Nevin Manimala

JAMA Netw Open. 2023 Apr 3;6(4):e237489. doi: 10.1001/jamanetworkopen.2023.7489.

ABSTRACT

IMPORTANCE: Early awareness of Kawasaki disease (KD) helps physicians administer appropriate therapy to prevent acquired heart disease in children. However, diagnosing KD is challenging and relies largely on subjective diagnosis criteria.

OBJECTIVE: To develop a prediction model using machine learning with objective parameters to differentiate children with KD from other febrile children.

DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study included 74 641 febrile children younger than 5 years who were recruited from 4 hospitals, including 2 medical centers and 2 regional hospitals, between January 1, 2010, and December 31, 2019. Statistical analysis was performed from October 2021 to February 2023.

MAIN OUTCOMES AND MEASURES: Demographic data and laboratory values from electronic medical records, including complete blood cell count with differential, urinalysis, and biochemistry, were collected as possible parameters. The primary outcome was whether the febrile children fulfilled the diagnostic criteria of KD. The supervised eXtreme Gradient Boosting (XGBoost) machine learning method was applied to establish a prediction model. The confusion matrix and likelihood ratio were used to evaluate the performance of the prediction model.

RESULTS: This study included a total of 1142 patients with KD (mean [SD] age, 1.1 [0.8] years; 687 male patients [60.2%]) and 73 499 febrile children (mean [SD] age, 1.6 [1.4] years; 41 465 male patients [56.4%]) comprising the control group. The KD group was predominantly male (odds ratio, 1.79; 95% CI, 1.55-2.06) with younger age (mean difference, -0.6 years [95% CI, -0.6 to -0.5 years]) compared with the control group. The prediction model’s best performance in the testing set was able to achieve 92.5% sensitivity, 97.3% specificity, 34.5% positive predictive value, 99.9% negative predictive value, and a positive likelihood ratio of 34.0, which indicates outstanding performance. The area under the receiver operating characteristic curve of the prediction model was 0.980 (95% CI, 0.974-0.987).

CONCLUSIONS AND RELEVANCE: This diagnostic study suggests that results of objective laboratory tests had the potential to be predictors of KD. Furthermore, these findings suggested that machine learning with XGBoost can help physicians differentiate children with KD from other febrile children in pediatric emergency departments with excellent sensitivity, specificity, and accuracy.

PMID:37040115 | DOI:10.1001/jamanetworkopen.2023.7489

JAMA Netw Open. 2023 Apr 3;6(4):e237497. doi: 10.1001/jamanetworkopen.2023.7497.

ABSTRACT

IMPORTANCE: Health-related consequences of multimorbidity (≥2 chronic diseases) are well documented. However, the extent and rate of accumulation of chronic diseases among US patients seeking care in safety-net clinics are not well understood. These insights are needed to enable clinicians, administrators, and policy makers to mobilize resources for prevention of disease escalations in this population.

OBJECTIVES: To identify the patterns and rate of chronic disease accumulation among middle-aged and older patients seeking care in community health centers, as well as any sociodemographic differences.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used electronic health record data from January 1, 2012, to December 31, 2019, on 725 107 adults aged 45 years or older with 2 or more ambulatory care visits in 2 or more distinct years at 657 primary care clinics in the Advancing Data Value Across a National Community Health Center network in 26 US states. Statistical analysis was performed from September 2021 to February 2023.

EXPOSURES: Race and ethnicity, age, insurance coverage, and federal poverty level (FPL).

MAIN OUTCOMES AND MEASURES: Patient-level chronic disease burden, operationalized as the sum of 22 chronic diseases recommended by the Multiple Chronic Conditions Framework. Linear mixed models with patient-level random effects adjusted for demographic characteristics and ambulatory visit frequency with time interactions were estimated to compare accrual by race and ethnicity, age, income, and insurance coverage.

