ResearchPad - online-only https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Use of Deep Learning to Develop and Analyze Computational Hematoxylin and Eosin Staining of Prostate Core Biopsy Images for Tumor Diagnosis]]> https://www.researchpad.co/article/elastic_article_12571 Histopathological diagnoses of tumors from tissue biopsy after hematoxylin and eosin (H&E) dye staining is the criterion standard for oncological care, but H&E staining requires trained operators, dyes and reagents, and precious tissue samples that cannot be reused.ObjectivesTo use deep learning algorithms to develop models that perform accurate computational H&E staining of native nonstained prostate core biopsy images and to develop methods for interpretation of H&E staining deep learning models and analysis of computationally stained images by computer vision and clinical approaches.Design, Setting, and ParticipantsThis cross-sectional study used hundreds of thousands of native nonstained RGB (red, green, and blue channel) whole slide image (WSI) patches of prostate core tissue biopsies obtained from excess tissue material from prostate core biopsies performed in the course of routine clinical care between January 7, 2014, and January 7, 2017, at Brigham and Women’s Hospital, Boston, Massachusetts. Biopsies were registered with their H&E-stained versions. Conditional generative adversarial neural networks (cGANs) that automate conversion of native nonstained RGB WSI to computational H&E-stained images were then trained. Deidentified whole slide images of prostate core biopsy and medical record data were transferred to Massachusetts Institute of Technology, Cambridge, for computational research. Results were shared with physicians for clinical evaluations. Data were analyzed from July 2018 to February 2019.Main Outcomes and MeasuresMethods for detailed computer vision image analytics, visualization of trained cGAN model outputs, and clinical evaluation of virtually stained images were developed. The main outcome was interpretable deep learning models and computational H&E-stained images that achieved high performance in these metrics.ResultsAmong 38 patients who provided samples, single core biopsy images were extracted from each whole slide, resulting in 102 individual nonstained and H&E dye–stained image pairs that were compared with matched computationally stained and unstained images. Calculations showed high similarities between computationally and H&E dye–stained images, with a mean (SD) structural similarity index (SSIM) of 0.902 (0.026), Pearson correlation coefficient (PCC) of 0.962 (0.096), and peak signal to noise ratio (PSNR) of 22.821 (1.232) dB. A second cGAN performed accurate computational destaining of H&E-stained images back to their native nonstained form, with a mean (SD) SSIM of 0.900 (0.030), PCC of 0.963 (0.011), and PSNR of 25.646 (1.943) dB compared with native nonstained images. A single blind prospective study computed approximately 95% pixel-by-pixel overlap among prostate tumor annotations provided by 5 board certified pathologists on computationally stained images, compared with those on H&E dye–stained images. This study also used the first visualization and explanation of neural network kernel activation maps during H&E staining and destaining of RGB images by cGANs. High similarities between kernel activation maps of computationally and H&E-stained images (mean-squared errors <0.0005) provide additional mathematical and mechanistic validation of the staining system.Conclusions and RelevanceThese findings suggest that computational H&E staining of native unlabeled RGB images of prostate core biopsy could reproduce Gleason grade tumor signatures that were easily assessed and validated by clinicians. Methods for benchmarking, visualization, and clinical validation of deep learning models and virtually H&E-stained images communicated in this study have wide applications in clinical informatics and oncology research. Clinical researchers may use these systems for early indications of possible abnormalities in native nonstained tissue biopsies prior to histopathological workflows. ]]> <![CDATA[Association of Homocysteine, Methionine, and <i>MTHFR</i> 677C&gt;T Polymorphism With Rate of Cardiovascular Multimorbidity Development in Older Adults in Sweden]]> https://www.researchpad.co/article/elastic_article_12570 Strong evidence links high total serum homocysteine (tHcy) and low methionine (Met) levels with higher risk of ischemic disease, but other cardiovascular (CV) diseases may also be associated with their pleiotropic effects.ObjectivesTo investigate the association of serum concentrations of tHcy and Met with the rate of CV multimorbidity development in older adults and to explore the role of methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism in this association.Design, Setting, and ParticipantsThe Swedish National Study on Aging and Care in Kungsholmen is a cohort study of randomly selected individuals aged 60 years or older. The present study included data on 1969 individuals with complete information and without CV diseases at baseline, collected from the baseline examination (2001-2004) to the fourth follow-up (2013-2016). Data analysis was conducted from January to May 2019.ExposuresConcentrations of tHcy and Met were measured from nonfasting venous blood samples. The Met:tHcy ratio was considered a possible indicator of methylation activity. MTHFR status was dichotomized as any T carriers vs noncarriers.Main Outcome and MeasuresThe number of CV diseases at each wave was ascertained based on medical interviews and records, laboratory test results, and drug data. Linear mixed models were used to study the association of baseline tHcy and Met levels and the rate of CV multimorbidity development, adjusting for sociodemographic characteristics, CV risk factors, chronic disease burden, and drug use.ResultsOf 1969 participants, most were women (1261 [64.0%]), with a mean (SD) age of 70.9 (9.8) years; 1703 participants (86.6%) had at least a high school level of education. Baseline measurements of serum tHcy, Met, and the Met:tHcy ratio were associated with the rate of CV disease accumulation (tHcy: β = 0.023 per year; 95% CI, 0.015 to 0.030; P < .001; Met: β = −0.007 per year; 95% CI, −0.013 to −0.001; P = .02; Met:tHcy ratio: β = −0.017 per year; 95% CI, −0.023 to −0.011; P < .001). The association between low Met concentrations and the rate of CV multimorbidity development was restricted to the group with CT/TT alleles of MTHFR (β = 0.023 per year; 95% CI, 0.006 to 0.041; P = .009). Results remained largely significant when individual CV diseases were removed from the total count 1 at a time (eg, ischemic heart disease, tHcy: β = 0.023 per year; 95% CI, 0.013 to 0.027; P < .001; Met: β = −0.006 per year; 95% CI, −0.011 to −0.0003; P = .04; Met:tHcy ratio: β = −0.015 per year; 95% CI, −0.020 to −0.009; P < .001).Conclusions and RelevanceIn this study, high tHcy and low Met levels were associated with faster CV multimorbidity development in older age. The interactive association of Met concentrations and MTHFR polymorphism, together with the association found for the Met:tHcy ratio, point toward the relevance of impaired methylation in the pathogenesis of CV aging. ]]> <![CDATA[Assessment of a Prediction Model for Antidepressant Treatment Stability Using Supervised Topic Models]]> https://www.researchpad.co/article/elastic_article_12569 In the absence of readily assessed and clinically validated predictors of treatment response, pharmacologic management of major depressive disorder often relies on trial and error.ObjectiveTo assess a model using electronic health records to identify predictors of treatment response in patients with major depressive disorder.Design, Setting, and ParticipantsThis retrospective cohort study included data from 81 630 adults with a coded diagnosis of major depressive disorder from 2 academic medical centers in Boston, Massachusetts, including outpatient primary and specialty care clinics from December 1, 1997, to December 31, 2017. Data were analyzed from January 1, 2018, to March 15, 2020.ExposuresTreatment with at least 1 of 11 standard antidepressants.Main Outcomes and MeasuresStable treatment response, intended as a proxy for treatment effectiveness, defined as continued prescription of an antidepressant for 90 days. Supervised topic models were used to extract 10 interpretable covariates from coded clinical data for stability prediction. With use of data from 1 hospital system (site A), generalized linear models and ensembles of decision trees were trained to predict stability outcomes from topic features that summarize patient history. Held-out patients from site A and individuals from a second hospital system (site B) were evaluated.ResultsAmong the 81 630 adults (56 340 women [69%]; mean [SD] age, 48.46 [14.75] years; range, 18.0-80.0 years), 55 303 reached a stable response to their treatment regimen during follow-up. For held-out patients from site A, the mean area under the receiver operating characteristic curve (AUC) for discrimination of the general stability outcome was 0.627 (95% CI, 0.615-0.639) for the supervised topic model with 10 covariates. In evaluation of site B, the AUC was 0.619 (95% CI, 0.610-0.627). Building models to predict stability specific to a particular drug did not improve prediction of general stability even when using a harder-to-interpret ensemble classifier and 9256 coded covariates (specific AUC, 0.647; 95% CI, 0.635-0.658; general AUC, 0.661; 95% CI, 0.648-0.672). Topics coherently captured clinical concepts associated with treatment response.Conclusions and RelevanceThe findings suggest that coded clinical data available in electronic health records may facilitate prediction of general treatment response but not response to specific medications. Although greater discrimination is likely required for clinical application, the results provide a transparent baseline for such studies. ]]> <![CDATA[Association of Pharmacist Prescription With Dispensed Duration of Hormonal Contraception]]> https://www.researchpad.co/article/elastic_article_12568 Since 2016, 11 states have expanded the scope of pharmacists to include direct prescription of hormonal contraception. Dispensing greater than 1 month’s supply is associated with improved contraceptive continuation rates and fewer breaks in coverage. Scant data exist on the practice of pharmacist prescription of contraception and its outcomes compared with traditional, clinic-based prescriptions.ObjectiveTo compare the amount of hormonal contraceptive supply dispensed between pharmacists and clinic-based prescriptions. Prescribing patterns were assessed by describing prescribing practices for women with contraindications to combined hormonal contraception. Characteristics of women seeking hormonal contraception directly from pharmacists were also described.Design, Setting, and ParticipantsThis cohort study surveyed women aged 18 to 50 years who presented to pharmacies in California, Colorado, Hawaii, and Oregon for hormonal contraception prescribed by a clinician or a pharmacist between January 30 and November 1, 2019.ExposuresPharmacist or clinic-based prescription of contraception.Main Outcomes and MeasuresMonths of contraceptive supply dispensed.ResultsFour hundred ten women (mean [SD] age, 27.1 [7.7] years) were recruited who obtained contraception directly from a pharmacist (n = 144) or by traditional clinician prescription (n = 266). Women obtaining contraception from a pharmacist were significantly younger (82 [56.9%] vs 115 [43.2%] participants aged 18-24 years; P = .03), had less education (38 [26.4%] vs 100 [37.6%] with a bachelor degree; P = .002), and were more likely to be uninsured (16 [11.1%] vs 8 [3.0%] participants; P = .001) compared with women with a prescription from a clinician. Pharmacists were significantly more likely to prescribe a 6-month or greater supply of contraceptives than clinicians (6.9% vs 1.5%, P < .001) and significantly less likely to only prescribe a 1-month supply (42 [29.2%] vs 118 [44.4%] prescriptions; P < .001). Controlling for all covariates, women seen by pharmacists had higher odds of receipt of a 6-month or greater supply of contraceptives compared with those seen by clinicians (odds ratio = 3.55; 95% CI, 1.88-6.70). Pharmacists were as likely as clinicians to prescribe a progestin-only method to women with a potential contraindication to estrogen (n = 60 women; 8 [20.0%] vs 6 [30.0%], P = .52).Conclusions and RelevanceThese findings suggest that pharmacist