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Objective: To investigate the incidence and risk factors for symptomatic urinary tract infection (UTI) following trial of void (TOV) to guide patient selection for antibiotic prophylaxis. Methods: A retrospective study considered all patients who underwent successful TOV across two separate 12-month periods at a tertiary hospital. Routine prophylactic antibiotics were not administered. Results: The 183 patients included were mostly men (91.3%) aged ⩾ 65 years (78.7%). Thirty-seven (20.3%) had recent urological surgery. The incidence of UTI following TOV was 12.6% (23/183); median duration of onset was 3 days (interquartile range = 2–9). Cystitis was most common (17/183; 9.3%), while four patients (2.2%) suffered urosepsis. There were no singular statistically significant risk factors for increasing the risk of UTI following TOV, however, ⩾ 2 risk factors showed numerically higher odds of UTI compared to ⩽ 1 risk factor (15.6% vs 4.2%; odds ratio = 4.24, 95% confidence interval = 0.96–18.80, p = 0.058). Atypical organisms resistant to most oral antibiotics were predominantly cultured, however, 89% sensitivity to ciprofloxacin was observed. Conclusion: The incidence of UTI following TOV was higher than anticipated. Reliable identification of at-risk patients for antibiotic prophylaxis is likely to be complicated. Further research is needed to confirm patient selection prior to confirmatory trials. Level of evidence: 2b [ABSTRACT FROM AUTHOR]

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has fostered collaboration among researchers around the world, catalyzing innovation and accelerating progress in the field. In Latin America, this initiative advanced the validation and development of Alzheimer's disease biomarkers for the first time in our region. In 2011, as part of the international ADNI, Argentina‐ADNI (Arg‐ADNI) was founded. The following years were characterized by strong support from entities such as the Alzheimer's Association, transforming into the emergence of several multinational studies focusing on prevention and diagnosis, and treatment of dementias. These studies are heirs to the tradition of Arg‐ADNI: the Dominantly Inherited Alzheimer Network, Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline, Longitudinal Early‐Onset Alzheimer's Disease Study, and Initiative for the Study of Down Syndrome and Alzheimer's Disease. These initiatives have contributed significantly to the development of regional research and serve as essential tools for health policy planning in Latin America. Highlights: In Latin America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) advanced the validation and development of Alzheimer's disease biomarkers for the first time in our region.ADNI has been the basis that boosted several multinational studies focusing on both prevention and diagnosis, and treatment of dementias (Dominantly Inherited Alzheimer Network, LatAm‐FINGER, LEADS).These initiatives with the support from the Alzheimer's Association have contributed significantly to the development of regional researchThis is an example of collaboration between high‐income countries with low‐ and middle‐income countries aimed at global scientific development and inclusion. [ABSTRACT FROM AUTHOR]

