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PURPOSE: The Area Deprivation Index (ADI) ranks neighborhoods by deprivation based on US Census data. This study utilizes ADI scores to investigate the impact of neighborhood deprivation on complication rates following breast reconstruction. PATIENTS AND METHODS: Patients who received implant-based reconstruction from 2019 to 2023 were identified at a single institution in New York. Patients were linked to a state-specific ADI score and categorized into groups: "High ADI" (6-10) and "Low ADI" (1-5). Patient characteristics and complication rates were compared between the ADI groups with Chi-Square analysis and t-tests. The predictive value of ADI scores on complication rates was assessed using logistic regression models. RESULTS: In total, 471 patients were included, of which 16% (n = 73) were in the High ADI group, and 84% (n = 398) were in the Low ADI group. There were no baseline differences between the 2 groups, except that there were more patients of Hispanic descent in the High ADI group (30% vs. 15%, P < .01). The High ADI group had a higher overall complication rate than the Low ADI group (34% vs. 21%, P < .01), as well as higher individual rates of hematoma (12% vs. 3%, P < .01) and unexpected reoperations (18% vs. 7%, P < .01). After adjusting for differences in race, High ADI scores predicted hematoma, reoperations, and any complication (P < .05). CONCLUSION: Patients living in neighborhoods with high ADI had a higher incidence of postoperative complications, independent of comorbidities and race. This measure of disparity should be considered when counselling patients about their risk of complications following procedures like implant-based breast reconstruction.
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IMPORTANCE: The lack of underrepresented in medicine physicians in academic plastic surgery has been a topic of interest for many years, and accordingly outreach has been undertaken to address the pipeline from medical school to residency and beyond. OBJECTIVE: This study aims to assess and identify the characteristics associated with plastic surgery match success for underrepresented in medicine applicants. DESIGN: Residency application data for first time, US allopathic medical school seniors from the 2017-2018 to 2021-2022 applicant cycles were abstracted from Electronic Residency Application Service applications, and match results were determined using the National Residency Matching Program database and online public sources. Data included self-reported race, and multiple application characteristics. Multivariable logistic regression of application characteristics were used to assess the relationship between underrepresented in medicine status and successfully matching. Binary logistic regression was used in subgroup analyses of each application characteristic, and interactions regression was used to evaluate the relative weight of each characteristic on successfully matching. RESULTS: Underrepresented in medicine applicants were 57% less likely to match than non-underrepresented in medicine applicants (OR 0.43, pâ¯=â¯0.001), though they were 60% less likely to match (ORadj 0.4, pâ¯=â¯0.216) when adjusted. Subgroup analysis revealed that odds of matching as an underrepresented in medicine applicant were significantly increased if the applicant had a home program, took a research year, and had an increased number of published research and presentations (ORs 0.43-0.48, all p < 0.05). Odds of matching as an underrepresented in medicine applicant were significantly decreased if the applicant went to a medical school ranked in the highest or lowest third (ORs 0.41-0.42, all p < 0.01); however, on interaction regression the odds of matching from a highly ranked medical school was increased (OR 3.5, 95% CI 0.98-12.55, pâ¯=â¯0.05). CONCLUSIONS: The likelihood of matching as an underrepresented in medicine applicant is lower than the rest of the applicant population, and there are no individual applicant characteristics that can increase these odds to equal that of the general applicant population.
