The cost-to-charge ratio reflects the markup of hospital services. A lower cost-to-charge ratio indicates lower costs and/or greater charges. This study examines factors associated with ...cost-to-charge ratio trends to determine whether decreasing cost-to-charge ratio is associated with worse surgical outcomes.
The Florida Agency for Healthcare Administration Inpatient database (2018–2020) was queried for common surgical procedures and linked to the Distressed Communities Index, RAND Corporation Hospital data, Center for Medicare Services Cost Reports, and American Hospital Association data. Only hospitals with monotonically increasing or decreasing cost-to-charge ratio were included in the study. Univariable analysis compared these hospitals. Using patient-level data, interpretable machine learning predicted cost-to-charge ratio trend while identifying influential factors.
The cohort had 67 hospitals (27 increasing cost-to-charge ratio and 40 decreasing cost-to-charge ratio) with 35,661 surgeries. Decreasing cost-to-charge ratio hospitals were more often proprietarily owned (78% vs 33%, P = .01) and had greater mean total charges ($134,349 ± $114,510 vs $77,185 ± $82,027, P < .01) with marginally greater mean estimated costs ($14,863 ± $12,343 vs $14,458 ± $15,440, P < .01). Patients from decreasing cost-to-charge ratio hospitals had greater rates of most comorbidities (P < .05) but no difference in mortality or overall complications. Machine-learning models revealed charges rather than clinical factors as most influential in cost-to-charge ratio trend prediction.
Decreasing cost-to-charge ratio hospitals charge vastly more despite minimally greater estimated costs and no difference in outcomes. Although differences in case-mix existed, charges were the predominant differentiators. Patient clinical factors had far less of an impact.
The impact of different phases of COVID-19 infection on outcomes from acute calculous cholecystitis (ACC) is not well understood. Therefore, we examined outcomes of acute cholecystitis during the ...COVID-19 pandemic, comparing the effect of different treatment modalities and COVID-19 infection status. We hypothesized that patients with acute COVID-19 would have worse outcomes than COVID-negative patients, but there would be no difference between COVID-negative and COVID-recovered patients.
We used 2020-2023 National COVID Cohort Collaborative data to identify adults with ACC. Treatment (antibiotics-only, cholecystostomy tube, or cholecystectomy) and COVID-19 status (negative, active, or recovered) were collected. Treatment failure of nonoperative managements was noted. Adjusted analysis using a series of generalized linear models controlled for confounders (age, sex, body mass index, Charlson comorbidity index, severity at presentation, and year) to better assess differences in outcomes among treatment groups, as well as between COVID-19 groups.
In total, 32,433 patients (skewed count) were included: 29,749 COVID-negative, 2112 COVID-active, and 572 (skewed count) COVID-recovered. COVID-active had higher rates of sepsis at presentation. COVID-negative more often underwent cholecystectomy. Unadjusted, COVID-active had higher 30-day mortality, 30-day complication, and longer length of stay than COVID-negative and COVID-recovered. Adjusted analysis revealed cholecystectomy carried lower odds of mortality for COVID-active and COVID-negative patients than antibiotics or cholecystostomy. COVID-recovered patients’ mortality was unaffected by treatment modality. Treatment failure from antibiotics was more common for COVID-negative patients.
Acute cholecystitis outcomes are affected by phase of COVID-19 infection and treatment modality. Cholecystectomy does not lead to worse outcomes for COVID-active and COVID-recovered patients than nonoperative treatments; thus, these patients can be considered for cholecystectomy if their physiology is not prohibitive.
Here, we show that
(
), an endogenous oral pathogen, dampens all aspects of interferon (IFN) signaling in a manner that is strikingly similar to IFN suppression employed by multiple viral pathogens.
...suppressed IFN production by down-regulating several IFN regulatory factors (IRFs 1, 3, 7, and 9), proteolytically degrading STAT1 and suppressing the nuclear translocation of the ISGF3 complex, resulting in profound and systemic repression of multiple interferon-stimulated genes.
-induced IFN paralysis was not limited to murine models but was also observed in the oral tissues of human periodontal disease patients, where overabundance of
correlated with suppressed IFN generation. Mechanistically, multiple virulence factors and secreted proteases produced by
transcriptionally suppressed IFN promoters and also cleaved IFN receptors, making cells refractory to exogenous IFN and inducing a state of broad IFN paralysis. Thus, our data show a bacterial pathogen with equivalence to viruses in the down-regulation of host IFN signaling.