The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies. In this context, designing the most efficient development programs to translate promising targets and treatments from preclinical studies to early‐phase clinical trials is vital. In September 2022, the Rainwater Charitable Foundation convened an international expert workshop focused on the translation of tauopathy therapeutics through early‐phase trials. Our report on the workshop recommends a framework for principled drug development and a companion lexicon to facilitate communication focusing on reproducibility and achieving common elements. Topics include the selection of targets, drugs, biomarkers, participants, and study designs. The maturation of pharmacodynamic biomarkers to demonstrate target engagement and surrogate disease biomarkers is a crucial unmet need. Highlights: Experts provided a framework to translate therapeutics (discovery to clinical trials).Experts focused on the "5 Rights" (target, drug, biomarker, participants, trial).Current research on frontotemporal degeneration, progressive supranuclear palsy, and corticobasal syndrome therapeutics includes 32 trials (37% on biologics)Tau therapeutics are being tested in Alzheimer's disease; primary tauopathies have a large unmet need. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether adherence to hip fracture clinical care quality indicators influences mortality among people who undergo surgery after hip fracture in New South Wales, both overall and by individual indicator. Study design: Retrospective population‐based study; analysis of linked Australian and New Zealand Hip Fracture Registry (ANZHFR), hospital admissions, residential aged care, and deaths data. Setting, participants: People aged 50 years or older with hip fractures who underwent surgery in 21 New South Wales hospitals participating in the ANZHFR, 1 January 2015 – 31 December 2018. Main outcome measures: Thirty‐day (primary outcome), 120‐day, and 365‐day mortality (secondary outcomes) by clinical care indicator adherence level (low: none to three of six indicators achieved; moderate: four indicators achieved; high: five or six indicators achieved) and by individual indicator. Results: Registry data were available for 9236 hip fractures in 9058 people aged 50 years or older during 2015–2018; the mean age of patients was 82.8 years (standard deviation, 9.3 years), 5510 patients were women (69.4%). Complete data regarding adherence to clinical care indicators were available for 7951 fractures (86.1%); adherence to these indicators was high for 5135 (64.6%), moderate for 2249 (28.3%), and low for 567 fractures (7.1%). After adjustment for age, sex, comorbidity, admission year, pre‐admission walking ability, and residential status, 30‐day mortality risk was lower for high (adjusted relative risk [aRR], 0.40; 95% confidence interval [CI], 0.30–0.52) and moderate indicator adherence hip fractures (aRR, 0.61; 95% CI, 0.46–0.82) than for low indicator adherence hip fractures, as was 365‐day mortality (high adherence: aRR, 0.59 [95% CI, 0.51–0.68]; moderate adherence: aRR, 0.74 [95% CI, 0.63–0.86]). Orthogeriatric care (365 days: aRR, 0.78; 95% CI, 0.61–0.98) and offering mobilisation by the day after surgery (365 days: aRR, 0.74; 95% CI, 0.67–0.83) were associated with lower mortality risk at each time point. Conclusions: Clinical care for two‐thirds of hip fractures attained a high level of adherence to the six quality care indicators, and short and longer term mortality was lower among people who received such care than among those who received low adherence care. [ABSTRACT FROM AUTHOR]

Sarcopenia is underappreciated in advanced heart failure and is not routinely assessed. In patients receiving a left ventricular assist device, preoperative sarcopenia, defined by using computed-tomography (CT)-derived pectoralis muscle-area index (muscle area indexed to body-surface area), is an independent predictor of postoperative mortality. The association between preoperative sarcopenia and outcomes after heart transplant (HT) is unknown. The primary aim of this study was to determine whether preoperative sarcopenia, diagnosed using the pectoralis muscle-area index, is an independent predictor of days alive and out of the hospital (DAOHs) post-transplant. Patients who underwent HT between January, 2018, and June, 2022, with available preoperative chest CT scans were included. Sarcopenia was diagnosed as pectoralis muscle-area index in the lowest sex-specific tertile. The primary endpoint was DAOHs at 1 year post-transplant. The study included 169 patients. Patients with sarcopenia (n = 55) had fewer DAOHs compared to those without sarcopenia, with a median difference of 17 days (320 vs 337 days; P = 0.004). Patients with sarcopenia had longer index hospitalizations and were also more likely to be discharged to a facility other than home. In a Poisson regression model, sarcopenia was a significant univariable and the strongest multivariable predictor of DAOHs at 1 year (parameter estimate = -0.17, 95% CI -0.19 to -14; P = < 0.0001). Preoperative sarcopenia, diagnosed using the pectoralis muscle-area index, is an independent predictor of poor outcomes after HT. This parameter is easily measurable from commonly obtained preoperative CT scans and may be considered in transplant evaluations. • Sarcopenia is underdiagnosed in patients with advanced heart failure who are eligible for cardiac transplantation and may impact post-transplant outcomes. • Patients with sarcopenia, defined by low pectoralis muscle-area index (muscle area indexed to body-surface area) using available preoperative CT scans, was independently associated with fewer days alive and out of the hospital compared to those without sarcopenia. • Pectoralis muscle-area index is easily measurable from routinely obtained preoperative CT scans and may aid in identifying sarcopenia during transplant evaluations. [ABSTRACT FROM AUTHOR]

