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BACKGROUND: There are persistent structural barriers that threaten inclusion and retention of underrepresented in medicine (UIM) residents and fellows (trainees) as future faculty in academic medicine. We developed the Leadership Education in Advancing Diversity (LEAD) Program at a single, academic institution, to address these barriers through a 10-month longitudinal curriculum across GME for trainees to develop leadership and scholarship skills in DEI. OBJECTIVE: Explore how participation in LEAD impacted UIM trainees' sense of belonging and professional identity formation in academic medicine; as well as perceptions about pursuing a career in academic medicine and future leadership roles. METHODS: IRB-approved qualitative study in August 2020-August 2021 with individual, semi-structured interviews of UIM LEAD graduates from the first 4 cohorts (2017-2021). Data were analyzed by two authors using modified grounded theory. RESULTS: 14 UIM trainees were interviewed; seven themes emerged. Critical aspects of the program: (1) Creation of a community of shared DEI values (2) Mentorship (3) Role of allies. Results of the program: (4) Deepened appreciation of personal and professional identity as UIM (5) Fostered belonging in academic medicine (6) Appreciation of different careers in academic medicine and how to integrate DEI interests (7) Inspired trainees to pursue leadership roles. CONCLUSIONS: LEAD can serve as a model for other institutions that seek to support UIM trainees' sense of belonging, professional identity formation, and perceptions about pursuing careers in academic medicine and future leadership roles.
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INTRODUCTION: Individuals with sickle cell disease (SCD) at increased risk for stroke should undergo annual stroke risk assessment using transcranial Doppler (TCD) screening between the ages of 2 and 16. Though this screening can significantly reduce morbidity associated with SCD, screening rates at Boston Children's Hospital (and nationwide) remain below the recommended 100% screening adherence rates. METHODS: Three plan-do-study-act (PDSA) cycles were designed and implemented. The Specific, Measurable, Achievable, Relevant, and Time-Bound (SMART) aim of our quality improvement (QI) initiative was to sustainably increase the proportion of eligible patients receiving a TCD within 15 months of their last TCD to greater than 95%. An interrupted time series (ITS) analysis was performed, comparing TCD adherence rates from PDSA Cycle 1 to those from PDSA Cycles 2 and 3. RESULTS: Mean TCD adherence increased across all three PDSA cycles, from a baseline of 67% in the first cycle (January 2015 to September 2020) to 92% in the third cycle (May 2021 to March 2023). In the ITS analysis of TCD adherence rates, there was a significant difference in the final TCD adherence rate achieved compared to the rate predicted, with a total estimated increase in adherence of 17.9% being attributable to the interventions from PDSA Cycles 2 and 3. DISCUSSION: Although other QI initiatives had demonstrated ability to increase adherence to TCD screening for patients with SCD, this is the first QI project to collect data over such a prolonged period of time to demonstrate a sustained increase in screening rates throughout the intervention (an 8-year period).
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Anemia Falciforme , Melhoria de Qualidade , Ultrassonografia Doppler Transcraniana , Humanos , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/complicações , Ultrassonografia Doppler Transcraniana/métodos , Criança , Feminino , Masculino , Adolescente , Pré-Escolar , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/diagnóstico por imagem , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Seguimentos , PrognósticoRESUMO
OBJECTIVE: The objective of this study was to investigate possible immune cytokine trends throughout a week-long surgical simulation mass-casualty training session in order to determine the effects of stress inoculation on the immune system. METHODS: Thirty-seven military medical students participated in a hyper-realistic surgical simulation training event conducted at Strategic Operations site in San Diego, California. Salivary samples were collected every morning of the stress training exercise for 4 consecutive days. Cortisol, along with a panel of 42 immune cytokines, was measured using multiplex enzyme-linked immunosorbent assays from Eve Technologies. The determined concentrations were averaged and plotted on a scatter plot, and then points were fit to a second-order polynomial trendline of best fit to measure. RESULTS: The cytokines epidermal growth factor, growth-related oncogene-α, interleukin (IL)-1α, and platelet-derived growth factor-AA followed a noted pattern of cortisol decrease throughout the week. In addition, cytokines IL-27, granulocyte colony stimulating factor, IL-10, and IL-13 demonstrated a late peak, followed by a return to baseline at the conclusion of training. Finally, the cytokine monocyte chemoattractant protein-1 displayed a decline throughout the week followed by an increase on the last day of stress training. CONCLUSIONS: Altogether, these results help to identify important biomarkers that may help to improve long-term stress adaptation and prevent post-traumatic stress disorder following exposure to repeated stress.
