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Pathogenic viruses in environmental water are usually present in levels too low for direct detection and thus, a concentration step is often required to increase the analytical sensitivity. The objective of this study was to evaluate an automated filtration device, the Innovaprep Concentrating Pipette Select (CP Select) for the rapid concentration of viruses in saline water samples, while considering duration of process and ease of use. Four bacteriophages (MS2, P22, Phi6, and PhiX174) and three animal viruses (adenovirus, coronavirus OC43, and canine distemper virus) were seeded in artificial seawater, aquarium water, and bay water samples, and processed using the CP Select. The recovery efficiencies of viruses were determined either using a plaque assay or droplet digital PCR (ddPCR). Using plaque assays, the average recovery efficiencies for bacteriophages ranged from 4.84 ± 3.8% to 82.73 ± 27.3%, with highest recovery for P22 phage. The average recovery efficiencies for the CP Select were 39.31 ± 26.6% for adenovirus, 19.04 ± 11.6% for coronavirus OC43, and 19.84 ± 13.6% for canine distemper virus, as determined by ddPCR. Overall, viral genome composition, not the size of the virus, affected the recovery efficiencies for the CP Select. The small sample volume size used for the ultrafilter pipette of the system hinders the use of this method as a primary concentration step for viruses in marine waters. However, the ease of use and rapid processing time of the CP Select are especially beneficial when rapid detection of viruses in highly contaminated water, such as wastewater or sewage-polluted surface water, is needed.
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Background: Diabetes mellitus is a common chronic metabolic disorder that is characterized by increased levels of glucose for prolonged periods of time. Incessant hyperglycemia leads to diabetic complications such as retinopathy, nephropathy, and neuropathy, and cardiovascular complications such as ischemic heart disease, peripheral vascular disease, diabetic cardiomyopathy, stroke, etc. There are many studies that suggest that various polyphenols affect glucose homeostasis and can help to attenuate the complications associated with diabetes. Objective: This review focuses on the possible role of various dietary polyphenols in palliating diabetes-induced cardiovascular complications. This review also aims to give an overview of the interrelationship among ROS production (due to diabetes), inflammation, glycoxidative stress, and cardiovascular complications as well as the anti-hyperglycemic effects of dietary polyphenols. Methods: Various scientific databases including Scopus, Web of Science, Google Scholar, PubMed, Science Direct, Springer Link, and Wiley Online Library were used for searching articles that complied with the inclusion and exclusion criteria. Results: This review lists several polyphenols based on various pre-clinical and clinical studies that have anti-hyperglycemic potential as well as a protective function against cardiovascular complications. Conclusion: Several pre-clinical and clinical studies suggest that various dietary polyphenols can be a promising intervention for the attenuation of diabetes-associated cardiovascular complications.
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INTRODUCTION: Body contouring procedures are commonly performed in the United States for patients seeking to sculpt specific areas of their bodies. The aim of this study was to provide an updated analysis of the factors that influence medical malpractice litigation surrounding body contouring surgery. METHODS: The following terms were used to search the Westlaw Campus Legal research Database for cases with earliest documentation after January 2013: ("contouring" OR "abdominoplasty" OR "liposuction" OR "tummy tuck" OR "body lift" OR "thigh lift" OR "arm lift" OR "brachioplasty" OR "thighplasty" OR "lipectomy" OR "panniculectomy") AND "surgery" AND "medical malpractice." Cases were only included if there was a complaint of medical malpractice subsequent to a body contouring procedure, and details of the cases were provided. Information was collected on the location of the lawsuit, the earliest year of available case documentation, patient demographics, procedure(s) performed, alleged injury, specialty involvement, and verdicts. RESULTS: A total of 32 cases were included in the study. Most of the patients involved in the cases were women (n = 30, 93.8%) and alive (n = 28, 87.5%). New York state had the most cases (n = 7, 21.9%). Abdominoplasty (56.3%), liposuction (53.1%), and buttock augmentations (15.6%) were the most common procedures. Plastic surgeons were involved in 93.8% (n = 30) of the cases, and anesthesia, emergency medicine, dermatology, and oncology were also involved. Claims of malpractice most often discussed negligent technique (71.9%) and poor postoperative management (62.5%). Common postoperative complications were infection/sepsis (40.6%), scarring (31.3%), and emotional distress/prolonged pain (31.3%). One available ruling was in favor of the plaintiff. CONCLUSION: Although many of the cases in this analysis cited negligent technique, none were founded in their argument. Because involvement in these cases can place a burden on attending physicians, clear expectations of postoperative infections, scarring, and prolonged pain should be addressed during the informed consent process.