RESULTS: The analytic sample included 725 107 patients (417 067 women [57.5%]; 359 255 [49.5%] aged 45-54 years, 242 571 [33.5%] aged 55-64 years, and 123 281 [17.0%] aged ≥65 years). On average, patients started with a mean (SD) of 1.7 (1.7) morbidities and ended with 2.6 (2.0) morbidities over a mean (SD) of 4.2 (2.0) years of follow-up. Compared with non-Hispanic White patients, patients in racial and ethnic minoritized groups had marginally lower adjusted annual rates of accrual of conditions (-0.03 [95% CI, -0.03 to -0.03] for Spanish-preferring Hispanic patients; -0.02 [95% CI, -0.02 to -0.01] for English-preferring Hispanic patients; -0.01 [95% CI, -0.01 to -0.01] for non-Hispanic Black patients; and -0.04 [95% CI, -0.05 to -0.04] for non-Hispanic Asian patients). Older patients accrued conditions at higher annual rates compared with patients 45 to 50 years of age (0.03 [95% CI, 0.02-0.03] for 50-55 years; 0.03 [95% CI, 0.03-0.04] for 55-60 years; 0.04 [95% CI, 0.04-0.04] for 60-65 years; and 0.05 [95% CI, 0.05-0.05] for ≥65 years). Compared with those with higher income (always ≥138% of the FPL), patients with income less than 138% of the FPL (0.04 [95% CI, 0.04-0.05]), mixed income (0.01 [95% CI, 0.01-0.01]), or unknown income levels (0.04 [95% CI, 0.04-0.04]) had higher annual accrual rates. Compared with continuously insured patients, continuously uninsured and discontinuously insured patients had lower annual accrual rates (continuously uninsured, -0.003 [95% CI, -0.005 to -0.001]; discontinuously insured, -0.004 [95% CI, -0.005 to -0.003]).

CONCLUSIONS AND RELEVANCE: This cohort study of middle-aged patients seeking care in community health centers suggests that disease accrued at high rates for patients’ chronological age. Targeted efforts for chronic disease prevention are needed for patients near or below the poverty line.

PMID:37040114 | DOI:10.1001/jamanetworkopen.2023.7497

JAMA Netw Open. 2023 Apr 3;6(4):e237588. doi: 10.1001/jamanetworkopen.2023.7588.

ABSTRACT

IMPORTANCE: Evaluation of trainees in graduate medical education training programs using Milestones has been in place since 2013. It is not known whether trainees who have lower ratings during the last year of training go on to have concerns related to interactions with patients in posttraining practice.

OBJECTIVE: To investigate the association between resident Milestone ratings and posttraining patient complaints.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included physicians who completed Accreditation Council for Graduate Medical Education (ACGME)-accredited programs between July 1, 2015, and June 30, 2019, and worked at a site that participated in the national Patient Advocacy Reporting System (PARS) program for at least 1 year. Milestone ratings from ACGME training programs and patient complaint data from PARS were collected. Data analysis was conducted from March 2022 to February 2023.

EXPOSURES: Lowest professionalism (P) and interpersonal and communication skills (ICS) Milestones ratings 6 months prior to the end of training.

MAIN OUTCOMES AND MEASURES: PARS year 1 index scores, based on recency and severity of complaints.

RESULTS: The cohort included 9340 physicians with median (IQR) age of 33 (31-35) years; 4516 (48.4%) were women physicians. Overall, 7001 (75.0%) had a PARS year 1 index score of 0, 2023 (21.7%) had a score of 1 to 20 (moderate), and 316 (3.4%) had a score of 21 or greater (high). Among physicians in the lowest Milestones group, 34 of 716 (4.7%) had high PARS year 1 index scores, while 105 of 3617 (2.9%) with Milestone ratings of 4.0 (proficient), had high PARS year 1 index scores. In a multivariable ordinal regression model, physicians in the 2 lowest Milestones rating groups (0-2.5 and 3.0-3.5) were statistically significantly more likely to have higher PARS year 1 index scores than the reference group with Milestones ratings of 4.0 (0-2.5 group: odds ratio, 1.2 [95% CI, 1.0-1.5]; 3.0-3.5 group: odds ratio, 1.2 [95% CI, 1.1-1.3]).

CONCLUSIONS AND RELEVANCE: In this study, trainees with low Milestone ratings in P and ICS near the end of residency were at increased risk for patient complaints in their early posttraining independent physician practice. Trainees with lower Milestone ratings in P and ICS may need more support during graduate medical education training or in the early part of their posttraining practice career.

PMID:37040112 | DOI:10.1001/jamanetworkopen.2023.7588

JAMA Netw Open. 2023 Apr 3;6(4):e237597. doi: 10.1001/jamanetworkopen.2023.7597.

