any Veterans Affairs Medical Center between June 1, 2011 and October 31, 2016 were included if they were treated with oral vancomycin with or without a tapering regimen. The 2 groups were matched by next-nearest approach from a propensity score formula derived from independent variables associated with the selection of a taper regimen. RESULTS: Propensity score matching resulted in 2 well-matched groups consisting of 226 episodes of patients treated with a vancomycin taper regimen and 678 episodes treated by vancomycin regimen without taper. No difference was found for the primary outcome of 180-day recurrence (59 of 226 [26.1%] for taper regimens versus 161 of 678 [23.8%], P = .48). A secondary outcome of 90-day all-cause mortality met statistical significance, favoring a taper regimen (5.31% vs 9.29%, P = .049); however, secondary outcomes of 90-day recurrence and 180-day all-cause mortality were not different. CONCLUSIONS: Vancomycin taper regimens did not provide benefit over vancomycin regimens without taper in preventing additional CDI recurrence in patients with first or second recurrent episodes in this propensity score-matched analysis.

Incidence of potentially human papillomavirus-related neoplasms in the United States, 1978 to 2007.

BACKGROUND: Population-based studies comprehensively describing incidence patterns of human papillomavirus (HPV)-related preinvasive and invasive neoplasms prior to widespread HPV vaccination are sparse. METHODS: Age-adjusted incidence rates (IRs), IR ratios (IRRs), and annual percent changes (APCs) in IRs were calculated for potentially HPV-related tumors diagnosed in the Surveillance, Epidemiology and End Results (SEER) Program during 1978 through 2007. RESULTS: Overall IRs for preinvasive tumors were significantly higher than for invasive squamous cell tumors of cervix (IRR = 3.42), vulva (IRR = 1.87), and vagina (IRR = 1.19) and significantly lower for adenomatous cervical tumors (IRR = 0.43), and squamous cell tumors of penis (IRR = 0.64), anus (males, IRR = 0.53; females, IRR = 0.14), and head and neck (H&N) (males, IRR = 0.01; females, IRR = 0.02). Incidence of preinvasive squamous tumors of cervix, vagina, and penis rose rapidly over time and decreased for invasive neoplasms. The most rapid increases occurred for preinvasive (males, APC = 16.0; females, APC = 7.3) and invasive anal tumors (males, APC = 3.6; females, APC = 2.3). IR patterns were generally similar among evaluable racial/ethnic groups, with the exception of H&N invasive tumor IRs which increased exclusively among white males. CONCLUSIONS: Contrary to the opposing trends of preinvasive and invasive squamous tumors of cervix, vagina, and penis, preinvasive and invasive anal tumor IRs increased significantly over time by sex, age, and racial/ethnic groups. Successful HPV vaccination programs are needed to measurably reduce incidence of HPV-related neoplasms in the future, particularly for cancer sites with rising incidence rates for which effective screening modalities are limited. Cancer 2013;119:2291-2299. © 2013 American Cancer Society.

Outcomes of health care-associated pneumonia empirically treated with guideline-concordant regimens versus community-acquired pneumonia guideline-concordant regimens for patients admitted to acute care wards from home.

BACKGROUND: The introduction of the health care-associated pneumonia (HCAP) categorization expanded recommendations for broad-spectrum empiric antibiotics to pneumonia patients presenting from the community with recent health care-system exposure. However, the efficacy of such regimens in improving clinical outcomes in these patients has not been well established. OBJECTIVE: To compare the clinical outcomes of HCAP patients treated initially with HCAP guideline-concordant antibiotic regimens to those treated initially with community-acquired pneumonia (CAP) guideline-concordant antibiotic regimens. METHODS: This retrospective study included HCAP patients presenting from home and admitted to general medical wards. HCAP regimen patients were treated empirically with at least 1 antipseudomonal agent. All other patients were assigned to the CAP regimen group. The primary end point was clinical cure at 30 days postdischarge. Subgroup analysis was performed in patients hospitalized 1-30 days and 31-90 days before the HCAP admission. RESULTS: Of 228 HCAP admissions, 122 patients received CAP regimens and 106 received HCAP regimens. The 2 groups were similar at baseline, including Pneumonia Severity Index scores. Attributable clinical cure occurred in 75.4% of CAP regimen patients and 69.8% of HCAP regimen patients (p = 0.34). Overall clinical cure occurred in 59.8% of CAP regimen patients and 54.7% of HCAP regimen patients (p = 0.44). The CAP regimen group used fewer days of intravenous antibiotics (4.39 vs 7.75, p < 0.0001) and had shorter lengths of stay (6.36 vs 8.58 days, p < 0.0001). For patients hospitalized 31-90 days earlier, clinical cure was higher in the CAP regimen group (attributable, 82.9% vs 60.0%, p = 0.0090; overall, 67.1% vs 47.5%, p = 0.044). CONCLUSIONS: Compared to CAP guideline-concordant regimens, treatment of HCAP with HCAP guideline-concordant regimens did not increase clinical cure rates and was associated with lower clinical cure rates in patients hospitalized 31-90 days prior to the HCAP admission. This study suggests that broad-spectrum empiric antibiotics may not be necessary in all HCAP patient groups.

Case-control study of statin prevention of mould infections.

Invasive mould infections (IMI) are associated with significant morbidity and mortality. In vitro studies have demonstrated that hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have activity against several pathogenic moulds including Zygomycetes and Aspergillus spp. The aim of our study was to determine if statin use is a preventive factor for the development of IMI. This was a retrospective case-control study of 10 United States Veterans Affairs Medical Centers that comprise the Veterans Integrated Service Network (VISN) 16. Cases with IMI and controls were identified from 2001 to 2008. Controls were matched by age, facility, history of transplantation, presence of chronic steroid use and presence of human immunodeficiency virus infection (HIV). Two hundred and thirty-eight patients were included. Independent variables associated with the development of IMI were history of solid malignant tumours (OR 2.63, 1.41-4.87) and hypertension (OR 2.29, 1.13-4.68). Statin use within 3 months of index date was not an independent variable for prevention or development of IMI. No level of exposure to a statin drug appeared to influence the development of infection. This retrospective case-control study suggests that despite evidence of in vitro activity, statins may not decrease risk of IMI. Prospective, controlled trials may be necessary to investigate any potential clinical benefit.

Trichomoniasis and its treatment.

Trichomonas vaginalis has long been recognized as a cause of infectious vaginitis in women. More recently, studies have demonstrated a significant burden of disease in men with urethritis or men at high risk for sexually transmitted diseases. There is increasing interest in this pathogen as more data accumulates linking it to HIV transmission and perinatal morbidity. New diagnostic methods have emerged that may increase sensitivity of diagnosis or improve point-of-care access to testing. Nitroimidazoles remain the mainstay of therapy. Metronidazole and tinidazole are highly effective as single-dose therapy. Unfortunately, despite the link between T. vaginalis infection and perinatal morbidity, nitroimidazole therapy during pregnancy remains controversial. Although metronidazole resistance is currently uncommon, pharmacological features and nitroimidazole resistance patterns suggest that tinidazole may be more effective in treating patients with metronidazole treatment failure. Alternatives to nitroimidazole therapy are few, and most have limited efficacy and significant toxicity.