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Contorneado Corporal , Mala Praxis , Cirujanos , Humanos , Femenino , Estados Unidos , Masculino , Contorneado Corporal/efectos adversos , Cicatriz , Dolor , Bases de Datos FactualesRESUMEN
The practice of outpatient medicine is demanding, encompasses a wide scope of practice, and leaves little time for internists to stay up to date with the current literature. This article reviews 5 studies published in 2022 and 2023 that have the potential to change the practice of outpatient medicine. Topics covered include chronic kidney disease, secondary cardiovascular disease, kidney stones, obesity, and lipid management.
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Atención Ambulatoria , Médicos , Humanos , Medicina Interna , Medicina Basada en la EvidenciaRESUMEN
OBJECTIVES: The recipient's gastroduodenal artery is often ligated before the hepatic artery anastomosis during orthotopic liver transplant, to gain either mobility or length of recipient's hepatic artery, potentially protecting the anastomosis by preventing "steal syndrome." In this study, our aim was to evaluate the consequences of gastroduodenal artery ligation and its effect on prevention of hepatic artery thrombosis. MATERIALS AND METHODS: We retrospectively analyzed deceased-donor orthotopic liver transplant procedures (n = 210) performed at a single center between January 2016 and July 2021 to compare outcomes between recipients with (group 1) and recipients without (group 2) gastroduodenal artery ligation. Group 1 included 78 patients (37%), in which the recipient's common hepatic artery was used for arterial anastomosis; group 2 included 132 patients (63%), in which the right hepatic artery orthe proper hepatic artery was used for arterial anastomosis. Occurrences of hepatic artery thrombosis, postoperative hyperamylasemia, nausea and vomiting, and delayed feeding were compared between the groups. RESULTS: There was no incidence of hepatic artery thrombosis reported in either group. In group 1, 31 patients (39.7%) were reported to have postoperative hyperamylasemia, ranging from 200 to 4700 U/L accompanied by delayed feeding, whereas, in group 2, only 16 of 132 patients (12%) had postoperative hyperamylasemia, ranging from 200 to 1400 U/L (P < .01). CONCLUSIONS: Ligation of recipient's gastroduodenal artery is not associated with decreased risk of hepatic artery thrombosis compared with nonligation. However, the procedure does have consequences in the form of possible postoperative hyperamylasemia, leading to delayed feeding probably due to decreased oral tolerance.
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Hiperamilasemia , Hepatopatías , Trasplante de Hígado , Trombosis , Humanos , Arteria Hepática/cirugía , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Estudios Retrospectivos , Hiperamilasemia/complicaciones , Hepatopatías/complicaciones , Trombosis/etiología , Trombosis/prevención & control , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodosRESUMEN
BACKGROUND: A frequently used feature of electronic patient portals is the viewing of test results. Research on patient portals is abundant and offers evidence to help portal implementers make policy and practice decisions. In contrast, no comparable comprehensive summary of research addresses the direct release of and patient access to test results. OBJECTIVE: This scoping review aims to analyze and synthesize published research focused on patient and health care provider perspectives on the direct release of laboratory, imaging, and radiology results to patients via web portals. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Searches were conducted in CINAHL, MEDLINE, and other databases. Citations were screened in Covidence using the inclusion and exclusion criteria. Primary studies that focused on patient and health care provider perspectives on patient access to laboratory and imaging results via web portals were included. An updated search was conducted up to August 2023. Our review included 27 articles-20 examining patient views, 3 examining provider views, and 4 examining both patient and provider views. Data extraction and inductive data analysis were informed by sensitizing concepts from sociomaterial perspectives, and 15 themes were generated. RESULTS: Patient perspectives (24 papers) were synthesized using nine themes: (1) patterns of use and patient characteristics; (2) emotional response when viewing the results and uncertainty about their implications; (3) understanding test results; (4) preferences for mode and timing of result release; (5). information seeking and patients' actions motivated by viewing results via a portal; (6) contemplating changes in behavior and managing own health; (7) benefits of accessing test results via a portal; (8) limitations of accessing test results via a portal; and (9) suggestions for portal improvement. Health care provider perspectives (7 papers) were synthetized into six themes: (1) providers' view of benefits of patient access to results via the portal; (2) effects on health care provider workload; (3) concerns about patient anxiety; (4) timing of result release into the patient portal; (5) the method of result release into the patient portal: manual versus automatic release; and (6) the effects of hospital health information technology system on patient quality outcomes. CONCLUSIONS: The timing of the release of test results emerged as a particularly important topic. In some countries, the policy context may motivate immediate release of most tests directly into patient portals. However, our findings aim to make policy makers, health administrators, and other stakeholders aware of factors to consider when making decisions about the timing of result release. This review is sensitive to the characteristics of patient populations and portal technology and can inform result release framework policies. The findings are timely, as patient portals have become more common internationally.