ABSTRACT

IMPORTANCE: Although digital cognitive behavioral therapy for insomnia (dCBT-I) has been studied in many randomized clinical trials and is recommended as a first-line treatment option, few studies have systematically examined its effectiveness, engagement, durability, and adaptability in clinical settings.

OBJECTIVE: To evaluate the clinical effectiveness, engagement, durability, and adaptability of dCBT-I.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using longitudinal data collected via a mobile app named Good Sleep 365 between November 14, 2018, and February 28, 2022. Three therapeutic modes (ie, dCBT-I, medication, and their combination) were compared at month 1, month 3, and month 6 (primary). Inverse probability of treatment weighting (IPTW) using propensity scores was applied to enable homogeneous comparisons between the 3 groups.

EXPOSURES: Treatment with dCBT-I, medication therapy, or combination therapy according to prescriptions.

MAIN OUTCOMES AND MEASURES: The Pittsburgh Sleep Quality Index (PSQI) score and its essential subitems were used as the primary outcomes. Effectiveness on comorbid somnolence, anxiety, depression, and somatic symptoms were used as secondary outcomes. Cohen d effect size, P value, and standardized mean difference (SMD) were used to measure differences in treatment outcomes. Changes in outcomes and response rates (≥3 points change in PSQI score) were also reported.

RESULTS: A total of 4052 patients (mean [SD] age, 44.29 [12.01] years; 3028 [74.7%] female participants) were selected for dCBT-I (n = 418), medication (n = 862), and their combination (n = 2772). Compared with the change in PSQI score at 6 months for participants receiving medication alone (from a mean [SD] of 12.85 [3.49] to 8.92 [4.03]), both dCBT-I (from a mean [SD] of 13.51 [3.03] to 7.15 [3.25]; Cohen d, -0.50; 95% CI, -0.62 to -0.38; P < .001; SMD = 0.484) and combination therapy (from a mean [SD] of 12.92 [3.49] to 6.98 [3.43]; Cohen d, 0.50; 95% CI, 0.42 to 0.58; P < .001; SMD = 0.518) were associated with significant reductions; dCBT-I had a comparable effect as combination therapy (Cohen d, 0.05; 95% CI, -0.05 to 0.15; P = .66; SMD = 0.05), but showed unstable durability. Outcomes of dCBT-I improved steadily and rapidly during the first 3 months, and then fluctuated. The response rates with dCBT-I and combination therapy were higher than with medication. Changes in secondary outcomes indicated statistically significant benefits from dCBT-I and combination therapy. The results of subgroup analysis were consistent with the main findings, demonstrating the superiority of dCBT-I vs medication therapy in various subpopulations.

CONCLUSIONS AND RELEVANCE: In this study, clinical evidence suggested that combination therapy was optimal, and dCBT-I was more effective than medication therapy, with long-term benefits for insomnia. Future studies are needed to analyze its clinical effectiveness and reliability in distinct subpopulations.

PMID:37040111 | DOI:10.1001/jamanetworkopen.2023.7597

Am J Occup Ther. 2023 Mar 1;77(2):7702185070. doi: 10.5014/ajot.2023.050108.

ABSTRACT

IMPORTANCE: Some autistic adults experience depression and anxiety related to their social relationships. There is a need for evidence-based occupational therapy interventions that decrease depression and anxiety and improve the health of social relationships for autistic adults.

OBJECTIVE: To determine the feasibility and preliminary effectiveness of the Healthy Relationships on the Autism Spectrum (HEARTS) intervention, a six-session, group-based psychoeducational intervention for the improvement of relationship health.

DESIGN: One-group pretest-posttest design with a 3-mo follow-up after baseline.

SETTING: United States; online intervention through community organization.

PARTICIPANTS: Fifty-five adults, ages 20 to 43 yr, with a professional or self-diagnosis of autism and the capacity to independently participate in an online, group-based, participatory class.

INTERVENTION: Participants received 6 90-min weekly sessions that addressed healthy relationship topics, including recognizing abuse, meeting people, maintaining relationships, setting interpersonal boundaries, neurohealth for relationships, and ending relationships. A psychoeducational approach that provided education and involved guided discovery and strategy acquisition was used.

