Hospitalization and readmission after single-level fall: a population-based sample.

BACKGROUND: Single-level falls (SLFs) in the older US population is a leading cause of hospital admission and rates are increasing. Unscheduled hospital readmission is regarded as a quality-of-care indication and a preventable burden on healthcare systems. We aimed to characterize the predictors of 30-day readmission following admission for SLF injuries among patients 65 years and older. METHODS: We conducted a retrospective cohort study using the Nationwide Readmission Database from 2018 to 2019. Included patients were 65 and older, admitted emergently following a SLF with a primary injury diagnosis. Hierarchical logit regression was used to model factors associated with readmission within 30 days of discharge. RESULTS: Of 1,338,905 trauma patients, 65 years or older, 61.3% had a single-level fall as the mechanism of injury. Among fallers, the average age was 81.1 years and 68.5% were female. SLF patients underwent more major therapeutic procedures (56.3% vs. 48.2%), spent over 2 million days in the hospital and incurred total charges of over $28 billion annually. Over 11% of SLF patients were readmitted within 30 days of discharge. Increasing income had a modest effect, where the highest zip code quartile was 9% less likely to be readmitted. Decreasing population density had a protective effect of readmission of 16%, comparing Non-Urban to Large Metropolitan. Transfer to short-term hospital, brain and vascular injuries were independent predictors of 30-day readmission in multivariable analysis (OR 2.50, 1.31, and 1.42, respectively). Palliative care consultation was protective (OR 0.41). The subsequent hospitalizations among those 30-day readmissions were primarily emergent (92.9%), consumed 260,876 hospital days and a total of $2.75 billion annually. CONCLUSIONS: SLFs exact costs to patients, health systems, and society. Transfer to short-term hospitals at discharge, along with brain and vascular injuries were strong predictors of 30-day readmission and warrant mitigation strategy development with consideration of expanded palliative care consultation.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

Omadacycline pharmacokinetics/pharmacodynamics in the hollow fiber model and clinical validation of efficacy to treat pulmonary Mycobacterium abscessus disease.

BACKGROUND: Guideline-based therapy (GBT) for pulmonary Mycobacterium abscessus (Mab) disease achieves sustained sputum culture conversion (SSCC) rates of 30%; this is reflected by poor efficacy of GBT in the hollow fiber system model of Mab (HFS-Mab), which killed ∼1.22 log10 CFU/mL. This study was performed to determine which clinical dose of omadacycline, a tetracycline antibiotic, should be used in combination therapy to treat pulmonary Mab disease for relapse-free cure. METHODS: First, omadacycline intrapulmonary concentration-time profiles of seven daily doses were mimicked in the HFS-Mab model and exposures associated with optimal efficacy were identified. Second, 10,000 subject Monte-Carlo simulations were performed to determine whether oral omadacycline 300 mg/day achieved these optimal exposures. Third, a retrospective clinical study on omadacycline vs. primarily tigecycline-based salvage therapy was conducted to assess rates of SSCC and toxicity. Fourth, a single patient was recruited to validate the findings. RESULTS: Omadacycline efficacy in the HFS-Mab was 2.09 log10 CFU/mL at exposures achieved in >99% of patients on 300 mg/day omadacycline. In the retrospective study of omadacycline 300 mg/day-based combinations vs. comparators, SSCC was achieved in 8/10 vs. 1/9 (P=0.006), symptom improvement in 8/8 vs. 5/9 (P=0.033), toxicity in 0 vs. 9/9 (P<0.001), and therapy discontinuation due to toxicity in 0 vs. 3/9 (P<0.001) cases, respectively. In one prospectively recruited patient, omadacycline 300 mg/day salvage therapy achieved SSCC and symptom-resolution in 3 months. CONCLUSION: Based on the preclinical and clinical data, omadacycline 300 mg/day in combination regimens could be appropriate for testing in Phase III trials in patients with Mab pulmonary disease.

Decreased Interleukin-1 Family Cytokine Production in Patients with Nontuberculous Mycobacterial Lung Disease.

