Tag: statistics

Hum Mutat. 2022 Oct 11. doi: 10.1002/humu.24481. Online ahead of print.

ABSTRACT

Psychiatric disorders have a polygenic architecture, often associated with dozens or hundreds of independent genomic loci. Most associated loci impact non-coding regions of the genome, suggesting that the majority of disease heritability originates from the disruption of regulatory sequences. While most research has focused on variants that modify regulatory DNA elements, those affecting cis-acting RNA sequences, such as miRNA binding sites, are also likely to have a significant impact. We intersected genome-wide association study (GWAS) summary statistics with the dbMTS database of predictions for miRNA binding site variants (MBSVs). We compared the distributions of MBSV association statistics to non-MBSVs within brain-expressed 3’UTR regions. We aggregated GWAS p-values at the gene, pathway, and miRNA family levels to investigate cellular functions and miRNA families strongly associated with each trait. We performed these analyses in several psychiatric disorders as well as non-psychiatric traits for comparison. We observed significant enrichment of MBSVs in schizophrenia, depression, bipolar disorder, and anorexia nervosa, particularly in genes targeted by several miRNA families, including miR-335-5p, miR-21-5p/590-5p, miR-361-5p, and miR-557, and a nominally significant association between miR-323b-3p MBSVs and schizophrenia risk. We identified evidence for association between MBSVs in synaptic gene sets in schizophrenia and bipolar disorder. We also observed significant association of MBSVs in other complex traits including type 2 diabetes. These observations support the role of miRNA in the pathophysiology of psychiatric disorders and suggest that MBSVs are an important class of regulatory variants that have functional implications for many disorders, as well as other complex human traits. This article is protected by copyright. All rights reserved.

PMID:36217923 | DOI:10.1002/humu.24481

Analyst. 2022 Oct 11. doi: 10.1039/d2an01222g. Online ahead of print.

ABSTRACT

Recent advancements in anatomical imaging of tumours as treatment targets have led to improvements in RT. However, it is unlikely that improved anatomical imaging alone will be the sole driver for new advances in personalised RT. Biochemically based radiobiological information is likely to be required for next-generation improvements in the personalisation of radiotherapy dose prescriptions to individual patients. In this paper, we use Raman spectroscopy (RS), an optical technique, to monitor individual biochemical response to radiation within a tumour microenvironment. We spatially correlate individual biochemical responses to augmentatively derived hypoxic maps within the tumour microenvironment. Furthermore, we pair RS with a data analytical framework combining (i) group and basis restricted non-negative matrix factorization (GBR-NMF), (ii) a random forest (RF) classifier, (iii) and a feature metric importance calculation method, Shapley Additive exPlanations (SHAP), in order to ascertain the relative importance of individual biochemicals in describing the overall biological response as observed with RS. The current study found that the GBR-NMF-RF-SHAP model helped identify a wide range of radiation response biomarkers and hypoxia indicators (e.g., glycogen, lipids, DNA, amino acids) in H460 human lung cancer cells and H460 xenografts. Correlations between the hypoxic regions and Raman chemical biomarkers (e.g., glycogen, alanine, and arginine) were also identified in H460 xenografts. To summarize, GBR-NMF-RF-SHAP combined with RS can be applied to monitor the RT-induced biochemical response within cellular and tissue environments. Individual biochemicals were identified that (i) contributed to overall biological response to radiation, and (ii) spatially correlated with hypoxic regions of the tumour. RS combined with our analytical pipeline shows promise for further understanding of individual biochemical dynamics in radiation response for use in cancer therapy.

PMID:36217911 | DOI:10.1039/d2an01222g

Am J Epidemiol. 2022 Oct 10:kwac172. doi: 10.1093/aje/kwac172. Online ahead of print.

ABSTRACT

There is a compelling need to evaluate the real-world health effects of medical products outside of tightly controlled pre-approval clinical trials. This is done through pharmacoepidemiology, which is the study of the health effects of medical products (including drugs, biologicals, and medical devices and diagnostics) in populations, often using non-randomized designs. Recent developments in pharmacoepidemiology span changes in the focus of research questions, research designs, data used, and statistical analysis methods. Developments in these areas are thought to improve the value of the evidence produced by such studies, and are prompting greater use of real-world evidence to inform clinical, regulatory, and reimbursement decisions.

PMID:36217921 | DOI:10.1093/aje/kwac172

Transbound Emerg Dis. 2022 Oct 11. doi: 10.1111/tbed.14739. Online ahead of print.