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Registros Electrónicos de Salud , Portales del Paciente , Humanos , Personal de Salud , Actitud del Personal de Salud , PacientesRESUMEN
Background: Evaluation of the efficacy and safety of mechanical ventilation settings is a cornerstone of the early phase of the management of acute respiratory distress syndrome (ARDS). This study aimed to evaluate the adherence to currently recommended lung-protective ventilator strategies (tidal volume, plateau pressure, driving pressure, prone positioning, and positive end-expiratory pressure [PEEP]) for adults with moderate-to-severe ARDS in a tertiary care setup, thereby evaluating if lung-protective ventilation is associated with improved outcomes. Methods: This was an observational study over 1 year in ventilated moderate-to-severe ARDS participants. All participants were mechanically ventilated when required using the protocol followed by the ARDS Network low-tidal volume lung-protective ventilation strategy and monitored. Results: The total number of participants in the study was 32. Septic shock was the most common cause of ARDS. The mean duration of intensive care unit (ICU) stay was 6.13 (±5.4) days, mean ventilator days were 3.66 (±3.75) days and mortality rate of 71.8%.Adherence to low-tidal volume was 78.12% with an improvement of 36% in the adherent group (P = 0.06). Adherence to high PEEP was 34.38% with a survival of 73% in the adherent group (P = 0.0004). Adherence to prone ventilation was 18.75% with a survival of 33% in the adherent group (P = 0.7). Conclusion: Intensivists should take an extra effort to focus on evidence-based ventilator strategies and increase adherence to these recommendations in their ICUs to improve patient survival.
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Hepatopulmonary syndrome (HPS) is a rare complication of liver disease characterized by intrapulmonary vascular dilatations leading to arterial hypoxemia. We present the case of a 59-year-old female with a past medical history of bilateral breast cancer status post mastectomy who presented with progressive dyspnea on exertion and fatigue. A comprehensive diagnostic workup was conducted to exclude other cardiac, pulmonary, and systemic etiologies. She was diagnosed with autoimmune hepatitis along with chronic hepatitis C. Echocardiography revealed characteristic findings of intrapulmonary shunting characteristic of HPS. The patient showed improvement in pulmonary symptoms and oxygenation status following the initiation of steroid therapy. Although corticosteroids are not the definitive treatment for HPS, they were considered a supportive measure in this case. However, it is important to note that liver transplantation remains the definitive treatment for HPS. This case underscores the importance of echocardiography and the potential role of supportive measures, like corticosteroids, in managing HPS-related symptoms, particularly in patients with autoimmune hepatitis, as a bridging therapy while awaiting liver transplantation.
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Obesity is increasingly prevalent among adolescents. Clinical and research data support the use of bariatric surgery (BS) as a treatment option for severely obese adolescents, with good results in terms of weight loss, improvement or resolution of comorbidities, and compliance to follow up. Nevertheless, concerns still remain, with significant disparities among countries and ethical concerns mainly raised by performing an irreversible and invasive procedure in adolescence, with potential life-long alterations. In this context, the purpose of this narrative review was to discuss the main current ethical challenges in performing BS in adolescence and to inform appropriate clinical management in the field. The core ethical principles of autonomy, beneficence, nonmaleficence, and justice were revised in terms of patient-centered healthcare through the lens of psychosocial implications. The review concludes with a discussion regarding the potential directives for future research for effective, patient-centered, and ethical management of obesity in the adolescent population.
