Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis.

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality. Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

Patient's Perception of the Role of Gym Activity in Abdominal Wall Herniation in Adults: A Prospective Study.

BACKGROUND: Despite significant changes in healthcare, work practices, and leisure activity, the proposed precipitating factors for abdominal wall hernias have remained largely unchanged for almost two centuries. We aimed to investigate if there have been shifts in these factors over time by examining patients' perception of precipitating factors for abdominal wall hernia development. This study was conducted in the Royal College of Surgeons In Ireland Department of Surgery, Connolly Hospital, Blanchardstown, Dublin, where patients with abdominal wall hernias completed a questionnaire  . RESULTS: A total of 277 patients (mean age 55.7; 85.6% male) with abdominal wall hernia completed the questionnaire (66.1% inguinal; 10.8% umbilical; 6.9% paraumbilical; 10.5% epigastric; 3.2% incisional; 1.4% femoral, and 1.1% port-site). One hundred and twenty patients (43.3%) believed their hernia was due to lifting, 71 (25.6%) cited gym activity and 17 (6.1%) cited other sporting activities as the precipitating factor. Traditional factors - chronic cough and constipation - were cumulatively cited only by 11 patients (4.0%), while prostatic obstruction was not cited by any. CONCLUSION: This study suggests that fitness pursuits may be an increasing contributor to the development of abdominal wall hernia. Greater attention should be paid to the proper use of gym equipment to minimise the risk of hernia development.

Meeting the Therapeutic Challenges of Emergent and Rare Invasive Fungal Diseases Through Novel Clinical Trial Designs.

Treatments for emerging and rare invasive fungal diseases (IFDs) represent a critical unmet medical need. For IFDs that occur less frequently than invasive aspergillosis, such as mucormycosis, hyalohyphomycosis, and phaeohyphomycosis, randomized controlled clinical trials are impractical and unlikely to meet urgent public health needs. Understanding regulatory approaches for approval of drugs for rare cancers and rare metabolic diseases could help meet the challenges of studying drugs for rare IFDs. A single-arm, controlled clinical trial with a high-quality external control(s), with confirmatory evidence from nonclinical studies, including pharmacokinetic/pharmacodynamic data in predictive animal models of the disease may support findings of effectiveness of new drugs and biologics. Control populations may include historical controls from published literature, patient registries, and/or contemporaneous external control groups. Continuous engagement among clinicians, industrial sponsors, and regulatory agencies to develop consensus on trial design and innovative development pathways for emergent and rare invasive fungal diseases is important.

Assessing the Environmental and Downstream Human Health Impacts of Decentralizing Cancer Care.

Importance: Greenhouse gas (GHG) emissions from health care are substantial and disproportionately harm persons with cancer. Emissions from a central component of oncology care, outpatient clinician visits, are not well described, nor are the reductions in emissions and human harms that could be obtained through decentralizing this aspect of cancer care (ie, telemedicine and local clinician care when possible). Objective: To assess potential reductions in GHG emissions and downstream health harms associated with telemedicine and fully decentralized cancer care. Design, Setting, and Participants: This population-based cohort study and counterfactual analyses using life cycle assessment methods analyzed persons receiving cancer care at Dana-Farber Cancer Institute between May 2015 and December 2020 as well as persons diagnosed with cancer over the same period from the Cancer in North America (CiNA) public dataset. Data were analyzed from October 2023 to April 2024. Main Outcomes and Measures: The adjusted per-visit day difference in GHG emissions in kilograms of carbon dioxide (CO2) equivalents between 2 periods: an in-person care model period (May 2015 to February 2020; preperiod) and a telemedicine period (March to December 2020; postperiod), and the annual decrease in disability-adjusted life-years in a counterfactual model where care during the preperiod was maximally decentralized nationwide. Results: Of 123 890 included patients, 73 988 (59.7%) were female, and the median (IQR) age at first diagnosis was 59 (48-68) years. Patients were seen over 1.6 million visit days. In mixed-effects log-linear regression, the mean absolute reduction in per-visit day CO2 equivalent emissions between the preperiod and postperiod was 36.4 kg (95% CI, 36.2-36.6), a reduction of 81.3% (95% CI, 80.8-81.7) compared with the baseline model. In a counterfactual decentralized care model of the preperiod, there was a relative emissions reduction of 33.1% (95% CI, 32.9-33.3). When demographically matched to 10.3 million persons in the CiNA dataset, decentralized care would have reduced national emissions by 75.3 million kg of CO2 equivalents annually; this corresponded to an estimated annual reduction of 15.0 to 47.7 disability-adjusted life-years. Conclusions and Relevance: This cohort study found that using decentralization through telemedicine and local care may substantially reduce cancer care's GHG emissions; this corresponds to small reductions in human mortality.

