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INTRODUCTION: This study compares home-based oscillometry and spirometry for characterizing respiratory system disease in school-aged children with bronchopulmonary dysplasia (BPD) in clinical research. We hypothesized higher rates of successful completion and abnormal cases identified through oscillometry, with correlations between device measurements. METHODS: Participants 6-12 years old with BPD in the ongoing Air Quality, Environment and Respiratory Outcomes in BPD (AERO-BPD) study performed oscillometry followed by spirometry at two separate home visits. Parameters measured included airway resistance at 5 Hz(R5), resistance from 5 to 19 Hz(R5-19), resonance frequency(Fres), reactance at 5 Hz(X5), area under the curve between Fres and X5(AX), forced expiratory volume in 1 second(FEV1), forced vital capacity(FVC), and FEV1/FVC. Descriptive statistics identified the proportion of successful tests, correlation in measurements, and rate of lung disease for each device. RESULTS: Among 76 subjects with 120 paired observations, 95% and 71% of participants successfully performed oscillometry and spirometry, respectively, at home visit one. 98% and 77% successfully performed oscillometry and spirometry, respectively, at home visit two. Odds ratios favored oscillometry (range 5.31-10.13, p < 0.01). FEV1 correlated with AX (correlation coefficient r = -0.27, p = 0.03); FEV1/FVC with AX (r = -0.32, p = 0.02); and FEV1/FVC with R5 (r = -0.37, p = 0.01). AX exhibited the highest prevalence of abnormality at 25%; other oscillometry parameters ranged from 5%-22%. Forty-five to sixty-four percent of participants had abnormal spirometry. Oscillometry assessments had significantly lower odds of capturing lung disease (odds ratios 0.07-0.24, p < 0.0001). CONCLUSIONS: School-aged children with BPD demonstrated higher success rates in field-based oscillometry than spirometry. Spirometry exhibited higher rates of abnormality than oscillometry. Moderate correlation exists between device measurements.
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BACKGROUND AND OBJECTIVES: The SARS-CoV-2 pandemic shifted medical training programs to utilize virtual interviews (VIs) starting with the 2020 interview cycle. Fellowship interviews continue in the virtual format. It is unknown how this shift has affected equity for applicants as compared to in-person interviews. Equity in this study includes consideration of the opportunity for an applicant to accept, access, and conduct a VI. This study assessed pediatric pulmonary fellows' perception of equity associated with VIs and preferences for future cycles. METHODS: An anonymous survey link was emailed to Pediatric Pulmonology Program Directors to disseminate to incoming and first-year pediatric pulmonary fellows who participated in the 2022-2023 and 2021-2022 VI seasons. Responses were summarized by frequency and percentages. Inductive coding was used to thematically analyze free-text responses. RESULTS: Nearly 30% of eligible incoming and first-year pulmonary fellows (n = 35/119, 29.4%) completed the survey. Seventy-four percent felt that VIs reduce inequities as compared to in-person interviews. Sixty percent felt that VIs were the most equitable format, and 51% chose a VI as their preferred future format. Important practice considerations to promote equity for future VIs included providing applicants with instruction for the expected dress code, followed by providing applicants with virtual technology (91% and 89% of respondents ranked as at least "somewhat important," respectively). CONCLUSION: VIs were perceived as a more equitable interview format by pediatric pulmonology fellows compared to in-person interviews in our study. To increase equity for VIs, program directors can consider additional adaptations such as providing standardized instruction for dress code and providing the required technology.
