Hippocampal Dopamine/DRD1 Signaling Dependent on the Ghrelin Receptor.

The ghrelin receptor (GHSR1a) and dopamine receptor-1 (DRD1) are coexpressed in hippocampal neurons, yet ghrelin is undetectable in the hippocampus; therefore, we sought a function for apo-GHSR1a. Real-time single-molecule analysis on hippocampal neurons revealed dimerization between apo-GHSR1a and DRD1 that is enhanced by DRD1 agonism. In addition, proximity measurements support formation of preassembled apo-GHSR1a:DRD1:Gαq heteromeric complexes in hippocampal neurons. Activation by a DRD1 agonist produced non-canonical signal transduction via Gαq-PLC-IP3-Ca(2+) at the expense of canonical DRD1 Gαs cAMP signaling to result in CaMKII activation, glutamate receptor exocytosis, synaptic reorganization, and expression of early markers of hippocampal synaptic plasticity. Remarkably, this pathway is blocked by genetic or pharmacological inactivation of GHSR1a. In mice, GHSR1a inactivation inhibits DRD1-mediated hippocampal behavior and memory. Our findings identify a previously unrecognized mechanism essential for DRD1 initiation of hippocampal synaptic plasticity that is dependent on GHSR1a, and independent of cAMP signaling.

Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension.

BACKGROUND: Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited. METHODS: In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed. RESULTS: A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups. CONCLUSIONS: Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).

Time-Restricted Feeding Reduces Atherosclerosis in LDLR KO Mice but Not in ApoE Knockout Mice.

BACKGROUND: Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. METHODS: We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. RESULTS: TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating ß-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. CONCLUSIONS: In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.

An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Efficient enumeration and visualization of helix-coil ensembles.

Helix-coil models are routinely used to interpret circular dichroism data of helical peptides or predict the helicity of naturally-occurring and designed polypeptides. However, a helix-coil model contains significantly more information than mean helicity alone, as it defines the entire ensemble-the equilibrium population of every possible helix-coil configuration-for a given sequence. Many desirable quantities of this ensemble are either not obtained as ensemble averages or are not available using standard helicity-averaging calculations. Enumeration of the entire ensemble can allow calculation of a wider set of ensemble properties, but the exponential size of the configuration space typically renders this intractable. We present an algorithm that efficiently approximates the helix-coil ensemble to arbitrary accuracy by sequentially generating a list of the M highest populated configurations in descending order of population. Truncating this list of (configuration, population) pairs at a desired accuracy provides an approximating sub-ensemble. We demonstrate several uses of this approach for providing insight into helix-coil ensembles and folding mechanisms, including landscape visualization.

Designing tailored maintenance strategies for systematic reviews and clinical practice guidelines using the Portfolio Maintenance by Test-Treatment (POMBYTT) framework.

BACKGROUND: Organizations face diverse contexts and requirements when updating and maintaining their portfolio, or pool, of systematic reviews or clinical practice guidelines they need to manage. We aimed to develop a comprehensive, theoretical framework that might enable the design and tailoring of maintenance strategies for portfolios containing systematic reviews and guidelines. METHODS: We employed a conceptual approach combined with a literature review. Components of the diagnostic test-treatment pathway used in clinical healthcare were transferred to develop a framework specifically for systematic review and guideline portfolio maintenance strategies. RESULTS: We developed the Portfolio Maintenance by Test-Treatment (POMBYTT) framework comprising diagnosis, staging, management, and monitoring components. To illustrate the framework's components and their elements, we provided examples from both a clinical healthcare test-treatment pathway and a clinical practice guideline maintenance scenario. Additionally, our literature review provided possible examples for the elements in the framework, such as detection variables, detection tests, and detection thresholds. We furthermore provide three example strategies using the framework, of which one was based on living recommendations strategies. CONCLUSIONS: The developed framework might support the design of maintenance strategies that could contain multiple options besides updating to manage a portfolio (e.g. withdrawing and archiving), even in the absence of the target condition. By making different choices for variables, tests, test protocols, indications, management options, and monitoring, organizations might tailor their maintenance strategy to suit specific contexts and needs. The framework's elements could potentially aid in the design by being explicit about the operational aspects of maintenance strategies. This might also be helpful for end-users and other stakeholders of systematic reviews and clinical practice guidelines.