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Internato e Residência , Cirurgia Plástica , Humanos , Internato e Residência/estatística & dados numéricos , Masculino , Feminino , Cirurgia Plástica/educação , Cirurgia Plástica/estatística & dados numéricos , Estados Unidos , Escolha da Profissão , Grupos Minoritários/estatística & dados numéricos , Adulto , Faculdades de Medicina/estatística & dados numéricos , Seleção de Pessoal/estatística & dados numéricosRESUMO
Previous cross-sectional studies suggest that birth weight (BW) is associated with aggression-, social- and attention problems differently in boys and girls. We sought to test if these differences could be confirmed in a longitudinal study. The 1989 Raine Study provided prospectively collected data on perinatal variables and repeated child behaviour checklist assessments from ages 5 to 17. Linear mixed effects models provided crude and adjusted relationships between BW and childhood behaviour at a conservative significance threshold using prenatal maternal covariables in adjusted models. Sensitivity analyses included an age10 teacher assessment. Data on behaviour, BW and sex, was available in 2269 participants. Male sex was associated with increased aggression problems at lower BW compared to females in the crude model (Interaction B: -0.436, 98.3%CI: [-0.844, -0.0253]), but not the adjusted model (Interaction B: -0.310, 98.3%CI: [-0.742, 0.140]). Male sex was associated with increased attention problems at lower BW compared to females in both the crude model (Interaction B: -0.334, 98.3%CI: [-0.530, -0.137]) and the adjusted model (Interaction B: -0.274, 98.3%CI: [-0.507, -0.0432]). Male sex was associated with increased social problems at lower BW compared to females in both the crude model (Interaction B: -0.164, 98.3%CI: [-0.283, -0.0441]) and the adjusted model (Interaction B: -0.148, 98.3%CI: [-0.285, -0.00734]). Using repeated measures from ages 5-17 we were able to show a crude and adjusted male vulnerability to lower BW in the development of attention problems and social problems. We did not find a BW x sex interaction for the development of aggressive behaviour.
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Background: Transcranial direct current stimulation (tDCS) is considered a potential therapeutic instrument for Alzheimer's disease (AD) because it affects long-term synaptic plasticity through the processes of long-term potentiation and long-term depression, thereby improving cognitive ability. Nevertheless, the efficacy of tDCS in treating AD is still debated. Dorsal lateral prefrontal cortex is the main role in executive functions. Objective: We investigate the cognitive effects of tDCS on AD patients. Methods: Thirty mild AD patients aged 66-86 years (meanâ=â75.6) were included in a double-blind, randomized, sham-controlled crossover study. They were randomly assigned to receive 10 consecutive daily sessions of active tDCS (2âmA for 30âmin) or a sham intervention and switched conditions 3 months later. The anodal and cathodal electrodes were placed on the left dorsal lateral prefrontal cortex and the right supraorbital area, respectively. Subjects underwent various neuropsychological assessments before and after the interventions. Results: The results showed that tDCS significantly improved Cognitive Abilities Screening Instrument scores, especially on the items of "concentration and calculation", "orientation", "language ability", and "categorical verbal fluency". Mini-Mental State Examination and Wisconsin Card Sorting Test scores in all domains of "concept formation", "abstract thinking", "cognitive flexibility", and "accuracy" also improved significantly after tDCS. For the sham condition, no difference was found between the baseline scores and the after-intervention scores on any of the neuropsychological tests. Conclusion: >: Using tDCS improves the cognition of AD patients. Further large size clinical trials are necessary to validate the data.
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Doença de Alzheimer , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Córtex Pré-Frontal Dorsolateral , Doença de Alzheimer/terapia , Estudos Cross-Over , Cognição , Método Duplo-Cego , Córtex Pré-Frontal/fisiologiaRESUMO
Quality indicators in kidney transplants are needed to identify care gaps and improve access to transplants. We used linked administrative health care databases to examine multiple ways of defining pre-emptive living donor kidney transplants, including different patient cohorts and censoring definitions. We included adults from Ontario, Canada with advanced chronic kidney disease between January 1, 2013, to December 31, 2018. We created 4 unique incident patient cohorts, varying the eligibility by the risk of progression to kidney failure and whether individuals had a recorded contraindication to kidney transplant (eg, home oxygen use). We explored the effect of 4 censoring event definitions. Across the 4 cohorts, size varied substantially from 20 663 to 9598 patients, with the largest reduction (a 43% reduction) occurring when we excluded patients with ≥1 recorded contraindication to kidney transplantation. The incidence rate (per 100 person-years) of pre-emptive living donor kidney transplant varied across cohorts from 1.02 (95% CI: 0.91-1.14) for our most inclusive cohort to 2.21 (95% CI: 1.96-2.49) for the most restrictive cohort. Our methods can serve as a framework for developing other quality indicators in kidney transplantation and monitoring and improving access to pre-emptive living donor kidney transplants in health care systems.
