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Nevin Manimala Statistics

Increased delay from initial concern to diagnosis of autism spectrum disorder and associated health care resource utilization and cost among children aged younger than 6 years in the United States

J Manag Care Spec Pharm. 2023 Apr;29(4):378-390. doi: 10.18553/jmcp.2023.29.4.378.

ABSTRACT

BACKGROUND: Prolonged delays between first caregiver concern and autism spectrum disorder (ASD) diagnosis have been reported, but associations between length of time to diagnosis (TTD) and health care resource utilization (HCRU) and costs have not been studied in a large sample of children with ASD. OBJECTIVE: To address these informational gaps in the ASD diagnostic pathway. METHODS: This retrospective, observational, single cohort analysis of Optum’s administrative claims data from January 1, 2011, to December 31, 2020, included commercially insured children who had 2 or more claims for an ASD diagnosis (earliest diagnosis designated as the index date), were between the ages of older than 1.5 years and 6 years or younger at index date, and were continuously enrolled for up to 48 months before and for 12 months after the index date. Two cohorts (between the ages of older than 1.5 years and 3 years or younger and between the ages of older than 3 years and 6 years or younger at ASD diagnosis) were divided into shorter (less than median) and longer (greater than or equal to median) TTD around each cohort median TTD calculated from the first documented ASD-related concern to the earliest ASD diagnosis, because TTD may vary by age at diagnosis. This exploratory analysis compared all-cause and ASD-related HCRU and costs during a 12-month period preceding ASD diagnosis among children with shorter vs longer TTD. RESULTS: 8,954 children met selection criteria: 4,205 aged 3 years or younger and 4,749 aged older than 3 years at diagnosis, with median TTD of 9.5 and 22.1 months, respectively. In the year preceding ASD diagnosis, children with longer TTD in both age cohorts experienced a greater number of all-cause and ASD-related health care visits compared with those with shorter TTD (mean and median number of office or home visits were approximately 1.5- and 2-fold greater in longer vs shorter TTD groups; P < 0.0001). The mean all-cause medical cost per child in the year preceding ASD diagnosis was approximately 2-fold higher for those with longer vs shorter TTD ($5,268 vs $2,525 in the younger and $5,570 vs $2,265 in the older cohort; P < 0.0001 for both). Mean ASD-related costs were also higher across age cohorts for those with longer vs shorter TTD ($2,355 vs $859 in the younger and $2,351 vs $1,144 in the older cohort; P < 0.0001 for both). CONCLUSIONS: In the year prior to diagnosis, children with longer TTD experienced more frequent health care visits and greater cost burden in their diagnostic journey compared with children with shorter TTD. Novel diagnostic approaches that could accelerate TTD may reduce costs and HCRU for commercially insured children. DISCLOSURES: This study was funded by Cognoa, Inc. Optum received funding from Cognoa to conduct this study. Dr Salomon is an employee and holds stock options of Cognoa, Inc. Dr Campbell was an employee of Cognoa, Inc., at the time this study was conducted. Dr Duhig was an employee of Cognoa, Inc., at the time the study was conducted and holds stock options. Dr Vu, Ms Kruse, Mr Gaur, and Ms Gupta are employees and/or stockholders of Optum. Dr Tibrewal was an employee of Optum at the time the research for this study was conducted. Dr Taraman is an employee and holds stock options of Cognoa, Inc., receives consulting fees from Cognito Therapeutics, volunteers as a board member of the American Academy of Pediatrics California and Orange County Chapter, is a paid advisor for MI10 LLC, and owns stock options of NTX, Inc., and HandzIn.

PMID:36989447 | DOI:10.18553/jmcp.2023.29.4.378

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Nevin Manimala Statistics

Predictive efficiency of phoenixin, spexin and kisspeptin neuropeptides concentration levels in diagnosis of bipolar disorder in paediatric population

Psychiatr Pol. 2022 Dec 8:1-13. doi: 10.12740/PP/OnlineFirst/155178. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the study was to assess concentrations of the following neuropeptides: phoenixin, spexin and kisspeptin in venous blood serum of children and adolescents suffering from bipolar disorder, and by this their predictive efficiency in this disorder.