In the United States, the Bald and Golden Eagle Protection Act prohibits take of golden eagles (Aquila chrysaetos) unless authorized by permit, and stipulates that all permitted take must be ...sustainable. Golden eagles are unintentionally killed in conjunction with many lawful activities (e.g., electrocution on power poles, collision with wind turbines). Managers who issue permits for incidental take of golden eagles must determine allowable take levels and manage permitted take accordingly. To aid managers in making these decisions in the western United States, we used an integrated population model to obtain estimates of golden eagle vital rates and population size, and then used those estimates in a prescribed take level (PTL) model to estimate the allowable take level. Estimated mean annual survival rates for golden eagles ranged from 0.70 (95% credible interval = 0.66–0.74) for first‐year birds to 0.90 (0.88–0.91) for adults. Models suggested a high proportion of adult female golden eagles attempted to breed and breeding pairs fledged a mean of 0.53 (0.39–0.72) young annually. Population size in the coterminous western United States has averaged ~31,800 individuals for several decades, with λ = 1.0 (0.96–1.05). The PTL model estimated a median allowable take limit of ~2227 (708–4182) individuals annually given a management objective of maintaining a stable population. We estimate that take averaged 2572 out of 4373 (59%) deaths annually, based on a representative sample of transmitter‐tagged golden eagles. For the subset of golden eagles that were recovered and a cause of death determined, anthropogenic mortality accounted for an average of 74% of deaths after their first year; leading forms of take over all age classes were shooting (~670 per year), collisions (~611), electrocutions (~506), and poisoning (~427). Although observed take overlapped the credible interval of our allowable take estimate and the population overall has been stable, our findings indicate that additional take, unless mitigated for, may not be sustainable. Our analysis demonstrates the utility of the joint application of integrated population and prescribed take level models to management of incidental take of a protected species.
Strategies for successful primary treatment of HER2-positive breast cancer include use of the HER2 inhibitors trastuzumab or lapatinib in combination with standard chemotherapy. While successful, ...many patients develop resistance to these HER2 inhibitors indicating an unmet need. Consequently, current research efforts are geared toward understanding mechanisms of resistance and the signaling modalities that regulate these mechanisms. We have undertaken a study to examine whether signaling molecules downstream of epidermal growth factor receptor, which often act as compensatory signaling outlets to circumvent HER2 inhibition, can be co-targeted to overcome resistance. We identified JNK signaling as a potential area of intervention and now show that inhibiting JNK using the pan-JNK inhibitor, SP600125, is effective in the HER2-positive, resistant JIMT-1 xenograft mammary tumor model. We also investigate potential combination strategies to bolster the effects of JNK inhibition and find that co-targeting of JNK and the protein kinase HUNK can prohibit tumor growth of resistant HER2-positive mammary tumors in vivo.
Identifying contributors to lung transplant survival is vital in mitigating mortality. To enhance individualized mortality estimation and determine variable interaction, we employed a survival tree ...algorithm utilizing recipient and donor data.
United Network Organ Sharing data (2000-2021) were queried for single and double lung transplants in adult patients. Graft survival time <7 d was excluded. Sixty preoperative and immediate postoperative factors were evaluated with stepwise logistic regression on mortality; final model variables were included in survival tree modeling. Data were split into training and testing sets and additionally validated with 10-fold cross validation. Survival tree pruning and model selection was based on Akaike information criteria and log-likelihood values. Estimated survival probabilities and log-rank pairwise comparisons between subgroups were calculated.
A total of 27,296 lung transplant patients (8175 single; 19,121 double lung) were included. Stepwise logistic regression yielded 47 significant variables associated with mortality. Survival tree modeling returned six significant factors: recipient age, length of stay from transplant to discharge, recipient ventilator duration post-transplant, double lung transplant, recipient reintubation post-transplant, and donor cytomegalovirus status. Eight subgroups consisting of combinations of these factors were identified with distinct Kaplan–Meier survival curves.
Survival trees provide the ability to understand the effects and interactions of covariates on survival after lung transplantation. Individualized survival probability with this technique found that preoperative and postoperative factors influence survival after lung transplantation. Thus, preoperative patient counseling should acknowledge a degree of uncertainty given the influence of postoperative factors.
The 2023–2024 Professional Affairs Committee was charged to (1) Create an action plan in response to the clear urgent need for transformation of community pharmacy practice; and (2) Develop ...“readiness for change” instrument that addresses multiple pharmacy stakeholder groups that are based on the ACT “community pharmacy enhanced services” definition. Due to the continuous and rapid-paced changes occurring in community pharmacy practice, the committee developed a document that provides the baseline elements that should be considered for community pharmacy practice currently and into the future. This document, Envisioning the Near Future of Community Pharmacy Patient Care Practice: Key Elements of Practice Redesign in Community Pharmacies, contains 8 sections and is recommended to be socialized within the pharmacy profession to ensure that it resonates with current and future community pharmacy practice.
Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a rare cause of chronic colonic ischemia characterized by intimal smooth muscle proliferation and luminal narrowing of the small ...to medium sized mesenteric veins. It predominantly affects the rectosigmoid colon in otherwise healthy, middle-aged males. Definitive diagnosis and treatment are surgical; however, patients are frequently misdiagnosed, which often results in a protracted clinical course. We describe a case of IMHMV presenting as left hemicolitis in a 53-year-old male, as well as the endoscopic, histopathologic, and radiographic findings that established the diagnosis.
All RecA-like recombinase enzymes catalyze DNA strand exchange as elongated filaments on DNA. Despite numerous biochemical and structural studies of RecA and the related Rad51 and RadA proteins, the ...unit oligomer(s) responsible for nucleoprotein filament assembly and coordinated filament activity remains undefined. We have created a RecA fused dimer protein and show that it maintains in vivo DNA repair and LexA co-protease activities, as well as in vitro ATPase and DNA strand exchange activities. Our results support the idea that dimeric RecA is an important functional unit both for assembly of nucleoprotein filaments and for their coordinated activity during the catalysis of homologous recombination.
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