OUTCOMES AND MEASURES: All measures were self-administered through an online survey. Depression and anxiety were assessed using instruments from the Patient-Reported Outcomes Measurement Information System.

RESULTS: Fifty-five participants completed the intervention. Postintervention scores revealed statistically significant improvements in depression and anxiety.

CONCLUSIONS AND RELEVANCE: HEARTS is a promising intervention for improving depression and anxiety among autistic adults and should be investigated further. What This Article Adds: HEARTS offers a potentially effective, nonpharmacological, psychoeducational group-based intervention option to promote healthy relationships for autistic adults. Positionality Statement: This article uses identity-first language (autistic person) in accordance with the preference of autistic self-advocates (Autistic Self Advocacy Network, 2020; Kenny et al., 2016; Lord et al., 2022).

PMID:37040101 | DOI:10.5014/ajot.2023.050108

Am J Occup Ther. 2023 Mar 1;77(2):7702205070. doi: 10.5014/ajot.2023.050129.

ABSTRACT

IMPORTANCE: Limited research has elucidated factors predicting occupational therapy-specific service utilization by children with autism. Such research is needed to inform reasons for receipt of services.

OBJECTIVE: To examine factors associated with occupational therapy service utilization by children with autism. We hypothesized that elevated sensory hyperresponsiveness; greater sensory interests, repetitions, and seeking; and lower adaptive behavior would predict more service utilization.

DESIGN: Analysis of extant data from a prospective, longitudinal survey study about autism symptom severity, adaptive behavior, sensory features, and demographic and service utilization information of children with autism ages 3 to 13 yr.

SETTING: Online parent survey regarding child behaviors during daily activities and contexts.

PARTICIPANTS: 892 parents of children with autism from 50 U.S. states.

OUTCOMES AND MEASURES: We used scores on the Vineland Adaptive Behavior Scale-Second Edition, the Social Responsiveness Scale, and the Sensory Experiences Questionnaire Version 3.0 and responses to a demographic questionnaire. We formulated hypotheses after data collection but before analysis.

RESULTS: Predictors of higher occupational therapy service utilization were lower enhanced perception; lower adaptive behavior; elevated sensory interests, repetitions, and seeking behaviors; younger child age; and higher household income.

CONCLUSION AND RELEVANCE: Results partially support our hypotheses. Sensory interests, repetitions, and seeking behavior predicted occupational therapy service utilization, whereas other sensory response patterns did not, suggesting a possible referral bias for certain sensory response patterns. Occupational therapy practitioners can educate parents and teachers about the scope of practice, which includes addressing sensory features beyond sensory interests, repetitions, and seeking behaviors. What This Article Adds: Children with autism who have impairments in adaptive functioning and high levels of sensory interests, repetitions, and seeking behaviors receive more occupational therapy services. Occupational therapy practitioners should be well trained to address such concerns and advocate for the profession’s role in mitigating the impact of sensory features on daily life.

PMID:37040100 | DOI:10.5014/ajot.2023.050129

Mol Inform. 2023 Apr 11. doi: 10.1002/minf.202200223. Online ahead of print.

ABSTRACT

The present work was devoted to explore the quantitative structure-property relationships for gas-to-ionic liquid partition coefficients (log K_ILA). A series of linear models were first established for the representative dataset ( IL01). The optimal model was a four-parameter equation (1Ed) consisting of two electrostatic potential-based descriptors ( Σ V s , ind – and V_s,max), one 2D matrix-based descriptor (J_D/Dt) and dipole moment (μ). All of the four descriptors introduced in the model can find the corresponding parameters, directly or indirectly, from Abraham’s linear solvation energy relationship (LSER) or its theoretical alternatives, which endows the model good interpretability. Gaussian process was utilized to build the nonlinear model. Systematical validations, including 5-fold cross-validation for the training set, the validation for test set, as well as a more rigorous Monte Carlo cross-validation were performed to verify the reliability of the constructed models. Applicability domain of the model was evaluated, and the Williams plot revealed that the model can be used to predict the log K_ILA values of structurally diverse solutes. The other 13 datasets were also processed in the same way, and all of the linear models with expressions similar to equation 1Ed were obtained. These models, whether linear of nonlinear, represent satisfactory statistical results, which confirms the universality of the method adopted in this study in QSPR modeling of gas-to-IL partition.