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COVID-19 , Bolsas de Estudo , Entrevistas como Assunto , Pediatria , Pneumologia , SARS-CoV-2 , Humanos , Pneumologia/educação , Pediatria/educação , Inquéritos e Questionários , Pandemias , Masculino , Feminino , Educação de Pós-Graduação em Medicina/métodosRESUMO
BACKGROUND: Gastrointestinal (GI) complications in lung transplant recipients can occur any time during the post-operative period, leading to prolonged morbidity and mortality. Despite the negative association between GI complications and patient outcomes, little is known about their incidence and risk factors for their development in pediatric lung transplant recipients. METHODS: We performed a retrospective chart review at one pediatric tertiary center to describe the frequency of GI complications in lung transplant recipients. We identified potential risk factors for the diagnosis of gastroparesis, gastroesophageal reflux disease (GERD) and aspiration in the post-transplant period. Lastly, we investigated the association of these complications with mortality and graft survival. RESULTS: 84.3% of lung transplant recipients experienced at least one GI complication in the post-transplant period. Gastroparesis (52.9%), GERD (41.2%), and oropharyngeal dysphagia/laryngeal penetration (33.3%) were the most common complications diagnosed. Post-operative opioid exposure was a risk factor for gastroparesis, with the odds increasing 3.0% each day a patient was prescribed opioids (p = .021). The risk of death or retransplant in individuals who experienced gastroparesis was 2.7 times higher than those not diagnosed with gastroparesis (p = .027). CONCLUSION: Exposure to opioids in the post-operative period is a risk factor for gastroparesis and a prolonged hospitalization placed patients at risk for aspiration. Gastroparesis was associated with increased patient mortality and graft failure, while aspiration and GERD had no effect on long term outcomes. Future prospective studies investigating the relationship between opioid use and the development of a gastroparesis are necessary to improve patient outcomes.
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Refluxo Gastroesofágico , Gastroenteropatias , Gastroparesia , Transplante de Pulmão , Humanos , Criança , Gastroparesia/etiologia , Gastroparesia/complicações , Estudos Retrospectivos , Incidência , Estudos Prospectivos , Analgésicos Opioides , Transplantados , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Fatores de Risco , Transplante de Pulmão/efeitos adversos , PulmãoRESUMO
Vascular remodeling is the process of structural alteration and cell rearrangement of blood vessels in response to injury and is the cause of many of the world's most afflicted cardiovascular conditions, including pulmonary arterial hypertension (PAH). Many studies have focused on the effects of vascular endothelial cells and smooth muscle cells (SMCs) during vascular remodeling, but pericytes, an indispensable cell population residing largely in capillaries, are ignored in this maladaptive process. Here, we report that hypoxia-inducible factor 2α (HIF2α) expression is increased in the lung tissues of PAH patients, and HIF2α overexpressed pericytes result in greater contractility and an impaired endothelial-pericyte interaction. Using single-cell RNAseq and hypoxia-induced pulmonary hypertension (PH) models, we show that HIF2α is a major molecular regulator for the transformation of pericytes into SMC-like cells. Pericyte-selective HIF2α overexpression in mice exacerbates PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2α overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the crucial role of NG2+ pericytes in pulmonary vascular remodeling via HIF2α signaling suggests a potential drug target for PH.
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Hipertensão Pulmonar , Remodelação Vascular , Camundongos , Humanos , Animais , Pericitos/metabolismo , Células Endoteliais/metabolismo , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , PulmãoRESUMO
Emergency departments are high-risk settings for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination. Environmental surface samples were obtained in rooms with patients suspected of having COVID-19 who did or did not undergo aerosol-generating procedures (AGPs). SARS-CoV-2 RNA surface contamination was most frequent in rooms occupied by coronavirus disease 2019 (COVID-19) patients who received no AGPs.