Nontuberculous mycobacteria (NTM) cause pulmonary disease in individuals without obvious immunodeficiency. This study was initiated to gain insight into the immunological factors that predispose persons to NTM pulmonary disease (NTMPD). Blood was obtained from 15 pairs of NTMPD patients and their healthy household contacts. Peripheral blood mononuclear cells (PBMCs) were stimulated with the Mycobacterium avium complex (MAC). A total of 34 cytokines and chemokines were evaluated in plasma and PBMC culture supernatants using multiplex immunoassays, and gene expression in the PBMCs was determined using real-time PCR. PBMCs from NTMPD patients produced significantly less interleukin-1ß (IL-1ß), IL-18, IL-1α, and IL-10 than PBMCs from their healthy household contacts in response to MAC. Although plasma RANTES levels were high in NTMPD patients, they had no effect on IL-1ß production by macrophages infected with MAC. Toll-like receptor 2 (TLR2) and TWIK2 (a two-pore domain K+ channel) were impaired in response to MAC in PBMCs of NTMPD patients. A TLR2 inhibitor decreased all four cytokines, whereas a two-pore domain K+ channel inhibitor decreased the production of IL-1ß, IL-18, and IL-1α, but not IL-10, by MAC-stimulated PBMCs and monocytes. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. A reduced monocyte ratio might contribute to the attenuated production of IL-1 family cytokines by PBMCs of NTMPD patients in response to MAC stimulations. Collectively, our findings suggest that the attenuated IL-1 response may increase susceptibility to NTM pulmonary infection through multiple factors, including impaired expression of the TLR2 and TWIK2 and reduced monocyte ratio. IMPORTANCE Upon MAC stimulation, the production of IL-1 family cytokines and IL-10 by PBMCs of NTMPD patients was attenuated compared with that of healthy household contacts. Upon MAC stimulation, the expression of TLR2 and TWIK2 (one of the two-pore domain K+ channels) was attenuated in PBMCs of NTMPD patients compared with that of healthy household contacts. The production of IL-1 family cytokines by MAC-stimulated PBMCs and MAC-infected monocytes of healthy donors was reduced by a TLR2 inhibitor and two-pore domain K+ channel inhibitor. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. Collectively, our data suggest that defects in the expression of TLR2 and TWIK2 in human PBMCs or monocytes and reduced monocyte ratio are involved in the reduced production of IL-1 family cytokines, and it may increase susceptibility to NTM pulmonary infection.

Agricultural Injury Surveillance Using a Regional Trauma Registry.

BACKGROUND: The burden of traumatic injury among workers in agriculture is substantial. Surveillance can inform injury prevention efforts to reduce farmworkers' risk. We posited that the regional trauma registry can provide surveillance for agricultural injury requiring trauma-center care. METHODS: The Northeast Texas regional trauma registry was queried for patients injured in agricultural settings during 2016-2019 occurring in the 23,580 square mile study area subdivided into 219 US Census Zip Code Tract Area (ZCTA). Population at risk was estimated from the 2017 Census of Agriculture. Kuldorff's SaTScan identified case hot spots. A multivariable, geographically weighted regression model was fit for cases/1000 workers. RESULTS: In total, 273 cases occurred, (mean 68 cases per year [95% confidence interval 55.1-80.9]) among 96 ZCTA. The mean injury rate was 3.9 (95% confidence interval 3.4-4.3) cases per 1000 farmworkers. Animals and farm machinery were the most common injury mechanisms, 52.0% and 20.9%, respectively. Trauma ZCTA demonstrated more farms (median 170 versus 95.5, P < 0.001), greater farm acreage (53,900 acres versus 32,800, P = 0.004), and higher median total product sales ($6.5 million versus $3.9 million, P < 0.001). Six hot spots were identified with relative risks from 2.85 to 5.31. The multivariable model of cases/1000 workers demonstrated significant associations with workers per ZCTA (a mean ß-coefficient of 0.004 with P values <0.05 in 145 of 219 [66.5%] ZCTA) and percent rural population (ß = -6.62, P values <0.05 in 76.1% of ZCTA). CONCLUSIONS: Regional trauma registry data, combined with census data and spatial analyses, can identify actionable geographic areas of high agriculture-related injury risk.

Elderly trauma associated with high-risk recreational activity: A population-based study, United States, 2010 through 2016.

BACKGROUND: Understanding trends in prevalence and etiology is critical to public health strategies for prevention and management of injury related to high-risk recreation in elderly Americans. METHODS: The National Emergency Department Sample from 2010 through 2016 was queried for patients with a principal diagnosis of trauma (ICD-9 codes 800.0-959.9) and who were 55 years and older. High-risk recreation was determined from e-codes a priori. Primary outcome measures were mortality and total hospital charges. RESULTS: Of the 29,491,352 patient cohort, 458,599 (1.56%) engaged in high-risk activity, including those age 85 and older. High-risk cases were younger (median age 61 vs 70) and majority male (71.87% vs 39.24%). The most frequent activities were pedal cycling (45.81%), motorcycling (29.08%), and off-road vehicles (9.13%). Brain injuries (8.82% vs 3.88%), rib/sternal fractures (13.35% vs 3.53%), and cardiopulmonary injury (5.25% vs 0.57%) were more common among high-risk cases. Mortality (0.75% vs 0.40%) and total median hospital charges ($3,360 vs $2,312) were also higher for high-risk admissions, where the odds of mortality increased exponentially per year of age (odds ratio, 1.06; 99.5% CI, 1.05-1.08). High-risk recreation was associated with more than $1 billion in total hospital charges and more than 100 deaths among elderly Americans per year. CONCLUSION: Morbidity, mortality, and resource utilization due to high-risk recreation extend into the ninth decade of life. The patterns of injury described here offer opportunities for targeted injury prevention education to minimize risk among this growing segment of the United States population.

Preliminary, Real-world, Multicenter Experience With Omadacycline for Mycobacterium abscessus Infections.

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen for Mycobacterium abscessus. The majority of infections were of pulmonary origin (7/12; 58.3%). The median (interquartile range) duration of OMC was 6.2 (4.2-11.0) months. Clinical success occurred in 9/12 (75.0%) patients. Three patients experienced a possible adverse effect while on therapy.