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1.
J Med Internet Res ; 26: e53367, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573752

ABSTRACT

BACKGROUND: Real-time surveillance of emerging infectious diseases necessitates a dynamically evolving, computable case definition, which frequently incorporates symptom-related criteria. For symptom detection, both population health monitoring platforms and research initiatives primarily depend on structured data extracted from electronic health records. OBJECTIVE: This study sought to validate and test an artificial intelligence (AI)-based natural language processing (NLP) pipeline for detecting COVID-19 symptoms from physician notes in pediatric patients. We specifically study patients presenting to the emergency department (ED) who can be sentinel cases in an outbreak. METHODS: Subjects in this retrospective cohort study are patients who are 21 years of age and younger, who presented to a pediatric ED at a large academic children's hospital between March 1, 2020, and May 31, 2022. The ED notes for all patients were processed with an NLP pipeline tuned to detect the mention of 11 COVID-19 symptoms based on Centers for Disease Control and Prevention (CDC) criteria. For a gold standard, 3 subject matter experts labeled 226 ED notes and had strong agreement (F1-score=0.986; positive predictive value [PPV]=0.972; and sensitivity=1.0). F1-score, PPV, and sensitivity were used to compare the performance of both NLP and the International Classification of Diseases, 10th Revision (ICD-10) coding to the gold standard chart review. As a formative use case, variations in symptom patterns were measured across SARS-CoV-2 variant eras. RESULTS: There were 85,678 ED encounters during the study period, including 4% (n=3420) with patients with COVID-19. NLP was more accurate at identifying encounters with patients that had any of the COVID-19 symptoms (F1-score=0.796) than ICD-10 codes (F1-score =0.451). NLP accuracy was higher for positive symptoms (sensitivity=0.930) than ICD-10 (sensitivity=0.300). However, ICD-10 accuracy was higher for negative symptoms (specificity=0.994) than NLP (specificity=0.917). Congestion or runny nose showed the highest accuracy difference (NLP: F1-score=0.828 and ICD-10: F1-score=0.042). For encounters with patients with COVID-19, prevalence estimates of each NLP symptom differed across variant eras. Patients with COVID-19 were more likely to have each NLP symptom detected than patients without this disease. Effect sizes (odds ratios) varied across pandemic eras. CONCLUSIONS: This study establishes the value of AI-based NLP as a highly effective tool for real-time COVID-19 symptom detection in pediatric patients, outperforming traditional ICD-10 methods. It also reveals the evolving nature of symptom prevalence across different virus variants, underscoring the need for dynamic, technology-driven approaches in infectious disease surveillance.


Subject(s)
Biosurveillance , COVID-19 , Physicians , SARS-CoV-2 , United States , Humans , Child , Artificial Intelligence , Retrospective Studies , COVID-19/diagnosis , COVID-19/epidemiology
2.
Evolution ; 78(6): 1183-1192, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38457362

ABSTRACT

Body size is a key morphological attribute, often used to delimit species boundaries among closely related taxa. But body size can evolve in parallel, reaching similar final states despite independent evolutionary and geographic origins, leading to faulty assumptions of evolutionary history. Here, we document parallel evolution in body size in the widely distributed leaf-nosed bat genus Hipposideros, which has misled both taxonomic and evolutionary inference. We sequenced reduced representation genomic loci and measured external morphological characters from three closely related species from the Solomon Islands archipelago, delimited by body size. Species tree reconstruction confirms the paraphyly of two morphologically designated species. The nonsister relationship between large-bodied H. dinops lineages found on different islands indicates that large-bodied ecomorphs have evolved independently at least twice in the history of this radiation. A lack of evidence for gene flow between sympatric, closely related taxa suggests the rapid evolution of strong reproductive isolating barriers between morphologically distinct populations. Our results position Solomon Islands Hipposideros as a novel vertebrate system for studying the repeatability of parallel evolution under natural conditions. We conclude by offering testable hypotheses for how geography and ecology could be mediating the repeated evolution of large-bodied Hipposideros lineages in the Solomon Islands.