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COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , RNA Viral , Aerossóis e Gotículas Respiratórios , HospitaisRESUMO
Introduction: Data on the use of remote spirometry are limited in the pediatric population. We sought to assess the feasibility and accuracy of a digital turbine spirometer, Medical International Research (MIR) Spirobank Smart (MIR, New Berlin, WI, USA), compared with a pneumotachography spirometer, Pneumotrac (Vitalograph Inc., Lenexa, KS, USA), in field-based clinical research. Methods: This is a cross-sectional study of a subgroup of school-aged participants enrolled in the Air quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia (BPD) study, who performed same-day paired coached baseline spirometry measurements from the Pneumotrac and MIR devices. Proportion of successful tests was estimated for each device and compared using McNemar's test. Correlation between devices forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was analyzed by Lin's concordance correlation, and Bland-Altman plots were generated. Results: Twenty-one participants with history of BPD completed home spirometry maneuvers on both devices. The mean age of participants was 8.7 years. The mean FEV1 and FVC measurement was 81% predicted and 90.4% predicted, respectively. The proportion of acceptable tests appeared higher using Pneumotrac (81%) than when using MIR (67%), although without evidence of discordance (P = 0.317). Among subjects with successful tests on both devices, Lin's concordance correlation demonstrated moderate agreement (FEV1 r = 0.955, 95% confidence interval [CI]: 0.87-0.98; FVC r = 0.971, CI: 0.91-0.99). The mean difference in FEV1 between Pneumotrac and MIR was 0.079 L (95% limits of agreement were -0.141 to 0.298 L) and FVC was 0.075 L (95% limits of agreement were -0.171 to 0.322 L). These were relatively small and without evidence of systematic or volume-dependent bias. Conclusions: Utilizing turbine spirometers may be a promising and feasible way to perform pulmonary function testing for field research in children.
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Poluição do Ar , Pesquisa Biomédica , Neoplasias da Mama , Displasia Broncopulmonar , Lesões Pré-Cancerosas , Criança , Recém-Nascido , Humanos , Feminino , Displasia Broncopulmonar/diagnóstico , Estudos Transversais , EspirometriaRESUMO
PURPOSE: The genomic underpinnings of inherited lung cancer risk are poorly understood. This prospective study characterized the clinical phenotype of patients and families with germline EGFR pathogenic variants (PVs). METHODS: The Investigating Hereditary Risk from T790M study (ClinicalTrials.gov identifier: NCT01754025) enrolled patients with lung cancer whose tumor profiling harbored possible germline EGFR PVs and their relatives, either in person or remotely, providing germline testing and follow-up. RESULTS: A total of 141 participants were enrolled over a 5-year period, 100 (71%) remotely. Based upon previous genotyping, 116 participants from 59 kindreds were tested for EGFR T790M, demonstrating a pattern of Mendelian inheritance with variable lung cancer penetrance. In confirmed or obligate carriers of a germline EGFR PV from 39 different kindreds, 50/91 (55%) were affected with lung cancer with 34/65 (52%) diagnosed by age 60 years. Somatic testing of lung cancers in carriers revealed that 35 of 37 (95%) had an EGFR driver comutation. Among 36 germline carriers without a cancer diagnosis, 15 had computed tomography (CT) imaging and nine had lung nodules, including a 28-year-old with >10 lung nodules. Given geographic enrichment of germline EGFR T790M in the southeast United States, genome-wide haplotyping of 46 germline carriers was performed and identified a 4.1-Mb haplotype shared by 41 (89%), estimated to originate 223-279 years ago. CONCLUSION: To our knowledge, this is the first prospective description of familial EGFR-mutant lung cancer, identifying a recent founder germline EGFR T790M variant enriched in the Southeast United States. The high prevalence of EGFR-driver lung adenocarcinomas and lung nodules in germline carriers supports effort to identify affected patients and family members for investigation of CT-based screening for these high-risk individuals.