METHODS: The study covered 75 individuals with a mean age of 15.26 years (95% CI: 14.86-15.67), of which the study group comprised of 57 individuals diagnosed with bipolar affective disorder and the control group – 18 individuals with no psychiatric diagnosis and no pharmacological treatment. Phoenixin, spexin and kisspeptin levels were determined in the peripheral venous blood serum. Neuropeptide concentrations were measured with the enzyme-linked immunosorbent assay (ELISA).

RESULTS: The mean phoenixin concentration in the studied group equalled 1.57 ng/ml (95% CI: 1.35-1.79), while in the control group – 2.69 ng/ml (95% CI: 2.38-3; U Mann-Whitney test p-value < 0.05). For spexin, these results were 639.65 pg/ml (95% CI: 558.86-720.44) in the studied group, and 354.28 pg/ml (95% CI: 310.33-398.22; U Mann-Whitney test p-value < 0.05) in the control group. The observed differences were statistically significant. The mean concentration of kisspeptin levels in the studied group was 126.02 pg/ml (95% CI: 39.82-212.23; median: 59.85), while in the control group – 54.83 pg/ml (95% CI: 39.23-70.43; median: 51.3; U Mann-Whitney test p-value = 0.29), and the observed difference was not statistically significant.

CONCLUSIONS: The occurrence of bipolar disorder symptoms is statistically significantly linked with a decreased phoenixin concentration and to a small degree – with an increased spexin concentration in blood serum of patients. However, it is not linked with the kisspeptin concentration.

PMID:36989336 | DOI:10.12740/PP/OnlineFirst/155178

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Nevin Manimala Statistics

Mental health and gender-based violence: An exploration of depression, PTSD, and anxiety among adolescents in Kenyan informal settlements participating in an empowerment intervention

PLoS One. 2023 Mar 29;18(3):e0281800. doi: 10.1371/journal.pone.0281800. eCollection 2023.

ABSTRACT

OBJECTIVE: This study examines the prevalence of depression, anxiety, and post-traumatic stress disorder (PTSD) among adolescents attending schools in several informal settlements of Nairobi, Kenya. Primary aims were estimating prevalence of these mental health conditions, understanding their relationship to gender-based violence (GBV), and assessing changes in response to an empowerment intervention.

METHODS: Mental health measures were added to the final data collection point of a two-year randomized controlled trial (RCT) evaluating an empowerment self-defense intervention. Statistical models evaluated how past sexual violence, access to money to pay for a needed hospital visit, alcohol use, and self-efficacy affect both mental health outcomes as well as how the intervention affected female students’ mental health.

FINDINGS: Population prevalence of mental health conditions for combined male and female adolescents was estimated as: PTSD 12.2% (95% confidence interval 10.5-15.4), depression 9.2% (95% confidence interval 6.6-10.1) and anxiety 17.6% (95% confidence interval 11.2% – 18.7%). Female students who reported rape before and during the study-period reported significantly higher incidence of all mental health outcomes than the study population. No significant differences in outcomes were found between female students in the intervention and standard-of-care (SOC) groups. Prior rape and low ability to pay for a needed hospital visit were associated with higher prevalence of mental health conditions. The female students whose log-PTSD scores were most lowered by the intervention (effects between -0.23 and -0.07) were characterized by high ability to pay for a hospital visit, low agreement with gender normative statements, larger homes, and lower academic self-efficacy.

CONCLUSION: These data illustrate a need for research and interventions related to (1) mental health conditions among the young urban poor in low-income settings, and (2) sexual violence as a driver of poor mental health, leading to a myriad of negative long-term outcomes.

PMID:36989329 | DOI:10.1371/journal.pone.0281800

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Nevin Manimala Statistics

Factors in nephrologists’ decision to treat pre-dialysis CKD patients with vitamin D insufficiency and SHPT: A discrete choice experiment

PLoS One. 2023 Mar 29;18(3):e0283531. doi: 10.1371/journal.pone.0283531. eCollection 2023.

