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BACKGROUND: Malnutrition is a common problem in developing countries, and the impact of severe malnutrition on optimal treatment outcomes of chemotherapy in pediatric cancer patients is well documented. However, despite being a more prevalent and distinct entity, moderate malnutrition is until now unexplored for its effects on treatment outcomes. AIMS: In this study we aimed to investigate the molecular basis of altered pharmacokinetics and cardiotoxicity of doxorubicin observed in early-life chronic moderate protein deficiency malnutrition. MATERIALS AND METHODS: We developed an animal model of early-life moderate protein-deficiency malnutrition and validated it using clinical samples. This model was used to study pharmacokinetic and toxicity changes and was further utilized to study the molecular changes in liver and heart to get mechanistic insights. KEY FINDINGS: Here we show that moderate protein-deficiency malnutrition in weanling rats causes changes in drug disposition in the liver by modification of hepatic ABCC3 and MRP2 transporters through the TNFα signalling axis. Furthermore, malnourished rats in repeat-dose doxorubicin toxicity study showed higher toxicity and mortality. A higher accumulation of doxorubicin in the heart was observed which was associated with alterations in cardiac metabolic pathways and increased cardiotoxicity. SIGNIFICANCE: Our findings indicate that moderate malnutrition causes increased susceptibility towards toxic side effects of chemotherapy. These results may necessitate further investigations and new guidelines on the dosing of chemotherapy in moderately malnourished pediatric cancer patients.
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Cardiotoxicidade , Doxorrubicina , Animais , Doxorrubicina/farmacocinética , Doxorrubicina/efeitos adversos , Ratos , Cardiotoxicidade/etiologia , Masculino , Desmame , Fígado/metabolismo , Desnutrição Proteico-Calórica/metabolismo , Humanos , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/toxicidade , Feminino , Modelos Animais de Doenças , Ratos WistarRESUMO
In this study, a self-healing, adhesive, and superabsorbent film made of gelatin, poly(acrylamide), and boric acid (GelAA) was successfully synthesized using a free radical reaction mechanism. The optimized film showed a remarkable 2865 ± 42% water absorptivity and also exhibited excellent self-healing behavior. The GelAA films were further loaded with silver nanoclusters (AgNCs) and ursodeoxycholic acid (UDC) (loading efficiency = 10%) to develop UDC/Ag/GelAA films. The loading of AgNCs in UDC/Ag/GelAA films helped in exhibiting 99.99 ± 0.01% antibacterial activity against both Gram-positive and Gram-negative bacteria, making them very effective against bacterial infections. Additionally, UDC/Ag/GelAA films had 77.19 ± 0.52% porosity and showed 90% of UDC release in 30 h, which helps in improving the cell proliferation. Our research provides an easy but highly effective process for synthesizing a hydrogel film, which is an intriguing choice for wound healing applications without the use of antibiotics.
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Resinas Acrílicas , Antibacterianos , Anti-Infecciosos , Metilgalactosídeos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Gelatina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , CicatrizaçãoRESUMO
BACKGROUND: Moderate malnutrition is a common problem in young children. It is observed that severe malnutrition affects the pharmacokinetics of chemotherapy drugs in pediatric cancer patients, but moderate malnutrition is not well studied in this context. OBJECTIVES: In this study, we aimed to understand how moderate malnutrition affects the pharmacokinetics of two chemotherapy drugs, etoposide and vincristine, using a murine model of early age moderate malnutrition. METHODS: We developed a murine model of moderate childhood malnutrition by subjecting freshly weaned Sprague-Dawley rats to 8% protein diet for 8 weeks. In two separate experiments, we administered etoposide and vincristine (N = 8 for etoposide and N = 12 for vincristine each in protein deficient and control groups) through tail vein injection for pharmacokinetics study. RESULTS: We found ~ 60% increase in area under the concentration-time curve (AUC) of etoposide in malnourished animals as compared to well-nourished animals. Furthermore, clearance, volume of distribution, and half-life were decreased by ~ 37, 53, and 24%, respectively, in malnourished animals. Pharmacokinetic parameters of vincristine showed only marginal differences between well-nourished and malnourished groups. CONCLUSIONS: Our results suggest that while moderate malnutrition significantly affects the pharmacokinetics of etoposide, pharmacokinetics of vincristine remain unchanged. Since chemotherapy drugs have a narrow therapeutic index, the difference in AUC observed in our study might explain the increased toxicity of etoposide in malnourished pediatric cancer patients. This brings forth a need for robust clinical studies to validate our findings and optimize dose for malnourished patients.