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Transplante de Rim , Doadores Vivos , Indicadores de Qualidade em Assistência à Saúde , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Seguimentos , Prognóstico , Ontário , Fatores de Risco , Falência Renal Crônica/cirurgia , Sobrevivência de Enxerto , Taxa de Filtração Glomerular , IdosoRESUMO
Purpose of program: A key barrier to becoming a living kidney donor is an inefficient evaluation process, requiring more than 30 tests (eg, laboratory and diagnostic tests), questionnaires, and specialist consultations. Donor candidates make several trips to hospitals and clinics, and often spend months waiting for appointments and test results. The median evaluation time for a donor candidate in Ontario, Canada, is nearly 1 year. Longer wait times are associated with poorer outcomes for the kidney transplant recipient and higher health care costs. A shorter, more efficient donor evaluation process may help more patients with kidney failure receive a transplant, including a pre-emptive kidney transplant (ie, avoiding the need for dialysis). In this report, we describe the development of a quality improvement intervention to improve the efficiency, effectiveness, and patient-centeredness of the donor candidate evaluation process. We developed a One-Day Living Kidney Donor Assessment Clinic, a condensed clinic where interested donor candidates complete all testing and consultations within 1 day. Sources of information: The One-Day Living Kidney Donor Assessment Clinic was developed after performing a comprehensive review of the literature, receiving feedback from patients who have successfully donated, and meetings with transplant program leadership from St. Joseph's Healthcare Hamilton. A multistakeholder team was formed that included health care staff from nephrology, transplant surgery, radiology, cardiology, social work, nuclear medicine, and patients with the prior lived experience of kidney donation. In the planning stages, the team met regularly to determine the objectives of the clinic, criteria for participation, clinic schedule, patient flow, and clinic metrics. Methods: Donor candidates entered the One-Day Clinic if they completed initial laboratory testing and agreed to an expedited process. If additional testing was required, it was completed on a different day. Donor candidates were reviewed by the nephrologist, transplant surgeon, and donor coordinator approximately 2 weeks after the clinic for final approval. The team continues to meet regularly to review donor feedback, discuss challenges, and brainstorm solutions. Key findings: The One-Day Clinic was implemented in March 2019, and has now been running for 4 years, making iterative improvements through continuous patient and provider feedback. To date, we have evaluated more than 150 donor candidates in this clinic. Feedback from donors has been uniformly positive (98% of donors stated they were very satisfied with the clinic), with most noting that the clinic was efficient and minimally impacted work and family obligations. Hospital leadership, including the health care professionals from each participating department, continue to show support and collaborate to create a seamless experience for donor candidates attending the One-Day Clinic. Limitations: Clinic spots are limited, meaning some interested donor candidates may not be able to enter a One-Day Clinic the same month they come forward. Implications: This patient-centered quality improvement intervention is designed to improve the efficiency and experience of the living kidney donor evaluation, result in better outcomes for kidney transplant recipients, and potentially increase living donation. Our next step is to conduct a formal evaluation of the clinic, measuring qualitative feedback from health care professionals working in the clinic and donor candidates attending the clinic, and measuring key process and outcome measures in donor candidates who completed the one-day assessment compared with those who underwent the usual care assessment. This program evaluation will provide reliable, regionally relevant evidence that will inform transplant centers across the country as they consider incorporating a similar one-day assessment model.