ABSTRACT

Little is known about the most important factors that inform a nephrologist’s decision to treat (DTT) pre-dialysis chronic kidney disease (CKD) patients with vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT). The objective of this study was to identify such factors and their relative importance in the DTT with a vitamin D therapy. A web-based, adaptive design conjoint analysis discrete-choice survey was developed to study factors that informed the DTT among a sample of 200 nephrologists located throughout the United States. Based on literature review and clinician input, eight attributes were selected that could influence a provider’s DTT: age, race, CKD stage, serum 25-hydroxyvitamin D (25D), parathyroid hormone (PTH), serum calcium (Ca), serum phosphorus (P), and history of comorbidities. Respondents were asked to select one patient profile most suitable for treatment from three profiles with varying attribute levels. Each attribute’s relative importance score was computed using hierarchical-Bayesian statistics to measure the influence of each factor where higher scores represented greater DTT consideration. The pooled analysis revealed the four most important factors: serum 25D (31.4%), serum Ca (22.7%), plasma PTH (11.5%) levels, and history of comorbidities (8.5%). Age (8.2%), serum P (7.7%), CKD stage (5.7%), and race (4.4%) were relatively less important. Patients’ 25D and Ca levels contributed to more than half of nephrologists’ DTT, with the consideration of PTH levels being less of a factor. Further understanding of the driving forces behind the factors that inform the DTT may help to standardize the management of CKD patients with SHPT and VDI and improve outcomes.

PMID:36989323 | DOI:10.1371/journal.pone.0283531

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Nevin Manimala Statistics

A Hamilton-Jacobi-based proximal operator

Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2220469120. doi: 10.1073/pnas.2220469120. Epub 2023 Mar 29.

ABSTRACT

First-order optimization algorithms are widely used today. Two standard building blocks in these algorithms are proximal operators (proximals) and gradients. Although gradients can be computed for a wide array of functions, explicit proximal formulas are known for only limited classes of functions. We provide an algorithm, HJ-Prox, for accurately approximating such proximals. This is derived from a collection of relations between proximals, Moreau envelopes, Hamilton-Jacobi (HJ) equations, heat equations, and Monte Carlo sampling. In particular, HJ-Prox smoothly approximates the Moreau envelope and its gradient. The smoothness can be adjusted to act as a denoiser. Our approach applies even when functions are accessible only by (possibly noisy) black box samples. We show that HJ-Prox is effective numerically via several examples.

PMID:36989305 | DOI:10.1073/pnas.2220469120

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Nevin Manimala Statistics

Metabolomic analysis of human plasma sample after exposed to high altitude and return to sea level

PLoS One. 2023 Mar 29;18(3):e0282301. doi: 10.1371/journal.pone.0282301. eCollection 2023.

ABSTRACT

When ascending to high altitude, it is a rigorous challenge to people who living in the low altitude area to acclimatize to hypoxic environment. Hypoxia exposure can cause dramatic disturbances of metabolism. This longitudinal cohort study was conducted to delineate the plasma metabolomics profile following exposure to altitude environments and explore potential metabolic changes after return to low altitude area. 25 healthy volunteers living in the low altitude area (Nor; 40m) were transported to high altitude (HA; 3,650m) for a 7-day sojourn before transported back to the low altitude area (HAP; 40m). Plasma samples were collected on the day before ascending to HA, the third day on HA(day 3) and the fourteenth day after returning to low altitude(14 day) and analyzed using UHPLC-MS/MS tools and then the data were subjected to multivariate statistical analyses. There were 737 metabolites were obtained in plasma samples with 133 significantly changed metabolites. We screened 13 differential metabolites that were significantly changed under hypoxia exposure; enriched metabolic pathways under hypoxia exposure including tryptophan metabolism, purine metabolism, regulation of lipolysis in adipocytes; We verified and relatively quantified eight targeted candidate metabolites including adenosine, guanosine, inosine, xanthurenic acid, 5-oxo-ETE, raffinose, indole-3-acetic acid and biotin for the Nor and HA group. Most of the metabolites recovered when returning to the low altitude area, however, there were still 6 metabolites that were affected by hypoxia exposure. It is apparent that high-altitude exposure alters the metabolic characteristics and two weeks after returning to the low altitude area a small portion of metabolites was still affected by high-altitude exposure, which indicated that high-altitude exposure had a long-term impact on metabolism. This present longitudinal cohort study demonstrated that metabolomics can be a useful tool to monitor metabolic changes exposed to high altitude, providing new insight in the attendant health problem that occur in response to high altitude.

