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IMPACT: Children are facing many threats to their health today that require system change at a sweeping level to have real-world impact. Pediatricians are positioned as natural leaders to advocate for these critical community and policy changes. Academic medical center (AMC) leaders recognize the importance of this advocacy and clear steps can be taken to improve the structure to support pediatricians in their advocacy careers through faculty development and promotion, including standardized scholarly measurement of the outcomes.
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Centros Médicos Acadêmicos , Pediatria , Humanos , Centros Médicos Acadêmicos/organização & administração , Pediatria/organização & administração , Liderança , Criança , Defesa da Criança e do Adolescente , Pediatras , Docentes de Medicina , Mobilidade OcupacionalRESUMO
Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3ß-hydroxysteroid dehydrogenase-1 (3ß-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3ß-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention.
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Asma/tratamento farmacológico , Asma/enzimologia , Glucocorticoides/administração & dosagem , Complexos Multienzimáticos/genética , Progesterona Redutase/genética , Esteroide Isomerases/genética , Adulto , Idoso , Alelos , Androgênios/metabolismo , Asma/genética , Asma/metabolismo , Estudos de Coortes , Resistência a Medicamentos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Complexos Multienzimáticos/metabolismo , Progesterona Redutase/metabolismo , Esteroide Isomerases/metabolismo , Adulto JovemRESUMO
Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of SARS-CoV-2 infection with overlapping features of Kawasaki disease and toxic shock syndrome. In May 2020, a provincial multidisciplinary working group was established in anticipation of emerging cases following the first wave of SARS-CoV-2 infections. Methodology: Our centre established a multidisciplinary working group for MIS-C cases in British Columbia. The group developed guidelines using the World Health Organization MIS-C case definition. Guidelines were updated using quality improvement methods as new reports and our local experience evolved. We included all children who were evaluated in person or had samples sent to our centre for MIS-C evaluation from May 2020 to April 2021. We prospectively collected patient demographics, clinical and laboratory characteristics, and treatment. Results: Fifty-two children were included. Eleven were diagnosed as confirmed MIS-C. Ten of the 11 MIS-C cases presented with shock. Gastrointestinal and mucocutaneous involvement were also prominent. Common laboratory features included elevated C-reactive protein, D-dimer, troponin, and brain natriuretic peptide. Four out of 11 (36%) had myocardial dysfunction and 3/11 (27%) had coronary artery abnormalities. All 11 patients had evidence of SARS-CoV-2 infection. Ten out of 11 (91%) received intravenous (IV) immunoglobulin and IV corticosteroids. Conclusion: Our provincial cohort of MIS-C patients were more likely to present with shock and cardiac dysfunction, require ICU admission, and be treated with corticosteroids compared to ruled out cases. Our working group's evolving process ensured children with features of MIS-C were rapidly identified, had standardized evaluation, and received appropriate treatment in our province.
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Dyspnea in cancer patients can lead to significant deleterious effects. There are multiple conditions that can cause dyspnea. It is important to determine which of these causes are potentially reversible and treatable, so that they can be promptly addressed. Both pharmacologic and nonpharmacologic approaches should be used to treat this difficult condition. As patients advance in their illness, palliative treatments can be considered, such as low-dose opioids, oxygen therapy, and treatments directed at anxiety relief. Physicians should also discuss goals of care with their patients.
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Dispneia/etiologia , Dispneia/terapia , Neoplasias/complicações , Dispneia/fisiopatologia , HumanosRESUMO
In recent years, nerve growth factor (NGF) and the NGF receptor have become potential therapeutic targets in the treatment of acute and chronic pain states. NGF is a neurotrophin involved in regulating the function of sensory and sympathetic neurons during development. Numerous pain states have been linked to elevated levels of NGF and its role in increasing the perception of pain. Tanezumab, a recombinant humanized monoclonal antibody (IgG), was developed to target NGF, binding both circulating and local tissue NGF preventing interaction with the tropomyosin-related kinase-A and p75 receptors. Recent clinical studies with tanezumab in different patient populations to date, including osteoarthritis, low back pain, and diabetic peripheral neuropathy, demonstrate efficacy with few side effects, including transient arthralgias, paresthesias, hypoesthesia, and rarely, osteonecrosis. Anti-NGF antibodies are a novel therapy in pain management and have shown promise in the treatment of certain pain conditions, which at present are poorly treated. Tanezumab offers an exciting new class of analgesics that has the potential to change the treatment of pain.
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COVID-19 , Pandemias , Criança , Criança Hospitalizada , Humanos , Consentimento Livre e Esclarecido , Políticas , Pesquisa , SARS-CoV-2RESUMO
We report a case series on the observed effects of low-dose ketamine infusions in 4 critically ill patients with varying complications related to prolonged critical illness. Doses of ketamine infusion ranged from 0.5 to 4 µg/kg/min. A low-dose ketamine infusion was used to reduce agitation in a patient requiring high doses of sedatives and analgesics. In a second patient, ketamine improved depression and anxiety symptoms. In a third patient, ketamine may have facilitated liberation from mechanical ventilation. In a fourth patient, ketamine was used for palliation to avoid lethargy. Ketamine may be considered to help decrease agitation, manage pain, facilitate opioid and benzodiazepine withdrawal, prevent respiratory depression, and potentially manage depression and anxiety in chronically critically ill patients.
