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1.
J Am Med Inform Assoc ; 31(4): 949-957, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38244997

RESUMO

OBJECTIVE: To measure pediatrician adherence to evidence-based guidelines in the treatment of young children with attention-deficit/hyperactivity disorder (ADHD) in a diverse healthcare system using natural language processing (NLP) techniques. MATERIALS AND METHODS: We extracted structured and free-text data from electronic health records (EHRs) of all office visits (2015-2019) of children aged 4-6 years in a community-based primary healthcare network in California, who had ≥1 visits with an ICD-10 diagnosis of ADHD. Two pediatricians annotated clinical notes of the first ADHD visit for 423 patients. Inter-annotator agreement (IAA) was assessed for the recommendation for the first-line behavioral treatment (F-measure = 0.89). Four pre-trained language models, including BioClinical Bidirectional Encoder Representations from Transformers (BioClinicalBERT), were used to identify behavioral treatment recommendations using a 70/30 train/test split. For temporal validation, we deployed BioClinicalBERT on 1,020 unannotated notes from other ADHD visits and well-care visits; all positively classified notes (n = 53) and 5% of negatively classified notes (n = 50) were manually reviewed. RESULTS: Of 423 patients, 313 (74%) were male; 298 (70%) were privately insured; 138 (33%) were White; 61 (14%) were Hispanic. The BioClinicalBERT model trained on the first ADHD visits achieved F1 = 0.76, precision = 0.81, recall = 0.72, and AUC = 0.81 [0.72-0.89]. Temporal validation achieved F1 = 0.77, precision = 0.68, and recall = 0.88. Fairness analysis revealed low model performance in publicly insured patients (F1 = 0.53). CONCLUSION: Deploying pre-trained language models on a variable set of clinical notes accurately captured pediatrician adherence to guidelines in the treatment of children with ADHD. Validating this approach in other patient populations is needed to achieve equitable measurement of quality of care at scale and improve clinical care for mental health conditions.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Criança , Humanos , Masculino , Pré-Escolar , Feminino , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Hispânico ou Latino , Fidelidade a Diretrizes , Pediatras , Processamento de Linguagem Natural
2.
Pediatrics ; 151(5)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37066669

RESUMO

BACKGROUND AND OBJECTIVES: Primary care pediatricians (PCP) are often called on to manage child and adolescent anxiety and depression. The objective of this study was to describe PCP care practices around prescription of selective serotonin reuptake inhibitors (SSRI) for patients with anxiety and/or depression by using medical record review. METHODS: We identified 1685 patients who had at least 1 visit with a diagnosis of anxiety and/or depression in a large primary care network and were prescribed an SSRI by a network PCP. We randomly selected 110 for chart review. We reviewed the visit when the SSRI was first prescribed (medication visit), immediately previous visit, and immediately subsequent visit. We abstracted rationale for prescribing medication, subspecialist involvement, referral for psychotherapy, and medication monitoring practices. RESULTS: At the medication visit, in 82% (n = 90) of cases, PCPs documented reasons for starting an SSRI, most commonly clinical change (57%, n = 63). Thirty percent (n = 33) of patients had documented involvement of developmental-behavioral pediatrics or psychiatry subspecialists at 1 of the 3 visits reviewed. Thirty-three percent (n = 37) were referred to unspecified psychotherapy; 4% (n = 4) were referred specifically for cognitive behavioral therapy. Of 69 patients with a subsequent visit, 48% (n = 33) had documentation of monitoring for side effects. CONCLUSIONS: When prescribing SSRIs for children with anxiety and/or depression, PCPs in this network documented appropriate indications for starting medication and prescribed without subspecialist involvement. Continuing medical education for PCPs who care for children with these conditions should include information about evidence-based psychotherapy and strategies for monitoring potential side effects.