Objectifs du programme: Devenir donneur de rein vivant est difficile, le principal obstacle étant le processus d'évaluation inefficace auquel les candidats doivent se soumettre. Ce processus comporte plus de 30 examens (p. ex. tests de laboratoire et tests diagnostiques), questionnaires et consultations avec des spécialistes. Les candidats donneurs font plusieurs visites dans les hôpitaux et cliniques, et passent souvent plusieurs mois à attendre des rendez-vous et des résultats de tests. En Ontario (Canada), le délai médian pour l'évaluation d'un candidat au don est de près d'un an. Les temps d'attente plus longs sont associés à de moins bons résultats pour les receveurs d'une greffe rénale, ainsi qu'à des coûts de soins de santé plus élevés. Un processus d'évaluation plus court et plus efficace des donneurs potentiels permettrait à un plus grand nombre de patients atteints d'insuffisance rénale de recevoir une greffe, y compris une greffe préventive (c.-à-d. permettant d'éviter la dialyse). Cet article décrit une intervention d'amélioration de la qualité visant à augmenter l'efficience, l'efficacité et la personnalisation du processus d'évaluation des candidats au don. Nous avons développé une clinique d'un jour pour l'évaluation des donneurs de reins vivants (One-Day Living Kidney Donor Assessment Clinic), soit une clinique condensée où les candidats passent tous les tests et consultent un spécialiste dans la même journée. Sources de l'information: La clinique d'un jour pour l'évaluation des donneurs de reins vivants a été développée à la suite d'un examen approfondi de la littérature, de la consultation des commentaires de patients ayant donné avec succès et de rencontres avec les dirigeants du programme de transplantation du St Joseph's Healthcare d'Hamilton. Une équipe multipartite a été formée; celle-ci réunit du personnel soignant en néphrologie, chirurgie de transplantation, radiologie, cardiologie, travail social et médecine nucléaire, ainsi que des patients ayant une expérience vécue du don de rein. L'équipe s'est réunie régulièrement pendant les étapes de planification pour déterminer les objectifs, les paramètres et le calendrier de la clinique, ainsi que les critères de participation et le flux de patients. Méthodologie: Les donneurs potentiels qui avaient complété les tests de laboratoire initiaux et qui acceptaient de se soumettre à un processus accéléré ont été évalués à la clinique d'un jour. Si des tests supplémentaires étaient nécessaires, ceux-ci étaient effectués un autre jour. Les candidats ont été rencontrés par le néphrologue, le chirurgien de transplantation et le coordonnateur des dons environ deux semaines après leur visite à la clinique pour l'approbation finale. L'équipe multipartite continue de se réunir régulièrement pour examiner les commentaires des donneurs, discuter des défis et trouver des solutions. Principaux résultats: La clinique d'un jour, mise sur pied en mars 2019, est en activité depuis quatre ans et permet des améliorations itératives grâce à la rétroaction continue des patients et des soignants. À ce jour, plus de 150 candidats au don ont été évalués à la clinique. Les commentaires des donneurs sont quasi unanimement positifs (98 % des candidats ont déclaré être très satisfaits de la clinique), la plupart soulignant l'efficacité de la clinique et les conséquences minimes du processus sur les obligations professionnelles et familiales. La direction de l'hôpital, tout comme les professionnels de la santé des services participants, continue d'appuyer la clinique d'un jour et de collaborer à la création d'une expérience fluide pour les donneurs potentiels qui la fréquentent. Limites: Les places à la clinique sont limitées; ainsi, certains candidats au don d'un rein vivant pourraient ne pas pouvoir être admis dans le mois où ils se présentent à la clinique. Conclusion: Cette intervention d'amélioration de la qualité axée sur les patients est conçue pour augmenter l'efficacité du processus d'évaluation et bonifier l'expérience des donneurs de rein vivants. Elle vise également à améliorer les résultats des receveurs d'une greffe rénale et, potentiellement, augmenter le don vivant. La prochaine étape sera une évaluation formelle de la clinique, c'est-à-dire la mesure de la rétroaction qualitative des professionnels de la santé qui y travaillent et des candidats au don qui la fréquentent, et l'analyse des processus clés et des résultats des candidats évalués à la clinique d'un jour par rapport à ceux qui suivent le processus d'évaluation habituel. Cette évaluation du programme fournira des données probantes fiables et propres à la région qui pourront informer les centres de transplantation de tout le pays qui envisagent d'intégrer un processus d'évaluation similaire.