prescription of contraception may be associated with improved contraceptive continuation by preventing breaks in coverage through the provision of a greater supply of medication. Efforts are needed to educate prescribing providers on the importance of dispensing 6 months or greater contraceptive supply. ]]> <![CDATA[Association of Individual-Level Factors With Visual Outcomes in Optic Neuritis]]> https://www.researchpad.co/article/elastic_article_7262 Using corticosteroids to treat acute demyelinating optic neuritis has been identified as an area for shared decision-making. However, no analysis exists to support personalized shared decision-making that considers long- and short-term treatment benefits.ObjectiveTo develop models of individual-level visual outcomes for patients with optic neuritis.Design, Setting, and ParticipantsThis secondary analysis of the Optic Neuritis Treatment Trial (ONTT), a randomized clinical trial, was performed at 14 academic eye centers and 1 large community eye center. Adults aged 18 to 46 years with incident acute unilateral optic neuritis within 8 days of vision loss onset were included. Data were collected from July 1988 to June 1991, downloaded on October 15, 2018, and analyzed from January 24, 2019, to February 20, 2020, using multivariable linear regression modeling.ExposuresIntravenous corticosteroids vs placebo.Main Outcomes and MeasuresVisual acuity (VA) at 1 year. Secondary outcomes were 1-year contrast sensitivity (CS) and VA and CS at 15 and 30 days. Independent variables included age, sex, race, multiple sclerosis status, optic neuritis episodes in the fellow eye, vision symptoms (days), pain, optic disc swelling, viral illness, treatment group, and baseline VA or CS.ResultsOf the 455 participants, median age was 31.8 (interquartile range [IQR], 26.3-37.0) years; 350 (76.9%) were women; and 388 (85.3%) were white. For 410 participants (90.1%) with 1-year outcomes, median VA improved from 20/66 (IQR, 20/28-20/630) at enrollment to 20/17 (IQR, 20/14-20/21) at 1 year. Baseline VA was the primary variable associated with 1-year VA (regression coefficient, 0.056 [95% CI, 0.008-0.103]; P = .02) if baseline VA was better than count fingers (CF). At 15 days, baseline VA and treatment status were associated with VA in those participants with baseline VA better than CF (regression coefficient, 0.305 [95% CI, 0.231-0.380]; F = 9.42; P < .001). However, the difference of medians (20/18 [95% CI, 20/17-20/19] with intravenous corticosteroids vs 20/23 [95% CI, 20/21-20/26] with placebo) was small for the median VA (20/66) in the trial. Treatment was not associated with 15-day or 1-year VA in participants with baseline VA of CF or worse.Conclusions and RelevanceIn this study, long-term VA was associated with severity of baseline vision loss. Early benefits with intravenous corticosteroid treatment were limited to participants with baseline VA better than CF. However, the early, temporary benefit of intravenous corticosteroids is of questionable clinical significance and should be weighed against potential harms. ]]> <![CDATA[Mode of Death Among Japanese Adults With Heart Failure With Preserved, Midrange, and Reduced Ejection Fraction]]> https://www.researchpad.co/article/elastic_article_7261 Despite intensive treatment, hospitalized patients with acute decompensated heart failure (ADHF) have a substantial risk of postdischarge mortality. Limited data are available on the possible differences in the incidence and mechanisms of death among patients with heart failure with reduced ejection fraction (HFrEF), heart failure with midrange ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF).ObjectivesTo examine the incidences and mode of postdischarge mortality among patients with ADHF and to compare the risk profile among patients with HFrEF, HFmrEF, and HFpEF.Design, Setting, and ParticipantsThis prospective cohort study of 4056 patients hospitalized for ADHF analyzed data from 3717 patients who were discharged from October 1, 2014, to March 31, 2016. Data analysis was performed from April 1 to August 31, 2019.ExposuresDeath among patients with ADHF after hospital discharge.Main Outcomes and MeasuresAll-cause death and cause of postdischarge mortality after the index hospitalization by left ventricular ejection fraction (LVEF) subgroup.ResultsA total of 3717 patients (mean [SD] age, 77.7 [12.0] years; 2049 [55.1%] male) were included in the study. The mean (SD) LVEF at baseline was 46.4% (16.2%). Among 3717 enrolled patients, 1383 (37.2%) were categorized as having HFrEF (LVEF, <40%), 703 (18.9%) as having HFmrEF (LVEF, 40%-49%), and 1631 (43.9%) as having HFpEF (LVEF, ≥50%). The incidence and causes of death were evaluated after discharge from the index hospitalization. The median follow-up period was 470 days (interquartile range, 357-649 days), and the 1-year follow-up rate was 96%. During follow-up, all-cause death occurred in 848 patients (22.8%; HFrEF group: 298 [21.5%; 95% CI, 19.5%-23.8%]; HFmrEF group: 158 [22.5%; 95% CI, 19.5%-25.7%]; and HRpEF group: 392 [24.0%; 95% CI, 22.0%-26.2%]; P = .26), cardiovascular deaths occurred in 523 patients (14.1%; HFrEF group: 203 [14.7%; 95% CI, 12.9%-16.6%]; HFmrEF group: 97 [13.8%; 95% CI, 11.4%-16.5%]; and HFpEF group: 223 [13.7%; 95% CI, 12.1%-15.4%]; P = .71), and sudden cardiac death occurred in 98 patients (2.6%; HFrEF group: 44 [3.2%; 95% CI, 2.4%-4.2%]; HFmrEF group: 14 [2.0%; 95% CI, 1.2%-3.3%]; and HFpEF group: 40 [2.5%; 95% CI, 1.8%-3.3%]; P = .23). The risks of causes of death were similar among the subtypes.Conclusions and RelevanceThe mode of death was similar among the heart failure subtypes. Given the nonnegligible incidence of sudden cardiac death in patients with HFpEF found in this study, further studies appear to be warranted to identify a high-risk subset in this population. ]]> <![CDATA[Association of Adjuvant Chemotherapy With Overall Survival in Patients With Early-Stage Breast Cancer and 21-Gene Recurrence Scores of 26 or Higher]]> https://www.researchpad.co/article/Nba4f4c0a-8488-46f6-9aba-327b7280fa82 This cohort study investigates the association of overall survival with receiving chemotherapy among patients with early-stage breast cancer and recurrence scores of 26 to 30 vs those with recurrence scores of 31 or greater.