Multiple roles for hypoxia inducible factor 1-alpha in airway epithelial cells during mucormycosis.

During pulmonary mucormycosis, inhaled sporangiospores adhere to, germinate, and invade airway epithelial cells to establish infection. We provide evidence that HIF1α plays dual roles in airway epithelial cells during Mucorales infection. We observed an increase in HIF1α protein accumulation and increased expression of many known HIF1α-responsive genes during in vitro infection, indicating that HIF1α signaling is activated by Mucorales infection. Inhibition of HIF1α signaling led to a substantial decrease in the ability of R. delemar to invade cultured airway epithelial cells. Transcriptome analysis revealed that R. delemar infection induces the expression of many pro-inflammatory genes whose expression was significantly reduced by HIF1α inhibition. Importantly, pharmacological inhibition of HIF1α increased survival in a mouse model of pulmonary mucormycosis without reducing fungal burden. These results suggest that HIF1α plays two opposing roles during mucormycosis: one that facilitates the ability of Mucorales to invade the host cells and one that facilitates the ability of the host to mount an innate immune response.

Shared Vision for Improving Outcomes for Serious Fungal Diseases: Report of a Patient, Caregiver, and Clinician Summit.

Background: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research. Methods: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions to identify commonalities and perceived gaps and to formulate recommendations. The 2 groups then reconvened to develop consensus recommendations. Results: IFD patients and their caregivers shared experiences reflecting the typically lengthy prediagnosis, acute treatment, long-term treatment, and posttreatment recovery stages of IFD. They reported substantial physical, psychological, and financial burdens associated with the IFD experience, particularly related to delayed diagnoses. They reaffirmed a need for coordinated patient-centered education, peer support, and advocacy to document the burden of serious fungal infections. Mycology experts discussed strategies to address gaps in the mycology field, such as insufficient training, inadequate workforce support, and a need to partner more with patient groups. Conclusions: A summit involving patients with IFD, family caregivers, and mycology experts identified a substantial nonclinical burden of disease associated with IFD. Patients and mycology experts prioritized several goals for education, advocacy, and research to raise awareness of IFD and improve outcomes.

Development of a Combat-Relevant Murine Model of Wound Mucormycosis: A Platform for the Pre-Clinical Investigation of Novel Therapeutics for Wound-Invasive Fungal Diseases.

Wound-invasive fungal diseases (WIFDs), especially mucormycosis, have emerged as life-threatening infections during recent military combat operations. Many combat-relevant fungal pathogens are refractory to current antifungal therapy. Therefore, animal models of WIFDs are urgently needed to investigate new therapeutic solutions. Our study establishes combat-relevant murine models of wound mucormycosis using Rhizopus arrhizus and Lichtheimia corymbifera, two Mucorales species that cause wound mucormycosis worldwide. These models recapitulate the characteristics of combat-related wounds from explosions, including blast overpressure exposure, full-thickness skin injury, fascial damage, and muscle crush. The independent inoculation of both pathogens caused sustained infections and enlarged wounds. Histopathological analysis confirmed the presence of necrosis and fungal hyphae in the wound bed and adjacent muscle tissue. Semi-quantification of fungal burden by colony-forming units corroborated the infection. Treatment with liposomal amphotericin B, 30 mg/kg, effectively controlled R. arrhizus growth and significantly reduced residual fungal burden in infected wounds (p < 0.001). This study establishes the first combat-relevant murine model of wound mucormycosis, paving the way for developing and evaluating novel antifungal therapies against combat-associated WIFDs.