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Cirugía Bariátrica , Obesidad Mórbida , Adolescente , Humanos , Obesidad Mórbida/cirugía , Obesidad/epidemiología , Comorbilidad , Pérdida de PesoRESUMEN
For the development and maintenance of neuron networks in the brain, epigenetic mechanisms are necessary, as indicated by recent findings. This includes some of the high-order brain processes, such as behavior and cognitive functions. Epigenetic mechanisms could influence the pathophysiology or etiology of some neuronal diseases, altering disease susceptibility and therapy responses. Recent studies support epigenetic dysfunctions in neurodegenerative and psychiatric conditions, such as Alzheimer's disease (AD). These dysfunctions in epigenetic mechanisms also play crucial roles in the transgenerational effects of the environment on the brain and subsequently in the inheritance of pathologies. The possible role of gonadal steroids in the etiology and progression of neurodegenerative diseases, including Alzheimer's disease, has become the subject of a growing body of research over the last 20 years. Recent scientific findings suggest that epigenetic changes, driven by estrogen and androgens, play a vital role in brain functioning. Therefore, exploring the role of estrogen and androgen-based epigenetic changes in the brain is critical for the deeper understanding of AD. This review highlights the epigenetic modifications caused by these two gonadal steroids and the possible therapeutic strategies for AD.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Andrógenos , Encéfalo , Cognición , EstrógenosRESUMEN
Diabetes insipidus (DI) is characterized by polyuria and polydipsia. In most cases, the condition results from either an inadequate release or resistance to the activity of antidiuretic hormone in the renal collecting tubules. The underlying pathophysiology may be related to destruction the destruction or degeneration of neurons from inflammatory, autoimmune diseases, vascular diseases, Langerhans cell histiocytosis, sarcoidosis, or trauma. However, a large majority of diabetes insipidus cases (50%) are considered idiopathic. An exceedingly rare cause of idiopathic central DI occurs in burn injuries, which has only been reported in eight cases. We present an extremely rare case of idiopathic DI in a 15-year-old male with 76% total body surface area (TBSA) burns with the development of idiopathic central DI. An extensive literature review was accomplished to compare this case with the small number of previously reported case reports of idiopathic DI in burn patients. Lay Summary: Diabetes insipidus (DI) is a rare complication of burn injuries that results from the destruction of neurons involved in the secretion of antidiuretic hormone from the pituitary gland. Only eight cases of DI have been reported in the literature in association to burn injuries. The patient in this case report received immediate fluid resuscitation, burn treatment, and intensive observation after the initial burn injury. The rapid response was likely the main reason for the absence of neurological damage as reported in the CT image. Therefore, the treatment of burn injuries remains an important step for reducing neurological damage and hormonal dysregulation leading to diabetes insipidus.
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Introduction: Diuretic use may reduce volume-related complications in hemodialysis. We evaluated the efficacy, safety, and tolerability of furosemide in patients with hemodialysis-dependent kidney failure. Methods: We conducted an open label, single-arm, 18-week, dose titration pilot study of oral furosemide (maximum dose 320 mg/day) among patients receiving maintenance hemodialysis who reported at least 1 cup of urine output per day. The primary efficacy outcome was an increase from baseline to a specified threshold of 24-hour urine volume, with the threshold based on baseline urine volume (<200 ml/day vs. ≥200 ml/day). Safety outcomes included hypokalemia and hypomagnesemia, and tolerability was assessed by prespecified patient-reported symptoms. Results: Of the 39 participants, 28 (72%) received the expected furosemide dose, 3 (8%) underwent dose reduction, 5 (12%) discontinued furosemide without dose reduction, and 3 (8%) underwent dose reduction and subsequently discontinued furosemide. The median (quartile 1, quartile 3) baseline 24-hour urine volume was 290 ml (110, 740), and the maximum, average daily study furosemide dose ranged from 69 mg/day to 320 mg/d. The urine output efficacy outcome was met by 12 (33%), 11 (33%), and 7 (22%) participants at weeks 5, 12, and 18, respectively, in the intention-to-treat analysis, and by 12 (39%), 9 (35%), and 7 (28%) participants at weeks 5, 12, and 18, respectively, in the on-treatment analysis. There were no electrolyte, furosemide level, or patient-reported hearing change safety events. Conclusion: Furosemide was generally safe and well tolerated, but only one-third of participants met the efficacy definition at week 5. The clinical importance of the efficacy findings is uncertain.