An approximately 3 yr old female Chihuahua was presented for evaluation of polyuria and polydipsia noted by the owner after adoption. Serum biochemistry and urinalysis revealed hyponatremia, hypochloremia, hypo-osmolality, and normal fractional excretion of sodium. Serum antidiuretic hormone concentration was 5.54 pg/mL and serum copeptin concentration was 135.40 pg/mL. The antidiuretic hormone value was above the reported range for healthy dogs and was considered inappropriate in light of serum osmolality. Idiopathic syndrome of inappropriate antidiuretic hormone secretion was considered the most likely diagnosis after excluding other potential causes, such as diuretic use, renal disease, adrenal disease, and thyroid dysfunction. The dog remains clinically well 2 yr after diagnosis without specific treatment other than minimal dietary salt supplementation. This case is unique because of the absence of systemic or neurologic signs, good long-term outcome without treatment, and use of novel diagnostic testing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Beneficial effects of breathing at FIO2 < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with FIO2 as low as 0.11 in 5 healthy volunteers. METHODS: All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from FIO2 of 0.16 on the first day to FIO2 of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' SpO2, heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments. RESULTS: Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased SpO2 and increased heart rate. At FIO2 of 0.14, the mean SpO2 was 92%; at FIO2 of 0.13, the mean SpO2 was 93%; at FIO2 of 0.12, the mean SpO2 was 88%; at FIO2 of 0.11, the mean SpO2 was 85%; and, finally, at an FIO2 of 0.21, the mean SpO2 was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension. CONCLUSIONS: Results of the current physiologic study suggests that, within a hospital setting, delivering FIO2 as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested. [ABSTRACT FROM AUTHOR]

Potassium-competitive acid blockers have documented efficacy for erosive esophagitis. We performed a randomized trial in United States subjects diagnosed with non-erosive reflux disease of vonoprazan vs placebo for 4 weeks, followed by a 20-week active-treatment extension. Adult subjects with heartburn ≥4 days/week during screening without erosive esophagitis on endoscopy were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg. After 4 weeks, subjects on placebo were re-randomized to vonoprazan 10 mg or 20 mg, and those already on vonoprazan continued at the same dose for 20 weeks. Electronic diaries were completed twice daily. The primary endpoint was percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days). Among 772 randomized subjects, the percentage of 24-hour heartburn-free days was 27.7% for placebo vs 44.8% for vonoprazan 10 mg (least squares mean difference, 17.1%; P <.0001) and 44.4% for vonoprazan 20 mg (least squares mean difference, 16.7%; P <.0001). Differences in percentage of subjects with a 24-hour heartburn-free day for vonoprazan 10 mg vs placebo and vonoprazan 20 mg vs placebo were 8.3% and 11.6% on day 1 and 18.1% and 23.2% on day 2. The mean/median percentages of 24-hour heartburn-free days over the extension period were similar across the 4 study arms: 61%-63%/76%-79%. Vonoprazan reduced heartburn symptoms in subjects diagnosed with non-erosive reflux disease, with the benefit appearing to begin as early as the first day of therapy. Treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period. The 2 vonoprazan doses (10 mg and 20 mg) were similar in efficacy. (ClinicalTrials.gov : NCT05195528) [Display omitted] [ABSTRACT FROM AUTHOR]

With advancements in perioperative blood management and the use of tranexamic acid, the rate of transfusions after total knee arthroplasty (TKA) has substantially decreased. As these principles are refined, other modifiable risk factors, such as preoperative anemia, may play an increasingly important role in transfusion risk for patients undergoing TKA. A multicenter, national database was utilized to identify patients undergoing TKA from 2010 to 2021. Anemia was defined by World Health Organization definitions as < 12 g/dL for women and < 13 g/dL for men. A predictive model was created using backwards elimination logistic regression to predict transfusion risk, controlling for demographic and medical covariates. The coefficient of anemia was then analyzed for each year. The trend over time was fitted with a best-fit linear regression equation. There were 509,117 patients who underwent TKA, and had a mean age of 67 years (range, 18 to 89). There were 57,716 (11%) patients who were anemic preoperatively, and 15,426 (3%) of patients required a transfusion. Rate of transfusion decreased from 10.6% in 2010 to 0.6% in 2021. The odds ratio associated with anemia as a predictor of transfusion increased from 3.1 (95% confidence interval: 2.1 to 4.6) in 2010 to 14.0 (95% confidence interval: 8.9 to 24) in 2021. The results of this study demonstrate that the importance of preoperative anemia as a predictor of transfusion has increased over the past decade as rates of transfusion have decreased. As perioperative blood management protocols improve, preoperative anemia should be considered an important focus of intervention to reduce the risk of transfusion prior to TKA. III. [ABSTRACT FROM AUTHOR]