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Citocinas , Hidrocortisona , HumanosRESUMO
BACKGROUND & AIMS: Fibrosis stage is a strong predictor of nonalcoholic steatohepatitis (NASH) outcomes. Two blinded studies evaluated the pharmacokinetics, pharmacodynamics and safety of obeticholic acid (OCA) in subjects with staged NASH fibrosis or cirrhosis. METHODS: Study 747-117 randomized 51 subjects with NASH (fibrosis stages F1-F4) to daily placebo, OCA 10 or OCA 25 mg (1:2:2) for 85 days. Study 747-118 randomized 24 subjects with NASH cirrhosis (F4; Child-Pugh [CP]-A) and normal liver control subjects matched for similar body weight to daily OCA 10 or OCA 25 mg (1:1) for 28 days. Individual and combined study data were analysed. RESULTS: No severe or serious adverse events (AEs) or AEs leading to discontinuation or death occurred. Pruritus was the most frequent AE. Plasma OCA exposure (dose-normalized area under the curve) increased with fibrosis stage but was a relatively poor predictor of hepatic OCA exposure (primary site of action), which remained constant across fibrosis stages F1-F3 and increased 1.8-fold compared with F1 in subjects with cirrhosis due to NASH. Both cohorts showed robust changes in farnesoid X receptor activation markers with OCA treatment and marked decreases in alanine transaminase, aspartate transaminase and gamma-glutamyltransferase. CONCLUSIONS: Despite higher drug exposures in subjects with NASH cirrhosis, short-term daily treatment with OCA 10 or 25 mg was generally safe and well tolerated in subjects with NASH fibrosis or NASH CP-A cirrhosis. Both cohorts experienced improvements in nonhistologic pharmacodynamic markers consistent with previously conducted OCA phase 2 and phase 3 studies in NASH fibrosis.
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Ácido Quenodesoxicólico/análogos & derivados , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Ácido Quenodesoxicólico/efeitos adversosRESUMO
A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation-based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics-guided medicine in canine oncology, we have developed and validated a canine cancer next-generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation-based biomarkers in veterinary oncology.
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Doenças do Cão , Neoplasias , Cães , Humanos , Animais , Doenças do Cão/genética , Neoplasias/genética , Neoplasias/veterinária , Genômica , Mutação , Biomarcadores Tumorais/genéticaRESUMO
OBJECTIVES: The G8 is a well-validated screening test for older cancer patients. The current study was undertaken to determine whether the G8 is predictive of short-term post-operative outcomes after head and neck cancer (HNC) surgery. METHODS: Consecutive patients aged 65 years or more and referred for a preoperative assessment by a speech-language pathologist were consecutively screened by clinicians at 2 academic medical centers using the G8. The G8 was used to screen for vulnerability prior to surgery. Patients were deemed vulnerable if they had a total G8 score ≤14 according to published guidelines. Data were also collected on demographic characteristics, tumor staging, post-operative course, and tracheostomy and feeding tube (FT) status. RESULTS: Ninety patients were consecutively screened during the study period. Using the G8, 64% of the patients were deemed vulnerable. Vulnerable patients differed significantly from non-vulnerable patients with regard to age, health, tumor stage, and baseline dysphagia, and underwent more extensive surgery. Postoperatively, vulnerable patients had a significantly longer hospital length of stay (LOS; 10.17 vs 5.50 days, respectively, P < .001), were less likely to discharge home (76% vs 94%, P = .044), and were more likely to be FT dependent for over a month (54% vs 21%, P = .006) compared to non-vulnerable patients. In regression models, controlling for T-stage and surgical variables, the G8 independently predicted 2 post-operative outcomes of interest, namely LOS and FT dependency. CONCLUSIONS: The G8 may be a useful screening tool for identifying older adults at risk of a protracted postoperative medical course after HNC surgery. Future research should aim to identify the optimal screening protocol and how this information can be incorporated into clinical pathways to enhance the post-operative outcomes of older HNC patients.