]]>
<![CDATA[Association of Long-term Strenuous Physical Activity and Extensive Sitting With Incident Radiographic Knee Osteoarthritis]]> https://www.researchpad.co/article/N22dbeded-b7f4-438c-8bb5-92155f4c1c67 Persons with knee symptoms recognize the health benefits of engaging in physical activity, but uncertainty persists about whether regular strenuous physical activity or exercise can accelerate tissue damage. A sedentary lifestyle of inactivity or underloading may also be associated with deleterious joint health.ObjectiveTo establish whether long-term strenuous physical activity participation and extensive sitting behavior are each associated with increased risk of developing radiographic knee osteoarthritis (KOA) in individuals at high risk for the disease.Design, Setting, and ParticipantsThis cohort study analyzed data from the Osteoarthritis Initiative, a prospective longitudinal cohort study of men and women with or at an increased risk of developing symptomatic, radiographic KOA. Community-dwelling adults were recruited from 4 US sites (Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island) and were followed up for up to 10 years. Individuals were included if they had a baseline Kellgren and Lawrence grade of 0 in both knees and completed a PASE (Physical Activity Scale for the Elderly) questionnaire at baseline and at least 2 follow-up visits over an 8-year interval. Data analyses were conducted from May 2018 to November 2018.ExposuresBaseline to 8-year trajectories of strenuous physical activity participation and extensive sitting behavior were identified using group-based trajectory models.Main Outcomes and MeasuresIncident radiographic KOA, defined as Kellgren and Lawrence grade 2 or higher in either knee by the 10-year follow-up visit.ResultsA total of 1194 participants were included in the sample (697 women [58.4%]), with a baseline mean (SD) age of 58.4 (8.9) years and mean body mass index (BMI) of 26.8 (4.5). Four distinct trajectories of weekly hours spent in strenuous physical activities and 3 distinct trajectories of extensive sitting were identified. Long-term engagement in low-to-moderate physical activities (adjusted odds ratio [OR], 0.69; 95% CI, 0.48-1.01) or any strenuous physical activities (adjusted OR, 0.75; 95% CI, 0.53-1.07) was not associated with 10-year incident radiographic KOA. Persistent extensive sitting was not associated with incident KOA. Despite relatively mild symptoms and high function in this early-stage sample, 594 participants (49.7%) did not engage in any strenuous physical activities (ie, 0 h/wk) across 8 years, and 507 (42.5%) engaged in persistent moderate-to-high frequency of extensive sitting. Older age, higher BMI, more severe knee pain, non–college graduate educational level, weaker quadriceps, and depression were each associated with a persistent lack of engagement in strenuous physical activities.Conclusions and RelevanceResults from this study appeared to show no association between long-term strenuous physical activity participation and incident radiographic KOA. The findings raise the possibility of a protective association between incident KOA and a low-to-moderate level of strenuous physical activities. ]]> <![CDATA[Association of Parental Socioeconomic Status and Newborn Telomere Length]]> https://www.researchpad.co/article/Ne9bf6227-0586-4513-a79a-b0ccda323397 This cohort study evaluates the association of parental socioeconomic status with telomere length at birth, a marker of biological aging.

]]>
<![CDATA[Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging]]> https://www.researchpad.co/article/N5bdc6f17-0d65-4c21-8e9e-558ebfe89d34 Epidemiological studies indicate a link between obsessive-compulsive disorder and infections, particularly streptococcal pharyngitis. Pediatric acute-onset neuropsychiatric syndrome (PANS) manifests suddenly with obsessions, compulsions, and other behavioral disturbances, often after an infectious trigger. The current working model suggests a unifying inflammatory process involving the central nervous system, particularly the basal ganglia.ObjectiveTo investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects microstructural abnormalities across the brain regions of children with PANS.Design, Setting, and ParticipantsCase-control study performed at a single-center, multidisciplinary clinic in the United States focusing on the evaluation and treatment of children with PANS. Sixty consecutive patients who underwent 3 Tesla (T) magnetic resonance imaging (MRI) before immunomodulation from September 3, 2012, to March 30, 2018, were retrospectively reviewed for study inclusion. Six patients were excluded by blinded investigators because of imaging or motion artifacts, 3 patients for major pathologies, and 17 patients for suboptimal atlas image registration. In total, 34 patients with PANS before initiation of treatment were compared with 64 pediatric control participants.Main Outcomes and MeasuresUsing atlas-based MRI analysis, regional brain volume, diffusion, and cerebral blood flow were measured in the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem. An age and sex–controlled multivariable analysis of covariance was used to compare patients with control participants.ResultsThis study compared 34 patients with PANS (median age, 154 months; age range, 55-251 months; 17 girls and 17 boys) and 64 pediatric control participants (median age, 139 months; age range, 48-213 months); 41 girls and 23 boys). Multivariable analysis demonstrated a statistically