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BACKGROUND: Near the beginning of the COVID-19 pandemic in the United States, medical students were pulled out of all in-person patient care activities. This resulted in massive disruption to the required clinical rotations (clerkships), necessitating creative curricular solutions to ensure continued education for medical students. APPROACH: In response to the lockout, our school adopted a "flipped" clinical rotations model that assigned students to remote learning activities prior to in-person patient care activities. This approach allowed students to continue their clinical education virtually with a focus on knowledge for practice while awaiting return to the shortened in-person portions of their rotation. In planning the modified clinical curriculum, educational leaders adhered to several guiding principles including ensuring flexible remote curricular components that would engage students in active learning, designating that no rotation would be completely virtual, and completing virtual educational activities and standardised exams before students returned to in-person experiences. EVALUATION: End of rotation evaluations and standardised exam scores were analysed to determine the effectiveness of this model. Despite the disruption associated with the pandemic and the rapid implementation of the "flipped" rotations, students continued to rate the overall experiences as highly as traditional clinical rotations. Students also performed similarly on standardised exams when compared to cohorts from other classes at the same experience level. IMPLICATIONS: While borne out of necessity during a pandemic, the lessons learned from our implementation of a "flipped" rotations model can be applied to address problems of capacity and clinical preparedness in the clinical setting.
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COVID-19 , Estudiantes de Medicina , COVID-19/epidemiología , Curriculum , Humanos , Pandemias , Aprendizaje Basado en Problemas/métodos , Estados UnidosRESUMEN
Drug resistance by pathogenic microbes has emerged as a matter of great concern to mankind. Microorganisms such as bacteria and fungi employ multiple defense mechanisms against drugs and the host immune system. A major line of microbial defense is the biofilm, which comprises extracellular polymeric substances that are produced by the population of microorganisms. Around 80% of chronic bacterial infections are associated with biofilms. The presence of biofilms can increase the necessity of doses of certain antibiotics up to 1000-fold to combat infection. Thus, there is an urgent need for strategies to eradicate biofilms. Although a few physicochemical methods have been developed to prevent and treat biofilms, these methods have poor efficacy and biocompatibility. In this review, we discuss the existing strategies to combat biofilms and their challenges. Subsequently, we spotlight the potential of enzymes, in particular, polysaccharide degrading enzymes, for biofilm dispersion, which might lead to facile antimicrobial treatment of biofilm-associated infections.
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Antiinfecciosos , Biopelículas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , PolisacáridosRESUMEN
Identification and isolation of contagious individuals along with quarantine of close contacts, is critical for slowing the spread of COVID-19. Large-scale testing in a surveillance or screening capacity for asymptomatic carriers of COVID-19 provides both data on viral spread and the follow-up ability to rapidly test individuals during suspected outbreaks. The COVID-19 early detection program at Michigan State University has been utilizing large-scale testing in a surveillance or screening capacity since fall of 2020. The methods adapted here take advantage of the reliability, large sample volume, and self-collection benefits of saliva, paired with a cost-effective, reagent conserving two-dimensional pooling scheme. The process was designed to be adaptable to supply shortages, with many components of the kits and the assay easily substituted. The processes outlined for collecting and processing SARS-CoV-2 samples can be adapted to test for future viral pathogens reliably expressed in saliva. By providing this blueprint for universities or other organizations, preparedness plans for future viral outbreaks can be developed.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Prueba de COVID-19 , Humanos , Reproducibilidad de los Resultados , Saliva , Manejo de EspecímenesRESUMEN
BACKGROUND: Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a viable mean to obtain core tissue, but the optimal tools and techniques are still an area of active investigation. AIMS: (1) To compare tissue adequacy using "wet saline" (WS) vs. "wet heparin" (WH) technique (2) To compare post-procedure pain between EUS-LB and percutaneous liver biopsy (PLB). METHODS: Retrospective review of consecutive patients who underwent EUS-LB and PLB for benign parenchymal liver disease between May 2017 to October 2019 at a single tertiary veterans affairs medical center. RESULTS: About 257 biopsies from 217 patients were included. Among the 102 EUS-LB specimens, 53 were obtained using WS technique and 49 were obtained using WH technique. Specimen adequacy was similar in both groups. Median Aggregate Specimen Length (ASL) and length of longest piece did not differ significantly between WS and WH groups. Clots were present more frequently in the WS group. Among patients who underwent EUS-LB of both right and left liver lobes, an adequate biopsy was obtained in 85% of patients in the WS group and 96% of patients in the WH group. The percentage of patients experiencing immediate post-procedure pain was higher with PLB compared to EUS-LB, but these results were not statistically significant. CONCLUSIONS: Both WS and WH EUS-LB techniques can offer high rates of specimen adequacy with low rates of pain and other post-procedure complications.