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Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Adulto , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Estudos Prospectivos , Receptores ErbB/genética , Mutação , Inibidores de Proteínas Quinases , Mutação em Linhagem Germinativa , PulmãoRESUMO
OBJECTIVE: To determine health-related quality of life (HRQOL) of school-aged children with bronchopulmonary dysplasia (BPD) using the standardized Patient-Reported Outcomes Measurement Information System (PROMIS) assessment tools. STUDY DESIGN: The Indoor Air Quality and Respiratory Morbidity in Children with BPD Study is an ongoing observational study of school-aged children with BPD. HRQOL is assessed at enrollment by 3 PROMIS questionnaires, Parent Proxy Scale-Global Health 7, Parent Proxy Psychological Stress Experiences-Short Form, and the Parent Proxy Profile-Profile-25. PROMIS data were tested for significant deviation from the standardized T-Score references for normative populations of children. RESULTS: Eighty-nine subjects enrolled in the AERO-BPD study had complete outcome data for HRQOL. The mean age was 9 (±2) years and 43% were female. Mean days on respiratory support totaled 96 (±40). Across all domains, school-aged children with BPD reported similar or slightly better outcomes than the reference sample. Statistically significant findings of lower depression (P < .0001), fatigue (P < .0001), and pain (P < .0001) scores were found; there was no difference in psychological stress experiences (P = .87), global health (P = .06), anxiety (P = .08), relationships (P = .80), and mobility (P = .59) domains. CONCLUSIONS: This study demonstrated that children with BPD may have less depression, fatigue, and pain HRQL than the general population. Once validated, these findings may offer reassurance to parents and providers caring for children with BPD.
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Displasia Broncopulmonar , Criança , Feminino , Humanos , Masculino , Displasia Broncopulmonar/epidemiologia , Fadiga , Estudos Longitudinais , Dor , Qualidade de Vida/psicologiaRESUMO
We examined COVID-19 pandemic-related changes on reproductive health care delivery and pregnancy rates in an adolescent clinic. Through a retrospective data collection as part of quality improvement project, we compared the number of pregnancies, visit percentages for newly diagnosed pregnancies, and number/percentage of long acting reversible contraception (LARC) visits. The percentage of visits for newly diagnosed pregnancies during the first 3 months of the COVID-19 pandemic (April-June 2020) increased significantly relative to pre-pandemic percentages while the absolute number of new pregnancies only trended upward. Over the same timeframe, the total number of LARC visits decreased, although they consisted of a higher percentage of all in-person visits than pre-pandemic. After the first few months of the pandemic, these values returned to pre-pandemic levels. The substantial increase in the rate of new pregnancies during the first 3 to 6 months of the COVID-19 pandemic demonstrates the importance of prioritizing access to reproductive health care services for adolescents and young adults.
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Serviços de Saúde do Adolescente , COVID-19 , Contracepção Reversível de Longo Prazo , Taxa de Gravidez , Gravidez na Adolescência , Humanos , Feminino , Gravidez , Adolescente , COVID-19/epidemiologia , Taxa de Gravidez/tendências , Hospitais Urbanos , Estudos Retrospectivos , Serviços de Planejamento Familiar/tendências , Contracepção Reversível de Longo Prazo/tendênciasRESUMO
OBJECTIVES: The objective of this study was to study the performance of two available home spirometers used by people with Cystic Fibrosis (PwCF) over a short-term period and to assess user experience. STUDY DESIGN: This was a prospective observational study. Participants age 6 years and older were recruited to participate if they could complete acceptable spirometry in the clinic setting. METHODS: Participants used either the NuvoAir Air Next or the ZEPHYRx MIR Spirobank Smart spirometer. They underwent a one-time virtual training session, then completed 2 weeks of daily spirometry followed by 2 months of weekly spirometry. Participants responded to surveys and completed a debrief interview to understand user experience. Statistical analyses examined feasibility, reliability, and accuracy of each spirometer in an unsupervised, real-world setting. RESULTS: We report high adherence (80% [95% CI 61%-92%]) to our study protocol in all session attempts, but lower rates of adherence after discarding sessions performed with inadequate technique (47% [95% CI 28%-66%] to 63% [95% CI 44%-80%]). We found high reliability of each device by analyzing day-to-day variability and good concordance to recent in-clinic testing (NuvoAir r = 0.91 [0.82-0.93]; ZEPHYRx r = 0.70 [0.45-0.84]). Patient experience in this cohort was favorable with most reporting ease of use and reassurance knowing lung function was being tracked over time. CONCLUSIONS: This real-world study showed good performance of two different available home spirometers used by children and adults with CF. While overall adherence was high, suboptimal technique reduced the total interpretable data, possibly limiting feasibility. Future work should focus on developing sustainable training and coaching programs to support the success of home spirometry in a CF chronic care model.