Subject(s)
Chiroptera , Animals , Chiroptera/genetics , Chiroptera/anatomy & histology , Chiroptera/classification , Melanesia , Body Size , Biological Evolution , Phylogeny , Gene Flow
3.
PLoS One ; 18(11): e0286035, 2023.
Article in English | MEDLINE | ID: mdl-37910582

ABSTRACT

OBJECTIVE: To quantify the increase in pediatric patients presenting to the emergency department with suicidality before and during the COVID-19 pandemic, and the subsequent impact on emergency department length of stay and boarding. METHODS: This retrospective cohort study from June 1, 2016, to October 31, 2022, identified patients ages 6 to 21 presenting to the emergency department at a pediatric academic medical center with suicidality using ICD-10 codes. Number of emergency department encounters for suicidality, demographic characteristics of patients with suicidality, and emergency department length of stay were compared before and during the COVID-19 pandemic. Unobserved components models were used to describe monthly counts of emergency department encounters for suicidality. RESULTS: There were 179,736 patient encounters to the emergency department during the study period, 6,215 (3.5%) for suicidality. There were, on average, more encounters for suicidality each month during the COVID-19 pandemic than before the COVID-19 pandemic. A time series unobserved components model demonstrated a temporary drop of 32.7 encounters for suicidality in April and May of 2020 (p<0.001), followed by a sustained increase of 31.2 encounters starting in July 2020 (p = 0.003). The average length of stay for patients that boarded in the emergency department with a diagnosis of suicidality was 37.4 hours longer during the COVID-19 pandemic compared to before the COVID-19 pandemic (p<0.001). CONCLUSIONS: The number of encounters for suicidality among pediatric patients and the emergency department length of stay for psychiatry boarders has increased during the COVID-19 pandemic. There is a need for acute care mental health services and solutions to emergency department capacity issues.


Subject(s)
COVID-19 , Suicide , Humans , Child , Retrospective Studies , Pandemics , COVID-19/epidemiology , Emergency Service, Hospital
4.
NPJ Digit Med ; 6(1): 175, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37730764

ABSTRACT

Participatory surveillance systems crowdsource individual reports to rapidly assess population health phenomena. The value of these systems increases when more people join and persistently contribute. We examine the level of and factors associated with engagement in participatory surveillance among a retrospective, national-scale cohort of individuals using smartphone-connected thermometers with a companion app that allows them to report demographic and symptom information. Between January 1, 2020 and October 29, 2022, 1,325,845 participants took 20,617,435 temperature readings, yielding 3,529,377 episodes of consecutive readings. There were 1,735,805 (49.2%) episodes with self-reported symptoms (including reports of no symptoms). Compared to before the pandemic, participants were more likely to report their symptoms during pandemic waves, especially after the winter wave began (September 13, 2020) (OR across pandemic periods range from 3.0 to 4.0). Further, symptoms were more likely to be reported during febrile episodes (OR = 2.6, 95% CI = 2.6-2.6), and for new participants, during their first episode (OR = 2.4, 95% CI = 2.4-2.5). Compared with participants aged 50-65 years old, participants over 65 years were less likely to report their symptoms (OR = 0.3, 95% CI = 0.3-0.3). Participants in a household with both adults and children (OR = 1.6 [1.6-1.7]) were more likely to report symptoms. We find that the use of smart thermometers with companion apps facilitates the collection of data on a large, national scale, and provides real time insight into transmissible disease phenomena. Nearly half of individuals using these devices are willing to report their symptoms after taking their temperature, although participation varies among individuals and over pandemic stages.

5.
J Med Chem ; 66(14): 9401-9417, 2023 07 27.
Article in English | MEDLINE | ID: mdl-37439511

ABSTRACT

We report the discovery of sulanemadlin (ALRN-6924), the first cell-permeating, stabilized α-helical peptide to enter clinical trials. ALRN-6924 is a "stapled peptide" that mimics the N-terminal domain of the p53 tumor suppressor protein. It binds with high affinity to both MDM2 and MDMX (also known as MDM4), the endogenous inhibitors of p53, to activate p53 signaling in cells having a non-mutant, or wild-type TP53 genotype (TP53-WT). Iterative structure-activity optimization endowed ALRN-6924 with favorable cell permeability, solubility, and pharmacokinetic and safety profiles. Intracellular proteolysis of ALRN-6924 forms a long-acting active metabolite with potent MDM2 and MDMX binding affinity and slow dissociation kinetics. At high doses, ALRN-6924 exhibits on-mechanism anticancer activity in TP53-WT tumor models. At lower doses, ALRN-6924 transiently arrests the cell cycle in healthy tissues to protect them from chemotherapy without protecting the TP53-mutant cancer cells. These results support the continued clinical evaluation of ALRN-6924 as an anticancer and chemoprotection agent.