How Dermatologic Surgeons Decide to Proceed with Surgery for Nonmelanoma Skin Cancer When Site Identification is Initially Uncertain: A Nationwide, Multicenter, Prospective Study.

BACKGROUND: Few studies show how dermatologic surgeons manage problems with site identification. OBJECTIVE: To estimate frequency and characterize management of skin cancer treated by surgery when the anatomic location of the tumor is in question. METHODS: Nationwide, prospective, multi-site cohort study. RESULTS: Among 17,076 cases at 22 centers, 98 (0.60%) were lesions in question (LIQ) for which site identification was initially uncertain, with these more often in patients who were male, older, and biopsied more than 30 days ago. Surgeons employed on average 5.0 (95% CI: 4.61-5.39) additional techniques to confirm the site location, with common approaches including: re-checking available documentation (90 lesions, 92%); performing an expanded physical examination (89 lesions, 91%); and asking the patient to point using a mirror (61 lesions, 62%). In 15%, photographs were requested from the biopsying provider, and also in 15%, frozen section biopsies were obtained. In 10%, the referring physician was contacted. Eventually, surgeons succeeded in definitively identifying 82% (80/98) of initially uncertain sites, with the remaining 18% (18/98) postponed. Most postponed surgeries were at non-facial sites. LIMITATIONS: Sites were academic centers. CONCLUSIONS: When the anatomic location of the tumor is uncertain, dermatologic surgeons use multiple methods to identify the site, and sometimes cases are postponed.

Chronic kidney disease prevalence and clinical outcomes in anterior circulation acute ischemic stroke patients with reperfusion therapy: A meta-analysis.

AIM: Chronic Kidney Disease (CKD) is a common comorbidity among acute ischaemic stroke (AIS) patients undergoing reperfusion therapies, including intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT). Acknowledging CKD's prevalence in this cohort and understanding its influence on outcomes is crucial for prognosis and optimizing care. This study aims to determine the prevalence of CKD among anterior circulation AIS (acAIS) patients undergoing reperfusion therapies and to analyse the role of CKD in mediating outcomes. METHODS: A random-effects meta-analysis was conducted to pool and examine prevalence data. A total of 263 633 patients were included in the meta-analysis. The study assessed CKD's association with functional outcomes, symptomatic intracranial haemorrhage (sICH) and mortality. RESULTS: The overall pooled prevalence of CKD among acAIS ranged from 30% to 56% in IVT-treated patients and 16%-42% for EVT-treated patients. CKD was associated with increased odds of unfavourable functional outcome at 90 days in both IVT (OR 1.837; 95% CI: [1.599; 2.110]; p < .001) and EVT (OR 1.804; 95% CI: [1.525; 2.133]; p < .001) groups. In IVT-treated patients, CKD was associated with increased odds of 30-day mortality (OR 6.211; 95% CI: [1.105; 34.909]; p = .038). CKD in IVT-treated patients exhibited increased odds of sICH, albeit statistically non-significant (OR 1.595; 95% CI: [0.567; 3.275]). CONCLUSIONS: The high prevalence of CKD and its significant impact on outcomes in acAIS patients treated with reperfusion therapies underscore its clinical significance. This insight can guide personalised care strategies and potentially improve the prognosis in the management of acAIS.

Environmental factors associated with Oncomelania hupensis lindoensis snails in a schistosomiasis-endemic area in Napu, Central Sulawesi.

The presence of the freshwater snail Oncomelania hupensis lindoensis in their habitats is influenced by abiotic environmental factors (nutrients, water salinity, and predators) that play a crucial role in maintaining snail survival. The objective of this study is to determine the relationship between environmental factors and the presence of O. hupensis lindoensis snails in the Napu Valley, one of the Schistosomiasis-endemic areas in Indonesia. Eight environmental factors were measured in three different habitats: a seepage, a ditch, and a pond. The study found O. hupensis lindoensis snails in all three habitats, with significant differences in their numbers (p < 0.05). The seepage habitat had the highest snail density (762.22 snails per m2) compared to the other habitats. Phosphorus levels were highest in the seepage habitat compared to the other habitats, while nitrogen levels were highest in the pond habitat. Pearson correlation analysis found a significant positive correlation between O. hupensis lindoensis snails and water salinity in the ditch habitat (p < 0.05). In addition to environmental factors, the presence of snails can also be influenced by other factors, such as the presence of snail predators, the presence of snail nutrients, and the population of snail host niche competitors.