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Fibrose Cística , Criança , Adulto , Humanos , Estudos de Viabilidade , Reprodutibilidade dos Testes , Espirometria , Fibrose Cística/diagnóstico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The COVID-19 pandemic and subsequent public health measures have resulted in a worsening of eating disorder symptoms and an increase in psychological distress. The present study examined symptoms and behaviors in adolescents and young adults with emotional eating, bingeing behaviors and binge eating disorder during the pandemic. Additionally, the study explored if individuals who experienced pandemic-related food availability and food affordability issues experienced increased binge-eating symptoms and negative feelings. METHOD: Participants (n = 39) were a convenience sample who participated between November 2020 and January 2021 in a weight and lifestyle management program at an urban New England pediatric hospital. Participants completed online surveys that assessed (1) participant's exposure to COVID-19 related stress and binge-eating behaviors using the COVID-19 Exposure and Family Impact Survey-Adolescent and Young Adult Version (CEFIS-AYA) and the Binge Eating Scale (BES) respectively, (2) participants' and their families' ability to attain and afford food and its association with bingeing behaviors, and (3) the relationship between food availability and affordability and negative emotions. RESULTS: Nearly half of all participants (48.7%) reported moderate to severe bingeing during the COVID-19 pandemic; those who experienced greater COVID-related stress reported more binge-eating behaviors (p = 0.03). There were no associations between indicators of food availability and affordability and binge eating or between food availability and affordability and negative feelings. CONCLUSIONS: Higher pandemic-related stress was associated with more binge-eating behaviors among adolescents and young adults. These results underscore the need to monitor symptoms and provide treatment for these patients despite barriers to care imposed by the COVID-19 pandemic. Research and clinical care for adolescents and young adults with EDs must recognize and respond to pandemic effects across the weight and disordered eating spectrum.
Research shows that the COVID-19 pandemic continues to have far-reaching adverse effects on mental health. For adolescents and young adults, the COVID-19 pandemic has altered critical aspects of their daily lives. The objective of this study is to investigate binge-eating behaviors in adolescents and young adults during the COVID-19 pandemic and to examine if individuals in households that experienced pandemic-related challenges such as food availability and food affordability had greater increases in bingeing behaviors and negative emotions such as feelings of anxiety, worry, mood, and loneliness. Thirty-nine adolescents and young adults previously assessed in an outpatient weight and lifestyle management program at an urban pediatric hospital were surveyed between November 2020 and January 2021. Almost half (48.7%) of these participants reported moderate to severe bingeing behaviors during the pandemic. Participants who reported higher impact of COVID-related stress on the CEFIS-AYA scale reported the highest level of binge-eating behaviors. There were no associations between food availability and affordability and binge eating or between food availability and affordability and negative feelings. This study highlights the importance of assessing patients' perception of how they experience the myriad impacts of COVID-19 on their daily lives, and the critical need for increases in accessible mental health services and continued support during the on-going pandemic.
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INTRODUCTION: There is evidence for increased risk of eating disorders in individuals with diet-treated chronic illnesses, however, data in patients with cystic fibrosis (CF) is less clear. No studies have evaluated avoidant/restrictive food intake disorder (ARFID) in the CF population. We investigated the prevalence of eating disorders, including ARFID, in adolescents and young adults with CF. METHODS: Patients with CF aged 14-35 years were recruited to complete three validated surveys: (1) Eating Disorder Examination Questionnaire (EDE-Q), (2) Nine-Item Avoidant/Restrictive Food Intake Disorder Scale (NIAS), and (3) Cystic Fibrosis Questionnaire-Revised (CFQ-R). Univariate linear regression analysis identified baseline risk factors associated with these survey scores. Variables with univariate p < 0.20 were considered for inclusion in a multivariable linear regression model. Backwards stepwise linear regression was used to identify the final model. RESULTS: A total of 52 patients enrolled. The prevalence of a positive screen on the EDE-Q was 9.6%, and on the NIAS was 13.5%. The CFQ-R eating and weight subscales were associated with scores on the EDE-Q, and CFQ-R eating subscale and being dF508 homozygous were correlated with the NIAS total score. DISCUSSION: A clinically significant number of participants screened positive for eating disorders on the EDE-Q and NIAS. Scores on the eating and weight scales of the CFQ-R were associated with the scores on these surveys. Further work is needed to better understand the optimal way to use such tools to screen and treat for eating disorders in individuals with CF.