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Rationale & Objective: Chronic kidney disease is associated with significant morbidity and mortality in the general population, but little is known about the incidence and risk factors associated with developing low estimated glomerular filtration rate (eGFR) and moderate-severe albuminuria in living kidney donors following nephrectomy. Study Design: Retrospective, population-based cohort study. Setting & Participants: Kidney donors in Alberta, Canada. Exposure: Donor nephrectomy between May 2001 and December 2017. Outcome: Two eGFR measurements <45 mL/min/1.73 m2 or 2 measurements of moderate or severe albuminuria from 1-year postdonation onwards that were at least 90 days apart. Analytical Approach: Associations between potential risk factors and the primary outcome were assessed using Cox proportional hazard regression analyses. Results: Over a median follow-up period of 8.6 years (IQR, 4.7-12.6 years), 47 of 590 donors (8.0%) developed sustained low eGFR or moderate-severe albuminuria with an incidence rate of 9.2 per 1,000 person-years (95% confidence interval, 6.6-11.8). The median time for development of this outcome beyond the first year after nephrectomy was 2.9 years (IQR, 1.4-8.0 years). Within the first 4 years of follow-up, a 5 mL/min/1.73 m2 lower predonation eGFR increased the hazard of developing postdonation low eGFR or moderate-severe albuminuria by 26% (adjusted HR, 1.26; 95% CI, 1.10-1.44). Furthermore, donors were at higher risk of developing low eGFR or albuminuria if they had evidence of predonation hypertension (adjusted HR, 2.52; 95% CI, 1.28-4.96) or postdonation diabetes (adjusted HR, 4.72; 95% CI, 1.54-14.50). Limitations: We lacked data on certain donor characteristics that may affect long-term kidney function, such as race, smoking history, and transplant-related characteristics. Conclusions: A proportion of kidney donors at an incidence rate of 9.2 per 1,000 person-years will develop low eGFR or albuminuria after donation. Donors with lower predonation eGFR, predonation hypertension, and postdonation diabetes are at increased risk of developing this outcome.
The purpose of this study was to understand the risk of developing kidney disease in living kidney donors after donation. We followed 590 donors in Alberta, Canada for almost 9 years. Approximately 8% of donors developed reduced kidney function (low estimated glomerular filtration rate) or increased protein in the urine (albuminuria). Donors with lower kidney function before donation, hypertension before donation, or diabetes after donation had a higher likelihood of experiencing these kidney outcomes. This research provides important insights to patients and health care providers to better support the long-term kidney health of living kidney donors.
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STUDY OBJECTIVE: To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023. PATIENTS: Patients undergoing non-obstetric surgery. INTERVENTIONS: Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid. MEASUREMENT: We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function. MAIN RESULTS: We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min. CONCLUSIONS: The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.
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Antifibrinolíticos , Nefropatias , Ácido Tranexâmico , Humanos , Antifibrinolíticos/efeitos adversos , Creatinina , Hemorragia/prevenção & controle , Ácido Tranexâmico/efeitos adversosRESUMO
BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet score lowers blood pressure (BP). We examined interactions between genotype and the DASH diet score in relation to systolic BP. METHODS: We analyzed up to 9â 420â 585 single nucleotide polymorphisms in up to 127â 282 individuals of 6 population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (n=35â 660) and UK Biobank (n=91â 622) and performed European population-specific and cross-population meta-analyses. RESULTS: We identified 3 loci in European-specific analyses and an additional 4 loci in cross-population analyses at Pinteraction<5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency, 0.03) and the DASH diet score (Pinteraction=4e-8; P for heterogeneity, 0.35) in European population, where the interaction effect size was 0.42±0.09 mmâ Hg (Pinteraction=9.4e-7) and 0.20±0.06 mmâ Hg (Pinteraction=0.001) in Cohorts for Heart and Aging Research in Genomic Epidemiology and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P=4e-273) and cis-DNA methylation quantitative trait loci variants (P=1e-300). Although the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by single nucleotide polymorphisms potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSIONS: We demonstrated gene-DASH diet score interaction effects on systolic BP in several loci. Studies with larger diverse populations are needed to validate our findings.
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Abordagens Dietéticas para Conter a Hipertensão , Hipertensão , Humanos , Pressão Sanguínea/genética , Dieta , GenótipoRESUMO
BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.