Subject(s)
Antineoplastic Agents , Tumor Suppressor Protein p53 , Tumor Suppressor Protein p53/metabolism , Proto-Oncogene Proteins c-mdm2/metabolism , Protein Binding , Peptides/chemistry , Antineoplastic Agents/chemistry , Cell Cycle Proteins/metabolism
6.
JAMA Netw Open ; 6(6): e2316190, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37261828

ABSTRACT

Importance: Children's role in spreading virus during the COVID-19 pandemic is yet to be elucidated, and measuring household transmission traditionally requires contact tracing. Objective: To discern children's role in household viral transmission during the pandemic when enveloped viruses were at historic lows and the predominance of viral illnesses were attributed to COVID-19. Design, Setting, and Participants: This cohort study of a voluntary US cohort tracked data from participatory surveillance using commercially available thermometers with a companion smartphone app from October 2019 to October 2022. Eligible participants were individuals with temperature measurements in households with multiple members between October 2019 and October 2022 who opted into data sharing. Main Outcomes and Measures: Proportion of household transmissions with a pediatric index case and changes in transmissions during school breaks were assessed using app and thermometer data. Results: A total of 862 577 individuals from 320 073 households with multiple participants (462 000 female [53.6%] and 463 368 adults [53.7%]) were included. The number of febrile episodes forecast new COVID-19 cases. Within-household transmission was inferred in 54 506 (15.4%) febrile episodes and increased from the fourth pandemic period, March to July 2021 (3263 of 32 294 [10.1%]) to the Omicron BA.1/BA.2 wave (16 516 of 94 316 [17.5%]; P < .001). Among 38 787 transmissions in 166 170 households with adults and children, a median (IQR) 70.4% (61.4%-77.6%) had a pediatric index case; proportions fluctuated weekly from 36.9% to 84.6%. A pediatric index case was 0.6 to 0.8 times less frequent during typical school breaks. The winter break decrease was from 68.4% (95% CI, 57.1%-77.8%) to 41.7% (95% CI, 34.3%-49.5%) at the end of 2020 (P < .001). At the beginning of 2022, it dropped from 80.3% (95% CI, 75.1%-84.6%) to 54.5% (95% CI, 51.3%-57.7%) (P < .001). During summer breaks, rates dropped from 81.4% (95% CI, 74.0%-87.1%) to 62.5% (95% CI, 56.3%-68.3%) by August 2021 (P = .02) and from 83.8% (95% CI, 79.2%-87.5) to 62.8% (95% CI, 57.1%-68.1%) by July 2022 (P < .001). These patterns persisted over 2 school years. Conclusions and Relevance: In this cohort study using participatory surveillance to measure within-household transmission at a national scale, we discerned an important role for children in the spread of viral infection within households during the COVID-19 pandemic, heightened when schools were in session, supporting a role for school attendance in COVID-19 spread.


Subject(s)
COVID-19 , Virus Diseases , Adult , Child , Humans , Female , COVID-19/epidemiology , Pandemics , Thermometers , Cohort Studies , Virus Diseases/epidemiology
7.
Clin Toxicol (Phila) ; 61(4): 234-240, 2023 04.
Article in English | MEDLINE | ID: mdl-36919488

ABSTRACT

INTRODUCTION: Prescription drug monitoring programs are state-run databases designed to support safe prescribing of controlled substances and reduce prescription drug misuse. We analyzed healthcare claims data to determine the association between prescription drug monitoring programs with mandated provider review and adolescent and young adult benzodiazepine prescription dispensing and overdose. METHODS: We performed a state-level retrospective cohort study to evaluate the association between implementation of prescription drug monitoring programs with mandated provider review and benzodiazepine prescription dispensing and benzodiazepine-related overdoses among adolescents (13-18 years) and young adults (19-25 years) between 1 January 2008 and 31 December 2019. Data were obtained from a United States commercial health insurance company. RESULTS: There were 74,539 (1.8%) adolescents and 246,760 (4.0%) young adults with at least one benzodiazepine prescription dispensed. Benzodiazepine overdoses occurred among 1,569 (0.04%) and 3,202 (0.05%) adolescents and young adults, respectively. Implementation of a prescription drug monitoring program with mandated provider review was associated with a 6.8% (95% CI, 1.6-11.8) yearly reduction in benzodiazepine prescription dispensing among adolescents and a 12.5% (95% CI, 9.3-15.5) yearly reduction among young adults. There was no decrease in benzodiazepine overdoses in either age group (-15.4% [95% CI, -21.5 to 3.0] and -8.0% [95% CI, -18.0 to 3.2] yearly change in adolescents and young adults, respectively). DISCUSSION: Consistent with prior work, our study did not find an association between prescription drug monitoring program implementation and reduction in benzodiazepine-related overdoses among adolescents and young adults. However, the substantial reduction in benzodiazepine prescription dispensing is encouraging. CONCLUSION: Prescription drug monitoring programs were associated with decreases in benzodiazepine prescription dispensing, but not benzodiazepine-related overdoses in this cohort of adolescents and young adults. These findings serve to inform development of further policies to address rising rates of benzodiazepine misuse and overdose in this patient population.