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Fibrose Cística , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Doença Crônica , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Humanos , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: To determine bone mineral density (BMD) of transgender girls before pubertal blockade, and correlate with lifestyle and clinical variables. METHODS: Six transfemale peri-pubertal girls had knee magnetic resonance imaging (MRI) with T1-weighted images and single-voxel proton magnetic resonance spectroscopy (MRS). BMD measurements were obtained via dual-energy X-ray absorptiometry. Questionnaires about physical activity, diet, and the Eating Attitudes Test (EAT-26) were completed. The T2 relaxation rate of water (R2 = 1/T2 in s -1) was correlated with scores on surveys. RESULTS: Three participants (50 %) had a low bone mineral density for age based on total body less head Z-score less than -2; two participants (33 %) had a low BMD for age at lumbar spine. All had EAT-26 scores below threshold for clinical concern. All participants self-reported regular exercise. Bone marrow MR variables (T1, fat fraction, unsaturation index and R2 of water) were not correlated with DXA measures. CONCLUSIONS: Participants had low BMD on beginning pubertal blockade. Clinicians should consider monitoring BMD among youth AMAB, a group at potential risk for poor bone health.
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Densidade Óssea , Pessoas Transgênero , Absorciometria de Fóton , Adolescente , Medula Óssea/diagnóstico por imagem , Feminino , Humanos , Vértebras Lombares , ÁguaRESUMO
OBJECTIVE: Vitamin D deficiency is prevalent in patients with inflammatory bowel disease (IBD). The goal of this study was to assess the efficacy and safety of high-dose, interval cholecalciferol administration in patients with IBD receiving infliximab. METHODS: This prospective, longitudinal, open-label study enrolled pediatric and young adult patients with IBD and vitamin D deficiency. Subjects received 50,000 IU every 4 to 5âweeks (nâ=â11) or 100,000 IU every 6 to 8âweeks (nâ=â32) of oral cholecalciferol for 1 year. Dosing was directly observed and administered in conjunction with infliximab infusions. The primary endpoint was vitamin D sufficiency, defined as a 25-hydroxy-vitamin D (25-OHD) level ≥30âng/mL. RESULTS: Forty-three participants constituted the primary analysis population. 25-OHD levels reached steady-state after the third dose, and mean increases in 25-OHD levels were 8 vs. 4.5âng/mL in the 100,000 IU vs. 50,000 IU treatment groups, respectively. Only 43.8% of patients receiving 100,000 IU and 18.2% of patients receiving 50,000 IU achieved sufficiency. There was no difference in the 25-OHD level responsiveness in patients with Crohn disease versus those with ulcerative colitis (Pâ=â0.72). There was no correlation between 25-OHD levels and clinical disease activity in patients with Crohn disease (Pâ=â0.85) or ulcerative colitis (Pâ=â0.24). CONCLUSIONS: Supplementation with cholecalciferol was well-tolerated and direct observation is a promising paradigm for ensuring compliance with therapy. Patients with IBD, however, appear to require high doses of cholecalciferol, with less than half of patients (37% overall) achieving vitamin D sufficiency. Additional studies are necessary to determine the optimal treatment regimens.