Clinical and Optical Coherence Tomography Correlation of Vascular Conditions Treated With a Novel, Variable-Sequenced, Long-Pulsed, 532 and 1,064 nm Laser With Cryogen Spray Cooling.

BACKGROUND: Patients frequently seek laser treatment for vascular conditions. More recently, a novel 532 and 1,064 nm laser was developed to offer greater flexibility. OBJECTIVE: A prospective clinical trial evaluated the safety and efficacy of a novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling (DermaV, Lutronic, South Korea). MATERIALS AND METHODS: Subjects with vascular conditions were enrolled for laser treatments. Clinical evaluations and optical coherence tomography (OCT) imaging were performed. RESULTS: Thirteen subjects were enrolled. The mean age was 51.3 years, and 92.3% were women. Fitzpatrick skin types I-IV were included. Treatment indications included broken blood vessels, rosacea, port-wine birthmark, and spider angioma. For physician investigator grading, all subjects were graded as improved at both 30-day and 90-day follow-up. Blinded photographic review by 3 independent, blinded physicians had a mean of 89.7% of cases selected correctly with at least 2 of 3 in agreement for 100.0% of cases. Optical coherence tomography imaging showed significant reductions in vessel density ( p = .018) and diameter ( p = .003) of the superficial vascular plexus. No serious adverse events occurred. CONCLUSION: A novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling can safely and effectively improve vascular conditions and lesions as determined by both clinical and OCT evaluation.

Paired Treatment Using Radiofrequency Microneedling and 755-nm Picosecond Laser With Fractionated Lens Array for Facial Rejuvenation.

BACKGROUND: Patients frequently complain about fine lines, wrinkles, dyschromia, and photoaging, for which lasers and energy-based devices can treat each of these. Pairing various devices in a single treatment session can be safe and effective, but different technologies, mechanisms, histologies, parameters, and techniques must be considered. OBJECTIVE: To examine the utility of a paired treatment regimen using radiofrequency microneedling and 755-nm picosecond laser with fractionated lens array to improve the clinical appearance of facial wrinkles and photoaging. MATERIALS AND METHODS: A prospective clinical study investigated this paired treatment regimen using 4 monthly sessions. RESULTS: Twenty-five subjects were enrolled, while 18 subjects completed 3-month follow-up. The mean age was 54 years, and 92% were women. Fitzpatrick Skin Types I to IV were represented. Assessments compared baseline with the 3-month follow-up. Two of 3 blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 94.4% of cases. For physician Global Aesthetic Improvement Scale, 100% of subjects had clinical improvement. Overall, 88.9% of subjects were considered to be satisfied with their treatment. No serious or unanticipated adverse events occurred. CONCLUSION: Paired treatment using radiofrequency microneedling and 755-nm picosecond laser with fractionated lens array can safely and effectively improve facial wrinkles and photoaging.

755-nm Picosecond Laser With Diffractive Lens Array for Acne Scars in Fitzpatrick Skin Types V and VI.

BACKGROUND: Patients commonly complain about the appearance of acne scars. While various lasers and energy-based devices can offer clinical improvement, many of them are limited in treating patients with skin of color. Concerns exist regarding efficacy and safety, including risks of scarring, prolonged dyspigmentation, necrosis, and burns. OBJECTIVE: To examine the utility of a 755-nm picosecond laser with fractionated lens array in improving the clinical appearance of acne scars in patients with Fitzpatrick skin types V and VI. MATERIALS AND METHODS: A prospective clinical study investigated this laser using up to 5 monthly treatments. RESULTS: Twenty-four subjects were enrolled, while 17 subjects completed a 3-month follow-up. The mean age was 33.9 years, and 95.8% of the subjects were women. Fitzpatrick skin types V and VI were represented. Assessments compared baseline to 3-month follow-up. Two of the 3 blinded reviewers agreed on identifying pretreatment and post-treatment photographs for 82.4% of the cases. For physician Global Aesthetic Improvement Scale, 100% of the subjects had clinical improvement. Overall, 94.1% of subjects were satisfied with their treatment. No serious or unanticipated adverse events occurred. CONCLUSION: A 755-nm picosecond laser with fractionated lens array can safely and effectively improve acne scars in patients with Fitzpatrick skin types V and VI.