Subject(s)
Drug Overdose , Prescription Drug Monitoring Programs , Humans , Adolescent , Young Adult , United States , Retrospective Studies , Benzodiazepines , Analgesics, Opioid/therapeutic use , Drug Overdose/epidemiology , Drug Prescriptions
8.
Ann Emerg Med ; 81(4): 429-437, 2023 04.
Article in English | MEDLINE | ID: mdl-36669914

ABSTRACT

STUDY OBJECTIVE: Prescription opioid use is associated with substance-related adverse outcomes among adolescents and young adults through a pathway of prescribing, diversion and misuse, and addiction and overdose. Assessing the effect of current prescription drug monitoring programs (PDMPs) on opioid prescribing and overdoses will further inform strategies to reduce opioid-related harms. METHODS: We performed interrupted time series analyses to measure the association between state-level implementation of PDMPs with annual opioid prescribing and opioid-related overdoses in adolescents (13 to 18 years) and young adults (19 to 25 years) between 2008 and 2019. We focused on PDMPs that included mandatory reviews by providers. Data were obtained from a commercial insurance company. RESULTS: Among 9,344,504 adolescents and young adults, 1,405,382 (15.0%) had a dispensed opioid prescription, and 6,262 (0.1%) received treatment for an opioid-related overdose. Mandated PDMP review was associated with a 4.2% (95% CI, 1.9% to 6.4%) reduction in annual opioid dispensations among adolescents and a 7.8% (95% CI, 4.7% to 10.9%) annual reduction among young adults. For opioid-related overdoses, mandated PDMP review was associated with a 16.1% (95% CI, 3.8 to 26.7) and 15.9% (95% CI, 7.6 to 23.4) reduction in annual opioid overdoses for adolescents and young adults, respectively. CONCLUSION: PDMPs were associated with sustained reductions in opioid prescribing and overdoses in adolescents and young adults. Although these findings support the value of mandated PDMPs as part of ongoing strategies to reduce opioid overdoses, further studies with prospective study designs are needed to characterize the effect of these programs fully.


Subject(s)
Drug Overdose , Opiate Overdose , Prescription Drug Misuse , Prescription Drug Monitoring Programs , Humans , Adolescent , Young Adult , Analgesics, Opioid/therapeutic use , Opiate Overdose/drug therapy , Prospective Studies , Practice Patterns, Physicians' , Drug Overdose/drug therapy , Drug Overdose/epidemiology , Drug Overdose/prevention & control , Prescription Drug Misuse/prevention & control
9.
PLoS One ; 18(1): e0266985, 2023.
Article in English | MEDLINE | ID: mdl-36598895

ABSTRACT

PURPOSE: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. METHODS: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. RESULTS: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). CONCLUSION: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Young Adult , Aged , Adolescent , Adult , Middle Aged , COVID-19/complications , COVID-19/epidemiology , SARS-CoV-2 , Cohort Studies , Retrospective Studies , Electronic Health Records , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/complications , Obesity/complications
10.
West J Nurs Res ; 45(1): 46-54, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35610951

ABSTRACT

This article describes a pilot test of a community engaged, culturally relevant, arts-based intervention. The purpose was to increase children's personal protective buffering resources. Protective buffering resources help children cope with stressful stimuli, reduce activation of their systemic stress response, mitigate allostatic load, and promote optimal health. The "Learning a Healthy Rhythm" intervention included a stress management component and an ongoing Afro-Latino percussion program for 18 children ages 9-11. The stress management component included educational content about stress, self-assessment of stress symptoms, and stress management techniques. A mixed-method intervention evaluation design was used. Qualitative data, quantitative data, and biometrics including hair cortisol were collected. Six intervention parameters were evaluated: effectiveness, fidelity, feasibility, acceptability, necessity, and safety. Positive results were obtained for all parameters. Reduction in physiological and subjective measures of stress was evident. This stress management intervention was well-received and supported by participants.