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Analgésicos/administração & dosagem , Ansiedade/tratamento farmacológico , Estado Terminal , Hipnóticos e Sedativos/administração & dosagem , Ketamina/administração & dosagem , Dor/tratamento farmacológico , Agitação Psicomotora/tratamento farmacológico , Ansiedade/psicologia , Doença Crônica , Cuidados Críticos/métodos , Estado Terminal/psicologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Agitação Psicomotora/psicologia , Resultado do TratamentoRESUMO
OBJECTIVES: This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC). METHODS: A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group). RESULTS: Of 27 patients, 17 had optimal CRS before RT. The actuarial survival at 5 and 10 years (in parenthesis) from date of radiation were LRFS (70% and 60%), overall survival (30% and 19%), and disease-free survival (33% and 20%). None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy. CONCLUSIONS: Long-term follow-up in this selected series confirmed the benefit of IFRT (±CRS) in localized ROC. Chemotherapy salvage in a similar NIFRT group was not equivalent, suggesting a role for locoregional therapies in selected patients with ROC.
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Adenocarcinoma de Células Claras/radioterapia , Cistadenocarcinoma Seroso/radioterapia , Neoplasias do Endométrio/radioterapia , Recidiva Local de Neoplasia/radioterapia , Neoplasias Ovarianas/radioterapia , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Gerenciamento Clínico , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Carga TumoralRESUMO
CONTEXT: A recent systematic review found that use of an immunization information system (IIS) is an effective intervention to increase vaccination rates. The purpose of this review was to evaluate costs and benefits associated with implementing, operating, and participating with an IIS. The speed of technology change has had an effect on costs and benefits of IIS and is considered in this review. EVIDENCE ACQUISITION: An economic evaluation for IIS was conducted using methods developed for Community Guide systematic reviews. The literature search covered the period from January 1994 to March 2012 and identified 12 published articles and 2 government reports. EVIDENCE SYNTHESIS: Most studies involving cost data evaluated (1) system costs of building an IIS and (2) cost of exchanging immunization data; most economic benefits focused on administrative efficiency. CONCLUSIONS: A major challenge to evaluating a technology-based intervention is the evolution that comes with technology improvements and advancements. Although the cost and benefit data may be less applicable today due to changes in system technology, data exchange methods, availability of vendor support, system functionalities, and scope of IIS, it is likely that more up-to-date estimates and comprehensive estimates of benefits would support the findings of cost savings in this review. More research is needed to update and address limitations in the available evidence and to enable assessment of economic costs and benefits of present-day IIS.
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Análise Custo-Benefício , Programas de Imunização/economia , Sistemas de Informação/economia , Vacinação em Massa/economia , Humanos , Saúde Pública/métodos , Vacinas/administração & dosagemRESUMO
CONTEXT: Immunizations are the most effective way to reduce incidence of vaccine-preventable diseases. Immunization information systems (IISs) are confidential, population-based, computerized databases that record all vaccination doses administered by participating providers to people residing within a given geopolitical area. They facilitate consolidation of vaccination histories for use by health care providers in determining appropriate client vaccinations. Immunization information systems also provide aggregate data on immunizations for use in monitoring coverage and program operations and to guide public health action. EVIDENCE ACQUISITION: Methods for conducting systematic reviews for the Guide to Community Preventive Services were used to assess the effectiveness of IISs. Reviewed evidence examined changes in vaccination rates in client populations or described expanded IIS capabilities related to improving vaccinations. The literature search identified 108 published articles and 132 conference abstracts describing or evaluating the use of IISs in different assessment categories. EVIDENCE SYNTHESIS: Studies described or evaluated IIS capabilities to (1) create or support effective interventions to increase vaccination rates, such as client reminder and recall, provider assessment and feedback, and provider reminders; (2) determine client vaccination status to inform decisions by clinicians, health care systems, and schools; (3) guide public health responses to outbreaks of vaccine-preventable disease; (4) inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities; and (5) facilitate vaccine management and accountability. CONCLUSIONS: Findings from 240 articles and abstracts demonstrate IIS capabilities and actions in increasing vaccination rates with the goal of reducing vaccine-preventable disease.
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Programas de Imunização/métodos , Sistemas de Informação , Vacinação em Massa/métodos , Humanos , Vacinação em Massa/estatística & dados numéricos , Saúde Pública/métodos , Saúde Pública/normas , Vacinas/administração & dosagem , Vacinas/uso terapêuticoRESUMO
On August 26, 2011, crizotinib received accelerated approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by a test approved by the U.S. Food and Drug Administration (FDA). Approval was based on two single-arm trials demonstrating objective response rates (ORRs) of 50% and 61% and median response durations of 42 and 48 weeks. On November 20, 2013, crizotinib received regular approval based on confirmation of clinical benefit in study A8081007, a randomized trial in 347 patients with ALK-positive advanced NSCLC who had previously received one platinum-containing regimen. Patients were assigned (1:1) to receive crizotinib 250 mg orally twice daily or standard of care (docetaxel or pemetrexed). The primary endpoint was progression-free survival (PFS) determined by independent radiology review; secondary endpoints were ORR and overall survival (OS). PFS was significantly longer in the crizotinib arm, with median PFS of 7.7 and 3.0 months in the crizotinib and chemotherapy arms, respectively, and a 46% absolute increase in ORR but no difference in OS between treatment arms at the interim analysis. The most common adverse drug reactions (>25%) in crizotinib-treated patients were vision disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue. The most serious toxicities of crizotinib were hepatotoxicity, interstitial lung disease or pneumonitis, and QT-interval prolongation. Crizotinib's rapid clinical development program (6 years from identification of ALK rearrangements in a subset of NSCLC to full FDA approval) is a model of efficient drug development in this new era of molecularly targeted oncology therapy.