Open-Channel Droplet Microfluidic Platform for Passive Generation of Human Sperm Microdroplets.

Sperm cryopreservation is important for individuals undergoing infertility treatment, and for those who wish to preserve fertility potential, prior to treatments like chemotherapy, radiation therapy, gender-affirming medical interventions, elective fertility delay, or individuals in high-risk professions such as the military. Current methods for sperm cryopreservation result in approximately 30-50% decrease in sperm motility. However, recent studies have shown that ultra-rapid freezing (vitrification) is a valuable approach for maintaining sperm quality after freeze-thawing processes in the clinical laboratory setting and requires submicroliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipette small volumes of sample. Here, we present a method that leverages open-channel droplet microfluidics to autonomously generate sub-microliter to microliter volumes of purified human sperm samples. Using a novel, open-channel droplet generator, we found no change in sperm movement and kinematic data after exposure to device and reagents in our platform. We conclude that our platform is compatible with human sperm, an important foundation for future implementation of vitrification in fertility laboratories.

Transitioning to home and beyond following stroke: a prospective cohort study of outcomes and needs.

INTRODUCTION: Understanding of the needs of people with stroke at hospital discharge and in the first six-months is limited. This study aim was to profile and document the needs of people with stroke at hospital discharge to home and thereafter. METHODS: A prospective cohort study recruiting individuals with stroke, from three hospitals, who transitioned home, either directly, through rehabilitation, or with early supported discharge teams. Their outcomes (global-health, cognition, function, quality of life, needs) were described using validated questionnaires and a needs survey, at 7-10 days, and at 3-, and 6-months, post-discharge. RESULTS: 72 patients were available at hospital discharge; mean age 70 (SD 13); 61% female; median NIHSS score of 4 (IQR 0-20). 62 (86%), 54 (75%), and 45 (63%) individuals were available respectively at each data collection time-point. Perceived disability was considerable at hospital discharge (51% with mRS ≥ 3), and while it improved at 3-months, it increased thereafter (35% with mRS ≥ 3 at 6-months). Mean physical health and social functioning were "fair" at hospital discharge and ongoing; while HR-QOL, although improved over time, remained impaired at 6-months (0.69+/-0.28). At 6-months cognitive impairment was present in 40%. Unmet needs included involvement in transition planning and care decisions, with ongoing rehabilitation, information, and support needs. The median number of unmet needs at discharge to home was four (range:1-9), and three (range:1-7) at 6-months. CONCLUSION: Stroke community reintegration is challenging for people with stroke and their families, with high levels of unmet need. Profiling outcomes and unmet needs for people with stroke at hospital-to-home transition and onwards are crucial for shaping the development of effective support interventions to be delivered at this juncture. ISRCTN REGISTRATION: 02/08/2022; ISRCTN44633579.

Development of rabbit models of ventilator-associated bacterial pneumonia produced by carbapenem-resistant Pseudomonas aeruginosa.