• Relationships between skeletal muscle echogenicity and physical function were small to moderate but highly consistent. • Sub-analyses determined minimal between-muscle differences in predictive ability. • Ultrasonic echogenicity should be considered part of early detection screens for sarcopenia and other diseases. • Combining muscles tended to strengthen the model, although muscle quality appears systemic, allowing for a single scan to represent the total body. Assessment and quantification of skeletal muscle within the aging population is vital for diagnosis, treatment, and injury/disease prevention. The clinical availability of assessing muscle quality through diagnostic ultrasound presents an opportunity to be utilized as a screening tool for function-limiting diseases. However, relationships between muscle echogenicity and clinical functional assessments require authoritative analysis. Thus, we aimed to (a) synthesize the literature to assess the relationships between skeletal muscle echogenicity and physical function in older adults (≥60 years), (b) perform pooled analyses of relationships between skeletal muscle echogenicity and physical function, and (c) perform sub-analyses to determine between-muscle relationships. CINAHL, Embase, MEDLINE, PubMed, and Web of Science databases were systematically searched to identify articles relating skeletal muscle echogenicity to physical function in older adults. Risk-of-bias assessments were conducted along with funnel plot examination. Meta-analyses with and without sub-analyses for individual muscles were performed utilizing Fisher's Z transformation for the most common measures of physical function. Fisher's Z was back-transformed to Pearson's r for interpretation. Fifty-one articles (n = 5095, female = ∼2759, male = ∼2301, 72.5 ± 5.8 years, mean ± SD (1 study did not provide sex descriptors)) were extracted for review, with previously unpublished data obtained from the authors of 13 studies. The rectus femoris (n = 34) and isometric knee extension strength (n = 22) were the most accessed muscle and physical qualities, respectively. The relationship between quadriceps echogenicity and knee extensor strength was moderate (n = 2924, r = –0.36 (95% confidence interval: –0.38 to –0.32), p < 0.001), with all other meta-analyses (grip strength, walking speed, sit-to-stand, timed up-and-go) resulting in slightly weaker correlations (r : –0.34 to –0.23, all p < 0.001). Sub-analyses determined minimal differences in predictive ability between muscle groups, although combining muscles (e.g., rectus femoris + vastus lateralis) often resulted in stronger correlations with maximal strength. While correlations are modest, the affordable, portable, and noninvasive ultrasonic assessment of muscle quality is a consistent predictor of physical function in older adults. Minimal between-muscle differences suggest that echogenicity estimates of muscle quality are systemic. Therefore, practitioners may be able to scan a single muscle to estimate full-body skeletal muscle quality/composition, while researchers should consider combining multiple muscles to strengthen the model. [Display omitted] [ABSTRACT FROM AUTHOR]

The article discusses the importance of implementability in clinical trial planning, design, and reporting to optimize the impact of late-phase trials. It emphasizes the need for trials to be designed for implementability to improve practice, health systems, and policy. Key considerations include trial design, conduct, and reporting, as well as the involvement of end users in the process. The article also highlights the role of clinical trial networks in supporting quality consumer and community involvement and facilitating the implementation of trial outcomes. [Extracted from the article]

