The impact of glucocorticoids, comorbidities, and immunosuppressive therapies on Pneumocystis jirovecii pneumonia (PJP) risk remains understudied, and prophylaxis is underutilized. Among U.S. adults in TriNetX prescribed glucocorticoids for ≥2 weeks in TriNetX, 44.6% received >20mg prednisone equivalents/day. Prophylaxis rates were low, with higher glucocorticoid doses associated with lower prophylaxis odds.
Background: Outpatient Parenteral Antibiotic Therapy(OPAT) patients require complex multidisciplinary coordination outside billable visits. Predicting and funding sufficient staff capacity for OPAT programs is poorly understood.
Methods: OPAT episodes at our center from January 1,2019-December 31,2020 were identified and categorized as requiring therapeutic drug monitoring(TDM) or non-TDM. Electronic health record(EHR) ambulatory encounters by Infectious Diseases clinic(IDC) staff from OPAT start to 14 days post-completion, or until study cessation, were extracted and categorized as billable, or non-billable. Weekly registered nurse(RN) time for non-billable tasks, stratified by monitoring acuity, was quantified using time-in-motion studies. RN overextension beyond a 40 hour-week was used to calculate optimal staffing ratios. OPAT monitoring days were converted into projected profit margin attributable to hospitalization avoidance through OPAT program operations.
Results: During 2019-2020, 1,645 OPAT courses were associated with 17,476 EHR IDC encounters; 15,163(87%) were non-billable. TDM episodes were 24.9% by volume, but generated significantly more EHR encounters and workload hours than non-TDM episodes. An optimal ratio of 1 RN to support 436 OPAT episodes per year was derived within local context and monitoring acuity mix. An estimated $83,379,292 in cost savings, or $11,757,596 net revenue from admissions turnover, were attributable to 49,350 hospital bed-days avoided through OPAT.
Conclusions: A program staffing model was derived from multimethod evaluation of billable and non-billable OPAT activities. Programs seeking to delineate and fund optimal staffing levels may perform similar analyses based on total volume, monitoring acuity of their OPAT panel, alongside a holistic assessment of financial benefits of OPAT to their organization.
Background: Tuberculosis (TB) is a major global health concern, with long-term complications persisting even after successful treatment. Chronic pulmonary aspergillosis (CPA) is a progressive fungal disease that frequently develops in TB survivors, contributing to post-TB lung disease (PTLD). The true burden of CPA among TB patients remains unclear due to diagnostic challenges and limited data. We aimed to estimate the prevalence of CPA among patients with prior or concurrent TB.
Methods: We conducted a systematic search in PubMed, Cochrane Library, Web of Science, and Science Direct through 1/10/2025. Eligible cohort and cross-sectional studies reported CPA prevalence in diagnosed TB patients based on clinical symptoms, radiographic abnormalities, and microbiological evidence. Three reviewers screened 1,575 unique studies, assessed 118 full texts, and included 22 studies (2,884 patients). We conducted a meta-analysis using a random-effects model to estimate pooled CPA prevalence, with subgroup and meta-regression analyses exploring factors influencing CPA burden.
Results: CPA prevalence varied by timing of assessment and symptom status. Among all TB patients, CPA prevalence was 9% (95% CI: 6%, 12%) during treatment and 13% (95% CI: 6%, 27%) post-treatment. Among patients with persistent respiratory symptoms, CPA prevalence was 20% during treatment and 48% (95% CI: 36%, 61%) post-treatment. Meta-regression identified symptom status and timing of CPA assessment as significant predictors of CPA prevalence.
Conclusions: The high CPA burden among TB survivors, particularly those with persistent symptoms, underscores the need for routine CPA screening in TB programs. Early detection and targeted interventions could reduce respiratory complications and improve patient outcomes.
Background: Integrase strand transfer inhibitors (INSTIs) have been fundamental to HIV-1 treatment for over 15 years. VH4524184 (VH-184) is a third-generation INSTI with long-acting potential currently in development for HIV-1 treatment.
Methods: This double-blind, randomized, placebo-controlled, phase 1, first-time-in-human (FTIH) study evaluated oral VH-184 in adults without HIV-1 administered as single ascending doses (10-460 mg; part 1), multiple ascending doses (160-480 mg) for 14 days with concomitant midazolam (480 mg cohort; part 2), and as a single dose (100 mg) under fasted/fed conditions (part 3) to assess safety, tolerability, and pharmacokinetics. VH-184 resistance was evaluated in vitro against pseudotyped viruses containing participant-derived integrase sequences from the SAILING and DAWNING studies that conferred reduced susceptibility to second-generation INSTIs.
Results: Eighty-four participants (VH-184, n=63; placebo, n=21) were included in the FTIH study. VH-184 demonstrated a good safety and tolerability profile. Dose-proportional increases in exposures were observed after single doses of 10 to 300 mg, without further increase after 460-mg single or 480-mg multiple doses. Geometric mean half-life was ∼24 hours. Observed accumulation in exposures ranged from 1.3- to 1.9-fold after repeat VH-184 dosing of 480 and 160 mg, respectively. VH-184 had minimal impact on the pharmacokinetics of CYP3A substrates and exhibited a moderate positive food effect. The in vitro resistance profile of VH-184 was enhanced compared with prior INSTIs, retaining antiviral activity against second-generation INSTI-resistant pseudotyped viruses.
Conclusions: These data support the safety and further development of VH-184 as a third-generation INSTI with long-acting potential for HIV-1 treatment (ClinicalTrials.gov, NCT05631704).
Background: While neutropenic enterocolitis (NEC) is a well-known life-threatening complication during intensive chemotherapy, its incidence, impact and outcome on specific at-risk populations remain ill-defined.
Methods: We report 178 NEC episodes during 1963 myeloablative chemotherapy courses among 1259 adult patients with acute myeloid (AML) or lymphoid (ALL) leukemia or receiving autologous hematopoietic stem cell-transplant (auto-HCT) for lymphoma or multiple myeloma. Risk factors were assessed by multivariate logistic regression models.
Results: Most NEC cases (93.3%) occurred during AML induction (N=92, 13.8% of chemotherapy course) and auto-HCT (N=74, 9.5%). Independent risk factors for NEC during AML induction included high-dose corticosteroids (OR=2.07, 95%CI 1.29-3.30, P=0.002), elevated circulating blasts at the time of diagnosis (>50 G/L, OR=2.02, 95%CI 1.15-3.56, P=0.02) and use of azacitidine (OR=2.45, 95%CI 1.01-5.90, P=0.05); purine-based regimens (e.g. FLAG-Ida) was an independent protective factor (OR=0.27, 95%CI 0.15-0.47, P<0.001). Independent risk factors after auto-HCT included BEAM versus another conditioning protocol (OR=3.28; 95%CI 1.98-5.43, P<0.001) and age (OR=1.03 per year, 95%CI 1.01-1.06, P=0.007). For both AML induction and auto-HCT, NEC was associated with longer hospitalization (P=0.03 and P<0.001), sepsis (quick SOFA≥2, P=0.03 and P<0.001), fungemia (P<0.001 and P=0.01) and intensive care admission (P=0.03 and P<0.001, respectively). NEC was associated with increased in-hospital mortality during AML induction (6.5% versus 2.4%, P=0.04) but not during auto-HCT (P=0.3).
Conclusions: The incidence of NEC depended on chemotherapeutic regimens, with higher occurrence during standard "7+3" AML induction and BEAM conditioning for auto-HCT. NEC was associated with longer hospitalization and increased morbidity, but 30-day mortality was lower than previously reported.
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