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Neoplasias de Cabeça e Pescoço , Medicina , Humanos , Idoso , Detecção Precoce de Câncer , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgiaAssuntos
Criança Hospitalizada , Equidade em Saúde , Humanos , Criança , Restrição Física/efeitos adversos , Hospitalização , HospitaisRESUMO
Phlegmasia cerulea dolens is a serious manifestation of venous thrombosis that has a high risk of morbidity and mortality. If not promptly treated on presentation, progressive extremity ischemia and potential gangrene can lead to emergency amputation of the affected limb. Most commonly, the lower extremities are affected, and reports of upper extremity phlegmasia are scarce. We report the successful treatment of phlegmasia cerulea dolens of the distal upper extremity using leech therapy combined with anticoagulation.
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OBJECTIVES: Hospitalization in a PICU is a stressful experience for children and their parents, with many experiencing posttraumatic stress disorder (PTSD) after discharge. Risk factors may include preillness traumatic events, such as adverse childhood experiences (ACEs). We sought to assess the feasibility of screening ACEs in parents of children admitted to a PICU, their prevalence, and their association with post-PICU PTSD symptoms in them and their children. DESIGN: Single-center prospective observational study. SETTING: Urban academic children's hospital from January to December 2021. PATIENTS: One hundred forty-five children (2-18 yr old, admitted ≥ 2 d) and their parents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on parental demographics, ACEs, coping skills, and PICU environmental stressors, as well as patient clinical data, were collected. One month after PICU discharge, parents completed inventories assessing PTSD symptoms in them and their children. Bivariate and logistic regression analyses were used to explore associations of ACEs with post-PICU PTSD. Of 145 enrolled parents, 95% completed the ACE questionnaire, 58% of whom reported greater than or equal to 1 ACE, and 14% had substantial (≥ 4) ACEs. Parent and patient follow-up was 79% and 70%, respectively. Sixteen percent of parents had provisional PTSD. Regression analysis showed parents with greater than or equal to 4 ACEs had 10 times greater odds of parental PTSD, compared to parents with less than 4 ACEs, (adjusted odds ratio [aOR] = 10.2; 95% CI, 1.03-100.9; p = 0.047). Fifty-six percent of patients screened at risk for PTSD. There was no association between substantial parental ACEs and patients' risk for PTSD (aOR = 3.5 [95% CI, 0.56-21.31]; p = 0.18). CONCLUSIONS: ACEs were common among parents of critically ill children. Having substantial parental ACEs was associated with provisional parental PTSD after their child's PICU admission, but not with PTSD in the children. Family-centered care that seeks to mitigate post-PICU stress should be mindful of the potential relevance of parental ACEs.
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Experiências Adversas da Infância , Transtornos de Estresse Pós-Traumáticos , Criança , Humanos , Pais , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inquéritos e Questionários , Unidades de Terapia Intensiva PediátricaRESUMO
Prolonged critical illness in children has emotional consequences for both parents and providers. In this observational cohort study, we longitudinally surveyed anxiety and depression in parents and moral distress in pediatric intensive care unit (PICU) providers (attendings, fellows, and bedside registered nurses) and explored their trajectories and relationships. Anxiety/depression and provider moral distress were measured using the Hospital Anxiety and Depression Scale and the Moral Distress Thermometer, respectively. The relationships of parental and provider distress were evaluated using Spearman's correlations, and their trajectories and potentially associated variables were explored using quadratic random slope and intercept models. Predetermined associated factors included demographic and clinical factors, including parent psychosocial risk and intubation status. We found parental anxiety and depression decreased over their child's admission, and parental psychosocial risk was significantly associated with anxiety (coefficient = 4.43, p < 0.001). Clinicians in different roles had different mean levels and trajectories of moral distress, with fellows reporting greater distress early in admissions and nurses later in admissions. Parental anxiety/depression and provider distress were significantly, though moderately, correlated. We conclude that anxiety and depression in parents of children with prolonged PICU admissions and the moral distress of their clinicians correlate and vary over time and by provider role.