Numerous studies have demonstrated that mouth rinsing with glucose enhance exercise; however, research on fructose is comparatively limited. Owing to unexpected taste preferences, fructose is rarely used in carbohydrate mouth rinsing studies. Therefore, the objective of this study is to compare perceived taste between glucose and fructose solutions. Ninety-six participants were assigned perform a set of mouth rinse trials with three different solutions in double blind-manner. Participants were instructed to rinse 25 mL of 6% glucose, 5.3% fructose, and 21.2% fructose for 10 seconds. Prior to using the second and third solutions for rinsing, participants were instructed to cleanse their mouth by rinsing with warm water. Following the warm water mouth rinse, participants were asked to assess the visual analog scale and taste test questionnaire before proceeding to rinse with the subsequent solution. The research revealed that the mean score of 21.2% for fructose was significantly higher (p < 0.05) in terms of preferred, sweetness and intensity compared to glucose at 6% and fructose at 5.3%. However, for taste, fructose 5.3% has greater mean than others. In general, fructose was predominantly favoured as preferred choice, likely due to its appealing sweetness and intensity. The findings recommend considering higher caloric intake of fructose during mouth rinsing to enhance brain activation and exercise performance, as fructose appears to be a more favoured option compared to glucose. This insight could guide future studies in this direction. [ABSTRACT FROM AUTHOR]

Objective: To test the efficacy of metformin (MET) during the induction of coronary ischemia on myocardial performance in a large animal model of coronary artery disease (CAD) and metabolic syndrome (MS), with or without concomitant extracellular vesicular (EV) therapy. Background: Although surgical and endovascular revascularization are durably efficacious for many patients with CAD, up to one-third are poor candidates for standard therapies. For these patients, many of whom have comorbid MS, adjunctive strategies are needed. EV therapy has shown promise in this context, but its efficacy is attenuated by MS. We investigated whether MET pretreatment could ameliorate therapeutic decrements associated with MS. Methods: Yorkshire swine (n = 29) were provided a high-fat diet to induce MS, whereupon an ameroid constrictor was placed to induce CAD. Animals were initiated on 1000 mg oral MET or placebo; all then underwent repeat thoracotomy for intramyocardial injection of EVs or saline. Swine were maintained for 5 weeks before the acquisition of functional and perfusion data immediately before terminal myocardial harvest. Immunoblotting and immuno-fluorescence were performed on the most ischemic tissue from all groups. Results: Regardless of EV administration, animals that received MET exhibited significantly improved ejection fraction, cardiac index, and contractility at rest and during rapid myocardial pacing, improved perfusion to the most ischemic myocardial region at rest and during pacing, and markedly reduced apoptosis. Conclusions: MET administration reduced apoptotic cell death, improved perfusion, and augmented both intrinsic and loaddependent myocardial performance in a highly translatable large animal model of chronic myocardial ischemia and MS. [ABSTRACT FROM AUTHOR]

The fusion of cutting-edge imaging technologies with radiation therapy (RT) has catalyzed transformative breakthroughs in cancer treatment in recent decades. It is critical for us to review our achievements and preview into the next phase for future synergy between imaging and RT. This paper serves as a review and preview for fostering collaboration between these two domains in the forthcoming decade. Firstly, it delineates ten prospective directions ranging from technological innovations to leveraging imaging data in RT planning, execution, and preclinical research. Secondly, it presents major directions for infrastructure and team development in facilitating interdisciplinary synergy and clinical translation. We envision a future where seamless integration of imaging technologies into RT will not only meet the demands of RT but also unlock novel functionalities, enhancing accuracy, efficiency, safety, and ultimately, the standard of care for patients worldwide. [ABSTRACT FROM AUTHOR]