Ventilator-associated bacterial pneumonia (VABP) is among the most intractable of carbapenem-resistant Gram-negative bacterial infections. New antimicrobial agents are critically needed for the treatment of VABP. However, current conventionally used animal model systems are inadequate to meet this challenge. We, therefore, developed rabbit models of VABP caused by carbapenem-resistant Pseudomonas aeruginosa. Persistently neutropenic New Zealand White rabbits were used throughout the study. The early-phase intubated model (0-24 h) received mechanical ventilation, while the late-phase intubated model (72-96 h) was ambulatory. The following outcome parameters were studied: survival, residual tissue bacterial burden (CFU/g), residual BAL bacterial burden (CFU/mL), lung weights, pulmonary lesion score, histology, O2 saturation, radiographic imaging, and histology. Each anesthetized rabbit received a predetermined endotracheal bacterial inoculum, and ventilators were set to FiO2 = 40% and PEEP = 8 mmHg. Within the first 12 h post-inoculation, mean bacterial burdens in lung tissue and BAL fluid, respectively, were established at approximately 107 CFU/g and 106 CFU/mL, persisted through 24 h in the early-phase model and increased in the late-phase model to approximately 108 CFU/g and 107 CFU/mL. Mean max SpO2 was ≥98 mmHg, and mean nadir SpO2 was ≥68 mmHg. Serial thoracic radiographs demonstrated progressive multilobar pneumonic infiltrates. Lung histology revealed progressive focal bronchopneumonia, coagulative necrosis, intra-alveolar hemorrhage, alveolar epithelial cell necrosis, and bacterial microcolonies. The new rabbit model of VABP produced by carbapenem-resistant Pseudomonas aeruginosa recapitulates the pathophysiological, microbiological, diagnostic imaging, and histological patterns of human disease by which to assess critically needed new antimicrobial agents against this lethal infection.

Combination of Systemic and Lock-Therapies with Micafungin Eradicate Catheter-Based Biofilms and Infections Caused by Candida albicans and Candida parapsilosis in Neutropenic Rabbit Models.

Vascular catheter-related infections, primarily caused by Candida albicans and Candida parapsilosis, pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 103 CFU/mL of C. albicans or C. parapsilosis, establishing catheter-based biofilm, and subjected to various treatments. Neutropenic rabbits treated with a combination of lock therapy and systemic micafungin demonstrated the most significant reduction in fungal burden, from 5.0 × 104 to 1.8 × 102 CFU/mL of C. albicans and from 5.9 × 104 to 2.7 × 102 CFU/mL of C. parapsilosis (p ≤ 0.001), in the CVC after 24 h, with full clearance of blood cultures after 72 h from treatment initiation. The combination of lock and systemic micafungin therapy achieved eradication of C. albicans from all studied tissues (0.0 ± 0.0 log CFU/g) vs. untreated controls (liver 7.5 ± 0.22, spleen 8.3 ± 0.25, kidney 8.6 ± 0.07, cerebrum 6.3 ± 0.31, vena cava 6.6 ± 0.29, and CVC wash 2.3 ± 0.68 log CFU/g) (p ≤ 0.001). Rabbits treated with a combination of lock and systemic micafungin therapy demonstrated a ≥2 log reduction in C. parapsilosis in all treated tissues (p ≤ 0.05) except kidney. Serum (1→3)-ß-D-glucan levels demonstrated significant decreases in response to treatment. The study demonstrates that combining systemic and lock therapies with micafungin effectively eradicates catheter-based biofilms and infections caused by C. albicans or C. parapsilosis, particularly in persistently neutropenic conditions, offering promising implications for managing vascular catheter-related candidemia and providing clinical benefits in cases where catheter removal is not feasible.

Metabolic disruptions and impaired reproductive fitness in wild-caught freshwater turtles (Emydura macquarii macquarii) exposed to elevated per- and polyfluoroalkyl substances (PFAS).

Per- and poly-fluoroalkyl substances (PFAS) pose a threat to organisms and ecosystems due to their persistent nature. Ecotoxicology endpoints used in regulatory guidelines may not reflect multiple, low-level but persistent stressors. This study examines the biological effects of PFAS on Eastern short-necked turtles in Queensland, Australia. In this study, blood samples were collected and analysed for PFAS, hormone levels, and functional omics endpoints. High levels of PFAS were found in turtles at the impacted site, with PFOS being the dominant constituent. The PFAS profiles of males and females differed, with males having higher PFAS concentrations. Hormone concentrations differed between impacted and reference sites in male turtles, with elevated testosterone and corticosterone indicative of stress. Further, energy utilisation, nucleotide synthesis, nitrogen metabolism, and amino acid synthesis were altered in both male and female turtles from PFAS-impacted sites. Both sexes show similar metabolic responses to environmental stressors from the PFAS-contaminated site, which may adversely affect their reproductive fitness. Purine metabolism, caffeine metabolism, and ferroptosis pathway changes in turtles can cause gout, cell death, and overall health problems. Further, the study showed that prolonged exposure to elevated PFAS levels in the wild could compromise turtle reproductive fitness by disrupting reproductive steroids and metabolic pathways.

Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections.

Early initiation of antimicrobial therapy targeting resistant bacterial pathogens causing sepsis and bloodstream infections (BSIs) is critical for a successful outcome. The T2Resistance Panel (T2R) detects the following resistance genes within organisms that commonly cause BSIs directly from patient blood samples: blaKPC, blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, blaOXA, vanA, vanB, and mecA/mecC. We conducted a prospective study in two major medical centers for the detection of circulating resistance genes by T2R in patients with BSIs. T2R reports were compared to antimicrobial susceptibility testing (AST), phenotypic identification, and standard molecular detection assays. Among 59 enrolled patients, 25 resistance genes were identified: blaKPC (n = 10), blaNDM/bla/IMP/blaVIM (n = 5), blaCTXM-14/15 (n = 4), blaAmpC (n = 2), and mecA/mecC (n = 4). Median time-to-positive-T2R in both hospitals was 4.4 hours [interquartile range (IQR): 3.65-4.97 hours] in comparison to that for positive blood cultures with final reporting of AST of 58.34 h (IQR: 45.51-111.2 hours; P < 0.0001). The sensitivity of T2R to detect the following genes in comparison to AST was 100% for blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, mecA/mecC and 87.5% for blaKPC. When monitored for the impact of significant antimicrobial changes, there were 32 events of discontinuation of unnecessary antibiotics and 17 events of escalation of antibiotics, including initiation of ceftazidime/avibactam in six patients in response to positive T2R results for blaKPC. In summary, T2R markers were highly sensitive for the detection of drug resistance genes in patients with bacterial BSIs, when compared with standard molecular resistance detection systems and phenotypic identification assays while significantly reducing by approximately 90% the time to detection of resistance compared to standard methodology and impacting clinical decisions for antimicrobial therapy. IMPORTANCE: This is the first reported study to our knowledge to identify key bacterial resistance genes directly from the bloodstream within 3 to 5 hours in patients with bloodstream infections and sepsis. The study further demonstrated a direct effect in modifying initial empirical antibacterial therapy in response to T2R signal to treat resistant bacteria causing bloodstream infections and sepsis.

Perspectives of Oncologists on the Ethical Implications of Using Artificial Intelligence for Cancer Care.

Importance: Artificial intelligence (AI) tools are rapidly integrating into cancer care. Understanding stakeholder views on ethical issues associated with the implementation of AI in oncology is critical to optimal deployment. Objective: To evaluate oncologists' views on the ethical domains of the use of AI in clinical care, including familiarity, predictions, explainability (the ability to explain how a result was determined), bias, deference, and responsibilities. Design, Setting, and Participants: This cross-sectional, population-based survey study was conducted from November 15, 2022, to July 31, 2023, among 204 US-based oncologists identified using the National Plan & Provider Enumeration System. Main Outcomes and Measures: The primary outcome was response to a question asking whether participants agreed or disagreed that patients need to provide informed consent for AI model use during cancer treatment decisions. Results: Of 387 surveys, 204 were completed (response rate, 52.7%). Participants represented 37 states, 120 (63.7%) identified as male, 128 (62.7%) as non-Hispanic White, and 60 (29.4%) were from academic practices; 95 (46.6%) had received some education on AI use in health care, and 45.3% (92 of 203) reported familiarity with clinical decision models. Most participants (84.8% [173 of 204]) reported that AI-based clinical decision models needed to be explainable by oncologists to be used in the clinic; 23.0% (47 of 204) stated they also needed to be explainable by patients. Patient consent for AI model use during treatment decisions was supported by 81.4% of participants (166 of 204). When presented with a scenario in which an AI decision model selected a different treatment regimen than the oncologist planned to recommend, the most common response was to present both options and let the patient decide (36.8% [75 of 204]); respondents from academic settings were more likely than those from other settings to let the patient decide (OR, 2.56; 95% CI, 1.19-5.51). Most respondents (90.7% [185 of 204]) reported that AI developers were responsible for the medico-legal problems associated with AI use. Some agreed that this responsibility was shared by physicians (47.1% [96 of 204]) or hospitals (43.1% [88 of 204]). Finally, most respondents (76.5% [156 of 204]) agreed that oncologists should protect patients from biased AI tools, but only 27.9% (57 of 204) were confident in their ability to identify poorly representative AI models. Conclusions and Relevance: In this cross-sectional survey study, few oncologists reported that patients needed to understand AI models, but most agreed that patients should consent to their use, and many tasked patients with choosing between physician- and AI-recommended treatment regimens. These findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions as well as decisional responsibility when problems related to AI use arise.