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Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory-e.g., the amygdala and hippocampus-are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing ß-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects.
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Mifepristona , Roedores , Ratos , Masculino , Animais , Mifepristona/farmacologia , Ratos Sprague-Dawley , Propranolol/farmacologia , Derrota Social , Hipocampo/metabolismo , Plasticidade Neuronal , Tonsila do Cerebelo/metabolismo , Expressão Gênica , Estresse Psicológico/complicaçõesRESUMO
Long-stay patients are an impactful, vulnerable, growing group of inpatients in today's (and tomorrow's) tertiary hospitals. They can outlast dozens of clinicians that necessarily rotate on and off clinical service. Yet, care from such rotating clinicians can result in fragmented care due to a lack of continuity that insufficiently meets the needs of these patients and their families. Using long-stay PICU patients as an example, this focused review discusses the impact of prolonged admissions and how our fragmented care can compound this impact. It also argues that it is an ethical imperative to provide a level of continuity of care beyond what is considered standard of care and offers a number of strategies that can provide such continuity.
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Continuidade da Assistência ao Paciente , Pacientes Internados , Tempo de Internação , HumanosRESUMO
Objective: To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods: This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results: There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions: While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.
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Objectives: To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence. Methods: This was a cross-sectional study of secondary data from the Colombian Integrated Social Protection Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1-4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, direct payment, pay per case, pay for event). Results: Of 215 925 cases of community-acquired pneumonia reported during 2017-2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guidelines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion: In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.
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BACKGROUND: Persons living with HIV may be at risk of more severe forms of COVID-19 infection and minimizing health risks largely depends on their acceptance of the COVID-19 vaccinations. OBJECTIVE: This study examined the correlates and predictors of COVID-19 vaccine hesitancy among persons living with HIV in Trinidad and Tobago. METHODS: A cross-sectional survey using a structured interview was conducted. Data were compiled on patient socio-demographics, diagnosed chronic diseases, psychological factors, and decisions to take the COVID-19 vaccine. Pearson χ2 tests examined the associations between study variables and COVID-19 vaccine hesitancy, and multivariable logistic regression analyses examined its predictors. RESULTS: In this study, 84% were virally suppressed, i.e., HIV viral load <1000 copies/ml. COVID-19 vaccine hesitancy was found to be 39%. Univariate analysis showed that higher vaccine hesitancy was significantly associated with females (OR 2.02, 95% CI 1.23-3.33) and patients of mixed ethnicity (OR 1.84, 95% CI 1.07-3.15). In our multivariable analysis, psychological factors namely, confidence in the COVID-19 vaccine (OR 0.16, 95% CI 0.05-0.47), the perceived benefits of the vaccine (OR 0.54, 95% CI 0.37-0.79), and cues to action (OR 0.68, 95% CI 0.47-0.97) were observed as predictors of COVID-19 vaccine hesitancy. CONCLUSION: Psychological factors such as confidence in the COVID-19 vaccine, perceived benefits of the vaccine, and cues to action were possible predictors of COVID-19 vaccine hesitancy. This study underscored the continued need for strategies to increase confidence and knowledge about the benefits of taking the COVID-19 vaccine among persons living with HIV.