Background: Leadership can be an isolating experience and leaders from underrepresented groups (URGs) may experience even greater isolation and vulnerability because of lack of representation. Given the collaborative nature of medicine, leadership programs for physicians need to address isolation. Social support is one mechanism to combat this isolation; however, most leadership programs focus exclusively on skills building. Purpose: The Stanford Network for Advancement and Promotion (SNAP) program was developed to reduce isolation among physician leaders from URGs in academic medicine leadership by building a supportive network of peers. Methodology/Approach: Ten women physicians from diverse racial/ethnic backgrounds were invited to participate in SNAP. Annual surveys were administered to participants to assess the effectiveness of SNAP on decreasing feelings of isolation and increasing professional leadership growth. The authors charted the expansion and adaptation of the program model across gender and in additional settings. Results: SNAP effectively created a sense of community among the physician leaders. Participants also reported feeling challenged by the program and that they had grown in terms of critical thinking, organizational knowledge, and empowerment as leaders. Participants found community building to be the most valuable program component. Because of this success, the SNAP model has been adapted to create 10 additional cohorts. Conclusion: Leadership programs like SNAP that focus on reducing isolation are instrumental for retaining and promoting the career advancement of physicians from URGs. Practice Implications: Developing a diverse workforce of academic physicians is essential to providing high-quality and equitable clinical care, research, and medical education. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is common in preterm infants, especially infants less than 32 weeks gestation. Mortality from NEC is 7% and occurs in 1 out of 1000 preterm infants. Studies have shown the efficacy of an exclusive milk from mother diet in decreasing rates of NEC and associated mortality. Purpose: To evaluate the effectiveness of an existing exclusive human milk diet (EHMD) protocol on the incidence of NEC in extremely premature infants. EHMD, for the purposes of this project is defined as breast milk of mother, with or without human milk-based fortifier. Methods: A single-center retrospective quasi-experimental study. The sample included 201 infants born less than 32 weeks gestation, weighing less than 1250 grams, small for gestational age (SGA) and with low Apgar scores. Outcomes measured included incidences of NEC, mortality, and co-morbidities in infants pre- and postinitiation of an EHMD protocol. Results: Just 4.8% of the EHMD group had a NEC diagnosis compared to 10.5% of the bovine-based (BOV) group. There was a 1% mortality rate of the EHMD group as compared to 6% in the BOV group. The EHMD group had a statistically significant greater weight gain during hospitalization as compared to infants fed BOV (P = < .05). Implications for Practice and Research: Neonatal intensive care units should consider EHMDs for use in this infant population. Future research is needed to support dissemination of the use of EHMD as standard of practice. [ABSTRACT FROM AUTHOR]

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Capecitabine is an oral pro-drug of 5-flourouracil used in treatment of different cancers. It has cardiotoxicity incidence of 3-35%, which can be significant enough to cause myocardial infarction. To evaluate the efficacy of glyceryl trinitrate in reducing cardiac events when given concomitantly with capecitabine for at least 3 months in various tumors. A quasi-experimental study was conducted in Hameed Latif Hospital from January 2019 to December 2023. A total of 65 patients with various malignancies and ECOG 0-2 were included. Glyceryl trinitrate was given before capecitabine for at least 3 cycles with 2.6 mg dosage twice a day. Cardiotoxicity was assessed after each 21-days cycle by taking history and ECG. Echocardiogram was done at 3-month follow up Patients aged from 49 to 86 years. Adverse events were noted in 3 (4.6%) patients. Two patients (3.1%) suffered from angina (grade 2 cardiotoxicity) while 1 (1.5%) suffered from a myocardial infarction (grade 3 cardiotoxicity). On stratification, only treatment in adjuvant setting (p<0.001) was found to be a possible risk factor. Glyceryl trinitrate may have potential to be used concomitantly with capecitabine to reduce the frequency of serious cardiac events in cancer patients. However, further studies are needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Over the past 25 years, diagnosis and therapy for acute aortic dissection (AAD) have evolved. We aimed to study the effects of these iterative changes in care. METHODS: Patients with nontraumatic AAD enrolled in the International Registry of Acute Aortic Dissection (61 centers; 15 countries) were divided into time-based tertiles (groups) from 1996 to 2022. The impact of changes in diagnostics, therapeutic care, and in-hospital and 3-year mortality was assessed. Cochran-Armitage trend and Jonckheere-Terpstra tests were conducted to test for any temporal trend. RESULTS: Each group consisted of 3785 patients (mean age, ≈62 years old; ≈65.5% males); nearly two-thirds had type A AAD. Over time, the rates of hypertension increased from 77.8% to 80.4% (P=0.002), while smoking (34.1% to 30.6%, P=0.033) and atherosclerosis decreased (25.6%-16.6%; P<0.001). Across groups, the percentage of surgical repair of type A AAD increased from 89.1% to 92.5% (P<0.001) and was associated with decreased hospital mortality (from 24.1% in group 1 to 16.7% in group 3; P<0.001). There was no difference in 3-year survival (P=0.296). For type B AAD, stent graft therapy (thoracic endovascular aortic repair) was used more frequently (22.3%-35.9%; P<0.001), with a corresponding decrease in open surgery. Endovascular in-hospital mortality decreased from 9.9% to 6.2% (P=0.003). As seen with the type A AAD cohort, overall 3-year mortality for patients with type B AAD was consistent over time (P=0.084). CONCLUSIONS: Over 25 years, substantial improvements in-hospital survival were associated with a more aggressive surgical approach for patients with type A AAD. Open surgery has been partially supplanted by thoracic endovascular aortic repair for complicated type B AAD, and in-hospital mortality has decreased over the time period studied. Postdischarge survival for up to 3 years was similar over time. [ABSTRACT FROM AUTHOR]