PMID:37040091 | DOI:10.1002/minf.202200223

J Natl Cancer Inst. 2023 Apr 11:djad046. doi: 10.1093/jnci/djad046. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.

METHODS: This multi-center collaboration included patients with ICC or ECC treated at one of eight participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were two-sided.

RESULTS: Among 1,039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early-stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%), (all p < 0.00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%), (all p < 0.001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months, p < 0.001).

CONCLUSIONS: Patients with advanced ECC have low rates of molecular profiling, possibly in part due to insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.

PMID:37040087 | DOI:10.1093/jnci/djad046

J Natl Cancer Inst. 2023 Apr 11:djad064. doi: 10.1093/jnci/djad064. Online ahead of print.

ABSTRACT

BACKGROUND: WHO recommends a one- or two-dose human papillomavirus (HPV) vaccination schedule for females aged nine to twenty years. Studies confirming the efficacy of a single dose and of vaccine modifications are needed but randomized controlled trials (RCTs) are costly and face logistical and ethical challenges. We propose a resource-efficient single-arm trial design that uses untargeted and unaffected HPV types as controls.

METHODS: We estimated HPV vaccine efficacy (VE) from a single arm by comparing two ratios: the ratio of the rate of persistent incident infection with vaccine-targeted and cross-protected types (HPV16/18/31/33/45) to vaccine-unaffected HPV types (HPV35/39/51/52/56/58/59/66) versus the ratio of prevalences of these types at the time of trial enrollment. We compare VE estimates using only data from the bivalent HPV16/18 vaccine arm of the Costa Rica Vaccine Trial to published VE estimates that used both the vaccine and control arms.

RESULTS: Our single-arm approach among 3,727 women yielded VE estimates for persistent HPV16/18 infections similar to published two-arm estimates from the trial (according-to-protocol cohort: 91.0% (95% CI = 82.9%-95.3%) [single-arm] vs. 90.9% (95% CI: 82.0%-95.9%) [two arm]; intention-to-treat cohort: 41.7% (95% CI = 32.4%-49.8%) [single-arm] vs. 49.0% (95% CI = 38.1%-58.1%) [two-arm]). VE estimates were also similar in analytic sub-groups (number of doses received; baseline HPV serology status).

CONCLUSION: We demonstrate that a single-arm design yields valid VE estimates with similar precision to an RCT. Single-arm studies can reduce the sample size and costs of future HPV vaccine trials while avoiding concerns related to unvaccinated control groups.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00128661.

PMID:37040086 | DOI:10.1093/jnci/djad064

JNCI Cancer Spectr. 2023 Apr 11:pkad029. doi: 10.1093/jncics/pkad029. Online ahead of print.

ABSTRACT

BACKGROUND: Oral health is a key indicator of overall health, well-being, and quality of life. Several studies have provided new evidence about the role of oral diseases, specifically periodontitis, in generating risk for various forms of cancers including lung, colorectal, and pancreatic cancers.

METHODS: Incident lung cancer cases (n = 192) and matched controls (n = 192) were selected from participants of the CLUE I and CLUE II cohorts. Archived serum samples collected from participants in 1974 (in CLUE I) were analyzed using immunoblotting for IgG antibody levels to 13 bacteria of the periodontium. Associations between antibody levels and lung cancer were estimated using conditional logistic regression.

RESULTS: Most of the periodontal bacterial antibodies measured were inversely associated with lung cancer risk; of these, three were statistically significant (P. intermedia, A. naeslundii, and V. parvula). A statistically significant positive association was observed for one of the P. gingivalis strains after adjusting for P. intermedia. The sum of the logarithm of antibodies against the 13 measured bacteria was inversely associated with risk of lung cancer when the analysis was restricted to a longer follow-up (31-44 years after blood collection, highest vs lowest quartile: OR = 0.26, 95% CI = 0.08-0.84).

CONCLUSION: Findings from this study highlight the complexity of using serum IgG antibodies to periodontal bacteria to identify associations between oral pathogens and risk of lung cancer. The inverse associations observed for antibodies to periodontal bacteria suggest that these may represent markers of immunity that provide some advantage in reducing the development of lung cancer.

PMID:37040077 | DOI:10.1093/jncics/pkad029