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Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases caused by a deficiency of one of the enzymes or transporters that constitute the urea cycle. Defects in these enzymes lead to acute accumulation (hyperammonemic crises, HAC) or chronically elevated levels (hyperammonemia) of ammonia in the blood and/or various tissues including the brain, which can cause persistent neurological deficits, irreversible brain damage, coma, and death. Ongoing treatment of UCDs include the use of nitrogen-scavenging agents, such as sodium phenylbutyrate (salt of 4-phenylbutyric acid; NaPBA) or glycerol phenylbutyrate (GPB). These treatments provide an alternative pathway for nitrogen disposal through the urinary excretion of phenylacetylglutamine. ACER-001 is a novel formulation of NaPBA with polymer coated pellets in suspension, which is designed to briefly mask the unpleasant bitter taste of NaPBA and is being developed as a treatment option for patients with UCDs. Four Phase 1 studies were conducted to characterize the bioavailability (BA) and/or bioequivalence (BE) of ACER-001 (in healthy volunteers) and taste assessment relative to NaPBA powder (in taste panelists). ACER-001 was shown to be bioequivalent to NaPBA powder under both fed and fasting conditions. Lower systemic exposure of phenylacetate (PAA) and phenylbutyrate (PBA) was observed when ACER-001 was administered with a high-fat meal relative to a fasting state suggesting that the lower doses of PBA administered under fasting conditions may yield similar efficacy with potentially fewer dose dependent adverse effects relative to higher doses with a meal. ACER-001 appeared to be adequately taste-masked, staying below the aversive taste threshold for the first 3 min after the formulation was prepared and remaining palatable when taken within 5 min.
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Hiperamonemia , Distúrbios Congênitos do Ciclo da Ureia , Humanos , Fenilbutiratos , Paladar , Pós/uso terapêutico , Hiperamonemia/tratamento farmacológico , Nitrogênio , Doenças Raras/tratamento farmacológico , UreiaRESUMO
The ventral tegmental area (VTA) is an essential component of the mesocorticolimbic dopamine (DA) circuit that processes reward and motivated behaviors. The VTA contains DA neurons essential in this process, as well as GABAergic inhibitory cells that regulate DA cell activity. In response to drug exposure, synaptic connections of the VTA circuit can be rewired via synaptic plasticity-a phenomenon thought to be responsible for the pathology of drug dependence. While synaptic plasticity to VTA DA neurons as well as prefrontal cortex to nucleus accumbens GABA neurons are well studied, VTA GABA cell plasticity, specifically inhibitory inputs to VTA GABA neurons, is less understood. Therefore, we investigated the plasticity of these inhibitory inputs. Using whole cell electrophysiology in GAD67-GFP mice to identify GABA cells, we observed that these VTA GABA cells experience either inhibitory GABAergic long-term potentiation (iLTP) or inhibitory long-term depression (iLTD) in response to a 5 Hz stimulus. Paired pulse ratios, coefficient of variance, and failure rates suggest a presynaptic mechanism for both plasticity types, where iLTP is NMDA receptor-dependent and iLTD is GABAB receptor-dependent-this being the first report of iLTD onto VTA GABA cells. As illicit drug exposure can alter VTA plasticity, we employed chronic intermittent exposure (CIE) to ethanol (EtOH) vapor in male and female mice to examine its potential impact on VTA GABA input plasticity. Chronic EtOH vapor exposure produced measurable behavioral changes illustrating dependence and concomitantly prevented previously observed iLTD, which continued in air-exposed controls, illustrating the impact of EtOH on VTA neurocircuitry and suggesting physiologic mechanisms at play in alcohol use disorder and withdrawal states. Taken together, these novel findings of unique GABAergic synapses exhibiting either iLTP or iLTD within the mesolimbic circuit, and EtOH blockade specifically of iLTD, characterize inhibitory VTA plasticity as a malleable, experience-dependent system modified by EtOH.