This Aotearoa New Zealand–based study addresses a gap in literature focusing on individual experiences of racism among adolescents and young adults and its links to health. This cross-sectional study uses data from multiple instances of the New Zealand Health Survey (2002/03, 2006/07, 2011/12, 2016/17) and General Social Survey (2008–2016) restricted to participants aged 15–24 years. Prevalence of reported experiences of racism are estimated. Meta-analytic techniques to pool data and multiple regression analyses are used to examine associations between experiences of racism and outcomes measures (mental and physical health, general health and well-being, life satisfaction, inability to access health care, and identity). The study used an ethical co-design process between university researchers and a rangatahi Māori (Māori young people) partnership group. Racism was higher among Māori, Pacific, and Asian young people compared to European young people. Racism was associated with all negative health and well-being measures examined for young people, including negative mental and physical health measures (12-Item Short Form Survey, Kessler Psychological Distress Scale), lower self-rated health, negative life satisfaction, higher unmet need for primary care, and identity measures (feelings of not belonging in New Zealand, less able to express their identity). The results of this study are concerning. Non-European young people disproportionately bear the burden of racism in Aotearoa New Zealand with a potentially substantial impact on their health and well-being. This is a breach of Indigenous (for Māori) and other international human rights and should be motivation to act to eliminate racism in all its forms. [ABSTRACT FROM AUTHOR]

In an immersive virtual reality (IVR) environment, this study investigated: (1) the role of learner characteristics in various learning and psychological outcomes, including knowledge retention, perceived learning, cognitive load, self-efficacy, enjoyment, presence, and usefulness; and (2) the relationship among these intended outcomes. Forty adult participants experienced an IVR nature trail tour involving science learning topics, followed by a knowledge test and multiple surveys. Multivariate analysis of covariance results indicated age by gender interaction effects on perceived presence and usefulness as well as an age by IVR prior experience interaction effect on perceived presence. Additionally, multiple correlational relationships were detected among the intended outcomes. This study contributes to the limited research on the role of learner characteristics in STEM learning and psychological outcomes in IVR environments. [ABSTRACT FROM AUTHOR]