significant difference in MRI parameters between patients with PANS and control participants (F21,74 = 6.91; P < .001; partial η2 = 0.662). All assessed brain regions had statistically significantly increased median diffusivity compared with 64 control participants. Specifically, the deep gray matter (eg, the thalamus, basal ganglia, and amygdala) demonstrated the most profound increases in diffusivity consistent with the cardinal clinical symptoms of obsessions, compulsions, emotional dysregulation, and sleep disturbances. No statistically significant differences were found regarding volume and cerebral blood flow.Conclusions and RelevanceThis study identifies cerebral microstructural differences in children with PANS in multiple brain structures, including the deep gray matter structures (eg, the thalamus, basal ganglia, and amygdala). Further study of MRI is warranted in prospective, clinical trials as a potential quantitative method for assessing patients under evaluation for PANS. ]]> <![CDATA[Association of Neurodevelopmental Outcomes With Environmental Exposure to Cyclohexanone During Neonatal Congenital Cardiac Operations]]> https://www.researchpad.co/article/Na11688b5-f737-4534-bf13-eeee96be979e Cyclohexanone is an industrial solvent used as a coupling agent in medical plastics. Perioperative exposure to cyclohexanone could play a role in lower scores on measures of neurodevelopmental outcomes after neonatal cardiac operations.ObjectiveTo examine the presence and association of serum cyclohexanone level with neonatal cardiac operations and neurodevelopmental outcomes.Design, Setting, and ParticipantsThis ad hoc secondary analysis used data from the Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass randomized clinical trial. The cohort included neonates younger than 31 days and with at least 37 weeks postgestational age at surgical treatment who were enrolled at a single center between June 1, 2012, and October 31, 2016, and who had completed a neurodevelopmental assessment at age 12 months. Data were analyzed from July 8 to August 20, 2019.ExposuresSerum cyclohexanone and its metabolites were measured preoperatively (prior to skin incision), postoperatively (immediately after the surgical procedure was completed), and 12 hours postoperatively. Cyclohexanone and the molar sum of its metabolites were examined at each point and as a geometric mean of all 3 points.Main Outcomes and MeasuresNeurodevelopment was assessed at age 12 months with the Bayley Scales of Infant and Toddler Development III, assessing cognitive, language, and motor function composite scores standardized to a population mean (SD) of 100 (15). Linear regression models were used to determine covariate-adjusted differences in 12-month cognitive, language, and motor composite scores per interquartile range increase in cyclohexanone level or summed metabolite molar concentrations.ResultsAmong 85 included neonates, mean (SD) age at surgical treatment was 9.7 (5.3) days, 49 (58%) were boys, and 54 (64%) underwent corrective repair. Mean (SD) Bayley Scales of Infant and Toddler Development III composite scores were 108.2 (12.2) for cognitive function, 104.7 (11.0) for language function, and 94.7 (15.7) for motor function. Median (interquartile range) cyclohexanone levels increased approximately 3-fold from immediately prior to surgical treatment to immediately after surgical treatment (572 [389-974] vs 1744 [1469-2291] μg/L; P = .001). In adjusted analyses, higher geometric mean cyclohexanone levels were associated with significantly lower composite scores for cognitive (−4.23; 95% CI, −7.39 to −1.06; P = .01) and language (−3.65; 95% CI, −6.41 to −0.88; P = .01) function. The difference in composite scores for motor function among infants with higher geometric mean cyclohexanone levels was not statistically significant(−3.93, 95% CI: −8.19 to 0.33, P = .07).Conclusions and RelevanceThe findings of this secondary analysis of a randomized clinical trial suggest that infants who underwent neonatal cardiac surgical treatment with cardiopulmonary bypass had substantial cyclohexanone levels, which were associated with adverse neurodevelopmental function at age 12 months.Trial RegistrationClinicalTrials.gov identifier: NCT01579513 ]]> <![CDATA[Factors Associated With Urgent Care Reliance and Outpatient Health Care Use Among Children Enrolled in Medicaid]]> https://www.researchpad.co/article/Nff6a212c-e640-49db-b97f-e8baba63713c This cohort study examines factors associated with high usual care reliance among children enrolled in Medicaid and examines the association between usual care reliance and outpatient health care use.

]]>
<![CDATA[Prevalence, Incidence, and Sensitization Profile of β-lactam Antibiotic Allergy in Hong Kong]]> https://www.researchpad.co/article/N9404c99e-6567-4056-be56-48ba9251af27 Allergy to β-lactam antibiotics is one of the most frequently reported drug reactions, but epidemiological data in Chinese populations are lacking. Ethnic- and region-specific sensitization patterns of skin testing for β-lactam antibiotic allergy are also unknown.ObjectiveTo identify the prevalence, 1-year incidence, and sensitization patterns of β-lactam antibiotic allergy in patients in Hong Kong.Design, Setting, and ParticipantsThis cross-sectional study obtained territorywide, anonymized electronic patient data from the Clinical Management Systems of the Hospital Authority, the sole publicly funded health care system in Hong Kong with facilities in 7 regions (Hong Kong East, Hong Kong