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Desnutrição , Neoplasias , Humanos , Criança , Ratos , Camundongos , Animais , Pré-Escolar , Etoposídeo/farmacocinética , Vincristina , Modelos Animais de Doenças , Ratos Sprague-Dawley , Desnutrição/metabolismoRESUMO
This review aimed to summarise the relative risk (RR) of the main symptoms of long COVID in people infected with SARS-CoV-2 compared to uninfected controls, as well as the difference in health-related quality of life (HRQoL) after infection. MEDLINE, EMBASE, PubMed, NLM-LitCovid, WHO-COVID-19, arXiv and Europe-PMC were searched up to 23rd March 2022. Studies reporting risk (four or more weeks after infection) of fatigue, shortness of breath, and cognitive dysfunction, as well as comparative HRQoL outcomes, were included. Pairwise random-effects meta-analyses were performed to pool risks of individual symptoms. Thirty-three studies were identified; twenty studies reporting symptom risks were included in the meta-analyses. Overall, infection with SARS-CoV-2 carried significantly higher risk of fatigue (RR 1.72, 95% confidence intervals [CIs] 1.41, 2.10), shortness of breath (RR 2.60, 95% CIs 1.96, 3.44), memory difficulties (RR 2.53, 95% CIs 1.30, 4.93), and concentration difficulties (RR 2.14, 95% CIs 1.25, 3.67). Quality of life findings were varied and comparisons between studies were challenging due to different HRQoL instruments used and study heterogeneity, although studies indicated that severe hospitalised COVID is associated with a significantly poorer HRQoL after infection. These risks are likely to constantly change as vaccines, reinfections, and new variants alter global immunity.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/complicações , Qualidade de Vida , SARS-CoV-2 , Dispneia , Fadiga/etiologiaRESUMO
Microneedle (MN) technology plays a significant role in bioengineering as it allows for minimally invasive exposure to the skin via the non-invasive procedure, increased drug permeability, and improved biological molecule detectability in the epidermal layers, all while improving therapeutic safety and effectiveness. However, MNs have several significant drawbacks, including difficulty scaling up, variability in drug delivery pattern regarding the skin's external environment, blockage of dermal tissues, induction of inflammatory response at the administration site, and limitation of dosing based on the molecular weight of drug and size. Despite these drawbacks, MNs have emerged as a special transdermal theranostics instrument in clinical research to assess physiological parameters. Bioimaging technology relies on microneedles that can measure particular analytes in the extracellular fluid effectively by crossing the stratum corneum, making them "a unique tool in diagnostics detection and therapeutic application inside the body." This review article discusses the recent advances in the applications especially related to the diagnostics and toxicity challenges of microneedles. In addition, this review article discusses the clinical state and commercial accessibility of microneedle technology-based devices in order to provide new information to scientists and researchers.