Assuntos
Depressão , Pediatria , Adolescente , Humanos , Criança , Depressão/diagnóstico , Depressão/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Ansiedade/terapia , Atenção Primária à Saúde
3.
J Dev Behav Pediatr ; 44(3): e196-e203, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36978234

RESUMO

OBJECTIVE: The purpose of this study is to determine the rate and age at first identification of speech-language delay in relation to child sociodemographic variables among a pediatric primary care network. METHODS: We analyzed a deidentified data set of electronic health records of children aged 1- to 5-years-old seen between 2015 and 2019 at 10 practices of a community-based pediatric primary health care network. Primary outcomes were numbers (proportions) of patients with relevant ICD-10 visit-diagnosis codes and patient age (months) at first documentation of speech-language delay. Regression models estimated associations between outcomes and patient characteristics, adjusting for practice affiliation. RESULTS: Of 14,559 included patients, 2063 (14.1%) had speech-language delay: 68.4% males, 74.4% with private insurance, and 96.1% with English as a primary household language. Most patients (60%) were first identified at the 18- or 24-month well-child visit. The mean age at first documentation was 25.4 months (SD = 9.3), which did not differ between practices reporting the use of standardized developmental screener and those using surveillance questionnaires. Regression models showed that males were more than twice as likely than females to be identified with speech-language delay (adjusted odds ratio [aOR] = 2.05, 95% CI: [1.86-2.25]); publicly insured were more likely than privately insured patients to be identified with speech-language delay (aOR = 1.48, 95% CI: [1.30-1.68]). Females were older than males at first identification (+1.2 months, 95% CI: [0.3-2.1]); privately insured were older than military insured patients (private +3.3 months, 95% CI: [2.2-4.4]). CONCLUSION: Pediatricians in this network identified speech-language delays at similar rates to national prevalence. Further investigation is needed to understand differences in speech-language delay detection across patient subgroups in practices that use developmental screening and/or surveillance.


Assuntos
Transtornos do Desenvolvimento da Linguagem , Fala , Masculino , Feminino , Criança , Humanos , Pré-Escolar , Lactente , Registros Eletrônicos de Saúde , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Inquéritos e Questionários , Atenção Primária à Saúde
4.
J Assist Reprod Genet ; 40(5): 1055-1062, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37000344

RESUMO

PURPOSE: To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos. METHODS: This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m2) category: normal weight (18.5-24.9), overweight (25-29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes. RESULTS: 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4% normal weight, 61.2% overweight, and 64.2% obese). There was also no difference for the secondary outcome, CPR, across all categories (58.5%, 65.5%, and 66.7%, respectively). This was confirmed in GEE analysis when adjusting for confounders. CONCLUSION: While increased weight has commonly been implicated in poor pregnancy outcomes, the effect of BMI on the success of mNC-FET remains debated. Across five years of data from a single institution using euploid embryos in mNC-FET cycles, elevated BMI was not associated with reduced LBR or CPR.


Assuntos
Coeficiente de Natalidade , Sobrepeso , Gravidez , Feminino , Humanos , Taxa de Gravidez , Estudos Retrospectivos , Índice de Massa Corporal , Criopreservação , Transferência Embrionária , Obesidade , Nascido Vivo
5.
J Allergy Clin Immunol Pract ; 11(4): 1243-1252.e6, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36736957