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Potenciação de Longa Duração , Área Tegmentar Ventral , Camundongos , Masculino , Feminino , Animais , Potenciação de Longa Duração/fisiologia , Área Tegmentar Ventral/metabolismo , Etanol/farmacologia , Plasticidade Neuronal , Neurônios GABAérgicos/fisiologia , Neurônios Dopaminérgicos/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
OBJECTIVES: To determine the prevalence of the utilization of primary intensivists and primary nurses for long-stay patients in large, academic PICU and ascertain how these practices are operationalized and perceived. DESIGN: A cross-sectional survey. SETTING: U.S. PICUs with accredited Pediatric Critical Care Medicine fellowships. SUBJECTS: One senior physician and one senior nurse at each institution. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Separate but largely analogous questionnaires for intensivists and nurses were created using an iterative process to enhance content/face validity and readability. Sixty-seven intensivists (representing 93% of the 72 institutions with fellowship programs and their PICUs) and 59 nurses (representing 82%) responded. Twenty-four institutions utilize primary intensivists; 30 utilize primary nurses; and 13 utilize both. Most institutions use length of stay and/or other criteria (e.g., medical complexity) for eligibility. Commonly, not all patients that meet eligibility criteria receive primaries. Primary providers are overwhelmingly volunteers, and often only a fraction of providers participate. Primary intensivists at a large majority (>75%) of institutions facilitate information sharing and decision-making, attend family/team meetings, visit patients/families regularly, and are otherwise available upon request. Primary nurses at a similar majority of institutions provide consistent bedside care, facilitate information sharing, and attend family/team meetings. A large majority of respondents thought that primary intensivists increase patient/family satisfaction, reduce their stress, improve provider communication, and reduce conflict, whereas primary nurses similarly increase patient/family satisfaction. More than half of respondents shared that these practices can sometimes require effort (e.g., time and emotion), complicate decision-making, and/or reduce staffing flexibility. CONCLUSIONS: Primary practices are potential strategies to augment rotating PICU care models and better serve the needs of long-stay and other patients. These practices are being utilized to varying extents and with some operationalization uniformity at large, academic PICUs.
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Comunicação , Unidades de Terapia Intensiva Pediátrica , Criança , Humanos , Estudos Transversais , Inquéritos e Questionários , Disseminação de InformaçãoRESUMO
An important preventive measure in the fight against the HIV epidemic is the adoption of HIV testing. The government of the Republic of Trinidad and Tobago conducted a registration exercise in 2019 for undocumented migrants and refugees from Venezuela residing in the country. These migrants were allowed access to the public health system. In this study, we observed the correlates of HIV testing in Venezuelan migrants residing in Trinidad. A convenience sample of n = 250 migrants was collected via telephone survey from September through December 2020. Variables of interest included social factors, health needs, and uptake of HIV testing. Pearson χ2 tests examined the associations between study variables, and multivariable logistic regression with backward elimination produced the odds of taking an HIV test. In our study, 40.8% of migrants reported having received an HIV test since arriving in Trinidad. Persons who migrated with family or friends had greater odds of getting an HIV test relative to persons who arrived alone (OR = 2.912, 95% CI: 1.002-8.466), and migrants who knew where to get an HIV test also greater odds of getting a test relative to person who did not know where to get a test (OR = 3.173, 95% CI: 1.683-5.982). Migrants with known physical health problems had greater odds of getting an HIV test relative to migrants without these health problems (OR = 1.856, 95% CI: 1.032-3.337). Persons who arrived with family or friends had greater odds of experiencing difficulties accessing public health care relative to persons who arrived alone (OR = 3.572, 95% CI: 1.352-9.442). Migrants earning between $1000 and $2999 TT per month had greater odds of experiencing trouble accessing public health services relative to persons who had monthly earnings of less than $1000 TT (OR = 2.567, 95% CI: 1.252-5.264). This was the first quantitative study on HIV testing among Venezuelan migrants in Trinidad. Migrants still experience difficulties accessing healthcare, which, in turn influences national HIV prevention and control efforts. The results gathered may help in developing HIV prevention plans that are led by a national health policy that takes migrant communities' needs into account.