PMID:36989280 | DOI:10.1371/journal.pone.0282301

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Nevin Manimala Statistics

Comparison of whole transcriptome sequencing of fresh, frozen, and formalin-fixed, paraffin-embedded cardiac tissue

PLoS One. 2023 Mar 29;18(3):e0283159. doi: 10.1371/journal.pone.0283159. eCollection 2023.

ABSTRACT

The use of fresh tissue for molecular studies is preferred but often impossible. Instead, frozen or formalin-fixed, paraffin-embedded (FFPE) tissues are widely used and constitute valuable resources for retrospective studies. We assessed the utility of cardiac tissue stored in different ways for gene expression analyses by whole transcriptome sequencing of paired fresh, frozen, and FFPE tissues. RNA extracted from FFPE was highly degraded. Sequencing of RNA from FFPE tissues yielded higher proportions of intronic and intergenic reads compared to RNA from fresh and frozen tissues. The global gene expression profiles varied with the storage conditions, particularly mitochondrial and long non-coding RNAs. However, we observed high correlations among protein-coding transcripts (ρ > 0.94) with the various storage conditions. We did not observe any significant storage effect on the allele-specific gene expression. However, FFPE had statistically significantly (p < 0.05) more discordant variant calls compared to fresh and frozen tissue. In conclusion, we found that frozen and FFPE tissues can be used for reliable gene expression analyses, provided that proper quality control is performed and caution regarding the technical variability is withheld.

PMID:36989279 | DOI:10.1371/journal.pone.0283159

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Nevin Manimala Statistics

The sizes of life

PLoS One. 2023 Mar 29;18(3):e0283020. doi: 10.1371/journal.pone.0283020. eCollection 2023.

ABSTRACT

Recent research has revealed the diversity and biomass of life across ecosystems, but how that biomass is distributed across body sizes of all living things remains unclear. We compile the present-day global body size-biomass spectra for the terrestrial, marine, and subterranean realms. To achieve this compilation, we pair existing and updated biomass estimates with previously uncatalogued body size ranges across all free-living biological groups. These data show that many biological groups share similar ranges of body sizes, and no single group dominates size ranges where cumulative biomass is highest. We then propagate biomass and size uncertainties and provide statistical descriptions of body size-biomass spectra across and within major habitat realms. Power laws show exponentially decreasing abundance (exponent -0.9±0.02 S.D., R2 = 0.97) and nearly equal biomass (exponent 0.09±0.01, R2 = 0.56) across log size bins, which resemble previous aquatic size spectra results but with greater organismal inclusivity and global coverage. In contrast, a bimodal Gaussian mixture model describes the biomass pattern better (R2 = 0.86) and suggests small (~10-15 g) and large (~107 g) organisms outweigh other sizes by one order magnitude (15 and 65 Gt versus ~1 Gt per log size). The results suggest that the global body size-biomass relationships is bimodal, but substantial one-to-two orders-of-magnitude uncertainty mean that additional data will be needed to clarify whether global-scale universal constraints or local forces shape these patterns.

PMID:36989258 | DOI:10.1371/journal.pone.0283020

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Nevin Manimala Statistics

Effect of prenatal care quality on the risk of low birth weight, preterm birth and vertical transmission of HIV, syphilis, and hepatitis

PLOS Glob Public Health. 2023 Mar 29;3(3):e0001716. doi: 10.1371/journal.pgph.0001716. eCollection 2023.