RESUMO

BACKGROUND: Frontline providers frequently make time-sensitive antibiotic choices, but many feel poorly equipped to handle antibiotic allergies. OBJECTIVE: We hypothesized that a digital decision support tool could improve antibiotic selection and confidence when managing ß-lactam allergies. METHODS: A digital decision support tool was designed to guide non-allergist providers in managing patients with ß-lactam allergy labels. Non-allergists were asked to make decisions in clinical test cases without the tool, and then with it. These decisions were compared using paired t tests. Users also completed surveys assessing their confidence in managing antibiotic allergies. RESULTS: The tool's algorithm was validated by confirming its recommendations aligned with that of five allergists. Non-allergist providers (n = 102) made antibiotic management decisions in test cases, both with and without the tool. Use of the tool increased the proportion of correct decisions from 0.41 to 0.67, a difference of 0.26 (95% CI, 0.22-0.30; P < .001). Users were more likely to give full-dose antibiotics in low-risk situations, give challenge doses in medium-risk situations, and avoid the antibiotic and/or consult allergy departments in high-risk situations. A total of 98 users (96%) said the tool would increase their confidence when choosing antibiotics for patients with allergies. CONCLUSIONS: A point-of-care clinical decision tool provides allergist-designed guidance for non-allergists and is a scalable system for addressing antibiotic allergies, irrespective of allergist availability. This tool encouraged appropriate antibiotic use in low- and medium-risk situations and increased caution in high-risk situations. A digital support tool should be considered in quality improvement and antibiotic stewardship efforts.


Assuntos
Hipersensibilidade a Drogas , Hipersensibilidade , Humanos , beta-Lactamas/efeitos adversos , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/terapia , Inquéritos e Questionários , Penicilinas
6.
J Assist Reprod Genet ; 40(4): 873-881, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36849755

RESUMO

PURPOSE: To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET). METHODS: Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5 mg of daily letrozole for 5 days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness. RESULTS: The demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7 days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38 weeks and 1 day for LTZ; 39 weeks and 0 day for NC) were full term. CONCLUSION: There were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6 days does not appear to be clinically significant, this warrants larger studies.


Assuntos
Criopreservação , Transferência Embrionária , Gravidez , Feminino , Recém-Nascido , Humanos , Letrozol/uso terapêutico , Estudos Retrospectivos , Criopreservação/métodos , Transferência Embrionária/métodos , Taxa de Gravidez , Blastocisto
7.
Acad Pediatr ; 23(2): 314-321, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35858663

RESUMO

OBJECTIVES: 1) To assess continuity of care (CoC) within primary-care practices for children with asthma and autism spectrum disorder (ASD) compared to children without chronic conditions, and 2) to determine patient and clinical-care factors associated with CoC. METHODS: Retrospective cohort study of electronic health records from office visits of children <9 years, seen ≥4 times between 2015 and 2019 in 10 practices of a community-based primary health care network in California. Three cohorts were constructed: 1) Asthma: ≥2 visits with asthma visit diagnoses; 2) ASD: same method; 3) Controls: no chronic conditions. CoC, using Usual Provider of Care measure (range > 0-1), was calculated for 1) all visits (overall) and 2) well-care visits. Fractional regression models examined CoC adjusting for patient age, medical insurance, practice affiliation, and number of visits. RESULTS: Of 30,678 children, 1875 (6.1%) were classified with Asthma, 294 (1.0%) with ASD, and 15,465 (50.4%) as Controls. Overall CoC was lower for Asthma (Mean = 0.58, SD 0.21) and ASD (M = 0.57, SD = 0.20) than Controls (M = 0.66, SD = 0.21); differences in well-care CoC were minimal. In regression models, lower overall CoC was found for Asthma (aOR = 0.90, 95% CI, 0.85-0.94). Lower overall and well-care CoC were associated with public insurance (aOR = 0.77, CI, 0.74-0.81; aOR = 0.64, CI, 0.59-0.69). CONCLUSION: After accounting for patient and clinical-care factors, children with asthma, but not with ASD, in this primary-care network had significantly lower CoC compared to children without chronic conditions. Public insurance was the most prominent patient factor associated with low CoC, emphasizing the need to address disparities in CoC.