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Expedições , Pele , Administração Cutânea , Preparações Farmacêuticas , EpidermeRESUMO
Background: Our aim was to investigate the effectiveness of virtual wards on health outcomes in patients with acute respiratory infection. Methods: We searched four electronic databases from January 2000 to March 2021 for randomised controlled trials (RCTs). We included studies in people with acute respiratory illness or an acute exacerbation of a chronic respiratory illness, where a patient or carer measured vital signs (oximetry, blood pressure, pulse) for initial diagnosis and/or asynchronous monitoring, in a person living in private housing or a care home. We performed random-effects meta-analysis for mortality. Results: We reviewed 5834 abstracts and 107 full texts. Nine RCTs were judged to be relevant for inclusion, in which sample sizes ranged from 37 to 389 (total n=1627) and mean ages ranged between 61 and 77â years. Five were judged to be at low risk of bias. Five RCTs had fewer hospital admissions in the intervention (monitoring) group, out of which two studies reported a significant difference. Two studies reported more admissions in the intervention group, with one reporting a significant difference. We were unable to perform a meta-analysis on healthcare utilisation and hospitalisation data due to lack of outcome definition in the primary studies and variable outcome measurements. We judged two studies to be at low risk of bias. The pooled summary risk ratio for mortality was 0.90 (95% CI 0.55-1.48). Conclusion: The limited literature for remote monitoring of vital signs in acute respiratory illness provides weak evidence that these interventions have a variable impact on hospitalisations and healthcare utilisation, and may reduce mortality.
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PURPOSE OF REVIEW: Extracorporeal shock wave lithotripsy success rates depend on several stone and patient-related factors, one of which is stone density which is calculated on computed tomography scan in Hounsfield Units. Studies have shown inverse correlation between SWL success and HU; however, there remains considerable variation between studies. We performed a systematic review regarding the use of HU in SWL for renal calculi to consolidate the current evidence and address current knowledge gaps. RECENT FINDINGS: Database including MEDLINE, EMBASE, and Scopus were searched from inception through August 2022. Studies in English language analysing stone density/attenuation in adult patients undergoing SWL for renal calculi were included for assessment of Shockwave lithotripsy outcomes, use of stone attenuation to predict success, use of mean and peak stone density and Hounsfield unit density, determination of optimum cut-off values, nomograms/scoring systems, and assessment of stone heterogeneity. 28 studies with a total of 4,206 patients were included in this systematic review with sample size ranging from 30 to 385 patients. Male to female ratio was 1.8, with an average age of 46.3 years. Mean overall ESWL success was 66.5%. Stone size ranged from 4 to 30 mm in diameter. Mean stone density was used by two-third of the studies to predict the appropriate cut-off for SWL success, ranging from 750 to 1000 HU. Additional factors such as peak HU and stone heterogeneity index were also evaluated with variable results. Stone heterogeneity index was considered a better indicator for success in larger stones (cut-off value of 213) and predicting SWL stone clearance in one session. Prediction scores had been attempted, with researchers looking into combining stone density with other factors such as skin to stone distance, stone volume, and differing heterogeneity indices with variable results. Numerous studies demonstrate a link between shockwave lithotripsy outcomes and stone density. Hounsfield unit < 750 has been found to be associated with shockwave lithotripsy success, with likelihood of failure strongly associated with values over 1000. Prospective standardisation of Hounsfield unit measurement and predictive algorithm for shockwave lithotripsy outcome should be considered to strengthen future evidence and help clinicians in the decision making. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) database: CRD42020224647.
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Cálculos Renais , Litotripsia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/terapia , Litotripsia/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Health systems are integrating medical-legal partnerships (MLPs) into clinical care and increasingly center "complex care" patients. These patients have intersecting medical and social needs and often face systemic inequities that exacerbate their chronic health conditions. This paper describes a role for MLPs in hospital quality initiatives; examines the ethics of MLPs assisting with guardianship and institutionalization of hospital patients including marginalized groups; and advocates for MLP interventions designed to address intersectional and ethical concerns.