West, Kowloon Central, Kowloon East, Kowloon West, New Territories East, and New Territories West). All referrals to Queen Mary Hospital for β-lactam antibiotic allergy testing from January 1, 2018, to December 31, 2019, were also analyzed for sensitization patterns.Main Outcomes and MeasuresPrevalence and cumulative incidence of β-lactam antibiotic allergy reported in Hong Kong, and sensitization patterns according to β-lactam antibiotic allergy skin testing.ResultsComplete records of 7 184 271 unique patients were analyzed, with a men to women ratio of 1:1.2 and with a median age of 44 years. The prevalence of physician-reported β-lactam antibiotic allergy was 2.0%, and the cumulative incidence was 107 per 100 000 population. Of the 34 402 new drug allergies reported in 2018, 8032 (23.3%) were β-lactam antibiotic allergies. Three hundred fifty-five patients with reactions suggestive of β-lactam antibiotic allergy underwent skin testing, and only 49 (13.8%; 95% CI, 10.64%-17.90%) of them had positive test results. Of these 49 patients, 14 (28.6%; 95% CI, 18.35%-44.49%) had selective reaction and 35 (71.4%; 95% CI, 59.84%-85.27%) had nonselective reaction. The sensitization rate to either benzylpenicilloyl polylysine or a minor determinant (benzylpenicilloate) was 47.0% (n = 23; 95% CI, 34.85%-63.21%), with 10 patients monosensitized to benzylpenicilloyl polylysine only (20.4%; 95% CI, 11.74%-35.48%) and 5 to benzylpenicilloate only (10.2%; 95% CI, 4.45%-23.42%).Conclusions and RelevanceResults of this study suggest that patients in Hong Kong with β-lactam antibiotic allergy had much higher rates of monosensitization to benzylpenicilloyl polylysine and benzylpenicilloate, making these reagents essential in β-lactam antibiotic skin tests. Such a finding warrants future studies into whether this sensitization is specific to ethnicity or region. ]]> <![CDATA[Atypical Value-Driven Selective Attention in Young Children With Autism Spectrum Disorder]]> https://www.researchpad.co/article/N0c2d574f-e877-41a1-810e-7d658903a2b9 Enhanced selective attention toward nonsocial objects and impaired attention to social stimuli constitute key clinical features of autism spectrum disorder (ASD). Yet, the mechanisms associated with atypical selective attention in ASD are poorly understood, which limits the development of more effective interventions. In typically developing individuals, selective attention to social and nonsocial stimuli is associated with the informational value of the stimuli, which is typically learned over the course of repeated interactions with the stimuli.ObjectiveTo examine value learning (VL) of social and nonsocial stimuli and its association with selective attention in preschoolers with and without ASD.Design, Setting, and ParticipantsThis case-control study compared children with ASD vs children with developmental delay (DD) and children with typical development (TD) recruited between March 3, 2017, and June 13, 2018, at a university-based research laboratory. Participants were preschoolers with ASD, DD, or TD.Main Outcomes and MeasuresProcedure consisted of an eye-tracking gaze-contingent VL task involving social (faces) and nonsocial (fractals) stimuli and consisting of baseline, training, and choice test phases. Outcome measures were preferential attention to stimuli reinforced (high value) vs not reinforced (low value) during training. The hypotheses were stated before data collection.ResultsIncluded were 115 preschoolers with ASD (n = 48; mean [SD] age, 38.30 [15.55] months; 37 [77%] boys), DD (n = 31; mean [SD] age, 45.73 [19.49] months; 19 [61%] boys), or TD (n = 36; mean [SD] age, 36.53 [12.39] months; 22 [61%] boys). The groups did not differ in sex distribution; participants with ASD or TD had similar chronological age; and participants with ASD or DD had similar verbal IQ and nonverbal IQ. After training, the ASD group showed preference for the high-value nonsocial stimuli (mean proportion, 0.61 [95% CI, 0.56-0.65]; P < .001) but not for the high-value social stimuli (mean proportion, 0.51 [95% CI, 0.46-0.56]; P = .58). In contrast, the DD and TD groups demonstrated preference for the high-value social stimuli (DD mean proportion, 0.59 [95% CI, 0.54-0.64]; P = .001 and TD mean proportion, 0.57 [95% CI, 0.53-0.61]; P = .002) but not for the high-value nonsocial stimuli (DD mean proportion, 0.52 [95% CI, 0.44-0.59]; P = .64 and TD mean proportion, 0.50 [95% CI, 0.44-0.57]; P = .91). Controlling for age and nonverbal IQ, autism severity was positively correlated with enhanced learning in the nonsocial domain (r = 0.22; P = .03) and with poorer learning in the social domain (r = −0.26; P = .01).Conclusions and RelevanceIncreased attention to objects in preschoolers with ASD may be associated with enhanced VL in the nonsocial domain. When paired with poor VL in the social domain, enhanced value-driven attention to objects may play a formative role in the emergence of autism symptoms by altering attentional priorities and thus learning opportunities in affected children. ]]> <![CDATA[Assessment of Treatment Strategies to Achieve Hepatitis C Elimination in Canada Using a Validated Model]]> https://www.researchpad.co/article/Ne66479d8-d944-42fa-a2ea-4ea968a224e0 This decision analytical model study explores the association of different treatment strategies with hepatitis C virus epidemiology and associated mortality among individuals with hepatitis C virus infection in Canada and assesses whether Canada can achieve hepatitis C virus elimination by 2030.