Assuntos
Asma , Transtorno do Espectro Autista , Humanos , Criança , Pré-Escolar , Estudos Retrospectivos , Hospitalização , Doença Crônica , Continuidade da Assistência ao Paciente
8.
J Pers Med ; 12(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36556212

RESUMO

This study aims to compare endometrial growth before and after the addition of human growth hormone (hGH) in controlled ovarian hyperstimulation (COH) cycles. A 5-year retrospective cohort study of patients treated with hGH to improve oocyte development during COH cycles was conducted. Each patient's cycle without hGH immediately preceding cycle(s) with hGH was used for patients to serve as their own controls. Primary outcome was absolute growth in endometrial thickness from pre-stimulation start to day of hCG trigger. Mixed-model regression analysis controlled for patient correlation over repeat cycles and potential confounders. 80 patients were included. Mean age was 39.7 years; mean BMI was 23.8 kg/m2. Majority of patients were nulliparous, non-smoking, and White or Asian. Most common diagnosis was diminished ovarian reserve. Endometrial growth was compared between 159 COH cycles with hGH and 80 COH control cycles; mean increase was 4.5 mm and 3.9 mm, respectively-an unadjusted difference of 0.6 mm (95% CI: 0.2−1.1, p = 0.01). After adjusting for demographic/clinical factors, hGH was associated with 0.9 mm greater endometrial growth (0.4−1.4, p < 0.01). Absolute increase in endometrial thickness was higher in COH cycles that included hGH. Further prospective studies in embryo transfer cycles are needed.

9.
Neurohospitalist ; 12(4): 624-631, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36147760

RESUMO

Background and Purpose: Magnetic resonance imaging (MRI) is safe for most patients with cardiovascular implantable electronic devices (CIEDs). However, patients presenting with acute ischemic stroke or transient ischemic attack (AIS/TIA) who have CIEDs may undergo MRI less frequently than patients without devices. We assessed contemporary use of MRI for patients with AIS/TIA and the effect of a recent coverage revision by the Center for Medicare and Medicaid Services (CMS) on MRI utilization. Methods: Using Optum® claims data from January 2012 to June 2019, we performed an interrupted time series analysis of MRI utilization during AIS/TIA hospitalizations with the April 2018 CMS coverage revision serving as the intervention. For patients treated after the coverage revision, we used multivariable logistic regression to determine the association between lack of CIED and MRI utilization for AIS/TIA. Results: We identified 417,899 patient hospitalizations for AIS/TIA, of which 30,425 (7%) had a CIED present (CIED vs non-CIED patients: age 77.6 ± 9.8 vs 72.7 ± 12.3 years; 45.5% vs 54.3% female). From 2012 to 2019, annual MRI utilization increased from 3% to 20% for CIED patients and 58% to 66% for non-CIED patients. The CMS coverage revision was associated with a 4.2% absolute additional increase in MRI utilization for CIED patients. Non-CIED patients treated after the CMS coverage revision were substantially more likely than CIED patients to undergo MRI (adjusted OR 6.7, 95% CI: 6.3-7.1, P<.001). Conclusions: MRI utilization has increased for stroke patients with CIEDs but remains far lower than in similar patients without devices.

10.
Front Pediatr ; 10: 794722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372169

RESUMO

Objectives: To describe medication management of children diagnosed with anxiety and/or depression by primary care providers within a primary care network. Study Design/Methods: We performed a retrospective cross-sectional analysis of electronic health record (EHR) structured data from all children seen at least twice in a 4-year observation period within a network of primary care clinics in Northern California. For children who had visit diagnoses of anxiety, depression, anxiety+depression or symptoms characteristic of these conditions, we analyzed the rates and types of medications prescribed. A logistic regression model considered patient variables for the combined sample. Results: Of all patients 6-18 years old (N = 59,484), 4.4% (n = 2,635) had a diagnosis of anxiety only, 2.4% (n = 1,433) depression only, and 1.2% (n = 737) both anxiety and depression (anxiety + depression); 18% of children with anxiety and/or depression had comorbid ADHD. A total of 15.0% with anxiety only (n = 357), 20.5% with depression only (n = 285), and 47.4% with anxiety+depression (n=343) were prescribed a psychoactive non-stimulant medication. For anxiety and depression only, the top three medications prescribed were sertraline, fluoxetine, and citalopram. For anxiety + depression, the top three medications prescribed were citalopram, sertraline, and escitalopram. Frequently prescribed medications also included benzodiazepines. Logistic regression modeling showed that the depression only and anxety + depression categories had increased likelihood of medication prescription. Older age and mental health comorbidities were independently associated with increased likelihood of medication prescription. Conclusions: In this network, ~8% of children carried a diagnosis of anxiety and/or depression. Medication choices generally aligned with current recommendations with the exception of use of benzodiazepines.