Subject(s)
Adaptation, Psychological , Humans , Child , Hispanic or Latino , Hydrocortisone , Learning
11.
JAMA Pediatr ; 176(12): 1265-1266, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36215054

ABSTRACT

This cohort study examines trends from 2008 to 2019 in dispensations of controlled medications to US adolescents and young adults.


Subject(s)
Biopharmaceutics , Adolescent , Humans , Young Adult
14.
J Am Med Inform Assoc ; 28(7): 1411-1420, 2021 07 14.
Article in English | MEDLINE | ID: mdl-33566082

ABSTRACT

OBJECTIVE: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing coronavirus disease 2019 (COVID-19) with federated analyses of electronic health record (EHR) data. We sought to develop and validate a computable phenotype for COVID-19 severity. MATERIALS AND METHODS: Twelve 4CE sites participated. First, we developed an EHR-based severity phenotype consisting of 6 code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of intensive care unit (ICU) admission and/or death. We also piloted an alternative machine learning approach and compared selected predictors of severity with the 4CE phenotype at 1 site. RESULTS: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability-up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean area under the curve of 0.903 (95% confidence interval, 0.886-0.921), compared with an area under the curve of 0.956 (95% confidence interval, 0.952-0.959) for the machine learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared with chart review. DISCUSSION: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly owing to heterogeneous pandemic conditions. CONCLUSIONS: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites.


Subject(s)
COVID-19 , Electronic Health Records , Severity of Illness Index , COVID-19/classification , Hospitalization , Humans , Machine Learning , Prognosis , ROC Curve , Sensitivity and Specificity
15.
Genet Med ; 23(4): 782-786, 2021 04.
Article in English | MEDLINE | ID: mdl-33420348

ABSTRACT

PURPOSE: Pharmacogenomic biomarkers are increasingly listed on medication labels and authoritative guidelines but pharmacogenomic-guided prescribing is not yet common. Our objective was to assess the potential for incorporating knowledge of patients' genomic characteristics into prescribing practices. METHODS: We performed a retrospective analysis of claims data for 2,096,971 beneficiaries with pharmacy coverage from a national, commercial health insurance plan between January 2017 and December 2019. Children between 0 and 17 years comprised 21% of the cohort. Adults were age 18 to 64. Medications with actionable pharmacogenomic biomarkers (MAPBs) were identified using public information from the US Food and Drug Administration (FDA), Clinical Pharmacogenomics Implementation Consortium (CPIC), and PharmGKB. RESULTS: MAPBs were dispensed to 63% of the adults and 29% of the children in the cohort. Most frequently dispensed were ibuprofen, ondansetron, codeine, and oxycodone. Most common were medications with CYP2D6, G6PD, or CYPC19 pharmacogenomic biomarkers. Ten percent of the cohort were codispensed more than one MAPB for at least 30 days. CONCLUSION: The number of people who might benefit from pharmacogenomic-guided prescribing is substantial. Future work should address obstacles to integrating genomic data into prescriber workflows, complex factors contributing to the magnitude of benefit, and the clinical availability of reliable on-demand or pre-emptive pharmacogenomic testing.


Subject(s)
Pharmacogenetics , Pharmacogenomic Testing , Adolescent , Adult , Biomarkers , Child , Drug Labeling , Humans , Middle Aged , Retrospective Studies , Young Adult
16.
Diabetes Care ; 43(9): 2176-2182, 2020 09.
Article in English | MEDLINE | ID: mdl-32661106