]]>
<![CDATA[Phenotypic Variability Among Patients With D4Z4 Reduced Allele Facioscapulohumeral Muscular Dystrophy]]> https://www.researchpad.co/article/N2473627d-012f-4242-9d3c-cabe346fb9c7 Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disorder, associated with the deletion of tandemly arrayed D4Z4 repetitive elements. The extensive use of molecular analysis of the D4Z4 locus for FSHD diagnosis has revealed wide clinical variability, suggesting that subgroups of patients exist among carriers of the D4Z4 reduced allele (DRA).ObjectiveTo investigate the clinical expression of FSHD in the genetic subgroup of carriers of a DRA with 7 to 8 repeat units (RUs).Design, Setting, and ParticipantsThis multicenter cross-sectional study included 422 carriers of DRA with 7 to 8 RUs (187 unrelated probands and 235 relatives) from a consecutive sample of 280 probands and 306 relatives from the Italian National Registry for FSHD collected between 2008 and 2016. Participants were evaluated by the Italian Clinical Network for FSHD, and all clinical and molecular data were collected in the Italian National Registry for FSHD database. Data analysis was conducted from January 2017 to June 2018.Main Outcomes and MeasuresThe phenotypic classification of probands and relatives was obtained by applying the Comprehensive Clinical Evaluation Form which classifies patients in the 4 following categories: (1) participants presenting facial and scapular girdle muscle weakness typical of FSHD (category A, subcategories A1-A3), (2) participants with muscle weakness limited to scapular girdle or facial muscles (category B, subcategories B1 and B2), (3) asymptomatic or healthy participants (category C, subcategories C1 and C2), and (4) participants with myopathic phenotypes presenting clinical features not consistent with FSHD canonical phenotype (category D, subcategories D1 and D2).ResultsA total of 187 probands (mean [SD] age at last neurological examination, 53.5 [15.2] years; 103 [55.1%] men) and 235 relatives (mean [SD] age at last neurologic examination, 45.1 [17.0] years; 104 [44.7%] men) with a DRA with 7 to 8 RUs and a molecular diagnosis of FSHD were evaluated. Of 187 probands, 99 (52.9%; 95% CI, 45.7%-60.1%) displayed the classic FSHD phenotype, whereas 86 (47.1%; 95% CI, 39.8%-54.3%) presented incomplete or atypical phenotypes. Of 235 carrier relatives from 106 unrelated families, 124 (52.8%; 95% CI, 46.4%-59.7%) had no motor impairment, whereas a small number (38 [16.2%; 95% CI, 9.8%-23.1%]) displayed the classic FSHD phenotype, and 73 (31.0%; 95% CI, 24.7%-38.0%) presented with incomplete or atypical phenotypes. In 37 of 106 families (34.9%; 95% CI, 25.9%-44.8%), the proband was the only participant presenting with a myopathic phenotype, while only 20 families (18.9%; 95% CI, 11.9%-27.6%) had a member with autosomal dominant FSHD.Conclusions and RelevanceThis study found large phenotypic variability associated with individuals carrying a DRA with 7 to 8 RUs, in contrast to the indication that a positive molecular test is the only determining aspect for FSHD diagnosis. These findings suggest that carriers of a DRA with 7 to 8 RUs constitute a genetic subgroup different from classic FSHD. Based on these results, it is recommended that clinicians use the Comprehensive Clinical Evaluation Form for clinical classification and, whenever possible, study the extended family to provide the most adequate clinical management and genetic counseling. ]]> <![CDATA[Adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) 2015 Guidelines in Acute Point-of-Care Ultrasound Research]]> https://www.researchpad.co/article/Nee6a5caa-fab9-467b-8d9f-86f377e063b5 Incomplete reporting of diagnostic accuracy research impairs assessment of risk of bias and limits generalizability. Point-of-care ultrasound has become an important diagnostic tool for acute care physicians, but studies assessing its use are of varying methodological quality.ObjectiveTo assess adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) 2015 guidelines in the literature on acute care point-of-care ultrasound.Evidence ReviewMEDLINE was searched to identify diagnostic accuracy studies assessing point-of-care ultrasound published in critical care, emergency medicine, or anesthesia journals from 2016 to 2019. Studies were evaluated for adherence to the STARD 2015 guidelines, with the following variables analyzed: journal, country, STARD citation, STARD-adopting journal, impact factor, patient population, use of supplemental material, and body region. Data analysis was performed in November 2019.FindingsSeventy-four studies were included in this systematic review for assessment. Overall adherence to STARD was moderate, with 66% (mean [SD], 19.7 [2.9] of 30 items) of STARD items reported. Items pertaining to imaging specifications, patient population, and readers of the index test were frequently reported (>66% of studies). Items pertaining to blinding of readers to clinical data and to the index or reference standard, analysis of heterogeneity, indeterminate and missing data, and time intervals between index and reference test were either moderately (33%-66%) or infrequently (<33%) reported. Studies in STARD-adopting journals (mean [SD], 20.5 [2.9] items in adopting journals vs 18.6 [2.3] items in nonadopting journals; P = .002) and studies citing STARD (mean [SD], 21.3 [0.9] items in citing studies vs 19.5 [2.9] items in nonciting studies; P = .01) reported more items. Variation by country and journal of publication were identified. No differences in STARD adherence were identified by body region imaged (mean [SD], abdominal, 20.0 [2.5] items; head and neck, 17.8 [1.6] items; musculoskeletal, 19.2 [3.1] items; thoracic, 20.2 [2.8] items; and other or procedural, 19.8 [2.7] items; P = .29), study design (mean [SD], prospective, 19.7 [2.9] items; retrospective, 19.7 [1.8] items; P > .99), patient population (mean [SD], pediatric, 20.0 [3.1] items; adult, 20.2 [2.7] items; mixed, 17.9 [1.9] items; P = .09), use of supplementary materials (mean [SD], yes, 19.2 [3.0] items; no, 19.7 [2.8] items; P = .91), or journal impact factor (mean [SD], higher impact factor, 20.3 [3.1] items; lower impact factor, 19.1 [2.4] items; P = .08).Conclusions and RelevanceOverall, the literature on acute care point-of-care ultrasound showed moderate adherence to the STARD 2015 guidelines, with more complete reporting found in studies citing STARD and those published in STARD-adopting journals. This study has established a current baseline for reporting; however, future studies are required to understand barriers to complete reporting and to develop strategies to mitigate them. ]]> <![CDATA[Geographic Variation and Associated Covariates of Diabetes Prevalence in India]]> https://www.researchpad.co/article/Nfae144f1-3668-4867-b48f-035ada0ebffd Diabetes