11.
J Assist Reprod Genet ; 39(3): 647-654, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35122177

RESUMO

PURPOSE: To evaluate whether morphology impacts the pregnancy and neonatal outcomes of euploid blastocysts, and whether maternal age still affects outcomes when top-graded, euploid blastocysts are used. METHODS: This retrospective cohort study included all natural-cycle frozen embryo transfers (NC-FET) using an autologous, euploid blastocyst from June 2016 to June 2020 (n = 610). There were five groups based on embryo grade: AA, AB, BA, BB, and "any C". For analysis of only AA-graded embryos, there were three maternal age groups: < 35, 35-39, and 40 + years. The main outcomes measured were clinical pregnancy and live birth rates, while the secondary outcomes included neonatal outcomes such as gestational age at delivery and birthweight. Multivariable logistic regression models were performed to adjust for confounders. RESULTS: Euploid blastocysts with poorer morphology had lower odds of pregnancy and live birth; specifically, embryos with inner cell mass (ICM) graded as "C" had statistically significant decreased odds of pregnancy (aOR 0.33, p = 0.04) and live birth (aOR 0.32, p = 0.03) compared with ICM grade "A". The differences in pregnancy rate between trophectoderm grades were not statistically significant. Even in cycles that transferred a top-graded (AA) euploid embryo, maternal age at transfer was independently associated with outcomes. Embryo grade and maternal age, however, did not significantly impact neonatal outcomes such as prematurity and birthweight. CONCLUSION: The morphology of euploid blastocysts and maternal age at NC-FET both independently impact pregnancy outcomes. Neonatal outcomes were similar across embryo morphology and maternal age groups, suggesting that lower morphology euploid embryos not be discounted as viable options for transfer.


Assuntos
Blastocisto , Transferência Embrionária , Peso ao Nascer , Implantação do Embrião , Feminino , Humanos , Recém-Nascido , Idade Materna , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
13.
J Natl Cancer Inst ; 114(1): 87-96, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34255071

RESUMO

BACKGROUND: With advancing therapeutics, lung cancer (LC) survivors are rapidly increasing in number. Although mounting evidence suggests LC survivors have high risk of second primary lung cancer (SPLC), there is no validated prediction model available for clinical use to identify high-risk LC survivors for SPLC. METHODS: Using data from 6325 ever-smokers in the Multiethnic Cohort (MEC) study diagnosed with initial primary lung cancer (IPLC) in 1993-2017, we developed a prediction model for 10-year SPLC risk after IPLC diagnosis using cause-specific Cox regression. We evaluated the model's clinical utility using decision curve analysis and externally validated it using 2 population-based data-Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Screening Trial (NLST)-that included 2963 and 2844 IPLC (101 and 93 SPLC cases), respectively. RESULTS: Over 14 063 person-years, 145 (2.3%) ever-smoking IPLC patients developed SPLC in MEC. Our prediction model demonstrated a high predictive accuracy (Brier score = 2.9, 95% confidence interval [CI] = 2.4 to 3.3) and discrimination (area under the receiver operating characteristics [AUC] = 81.9%, 95% CI = 78.2% to 85.5%) based on bootstrap validation in MEC. Stratification by the estimated risk quartiles showed that the observed SPLC incidence was statistically significantly higher in the 4th vs 1st quartile (9.5% vs 0.2%; P < .001). Decision curve analysis indicated that in a wide range of 10-year risk thresholds from 1% to 20%, the model yielded a larger net-benefit vs hypothetical all-screening or no-screening scenarios. External validation using PLCO and NLST showed an AUC of 78.8% (95% CI = 74.6% to 82.9%) and 72.7% (95% CI = 67.7% to 77.7%), respectively. CONCLUSIONS: We developed and validated a SPLC prediction model based on large population-based cohorts. The proposed prediction model can help identify high-risk LC patients for SPLC and can be incorporated into clinical decision making for SPLC surveillance and screening.