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Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Adulto , Adolescente , Humanos , Criança , Pré-Escolar , Puberdade/genética , Fenótipo , Estatura/genética , Avaliação de Resultados em Cuidados de Saúde , Estudos LongitudinaisRESUMO
We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.
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BACKGROUND: A growing number of studies suggest that job loss has detrimental effects on cancer survivors. However, the underlying mechanisms are not well understood. Furthermore, minorities including Asian American cancer survivors remain understudied, yet they suffer from job loss more often. The present study examined the prevalence of job loss in Chinese American breast cancer survivors (CABCS) and investigated the relationship between job loss and well-being in this group and the underlying mechanisms. METHOD: CABCS completed a questionnaire that included demographic, employment, and clinical information, as well as measures of psychosocial well-being. Descriptive analyses were conducted to gauge the prevalence of job loss, linear regressions were used to test associations between job loss and well-being, and path analyses were conducted to test mediations. RESULTS: About 45.4% of survivors lost their job after being diagnosed with cancer, and only 35.2% of those who lost their job regained employment up to the assessment time. Job loss was associated with reduced income, which was associated with higher perceived stress, which, in turn, was associated with lower overall quality of life (QoL) and greater depressive symptoms. CONCLUSIONS: Findings highlight the high prevalence of job loss and its negative effects on QoL and depression among CABCS. It is important for health care professionals to be sensitive to adverse financial events affecting minority BCS. In addition to offering BCS necessary practical assistance, psychosocial interventions focusing on reducing perceived stress associated with the cancer experience may be effective in mitigating some long-term consequences of job loss.
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BACKGROUND: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta-genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). METHODS: We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months), and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism-based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. RESULTS: Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08-0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = -0.74), highlighting developmental heterogeneity. CONCLUSIONS: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.
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Transtorno do Deficit de Atenção com Hiperatividade , Alfabetização , Adolescente , Humanos , Lactente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Cognição , Estudo de Associação Genômica Ampla , Estudos Longitudinais , Fenótipo , VocabulárioRESUMO
Importance: Patients with advanced chronic kidney disease (CKD) have the best chance for a longer and healthier life if they receive a kidney transplant. However, many barriers prevent patients from receiving a transplant. Objectives: To evaluate the effect of a multicomponent intervention designed to target several barriers that prevent eligible patients from completing key steps toward receiving a kidney transplant. Design, Setting, and Participants: This pragmatic, 2-arm, parallel-group, open-label, registry-based, superiority, cluster randomized clinical trial included all 26 CKD programs in Ontario, Canada, from November 1, 2017, to December 31, 2021. These programs provide care for patients with advanced CKD (patients approaching the need for dialysis or receiving maintenance dialysis). Interventions: Using stratified, covariate-constrained randomization, allocation of the CKD programs at a 1:1 ratio was used to compare the multicomponent intervention vs usual care for 4.2 years. The intervention had 4 main components, (1) administrative support to establish local quality improvement teams; (2) transplant educational resources; (3) an initiative for transplant recipients and living donors to share stories and experiences; and (4) program-level performance reports and oversight by administrative leaders. Main Outcomes and Measures: The primary outcome was the rate of steps completed toward receiving a kidney transplant. Each patient could complete up to 4 steps: step 1, referred to a transplant center for evaluation; step 2, had a potential living donor contact a transplant center for evaluation; step 3, added to the deceased donor waitlist; and step 4, received a transplant from a living or deceased donor. Results: The 26 CKD programs (13 intervention, 13 usual care) during the trial period included 20â¯375 potentially transplant-eligible patients with advanced CKD (intervention group [n = 9780 patients], usual-care group [n = 10â¯595 patients]). Despite evidence of intervention uptake, the step completion rate did not significantly differ between the intervention vs usual-care groups: 5334 vs 5638 steps; 24.8 vs 24.1 steps per 100 patient-years; adjusted hazard ratio, 1.00 (95% CI, 0.87-1.15). Conclusions and Relevance: This novel multicomponent intervention did not significantly increase the rate of completed steps toward receiving a kidney transplant. Improving access to transplantation remains a global priority that requires substantial effort. Trial Registration: ClinicalTrials.gov Identifier: NCT03329521.