is a severe metabolic disorder affecting human health worldwide, with increasing prevalence in low- and middle-income countries. Gaps in knowledge regarding factors that lead to diabetes and its association with tuberculosis (TB) endemicity at the national scale still exist, mainly because of the lack of large-scale dual testing and appropriate evaluation methods.ObjectivesTo identify locations in India where diabetes prevalence is concentrated, examine the association of diabetes with sociodemographic and behavioral covariates, and uncover where high regional TB endemicity overlaps with diabetes.Design, Setting, and ParticipantsThis cross-sectional study included 803 164 men aged 15 to 54 years and women aged 15 to 49 years who participated in the Demographic Health Survey (2015-2016), carried out by the India Ministry of Health and Family Welfare using a 2-stage clustered sampling, which included a diabetes estimation component. The survey was conducted from January 2015 to December 2016, and data analysis was conducted from July 2018 to January 2019.ExposuresSelf-reported diabetes status.Main Outcomes and MeasuresSelf-reported diabetes status was used to estimate the association of covariates, including educational level, sex, age, religion, marital status, alcohol use, tobacco use, obesity status, and household socioeconomic level, with diabetes prevalence. Additionally, regional tuberculosis endemicity level, estimated using the India TB report for 2014 from the Revised National TB Program, was included to evaluate the national extent of the spatial overlap of diabetes and TB.ResultsAmong 803 164 sampled individuals (691 982 [86.2%] women; mean [SD] age, 30.09 [9.97] years), substantial geographic variation in diabetes prevalence in India was found, with a concentrated burden at the southern coastline (cluster 1, Andhra Pradesh and Telangana: prevalence, 3.01% [1864 of 61 948 individuals]; cluster 2, Tamil Nadup and Kerala: prevalence, 4.32% [3429 of 79 435 individuals]; cluster 3, east Orissa: prevalence, 2.81% [330 of 11 758 individuals]; cluster 4, Goa: prevalence, 4.43% [83 of 1883 individuals]). Having obesity and overweight (odds ratio [OR], 2.44; 95% CI, 2.18-2.73; P < .001; OR, 1.66; 95% CI, 1.52-1.82; P < .001, respectively), smoking tobacco (OR, 3.04; 95% CI, 1.66-5.56; P < .001), and consuming alcohol (OR, 2.01; 95% CI, 1.37-2.95; P < .001) were associated with increased odds of diabetes. Regional TB endemicity and diabetes spatial distributions showed that there is a lack of consistent geographical overlap between these 2 diseases (eg, TB cluster 4: 60 213 TB cases; 186.79 diabetes cases in 20 183.88 individuals; 0.93% diabetes prevalence; TB cluster 8: 47 381 TB cases; 180.53 diabetes cases in 22 449.18 individuals; 0.80% diabetes prevalence; TB cluster 9: 37 620 TB cases, 601.45 diabetes cases in 12 879.36 individuals; 4.67% diabetes prevalence).Conclusions and RelevanceIn this study, identifying spatial clusters of diabetes on the basis of a nationally representative survey suggests that India may face different levels of disease severity, and each region might need to implement control strategies that are more appropriate for its unique epidemiologic context. ]]> <![CDATA[Assessment of Hospital Readmissions From the Emergency Department After Implementation of Medicare’s Hospital Readmissions Reduction Program]]> https://www.researchpad.co/article/Nfb136eae-d0ea-4d18-8e92-7c311f04021c The Medicare Hospital Readmissions Reduction Program (HRRP) is associated with reduced readmission rates, but it is unknown how this decrease occurred.ObjectiveTo examine whether the HRRP was associated with changes in the probability of readmission at emergency department (ED) visits after hospital discharge (ED revisits) overall and depending on whether admission is typically indicated for the patient’s condition at the ED revisit.Design, Setting, and ParticipantsThis retrospective cohort study used hospital and ED discharge data from California, Florida, and New York from January 1, 2010, to December 31, 2014. A difference-in-differences analysis examined change in readmission probability at ED revisits for recently discharged patients; ED revisits with clinical presentations for which admission is typically indicated vs those for which admission is more variable (ie, discretionary) were examined separately. Inclusion criteria were Medicare patients 65 years and older who revisited an ED within 30 days of inpatient discharge. Data were analyzed from December 18, 2018, to September 11, 2019.ExposuresBefore and after HRRP implementation among patients initially hospitalized for targeted vs nontargeted conditions.Main Outcomes and MeasuresThirty-day unplanned hospital readmissions at the ED revisit.ResultsA total of 9 914 068 index hospitalizations were identified in California, Florida, and New York from 2010 to 2014. Of 2 052 096 discharges in 2010, 1 168 126 (56.9%) discharges were women and 566 957 discharges (27.6%) were among patients older than 85 years. Among 1 421 407 patients with an unplanned readmission within 30 days of discharge, 1 266 107 patients (89.1%) were admitted through the ED. A total of 1 906 498 ED revisits were identified. After adjusting for patient demographic and clinical characteristics from the index hospitalization, HRRP implementation was associated with fewer readmissions from the ED, with a difference-in-difference estimate of −0.9 (95% CI, −1.4 to −0.4) percentage points (P < .001), or a 1.4% relative decrease from the 65.8% pre-HRRP readmission rates. Implementation of the HRRP was associated with fewer readmissions at the ED revisit involving clinical presentations for which admission is typically indicated (difference-in-differences estimate, −1.1 [95% CI, −1.6 to −0.6] percentage points; P < .001), or a 1.2% relative decrease from the 93.6% pre-HRRP rate. These results appear to be associated with patients presenting at the ED revisit with congestive heart failure (difference-in-difference estimate, −1.2 [95% CI, −2.0 to −0.4] percentage points; P = .003).Conclusions and RelevanceThese findings suggest that implementation of the HRRP was associated with a lower likelihood of readmission for recently discharged patients presenting to the ED, specifically for congestive heart failure. This highlights the critical role of the ED in readmission reduction under the HRRP and suggests that patient outcomes after HRRP implementation should be further studied. ]]> <![CDATA[Concordance Between Electronic Health Record Data and Medicare Part D Claims Data for Oral Anticancer Drug Use]]> https://www.researchpad.co/article/N1471ba53-b3db-456b-a586-1aa1e4fa1a49 This cross-sectional study determines the concordance between electronic health record and Medicare Part D claims data for the receipt of oral anticancer agents.

]]>