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Hospitais , Enquadramento Interseccional , HumanosRESUMO
Importance: The internal medicine (IM) chief residency is a position of leadership and honor common in IM programs, but the goals, responsibilities, and experiences of those who undertake it can be highly variable. Studies assessing the experience and impressions of the chief resident (CR) position from the viewpoint of the IM CRs are lacking. Objective: To describe the structure, responsibilities, and perceptions of the IM CR role across IM residency programs. Design, Setting, and Participants: A cross-sectional, simple descriptive electronic survey for current CRs was administered between April and June 2018 across US IM residency programs accredited by US Accreditation Council for Graduate Medical Education. A 2-step nonrandom sampling approach was used: first, snowball sampling was performed using the authors' professional networks, and second, the survey was sent to the Association of Program Directors in Internal Medicine (APDIM) CR listserv. Data analysis was performed from June 2020 to August 2020. Exposures: Participation as a CR for an IM residency program in the 2017 to 2018 academic year. Main Outcomes and Measures: Descriptive CR personal and program characteristics and CR perceptions of administrative, clinical, and leadership experiences. Results: Among 169 unique responses, 77 participants (46%) were female and 89 (53%) were White. The response rate was 57% (70 of 122 surveys) in the snowball sample and 12% (99 of 842 surveys) in the APDIM listserv. The 2 sampled groups were combined for analysis. Most respondents (125 CRs [74%]) were from academic or university-based programs. Common across CR responses was responsibility for administrative tasks, clinical work, and educational efforts. Most CRs (111 of 157 respondents [71%]) reported being the primary schedulers for the residency program. Clinical work differed widely across respondents. Only 70 of 156 respondents (45%) reported having an academic title associated with the CR role. CRs reported inconsistent evaluation throughout the year, with high percentages reporting never receiving feedback on teaching (34 respondents [23%]), clinical abilities (67 respondents [45%]), or leadership abilities (60 respondents [40%]). Most CRs (107 respondents [69%]) agreed that they find work as a CR fulfilling and 117 (74%) agreed they would do chief residency again. Conclusions and Relevance: Despite its ubiquity in training programs across the US, the IM CR experience is very different across programs. Recommendations are provided to consider for improvement of the CR experience, including structured feedback opportunities, maximizing educational and clinical experiences, and standardizing policies.
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Medicina Interna , Internato e Residência , Estudos Transversais , Educação de Pós-Graduação em Medicina , Feminino , Humanos , Medicina Interna/educação , LiderançaRESUMO
BACKGROUND: Firearm violence is a unique public health crisis in the USA (US). A majority of U.S. physicians believe they should discuss firearm safety with patients. However, little education on firearm injury prevention and counseling exists in medical school. We sought to address this gap by creating a curriculum on firearm violence as a part of a required preclinical medical school course focused on health policy issues. METHODS: The Kerns 6-step model for curriculum development was used to define the problem and assess learner needs. The two-hour small group session was co-authored by a student and faculty member to address the course theme of health policy as applied to firearm violence. The Issue-Attention Cycle, history of firearm policy, and US politics were incorporated from published literature, with a patient counseling role-play added in 2019. RESULTS: The 'Current Case in Health Policy - Firearm Violence' small group was implemented in 2018 and 2019 for all first-year medical students. Of the 2018 student evaluations, 57% selected this small group as the most valuable in the course. In a follow-up survey in 2020, 78% of the respondents agreed that they felt more confident counseling patients on firearm safety following the role-play. CONCLUSION: Students broadly endorsed the incorporation of firearm policy and counseling skills into medical education. This curriculum can be adapted for learners at all stages of training, especially given the limited exposure to this topic in medical education.