Assuntos
Neoplasias Pulmonares , Segunda Neoplasia Primária , Detecção Precoce de Câncer , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Fumar/efeitos adversos , Fumar/epidemiologia
14.
Clin Lung Cancer ; 23(3): e210-e221, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34887193

RESUMO

INTRODUCTION: Patients with EGFR-mutant lung cancer who have had disease progression on osimertinib commonly receive platinum doublet chemotherapy, but whether adding immunotherapy or bevacizumab provides additional benefit is unknown. MATERIALS AND METHODS: This was a retrospective analysis at 2 university-affiliated institutions. Patients with EGFR-mutant lung cancer who had progression on osimertinib and received next-line therapy with platinum doublet chemotherapy (chemo), platinum doublet chemotherapy plus immunotherapy (chemo-IO), or platinum doublet chemotherapy plus bevacizumab (chemo-bev), were identified; patients who continued osimertinib with these regimens were included. Efficacy outcomes including duration on treatment (DOT) and overall survival (OS) from the start of chemotherapy were assessed. Associations of treatment regimen with outcomes were evaluated using adjusted Cox regression models, using pairwise comparisons between groups. RESULTS: 104 patients were included: 57 received chemo, 12 received chemo-IO, and 35 received chemo-bev. In adjusted models, patients who received chemo-IO had worse OS than did those who received chemo (hazard ratio (HR) 2.66, 95% CI 1.25-5.65; P= .011) or those who received chemo-bev (HR 2.37, 95% CI 1.09-5.65; P= .030). A statistically significant difference in OS could not be detected in patients who received chemo-bev versus those who received chemo (HR 1.50, 95% CI 0.84-2.69; P= .17). CONCLUSION: In this retrospective study, giving immunotherapy with platinum doublet chemotherapy after progression on osimertinib was associated with a worse OS compared with platinum doublet chemotherapy alone. Platinum doublet chemotherapy without immunotherapy (with consideration of continuation of osimertinib, in selected cases) is a reasonable choice in this setting, while we await results of clinical trials examining optimal next-line chemotherapy-based regimens in EGFR-mutant lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Platina/uso terapêutico , Estudos Retrospectivos
15.
Clin Lung Cancer ; 23(3): 264-272, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34838441

RESUMO

BACKGROUND: In most studies, patients with EGFR L858R mutant non-small cell lung cancer (NSCLC) have a shorter duration of response to EGFR tyrosine kinase inhibitor (TKI) therapy than do patients with EGFR exon 19 deletion NSCLC. The role that co-mutations play in this observation is unknown. METHODS: We performed a single-institution retrospective analysis of patients with EGFR-mutant NSCLC (exon 19 deletion or L858R mutation) who received frontline EGFR TKI for metastatic disease between 2014 and 2019, and who had STAMP next-generation sequencing (NGS), a 130-gene platform. Time to treatment failure (TTF) and overall survival were calculated using Cox models adjusted for age, race, and brain metastases. Co-mutations in key tumor suppressor genes (TP53, RB1, KEAP1, CDKN2A, or CTNNB1) were identified and their effects on outcomes were evaluated. Analyses were stratified according to receipt of osimertinib versus nonosimertinib as frontline EGFR TKI. RESULTS: Of 137 patients, 72 (57%) had EGFR exon 19 deletions and 65 (43%) had EGFR L858R mutations. Median TTF and OS on frontline TKI was shorter for the L858R cohort versus the exon 19 deletion cohort in univariate analysis. In adjusted models, this difference persisted for TTF but was no longer significant for OS. The difference in TTF in L858R mutant tumors was driven by the presence of co-mutations in key tumor suppressor genes. CONCLUSION: Patients with metastatic NSCLC with mutations in EGFR L858R had shorter TTF on frontline TKI compared to patients with EGFR exon 19 deletions. Co-mutations in tumor suppressor genes may play an important role in the differential response to TKI therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Éxons/genética , Genes Supressores de Tumor , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação/genética , Fator 2 Relacionado a NF-E2/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
16.
JPGN Rep ; 3(2): e185, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-37168915