ABSTRACT

OBJECTIVE: To distinguish the effects of hyperglycemia and hyperinsulinemia on exercise-induced increases in Rd and endogenous glucose production (EGP) in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied six participants without diabetes and six participants with type 1 diabetes on three visits in random order for the following: euglycemia, low insulin (EuLoI); euglycemia, high insulin (EuHiI); and hyperglycemia, low insulin (HyLoI). Glucose fluxes were measured using [6,6-2H2] glucose before, during, and after 60 min of exercise. RESULTS: Rd increased (P < 0.01) with exercise within groups, while peak Rd during exercise was lower (P < 0.01) in participants with type 1 diabetes than participants without diabetes during all visits. In type 1 diabetes participants, EGP increased (P < 0.001) with exercise during EuLoI and HyLoI but not during EuHiI. This demonstrates that hyperinsulinemia, but not hyperglycemia, blunts the compensatory exercise-induced increase in EGP in type 1 diabetes. CONCLUSIONS: The data from this pilot study indicate that 1) exercise-induced compensatory increase in EGP was inhibited in participants with type 1 diabetes with hyperinsulinemia but not with hyperglycemia; 2) in contrast, in participants without diabetes, exercise-induced increase in EGP was inhibited only during combined hyperinsulinemia and hyperglycemia. Taken together, these results suggest that low insulin coupled with euglycemia or modest hyperglycemia appear to be the most favorable milieu for type 1 diabetes during exercise.


Subject(s)
Diabetes Mellitus, Type 1/metabolism , Exercise/physiology , Glucose/metabolism , Hyperglycemia/metabolism , Hyperinsulinism/metabolism , Insulin/metabolism , Adolescent , Adult , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/physiopathology , Energy Metabolism/physiology , Female , Glucose Clamp Technique , Humans , Hyperglycemia/blood , Hyperglycemia/physiopathology , Hyperinsulinism/blood , Hyperinsulinism/physiopathology , Insulin/blood , Male , Pilot Projects , Young Adult
17.
Mol Phylogenet Evol ; 146: 106731, 2020 05.
Article in English | MEDLINE | ID: mdl-31904508

ABSTRACT

Recent phylogenetic studies of gekkonid lizards have revealed unexpected, widespread paraphyly and polyphyly among genera, unclear generic boundaries, and a tendency towards the nesting of taxa exhibiting specialized, apomorphic morphologies within geographically widespread "generalist" clades. This is especially true in Australasia, where monophyly of Gekko proper has been questioned with respect to phenotypically ornate flap-legged geckos of the genus Luperosaurus, the Philippine false geckos of the genus Pseudogekko, and even the elaborately "derived" parachute geckos of the genus Ptychozoon. Here we employ sequence capture targeting 5060 ultraconserved elements (UCEs) to infer phylogenomic relationships among 42 representative ingroup gekkonine lizard taxa. We analyze multiple datasets of varying degrees of completeness (10, 50, 75, 95, and 100 percent complete with 4715, 4051, 3376, 2366, and 772 UCEs, respectively) using concatenated maximum likelihood and multispecies coalescent methods. Our sampling scheme addresses four persistent systematic questions in this group: (1) Are Luperosaurus and Ptychozoon monophyletic, and are any of these named species truly nested within Gekko? (2) Are prior phylogenetic estimates of Sulawesi's L. iskandari as the sister taxon to Melanesian G. vittatus supported by our genome-scale dataset? (3) Is the high-elevation L. gulat of Palawan Island correctly placed within Gekko? (4) And, finally, where do the enigmatic taxa P. rhacophorus and L. browni fall in a higher-level gekkonid phylogeny? We resolve these issues; confirm with strong support some previously inferred findings (placement of Ptychozoon taxa within Gekko; the sister taxon relationship between L. iskandari and G. vittatus); resolve the systematic position of unplaced taxa (L. gulat, and L. browni); and transfer L. iskandari, L. gulat, L. browni, and all members of the genus Ptychozoon to the genus Gekko. Our unexpected and novel systematic inference of the placement of Ptychozoon rhacophorus suggests that this species is not grouped with Ptychozoon or even Luperosaurus (as previously expected) but may, in fact, be most closely related to several Indochinese species of Gekko. With our resolved and strongly supported phylogeny, we present a new classification emphasizing the most inclusive, original generic name (Gekko) for these ~60 taxa, arranged into seven subgenera.


Subject(s)
Lizards/classification , Animals , Australasia , Base Sequence , Conserved Sequence , Genomics , Indonesia , Lizards/genetics , Phylogeny , Sequence Analysis, DNA
18.
Med Care Res Rev ; 76(1): 115-128, 2019 02.
Article in English | MEDLINE | ID: mdl-29148301

ABSTRACT

Provider interactions other than explicit care coordination, which is challenging to measure, may influence practice and outcomes. We performed a network analysis using claims data from a commercial payor. Networks were identified based on provider pairs billing outpatient care for the same patient. We compared network variables among patients who had and did not have a 30-day readmission after hospitalization for heart failure. After adjusting for comorbidities, high median provider connectedness-normalized degree, which for each provider is the number of connections to other providers normalized to the number of providers in the region-was the network variable associated with reduced odds of readmission after heart failure hospitalization (odds ratio = 0.55; 95% confidence interval [0.35, 0.86]). We conclude that heart failure patients with high provider connectedness are less likely to require readmission. The structure and importance of provider relationships using claims data merits further study.