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Armas de Fogo , Ferimentos por Arma de Fogo , Aconselhamento , Currículo , Política de Saúde , Humanos , Faculdades de Medicina , Estados Unidos , Violência/prevenção & controle , Ferimentos por Arma de Fogo/prevenção & controleAssuntos
Corticosteroides/administração & dosagem , Queilite/tratamento farmacológico , Febre/etiologia , Lúpus Eritematoso Sistêmico/complicações , Corticosteroides/uso terapêutico , Adulto , Queilite/etiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Resultado do TratamentoRESUMO
PURPOSE: Medical societies have embraced advocacy as a core professional competency, but little is known about how entering medical students view physician advocacy. This study examined how first year medical students define advocacy, their motivations for and anticipated challenges to advocacy, and whether they believe advocacy should be a core competency. METHOD: This study used a qualitative content analysis approach to analyze first year medical student narrative responses about physician advocacy. The analysis included the written responses of 95% of the first-year medical students at the University of California, San Francisco (UCSF) School of Medicine during two academic years. RESULTS: Students shared consensus that physicians should advocate on behalf of their individual patients. Students had varying opinions on whether all physicians should engage in societal level advocacy and whether it should be a core competency in medical school. Students find several compelling reasons for physicians to engage in societal advocacy but nevertheless anticipate challenges to physician advocacy. CONCLUSION: Given increasing consensus that advocacy is a core competency of physicians, providing medical students the skills to successfully engage in advocacy is increasingly important. Any new mandatory curricula will need to focus on how to engage learners with varied views on advocacy.
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Educação de Graduação em Medicina , Médicos , Estudantes de Medicina , Currículo , Humanos , Faculdades de MedicinaRESUMO
The spread of COVID-19 in the United States has led to the use of virtual visits in lieu of in-person care for the high-risk population of patients in rheumatology. We asked patients to score their satisfaction with these visits and if they would have preferred in-person care instead. Of 679 patients seen in May 2020, 512 (75.4%) were virtual (267 [52.1%] by telephone and 245 [47.9%] by video), and 359 (70%) responded to the survey. The majority of patients (74%) were satisfied with their virtual visit, but they were more likely to be satisfied if their visit was over video rather than phone. They preferred an in-person visit if they were meeting a doctor for the first time, and patients who required a language interpreter were significantly less satisfied with virtual care. There was no correlation of age, sex, diagnosis, or testing ordered with satisfaction. The main concern against virtual care was the inability to have a physical exam, while the main reasons in favor of it were avoidance of potential infection and convenience.
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Rheumatoid vasculitis is a rare, extra-articular manifestation that can be seen in long-standing rheumatoid arthritis. Here we present the case of a 51-year-old man who presented with arthralgias, skin rash, dyspnoea and generalized leg swelling and who was diagnosed with rheumatoid arthritis flare. LEARNING POINTS: Extra-articular manifestations like rheumatoid vasculitis and pericarditis rarely present as initial manifestations of rheumatoid arthritis.A high index of suspicion is required to make the diagnosis, especially in an adult who presents with multiorgan manifestations, rash, and a high titre of rheumatoid factor and anti-CCP antibody levels.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been predominantly respiratory. This study aimed to evaluate the presence of virus in non-airborne body fluids as transmission vehicles. Medline, EMBASE, and Cochrane Library databases were searched from December 01, 2019, to July 01, 2020, using terms relating to SARS-CoV-2 and non-airborne clinical sample sources (feces, urine, blood, serum, serum, and peritoneum). Studies in humans, of any design, were included. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy 2 tool. Preferred Reporting Items for Systematic Reviews & Meta-Analyses) guidelines were used for abstracting data. If ≥5 studies reported proportions for the same non-respiratory site, a meta-analysis was conducted using either a fixed or random-effects model, depending on the presence of heterogeneity. A total of 22 studies with 648 patients were included. Most were cross-sectional and cohort studies. The SARS-CoV-2 RNA was most frequently detected in feces. Detectable RNA was reported in 17% of the blood samples, 8% of the serum, 16% in the semen, but rarely in urine. Prevalence of SARS-CoV-2 in non-airborne sites varies widely with a third of non-airborne fluids. Patients with bowel and non-specific symptoms have persistence of virus in feces for upto 2 weeks after symptom resolution. Although there was a very low detection rate in urine, given the more frequent prevalence in blood samples, the presence of SARS-CoV-2 in patients with disrupted urothelium or undergoing urinary tract procedures, is likely to be higher. Healthcare providers need to consider non-airborne transmission and persistence of SARS-CoV-2 in body fluids to enable appropriate precautions to protect healthcare workers and carers.