RESUMO

To characterize the population of children diagnosed with small intestinal bacterial overgrowth (SIBO) based on breath test (BT), correlate symptomatology, and describe SIBO treatments and treatment efficacy. Methods: A retrospective cohort study of pediatric patients seen at Stanford Children's Health Gastroenterology Clinics from 2012 to 2018 who had a positive BT, defined by a rise in hydrogen by ≥20 ppm, a baseline hydrogen level ≥20 ppm, or a methane value ≥10 ppm. The main outcome was symptom resolution, defined as complete or partial improvement after a course of treatment. Absolute standardized differences and Chi-square tests were used to assess associations. Results: From 98 children, 54 met inclusion and did not meet exclusion criteria (53.7% female). Lactulose substrate was used for 41 (75.9%) patients, whereas glucose was used for 13 (24.1%). Complete or partial resolution of symptoms was achieved in 13 of 16 (81.2%) patients who received probiotics with or without antibiotics versus 21 of 31 (67.7%) patients treated with antibiotics alone (P = 0.524). Metronidazole versus rifaximin versus other antibiotics showed no significant difference in symptom resolution (12 (63.2%), 13 (76.5%), 7 (77.8%), respectively, P = 0.601). Conclusion: Seventy-two percent of patients experienced at least partial symptom relief after treatment. We did not find a strong correlation between specific symptoms and analyte elevation. There was no difference in effectiveness between metronidazole and rifaximin to treat SIBO symptoms. Further research needs to be done to determine effective treatments for SIBO in pediatrics.

18.
F S Rep ; 2(3): 275-281, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34553151

RESUMO

OBJECTIVE: To compare the pregnancy outcomes of lesbian women undergoing donor sperm intrauterine insemination (IUI) with that of heterosexual women undergoing IUI using partner or donor sperm. DESIGN: Retrospective cohort analysis. SETTING: Two academic fertility practices. PATIENTS: All IUI cycles between 2007 and 2016. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary outcomes included clinical pregnancy (CP) rates and live birth/ongoing pregnancy (LB) rates. The baseline characteristics and cycle characteristics were compared between the two groups using absolute standardized differences (ASDs). To account for the correlation between cycles per patient, a generalized estimating equation method for multivariable logistic regression was used. RESULTS: A total of 11,870 IUI cycles were included, of which 393 were in lesbian women using donor sperm and 11,477 were in heterosexual women with infertility using either partner or donor sperm. The CP rates were similar between the lesbian and heterosexual groups (13.2% vs. 11.1%, respectively, ASD = 0.06). In addition, the LB rates were similar between the two groups (10.4% vs. 8.3%, respectively, ASD = 0.10). After implementing the generalized estimating equation in a multivariable logistic regression, the lesbian group had an overall higher odds of CP (adjusted odds ratio 1.40, 95% confidence interval: [1.04-1.88]) and LB (adjusted odds ratio 1.59, 95% confidence interval [1.15-2.20]) compared with the heterosexual group. The clinical miscarriage rate was higher in the heterosexual group compared with that in the lesbian group (23.8% vs. 15.4%, respectively, ASD = 0.21). CONCLUSION: Although the unadjusted rates were similar between the two groups, the adjusted CP and LB odds were significantly higher for lesbian women undergoing IUI for procreative management than those for heterosexual women undergoing IUI for infertility.