Access to inflatable penile prosthesis surgery as indicated by distances traveled among US men with Medicare.

Background: The significance of geographic barriers to receiving inflatable penile prosthesis (IPP) treatment is uncertain according to the existing medical literature. Aim: To describe the travel patterns of men with erectile dysfunction (ED) in the United States who underwent IPP surgery. Methods: This retrospective cohort study utilized data from the 100% Medicare Standard Analytical Files. Men aged ≥65 years with an ED diagnosis who underwent IPP surgery between January 2016 and December 2021 were identified from the database. Federal Information Processing Series codes from the National Bureau of Economic Research's County Distance Database were used to determine geographic distances from patients' homes to the facilities at which surgery was performed. Outcomes: Evaluations included the proportions of men who traveled outside their county of residence or state for IPP treatment and the average distances in miles traveled. Results: Among 15 954 men with ED undergoing IPP treatment, 56.4% received care out of their county for IPP, at a mean distance of 125.6 miles (range, 3.8-4935.0). Although patients aged ≥80 years were less likely to travel outside their county as compared with men aged 65 to 69 years (48.1% vs 57.1%, P < .001), if they traveled, they were likely to travel farther (mean, 171.8 vs 117.7 miles; P < .001). South Dakota had the highest proportion of men traveling outside their county for IPP treatment (91.3%; mean, 514.2 miles), while Vermont had the highest proportion traveling outside their home state (73.7%). Clinical Implications: By unveiling disparities in access, this study will potentially lead to tailored interventions that enhance patient care and health outcomes. Strengths and Limitations: Strengths include the uniqueness in (1) evaluating the proportions of patients who travel out of their county of residence or home state for IPP treatment and (2) quantifying the average distances that patients traveled. An additional strength is the large sample size due to the retrospective design and database used. The analysis did not capture all Medicare enrollees; however, it did encompass all traditional Medicare enrollees, representing approximately half of all men in the US aged ≥65 years. Limitations include not being generalizable to entire population of the US, as the study examined only Medicare enrollees. In addition, the study period includes the pandemic, which could have affected travel patterns. Furthermore, the coding and accuracy of the data are limitations of using administrative claims data for research. Conclusion: Study findings showed that many men with Medicare and ED traveled from their home geographic location for IPP treatment.

Optimization of Patient Progression in a New Era: A Comprehensive Framework.