Subject(s)
Ambulatory Care/methods , Heart Failure/therapy , Hospitalization , Patient Readmission , Aged , Female , Humans , Male , Middle Aged
19.
Pediatr Res ; 83(6): 1104-1109, 2018 06.
Article in English | MEDLINE | ID: mdl-29938699

ABSTRACT

BackgroundThe Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a standardized method for infant neurobehavioral assessment. Normative values are available for newborns, but the NNNS is not always feasible at birth. Unfortunately, 1-month NNNS normative data are lacking.AimsTo provide normative data for the NNNS examination at 1 month and to assess birth-to-one-month changes in NNNS summary scores.Study designThe NNNS was administered at birth and at 1 month within a longitudinal prospective study design.SubjectsA cohort of 99 clinically healthy full-term infants were recruited from a well-child nursery.Outcome measuresBirth-to-1-month NNNS variations were evaluated and the association of neonatal and sociodemographic variables with the rate of change of NNNS summary scores were investigated.Results and conclusionsNNNS scores from the 10th to the 90th percentile represent a range of normative performance at 1 month. A complex pattern of stability and change emerged comparing NNNS summary scores from birth to 1 month. Orienting, Regulation, and Quality of movements significantly increased, whereas Lethargy and Hypotonicity significantly decreased. Birth-to-1-month changes in NNNS performance suggest improvements in neurobehavioral organization. These data are useful for research purposes and for clinical evaluation of neurobehavioral performance in both healthy and at-risk 1-month-old infants.


Subject(s)
Developmental Disabilities/diagnosis , Intensive Care Units, Neonatal/standards , Neonatology/standards , Neurologic Examination/standards , Severity of Illness Index , Age Factors , Data Collection , Female , Humans , Infant , Infant Behavior , Infant, Newborn , Intensive Care, Neonatal/standards , Longitudinal Studies , Male , Neonatology/methods , Parturition , Prospective Studies , Psychometrics/methods , Risk , Social Class
20.
Acad Emerg Med ; 24(11): 1349-1357, 2017 11.
Article in English | MEDLINE | ID: mdl-28861915

ABSTRACT

OBJECTIVES: We sought to characterize the population of patients seeking care at multiple emergency departments (EDs) and to quantify the proportion of all ED visits and costs accounted for by these patients. METHODS: We performed a retrospective, cohort study of deidentified insurance claims for privately insured patients with one of more ED visits between 2010 and 2016. We measured the number of EDs visited by each patient and determined the overall proportion of all ED visits and ED costs accounted for by patients who visit multiple EDs. We identified factors associated with visiting multiple EDs. RESULTS: A total of 8,651,716 patients made 16,390,676 ED visits over the study period, accounting for $26,102,831,740 in ED costs. A significant minority (20.5%) of patients visited more than one ED over the study period. However, these patients accounted for a disproportionate amount of all ED visits (41.4%) and all ED costs (39.2%). A small proportion (0.4%) of patients visited five or more EDs but accounted for 2.8% of ED visits and costs. Among patients with two ED visits within 30 days, 32% were to different EDs. Having at least one ED visit for mental health or substance abuse-related diagnosis was associated with increased odds of visiting multiple EDs. CONCLUSIONS: A substantial minority of patients visit multiple EDs, but account for a disproportionate burden of overall ED utilization and costs. Future work should evaluate the impact of visiting multiple EDs on care utilization and outcomes and explore systems for improving access to patient records across care centers.


Subject(s)
Emergency Service, Hospital/economics , Emergency Service, Hospital/statistics & numerical data , Hospitals/statistics & numerical data , Medical Overuse/economics , Medical Overuse/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Mental Disorders/economics , Mental Disorders/epidemiology , Middle Aged , Retrospective Studies , Risk Factors , Substance-Related Disorders/economics , Substance-Related Disorders/epidemiology , United States/epidemiology , Young Adult
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