ABSTRACT

BACKGROUND: Averse birth-outcomes still affect newborns worldwide. Although high-quality prenatal care is the main strategy to prevent these outcomes, the effect of prenatal care based on Kotelchuck index combined with consultation contents is still unclear. Thus, this article to evaluate the effect of the quality of prenatal care (PC) process on birth indicators in a cohort of puerperaes who attended maternity hospitals in Brazilian western Amazon, city of Rio Branco, in the state of Acre, Brazil, in 2015.

METHODS: This research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in the city between April 6 and June 30, 2015. This research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in Rio Branco between April 6th. and June 30th., 2015. Prenatal care was classified as fully adequate when started ≤4th month; ≥80.0-109% expected consultations for GA according to the Kotelchuck Index; ≥5 records of blood pressure, weight, GA, fundal height, ≥4 records of fetal heart rate, fetal movements or equivalent to 75% of the number of consultations; in addition to recording ABO/RH, hemoglobin, VDRL, urine, glucose, anti-HIV and anti-toxoplamosis during the 1st trimester. The evaluated outcomes were low birth weight (LBW), preterm birth and vertical transmission of human immunodeficiency virus (HIV)/hepatitis/syphilis. Differences between proportions were assessed using the X² test, and the crude and adjusted odds ratios (OR) (95% CI) were estimated using unconditional logistic regression.

RESULTS: Overall cohort, the outcomes incidences were 8.8% for LBW, 9.2% for preterm birth, and 1.1% for vertical transmission (syphilis/HIV/hepatitis). Crude and adjusted OR showed that inadequate PC increased the risk statistically significant of LBW (ORcrude: 1.84; 95%CI: 0.99-3.44; ORadjusted: 1.87; 95%CI: 1.00-3.52), and preterm birth (ORcrude: 1.79; 95%CI: 1.00-3.29; ORadjusted: 3.98; 95%CI: 1.40-11.29).

CONCLUSION: The results draw attention to the importance of quality PC in reducing the risks of LBW, preterm birth, and vertical transmission of syphilis/HIV/hepatitis. Moreover, using this proposed quality prenatal care indicator based on Kotelchuck index combined with consultations contents adjusted by GA may accurately predict unfavorable outcomes.

PMID:36989229 | DOI:10.1371/journal.pgph.0001716

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Back to the basics: Clinical assessment yields robust mortality prediction and increased feasibility in low resource settings

PLOS Glob Public Health. 2023 Mar 29;3(3):e0001761. doi: 10.1371/journal.pgph.0001761. eCollection 2023.

ABSTRACT

INTRODUCTION: Mortality prediction aids clinical decision-making and is necessary for trauma quality improvement initiatives. Conventional injury severity scores are often not feasible in low-resource settings. We hypothesize that clinician assessment will be more feasible and have comparable discrimination of mortality compared to conventional scores in low and middle-income countries (LMICs).

METHODS: Between 2017 and 2019, injury data were collected from all injured patients as part of a prospective, four-hospital trauma registry in Cameroon. Clinicians used physical exam at presentation to assign a highest estimated abbreviated injury scale (HEAIS) for each patient. Discrimination of hospital mortality was evaluated using receiver operating characteristic curves. Discrimination of HEAIS was compared with conventional scores. Data missingness for each score was reported.

RESULTS: Of 9,635 presenting with injuries, there were 206 in-hospital deaths (2.2%). Compared to 97.5% of patients with HEAIS scores, only 33.2% had sufficient data to calculate a Revised Trauma Score (RTS) and 24.8% had data to calculate a Kampala Trauma Score (KTS). Data from 2,328 patients with all scores was used to compare models. Although statistically inferior to the prediction generated by RTS (AUC 0.92-0.98) and KTS (AUC 0.93-0.99), HEAIS provided excellent overall discrimination of mortality (AUC 0.84-0.92). Among 9,269 patients with HEAIS scores was strongly predictive of mortality (AUC 0.93-0.96).

CONCLUSION: Clinical assessment of injury severity using HEAIS strongly predicts hospital mortality and far exceeds conventional scores in feasibility. In contexts where traditional scoring systems are not feasible, utilization of HEAIS could facilitate improved data quality and expand access to quality improvement programming.

PMID:36989211 | DOI:10.1371/journal.pgph.0001761