PURPOSE/OBJECTIVES: The onset of the coronavirus disease 2019 pandemic increased the demand for inpatient services and led to widespread staffing shortages in the acute and post-acute setting, contributing to delayed inpatient throughput and leading to capacity crises. Novel strategies are needed to facilitate the efficient progression of hospitalized patients when medically ready for lower levels of care. The authors have developed a foundational strategic framework for patient progression to ensure capture of patient progression data, enhance efficiency, and optimal utilization of post-acute resources in increasingly complex and resource-constrained acute and post-acute environments. PRIMARY PRACTICE SETTINGS: Interventions were implemented, and metrics of success tracked as part of an overarching framework to test new models of care or optimize existing assets related to barriers to patient progression. Brigham and Women's Hospital (BWH) and Brigham and Women's Faulkner Hospital (BWFH) comprise an academic medical center and a community hospital, respectively, that are affiliated with Massachusetts General Brigham (MGB), a nonprofit health care system in Massachusetts. Key interventions include (1) screening to prioritize patients needing case management services through a modified early screening for discharge planning tool and process; (2) communicating, documenting, identifying patient progression status, barriers to discharge and post-acute needs through interdisciplinary care optimization rounds, a novel tool in the electronic health record, and an associated dashboard; (3) managing active high-risk patients through a novel complex care team and post-acute strategy development; (4) developing novel transportation and hospice pathways; and (5) establishing community hospital repatriation and a physical therapy "Why Not Home" campaign. FINDINGS: Key metrics of success were (1) modified discharge planning tool resulting in screening out low-risk patients (53%) and impacting length of stay (0.55-day reduction, p = .083) during a 3-month intervention versus control study; (2) documentation adherence in more than 98% of patients 10 months postimplementation; (3) complex care team achieving a 2.5% reduction in Case Mix Index-adjusted length of stay 6 months postimplementation; (4) use of care van offsetting ambulance/chair car in 10% of cases, and earlier discharge time/length of stay in 21% of cases 3 months postimplementation; and (5) implementation of community repatriation impacting delay days to discharge (10-month pilot, 40 patients accounting for 1,000 delay days). CONCLUSIONS: Implementation of a novel comprehensive framework focusing on optimizing patient progression resulted in increased operational efficiency and positively impacted length of stay at our academic and community hospitals. Additional study is actively ongoing to understand long-term benefit of the innovations that the authors have developed. Further interventions are needed to wholly mitigate evolving capacity challenges in the acute and post-acute settings. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The authors' implementation of the Brigham framework for progression demonstrates that innovative approaches to case management can help address the evolving challenges in care transitions planning. Notable opportunities include approaches that empower case managers as multidisciplinary team leaders, improve workflow, utilize patient progression data, prioritize patients with complex care needs support key patient populations, and promote post-acute collaboration.

Autologous Skin Cell Suspension for Full-Thickness Skin Defect Reconstruction: Current Evidence and Health Economic Expectations.

Despite differing etiologies, acute thermal burn injuries and full-thickness (FT) skin defects are associated with similar therapeutic challenges. When not amenable to primary or secondary closure, the conventional standard of care (SoC) treatment for these wound types is split-thickness skin grafting (STSG). This invasive procedure requires adequate availability of donor skin and is associated with donor site morbidity, high healthcare resource use (HCRU), and costs related to prolonged hospitalization. As such, treatment options that can facilitate effective healing and donor skin sparing have been highly anticipated. The RECELL® Autologous Cell Harvesting Device facilitates preparation of an autologous skin cell suspension (ASCS) for the treatment of acute thermal burns and FT skin defects. In initial clinical trials, the approach showed superior donor skin-sparing benefits and comparable wound healing to SoC STSG among patients with acute thermal burn injuries. These findings led to approval of RECELL for this indication by the US Food and Drug Administration (FDA) in 2018. Subsequent clinical evaluation in non-thermal FT skin wounds showed that RECELL, when used in combination with widely meshed STSG, provides donor skin-sparing advantages and comparable healing outcomes compared with SoC STSG. As a result, the device received FDA approval in June of 2023 for treatment of FT skin defects caused by traumatic avulsion or surgical excision or resection. Given that health economic advantages have been demonstrated for RECELL ± STSG versus STSG alone when used for burn therapy, it is prudent to examine similarities in the burn and FT skin defect treatment pathways to forecast the potential health economic advantages for RECELL when used in FT skin defects. This article discusses the parallels between the two indications, the clinical outcomes reported for RECELL, and the HCRU and cost benefits that may be anticipated with use of the device for non-thermal FT skin defects.

Testosterone replacement in men with sexual dysfunction.

BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.