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Colecalciferol , Doenças Inflamatórias Intestinais , Infliximab , Criança , Colecalciferol/administração & dosagem , Colecalciferol/efeitos adversos , Doença Crônica , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Suplementos Nutricionais , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Prospectivos , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Adulto JovemRESUMO
Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. Here we report the results of the phase 2 PrE0505 trial ( NCT02899195 ) of the anti-PD-L1 antibody durvalumab plus platinum-pemetrexed chemotherapy for 55 patients with previously untreated, unresectable pleural mesothelioma. The primary endpoint was overall survival compared to historical control with cisplatin and pemetrexed chemotherapy; secondary and exploratory endpoints included safety, progression-free survival and biomarkers of response. The combination of durvalumab with chemotherapy met the pre-specified primary endpoint, reaching a median survival of 20.4 months versus 12.1 months with historical control. Treatment-emergent adverse events were consistent with known side effects of chemotherapy, and all adverse events due to immunotherapy were grade 2 or lower. Integrated genomic and immune cell repertoire analyses revealed that a higher immunogenic mutation burden coupled with a more diverse T cell repertoire was linked to favorable clinical outcome. Structural genome-wide analyses showed a higher degree of genomic instability in responding tumors of epithelioid histology. Patients with germline alterations in cancer predisposing genes, especially those involved in DNA repair, were more likely to achieve long-term survival. Our findings indicate that concurrent durvalumab with platinum-based chemotherapy has promising clinical activity and that responses are driven by the complex genomic background of malignant pleural mesothelioma.
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Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Cisplatino/uso terapêutico , Mesotelioma Maligno/tratamento farmacológico , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Pemetrexede/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Reparo do DNA/genética , Feminino , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Mesotelioma Maligno/genética , Mesotelioma Maligno/mortalidade , Pessoa de Meia-Idade , Inibidores da Síntese de Ácido Nucleico/efeitos adversos , Pemetrexede/efeitos adversos , Intervalo Livre de Progressão , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genéticaRESUMO
BACKGROUND: Over 60% of military personnel in the United States currently use dietary supplements. Two types of dietary supplements, weight loss and sports performance (WLSP) supplements, are commonly used by military personnel despite the associated serious adverse effects such as dehydration and stroke. OBJECTIVE: To understand peer-to-peer communication about WLSP supplements among military personnel, we conducted a pilot study using the social media website, Reddit. METHODS: A total of 64 relevant posts and 243 comments from 2009 to 2019 were collected from 6 military subreddits. The posts were coded for year of posting, subreddit, and content consistent with the following themes: resources about supplement safety and regulation, discernability of supplement use through drug testing, serious adverse effects, brand names or identifiers, and reasons for supplement use. RESULTS: A primary concern posted by personnel who used supplements was uncertainty about the supplements that were not detectable on a drug test. Supplements to improve workout performance were the most frequently used. CONCLUSIONS: Our pilot study suggests that military personnel may seek out peer advice about WLSP supplements on Reddit and spread misinformation about the safety and effectiveness of these products through this platform. Future directions for the monitoring of WLSP supplement use in military personnel are discussed.
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INTRODUCTION: Glycoprotein NMB is a transmembrane protein linked with poor prognosis and is expressed in most squamous lung cancer. Glembatumumab vedotin is an antibody-drug conjugate targeting glycoprotein NMB, administered intravenously every 3 weeks in this phase 1 study to determine the safety, tolerability, and maximum tolerated dose in patients who had progressed on any number of previous therapies. RESULTS: A total of 13 patients were enrolled; adverse events (of any grade) including dyspnea, neutropenia, respiratory failure, anemia, increased aspartate transaminase/alanine transaminase, diarrhea, and hypophosphatemia were seen in 15% of patients. Grade 5 events included two cases of respiratory failure, either completely or partially attributed to cancer progression. The only other grade 5 event was "disease progression." The most common adverse events (23%) were decreased appetite, fatigue, rash, and weight loss.The median overall and progression-free survivals were 5.7 months (90% confidence interval: 2.5-16.8) and 2.5 months (90% confidence interval: 1.6-5.8) respectively. CONCLUSIONS: Glembatumumab vedotin exhibited no serious or unexpected toxicity in this heavily pretreated population, except those caused by disease progression. Modest anticancer activity was observed with a recommendation for a phase 2 dose of 1.9 mg/kg. This portion of the study was not undertaken owing to the company's decision to discontinue drug development.