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Hepatopatías , Humanos , Hepatopatías/diagnóstico por imagen , Hepatopatías/patología , Heparina , Estudios Prospectivos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Dolor , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Endosonografía/métodosRESUMEN
BACKGROUND: Coaching has been shown to improve resident well-being; however, not all benefit equally. OBJECTIVE: Assess predictors of changes in resident physician well-being and burnout in a multisite implementation of a Professional Development Coaching Program. DESIGN: Pre- and post-implementation surveys administered to participant cohorts at implementation sites in their intern year. Effect size was calculated comparing pre- and post-intervention paired data. PARTICIPANTS: In total, 272 residents in their intern year at five internal medicine residency programs (Boston Medical Center, University Hospitals Cleveland Medical Center, Duke University, Emory University, Massachusetts General Hospital). Analyses included 129 residents with paired data. INTERVENTIONS: Interns were paired with a faculty coach trained in positive psychology and coaching skills and asked to meet quarterly with coaches. MAIN MEASURES: Primary outcomes included Maslach Burnout Inventory depersonalization (DP) and emotional exhaustion (EE) subscales, and the PERMA well-being scale. Key predictors included site, demographics, intolerance of uncertainty, hardiness-resilience, gratitude, and coping. Program moderators included were reflection, goal setting, and feedback. KEY RESULTS: Well-being (PERMA) changed from baseline to follow-up in all participants; females showed a decline and males an increase (-1.41 vs. .83, p = 0.04). Self-reflection was associated with positive change in PERMA (mean positive change 1.93, p = 0.009). Burnout (EE) declined in non-Hispanic white residents vs. Black/Asian/Hispanic/other residents (-1.86, p = 0.021). Burnout improved with increased goal setting. CONCLUSION: Coaching programs should consider tailored approaches to support residents whose well-being is impacted by gender and/or race, and who have higher intolerance of uncertainty and lower resilience at baseline. Coaching skills of goal setting and reflection may positively affect interns and teach coping skills.
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Agotamiento Profesional , Internado y Residencia , Tutoría , Agotamiento Profesional/prevención & control , Agotamiento Profesional/psicología , Femenino , Humanos , Masculino , Massachusetts , Encuestas y CuestionariosRESUMEN
INTRODUCTION: A >25% increase in daily insulin dosing is suggestive of possible sepsis in burn patients, however, no conclusive evidence is available regarding the time point at which insulin dosing begins to increase. The purpose of this study is to determine the exact time point at which the insulin requirement increases among non-diabetic burn patients with sepsis. METHODS: A retrospective chart review in non-diabetic burn patients with ≥20% total body surface area burned (TBSA) during 2010-2018 who received a blood culture for suspected sepsis. Absolute insulin dosing at intervals (0, 24, 48, 72, and 96 h prior to blood culture) were Box-Cox transformed and compared vs.-96 h reference using mixed-effects models accounting for within-patient dependencies. RESULTS: Fifty-eight patients (84% males, age 44 ± 17 years, TBSA% 49 ± 17.5) were included. When cube root of daily insulin dosing was regressed on each time point in a mixed-effects model, statistically significant increase in insulin dosing compared to baseline was observed for -48 (p = 0.018), -24 (p = 0.011), and 0 h (p = 0.008). CONCLUSION: Daily insulin dosing increases 48 h prior to development of other clinical signs of sepsis and can be used as a sensitive early marker.