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Transplante de Rim , Insuficiência Renal Crônica , Humanos , Diálise Renal , Insuficiência Renal Crônica/cirurgia , Ontário , Rim , Análise de SistemasRESUMO
BACKGROUND: Nonunion is one of the most common and devastating complications following midfoot joint arthrodesis. Many different types of bone grafts and bone substitutes have been used to promote osseous fusion. However, there is no consensus on the gold standard bone grafting material and whether biologic materials should be used alone or in combination. The purpose of this study is to investigate the efficiency of highly porous ß-tricalcium phosphate (ß-TCP) with bone marrow aspirate concentrate (BMAC) in midfoot joint arthrodesis. METHODS: This retrospective comparative study included patients who underwent midfoot joint arthrodesis using compression screws. Patients were classified into 2 groups: arthrodesis with highly porous ß-TCP and BMAC (group A) and arthrodesis without them (group B). The osseous union rate was compared between the 2 groups. A total of 44 patients (46 feet) including 89 joints were included in this study. RESULTS: There was a significant difference in the union rate between the 2 groups: 91.5% (43/47 joints) in arthrodesis with highly porous ß-TCP and BMAC (group A) and 76.2% (32/42 joints) in arthrodesis without highly porous ß-TCP and BMAC (group B; P = .048). CONCLUSION: This study investigated the efficiency of highly porous ß-TCP and BMAC to promote bony healing in midfoot joint arthrodesis. A significantly higher union rate was shown when arthrodesis was performed with highly porous ß-TCP and BMAC, compared with arthrodesis performed without them. We suggest that highly porous ß-TCP and BMAC can be a viable and effective adjunct to the fixation in midfoot joint arthrodesis. LEVEL OF EVIDENCE: Level III: Retrospective comparative analysis.
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Objective: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP). Methods: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses. Results: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction < 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. Conclusion: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.
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Purpose: Changes in refractive error during young adulthood is common yet risk factors at this age are largely unexplored. This study explored risk factors for these changes, including gene-environmental interactions. Methods: Spherical equivalent refraction (SER) and axial length (AL) for 624 community-based adults were measured at 20 (baseline) and 28 years old. Participants were genotyped and their polygenic scores (PGS) for refractive error calculated. Self-reported screen time (computer, television, and mobile devices) from 20 to 28 years old were collected prospectively and longitudinal trajectories were generated. Past sun exposure was quantified using conjunctival ultraviolet autofluorescence (CUVAF) area. Results: Median change in SER and AL were -0.023 diopters (D)/year (interquartile range [IQR] = -0.062 to -0.008) and +0.01 mm/year (IQR = 0.000 to 0.026), respectively. Sex, baseline myopia, parental myopia, screen time, CUVAF, and PGS were significantly associated with myopic shift. Collectively, these factors accounted for approximately 20% of the variance in refractive error change, with screen time, CUVAF, and PGS each explaining approximately 1% of the variance. Four trajectories for total screen time were found: "consistently low" (n = 148), "consistently high" (n = 250), "consistently very high" (n = 76), and "increasing" (n = 150). Myopic shift was faster in those with "consistently high" or "consistently very high" screen time compared to "consistently-low" (P ≤ 0.031). For each z-score increase in PGS, changes in SER and AL increased by -0.005 D/year and 0.002 mm/year (P ≤ 0.045). Of the three types of screen time, only computer time was associated with myopic shift (P ≤ 0.040). There was no two- or three-way interaction effect between PGS, CUVAF, or screen time (P ≥ 0.26). Conclusions: Higher total or computer screen time, less sun exposure, and genetic predisposition are each independently associated with greater myopic shifts during young adulthood. Given that these factors explained only a small amount of the variance, there are likely other factors driving refractive error change during young adulthood.
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Miopia , Erros de Refração , Adulto , Humanos , Adulto Jovem , Predisposição Genética para Doença , Tempo de Tela , Luz Solar/efeitos adversos , Erros de Refração/genética , Miopia/genética , Túnica ConjuntivaRESUMO
Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.