Genotype-phenotype associations in recessive dystrophic epidermolysis bullosa (RDEB) have been difficult to elucidate. To investigate RDEB genotype-phenotype associations and explore a functional approach to genotype classification. Clinical examination and genetic testing of RDEB subjects, including assessment of clinical disease by RDEB subtype and extent of blistering. Genotypes were evaluated according to each variant's effect on type VII collagen function per updated literature and subsequently categorized by degree of impact on VII collagen function as low-impact (splice/missense, missense/missense), medium-impact (premature termination codon [PTC]/missense, splice/splice), and high-impact (PTC/PTC, PTC/splice). Genotype-phenotype associations were investigated using Kruskal-Wallis and Fisher's exact tests, and age-adjusted regressions. Eighty-three participants were included. High-impact variants were associated with worse RDEB subtype and clinical disease, including increased prevalence of generalized blistering (55.6% for low-impact vs 72.7% medium-impact vs 90.4% high-impact variants, P =.002). In age-adjusted regressions, participants with high-impact variants had 40.8-fold greater odds of squamous cell carcinoma compared to low-impact variants (P =.02), and 5.7-fold greater odds of death compared to medium-impact variants (P =.05). Cross-sectional design. Functional genotype categories may stratify RDEB severity; high-impact variants correlated with worse clinical outcomes. Further validation in larger cohorts is needed. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males. A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed. Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log 2 -fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log 2 -fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log 2 -fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log 2 -fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (−1.44, 95%CI −1.75,−1.13), g-guanidinobutyrate (−1.27, 95%CI 1.54,−0.99), creatinine (−1.17, 95%CI −1.44,−0.90), 2-methylbutyrylcarnitine (−1.76, 95%CI −2.17,−1.35), and leu-pro (−1.13, 95%CI −1.44,−0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males. MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study?—The question addressed by the study must limited to only one sentence. Psychedelic substances have gained increased interest as experimental therapeutics for a variety of neuropsychiatric disorders, yet evidence on the effects of psychedelics in older adults remains scarce. • What is the main finding of this study?—The finding must be limited to two sentences. Older adults reported well-being improvements similar to a matched sample of younger adults following participation in a psychedelic retreat, despite significantly attenuated acute subjective intensity scores. In contrast to the existing literature based largely on younger adults, well-being changes in older adults were not predicted by acute psychedelic effects, but rather by interpersonal experiences of togetherness ("communitas") during group activities across the entire retreat. • What is the meaning of the finding?—The meaning of the finding must be limited to one sentence. These findings bear significance for benefit-maximization and harm reduction practices for naturalistic psychedelic use in older adults, as well as clinical trial design, providing some initial evidence to address the critical knowledge gap regarding the effects of psychedelic substances in older adults. Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are currently investigated as novel interventions for affective disorders, yet little is known regarding their effects in OA. We investigated the mental health effects and psychological mechanisms of guided psychedelic group experiences in OA and a matched sample of younger adults (YA). Using a prospective observational cohort design, we identified 62 OA (age ≥60 years) and 62 matched YA who completed surveys two weeks before, a day, two weeks, four weeks, and six months after a psychedelic group session. Mixed linear regression analyses were used to investigate longitudinal well-being changes, as well as baseline, acute, and post-acute predictors of change. OA showed post-psychedelic well-being improvements similar to matched YA. Among baseline predictors, presence of a lifetime psychiatric diagnosis was associated with greater well-being increases in OA (B = 6.72, p =.016 at the four-week key-endpoint). Compared to YA, acute subjective psychedelic effects were less intense in OA and did not significantly predict prospective well-being changes. However, relational experiences before and after psychedelic sessions emerged as predictors in OA (r(36) =.37,p = 0.025). Guided psychedelic group sessions enhance well-being in OA in line with prior naturalistic and controlled studies in YA. Interestingly, acute psychedelic effects in OA are attenuated and less predictive of well-being improvements, with relational experiences related to the group setting playing a more prominent role. Our present findings call for further research on the effects of psychedelics in OA. [ABSTRACT FROM AUTHOR]

Pyogenic flexor tenosynovitis (PFT) comprises 2.5–9.4% of all primary hand infections. Management is variable, including surgical intervention, systemic antibiotics, or both. However, there are no evidence-based treatment guidelines. We conducted a systematic review to determine the best evidence for existing interventions and a meta-analysis to summarise published data quantitatively. MEDLINE and Embase (OVID) databases were searched in January 2023 and March 2024. Screening and data extraction were performed in duplicate. The risk of bias was assessed using National Institute of Health study assessment tools. A protocol is available on PROSPERO (CRD42023411142), and the review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data analysis was performed in RStudio. 24 studies (n = 1108 patients) were included following screening of 2386 abstracts. All were retrospective (18 case series and six cohort studies). Surgical interventions were assessed in 22 studies, combined with specific antibiotic regimes in four studies. Two studies described non-operative management alone. The pooled mean hospital stay for those undergoing operative intervention was 8.3 days (SD 7.5, n = 552), compared to 4.76 days (SD 0.12, n = 58) for non-operative intervention. Two studies reported PROMs (DASH), reporting no difference when comparing operative and non-operative interventions. Most studies were of poor quality (20), with four being fair. There is insufficient evidence in favour of one intervention regarding hospital stay or PROMs, including the superiority of operative management or non-operative approaches. Given the prevalence of PFT, management should be guided by robust data. Future experimental studies of surgical techniques and comparisons with non-operative management are warranted. [ABSTRACT FROM AUTHOR]

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