High-Intensity, High-Frequency, Parallel Ultrasound Beams for Cellulite of the Buttocks and Thighs.

BACKGROUND: Ultrasound energy can successfully treat fine lines and wrinkles, as well as lift the eyebrow and submentum. Ultrasound waves of high intensity induce thermal injury in the dermis with subsequent tissue remodeling. OBJECTIVE: To examine the utility of a novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams to improve the clinical appearance of cellulite on the thighs and buttocks. MATERIALS AND METHODS: A prospective, multicenter, clinical study investigated this novel ultrasound device using 2 treatments. RESULTS: Sixty-five subjects completed both treatments. The mean age was 46 years, and 100% were women. Fitzpatrick skin types I to VI were represented. Assessments compared 3-month follow-up with baseline. Two blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 89.2%. For Cellulite Severity Scale rating, there was significant improvement of 1.61 units ( p < .001). For cellulite Global Aesthetic Improvement Scale (GAIS), 89.2% had improvement, with a mean of 0.87 units ( p < .001). For Laxity Scale rating, there was significant improvement of 0.70 units ( p < .001). For skin laxity GAIS, 89.2% had improvement, with a mean of 0.76 units ( p < .001). No device-related adverse events occurred. CONCLUSION: A novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams can safely and effectively improve the clinical appearance of cellulite on the thighs and buttocks.

Clinical Efficacy and Safety of a Thermomechanical Fractional Injury Device for Neck Rejuvenation.

BACKGROUND: Neck rejuvenation has consistently become a popular cosmetic procedure. While various treatment modalities have been used, a novel fractional thermomechanical skin rejuvenation system was recently developed to create dermal coagulation through direct heat transfer with subsequent neocollagenesis. OBJECTIVE: A prospective clinical trial evaluated the efficacy and safety of a thermomechanical fractional injury device (Tixel 2, Novoxel, Netanya, Israel) for neck rhytides. MATERIALS AND METHODS: Subjects with moderate to severe neck rhytides were enrolled for 4 monthly treatments. RESULTS: Twenty-six subjects were enrolled and completed all study visits. The mean age was 58.4 years, and 100.0% were women. Fitzpatrick skin types I to IV were included. For Fitzpatrick Wrinkle Classification System (FWCS), the mean baseline score was 6.3. As per investigator, there was a mean 1.5-grade improvement in FWCS at 1-month follow-up (p < .00001) and 1.4-grade improvement in FWCS at 3-month follow-up (p < .00001). For physician Global Aesthetic Improvement Scale, all subjects (100%) had improvement at both 1- and 3-month follow-up visits. There were no severe adverse events, and subjects experienced minimal pain. CONCLUSION: A novel thermomechanical fractional injury device is effective and safe for the treatment of neck rhytides.

Extension Phase of a Multi-Center, Randomized, Blinded Clinical Study Evaluating the Efficacy and Safety of a Novel Topical Product for Facial Dyschromia.

BACKGROUND: Dyschromia can be associated with increased production and/or reduced clearance of pigmentation in the skin. Multiple pathways are involved in causality. A novel topical product was recently developed, which contains actives that have been validated through in-vitro and clinical studies to counteract pigmentation related to photodamage, PIH, and melasma. This study further evaluates the safety and efficacy of this product for facial dyschromia during an additional 3-month extension period following the completion of the previous 12-week multi-center trial.  Study Design: Subjects from the previous multi-center trial with mild to severe facial dyschromia at baseline were eligible to participate in this 3-month extension study upon completion of that trial. This extension study evaluated the continued use of the novel topical product with PATH-3 Technology (Alastin Skincare, Carlsbad, CA) over a 3-month period. Subjects who were previously randomized to the novel topical product continued using it and for those previously randomized to hydroquinone 4% discontinued its use. Both cohorts continued daily sunscreen use. Blinded investigators assessed subjects at follow-up visits at 16, 20, and 24 weeks. RESULTS: Twenty-six (26) subjects completed the extension phase of the pivotal trial, with 13 subjects in each of the AL and HQ-BREAK cohorts. Significant improvements were seen within the AL cohort from weeks 12 to 24 for facial dyschromia (P=0.0158) and skin tone/clarity/evenness (P=0.0067), while there were no significant improvements seen in the HQ-BREAK cohort. The HQ-BREAK cohort had more subjects who worsened with facial dyschromia and skin tone/clarity/evenness. For the mMASI, the HQ-BREAK cohort demonstrated regression at week 24 compared to week 12, while the AL cohort instead experienced continued improvement. This difference was found to be significant (P=0.02). No study-related adverse events were reported for either cohort.  Conclusion: A novel topical product designed to counteract various steps in pigmentation pathways using PATH-3 Technology has been demonstrated to be safe and effective in treating facial dyschromia on a long-term basis. In contrast to the significant rebound experienced by subjects with HQ, the AL cohort continued to demonstrate ongoing improvement. J Drugs Dermatol. 2024;23(1):1266-1270.     doi:10.36849/JDD.7622.