19.
F S Rep ; 2(3): 320-326, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34553158

RESUMO

OBJECTIVE: To assess the impact of low estradiol (E2) levels in letrozole-stimulated frozen embryo transfer (FET) cycles on pregnancy and neonatal outcomes. DESIGN: Retrospective cohort. SETTING: University-affiliated fertility center. PATIENTS: All patients who underwent letrozole-stimulated FET cycles from January 2017 to April 2020 (n = 217). The "Low E2" group was defined as those with E2 serum levels on the day of trigger <10th percentile level (E2 <91.16 pg/mL, n = 22) and the "Normal E2" group was defined as those with E2 serum levels ≥10th percentile level (E2 ≥91.16 pg/mL, n = 195). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pregnancy outcomes including rates of clinical pregnancy, clinical miscarriage, and live birth. Neonatal outcomes including gestational age at delivery, birth weight, and Apgar score. RESULTS: The mean ± SD estradiol level was 66.8 ± 14.8 pg/mL for the "Low E2" group compared with 366.3 ± 322.1 pg/mL for the "Normal E2" group. There were otherwise no substantial differences in cycle characteristics such as endometrial thickness on the day of ovulation trigger and progesterone levels in early pregnancy. The "Low E2" group had a significantly higher clinical miscarriage rate (36.4% vs. 8.8%, adjusted odds ratio 8.06) and lower live birth rate (31.8% vs. 57.9%, adjusted odds ratio 0.28). Neonatal outcomes such as gestational age at delivery, mean birth weight, Apgar scores, and incidence of newborn complications were not clinically different between the groups. CONCLUSION: Low E2 levels were associated with a significantly higher miscarriage rate and lower live birth rate, suggesting that E2 levels in the follicular phase may have an effect on cycle outcomes. Given the rise in use of FET, further studies are needed to confirm our findings and understand the mechanisms.

20.
Pediatrics ; 148(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34544847

RESUMO

BACKGROUND AND OBJECTIVES: Children entering kindergarten ready to learn are more likely to thrive. Inequitable access to high-quality, early educational settings creates early educational disparities. TipsByText, a text-message-based program for caregivers of young children, improves literacy of children in preschool, but efficacy for families without access to early childhood education was unknown. METHODS: We conducted a randomized controlled trial with caregivers of 3- and 4-year-olds in 2 public pediatric clinics. Intervention caregivers received TipsByText 3 times a week for 7 months. At pre- and postintervention, we measured child literacy using the Phonological Awareness Literacy Screening Tool (PALS-PreK) and caregiver involvement using the Parent Child Interactivity Scale (PCI). We estimated effects on PALS-PreK and PCI using multivariable linear regression. RESULTS: We enrolled 644 families, excluding 263 because of preschool participation. Compared with excluded children, those included in the study had parents with lower income and educational attainment and who were more likely to be Spanish speaking. Three-quarters of enrollees completed pre- and postintervention assessments. Postintervention PALS-PreK scores revealed an unadjusted treatment effect of 0.260 (P = .040); adjusting for preintervention score, child age, and caregiver language, treatment effect was 0.209 (P = .016), equating to ∼3 months of literacy gains. Effects were greater for firstborn children (0.282 vs 0.178), children in 2-parent families (0.262 vs 0.063), and 4-year-olds (0.436 vs 0.107). The overall effect on PCI was not significant (1.221, P = .124). CONCLUSIONS: The health sector has unique access to difficult-to-reach young children. With this clinic-based texting intervention, we reached underresourced families and increased child literacy levels.


Assuntos
Intervenção Educacional Precoce/métodos , Alfabetização , Envio de Mensagens de Texto , Pré-Escolar , Humanos , Pais , Fatores Socioeconômicos
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