Forensic neuropsychiatric aspects of epilepsy.

Epilepsy may be associated with automatisms that are classed as 'insane 'as they are deemed to have originated within the mind. 'Sane automatism' is said to occur from external factors, such as physical trauma, while 'insane automatism' is said to be innate to the individual experiencing them. To claim automatism within the context of a criminal matter requires a detailed evaluation of the behavior demonstrated and a questioning of the volitional and purposeful nature of this behavior. It is insufficient to rely upon past behavior in association with these seizures to justify the defense of automatism within a specific event. Epilepsy is often considered to be associated with an increase in violence. Proper epidemiological research, both in long-term, large population control studies and hospital-based studies, has suggested that epilepsy, per se, is not associated with an increase in violence when compared to the population at large and controlled for other familial and environmental factors.

Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial.

Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates. Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo. Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation. Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days. Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL. Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen. Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04291508.

A decade-long analysis of gender, race, and ethnic representation of incoming cardiothoracic anesthesiology fellows.

PURPOSE OF REVIEW: This study calls attention to the necessity for increasing representation of minority groups among cardiothoracic fellowship programs. RECENT FINDINGS: Demographics in medicine are changing, with more women and varying ethnicities contributing to the physician pool. Despite this change, diversity among cardiothoracic anesthesia fellows has not mirrored this trend. SUMMARY: In November of 2022, medical student, anesthesia resident and cardiothoracic fellow demographics were analyzed from 2011 to 2021 to assess the changes in program diversity. Although male and female individuals have relatively similar representation in medical schools, female individuals only represent 34.8% of total US anesthesia residents. Cardiothoracic anesthesia fellowship programs continue to be male-sex dominant and white racial representation has consistently made up a majority of the total trainees. Increasing diversity amongst healthcare providers increases the likelihood of providing culturally competent care, thereby decreasing the healthcare gap in minority communities.

Prevalence of swallowing difficulties and associated factors in older people with intellectual disabilities.

BACKGROUND: We investigated the prevalence of swallowing difficulties and associated factors in people with intellectual disability. METHODS: We included people aged 50+ receiving care for people with intellectual disabilities. The Dysphagia Disorder Survey (DDS) was used to assess swallowing difficulties. We determined the agreement between the DDS and swallowing difficulties in medical records. We used logistic regression analyses to explore associated factors. RESULTS: One thousand and fifty people were included. The prevalence of swallowing difficulties was 43.8%. Swallowing difficulties were not reported in the medical records of 83.3% of these cases. Frailty (odds ratio (OR) = 4.22, 95% CI = 2.05-8.71), mobility impairment (OR = 2.50, 95% CI = 1.01-6.19), and mealtime dependency (OR = 3.05, 95% CI = 1.10-8.47) were independently associated with swallowing difficulties. CONCLUSION: Swallowing difficulties are prevalent in older people with intellectual disability but may be under-recognised. Frailty may be a good indicator for population-based screening for swallowing difficulties.

Analysis of Part 1 of the latest Austroads Guidelines, June 2022.

The Austroads Fitness to Drive Guidelines were updated in 2022. Most of the focus to date has been on Part 2 of the Guidelines, which provide guidance as to specific medical conditions. Less attention has been paid to Part 1 of the Guidelines, which cover a medical practitioner's ethical and legal obligations. This paper addresses the imbalance by considering and amplifying the obligations discussed in Part 1 of the Guidelines.