ABSTRACT

Since the arrival of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, elimination and control programs have had partial success. The dynamics of its spread are hard to quantify, though previous work has shown that local transmission and the transfer of pigs within production systems are most associated with the spread of PEDV. Our work relies on the history of PEDV infections in a region of the southeastern United States. This infection data is complemented by farm-level features and extensive industry data on the movement of both pigs and vehicles. We implement a discrete-time survival model and evaluate different approaches to modeling the local-transmission and network effects. We find strong evidence in that the local-transmission and pig-movement effects are associated with the spread of PEDV, even while controlling for seasonality, farm-level features, and the possible spread of disease by vehicles. Our fully Bayesian model permits full uncertainty quantification of these effects. Our farm-level out-of-sample predictions have a receiver-operating characteristic area under the curve (AUC) of 0.779 and a precision-recall AUC of 0.097. The quantification of these effects in a comprehensive model allows stakeholders to make more informed decisions about disease prevention efforts. This article is protected by copyright. All rights reserved.

PMID:36217910 | DOI:10.1111/tbed.14739

Hosp Pediatr. 2022 Oct 11:e2021006118. doi: 10.1542/hpeds.2021-006118. Online ahead of print.

ABSTRACT

OBJECTIVES: Caregiver engagement during acute inpatient hospitalizations has been demonstrated to provide developmental and behavioral benefits for children, decrease readmissions and length of stay, and improve caregiver confidence. Caregiver engagement has been examined in acute care settings; however, there is a gap in information regarding caregiver engagement in a pediatric post-acute care hospital (pPACH). The objective of this study was to explore caregiver engagement in a pPACH.

PATIENTS AND METHODS: All patients, birth to 23 years of age, in the medical service of an independent pPACH in the Northeastern United States, January 1, 2013, through December 31, 2017, were identified. Retrospective review of electronic health records for patient demographics and caregiver engagement, identified as visit(s) and telephone call(s), was conducted. Descriptive statistics and logistic regression were used to distinguish differences and measure associations of caregiver visits and calls between demographic groups.

RESULTS: The primary mode of caregiver engagement for pPACH patients (n = 614) was by visits, whereas caregiver calls were less frequent. Multivariable logistic regression analysis identified significantly greater odds of caregiver visits among patients ages 1 to 17 years, with private payer, and having a single admission, whereas lower odds of visits were identified among those <1 year or ≥18 years, with ≥2 pPACH admissions, public insurance, Child Protective Services (CPS) involvement, and African American/Black, other, and unknown race/ethnicities.

CONCLUSIONS: Patients who were infants, had ≥2 admissions, had CPS involvement, and were covered under public payer experienced lower caregiver visit rates. Strategies are needed to further identify and address barriers to caregiver engagement.

PMID:36217894 | DOI:10.1542/hpeds.2021-006118

Przegl Epidemiol. 2022;76(2):164-167. doi: 10.32394/pe.76.16.

ABSTRACT

INTRODUCTION: How to reduce the fatality of coronavirus disease (COVID-19) is still challenging. A proper nutritional support has been always a matter of attention in critically ill patients.

MATERIAL AND METHODS: We assessed COVID-19 patients who had received intralipid infusion due to medical indications and compared them with those who did not receive it regarding fatality rate and prognosis. As a part of a data mining project using data of observational cohort of COVID-19 patients hospitalized in the educational centers of Iran University of Medical Sciences, Tehran, Iran, an inferential case series was performed. A total of 19 patients with SARS-CoV-2 infection were selected from the cohort. Briefly, 13 patients survived and 6 patients died, and 12 patients were admitted in intensive care unit (ICU). All dead cases were ICU admitted. The association of intralipid infusion and survival rate was examined using Fisher exact test. No association was observed between intralipid infusion and survival.

CONCLUSIONS: No significant protecting effect was observed for patients who received intralipid for medical indications. Since intralipid was administered according to medical indications, surviving of all the non-ICU admitted patients despite having underlying diseases was remarkable. Despite the fact, due to several bias factors that could not be controlled in such a retrospective study, the results might be accidental. We suggest to assess such an effect retrospectively in other centers as well.

PMID:36217879 | DOI:10.32394/pe.76.16

J Sleep Res. 2022 Oct 11:e13745. doi: 10.1111/jsr.13745. Online ahead of print.

ABSTRACT

Previous research shows that sleep quality may interact with some other predictors of depression, such that poor sleep could strengthen the association between these factors and depression. We aimed to determine the presence of statistical interactions between sleep quality and loneliness, risky alcohol use, perfectionistic concerns and/or physical inactivity in relation to depressive symptoms. Further, we aimed to describe the functional form of the statistical interactions and associations. We used a cross-sectional design and included 4262 Swedish university students. All measures were self-reported, sleep quality was measured with the Pittsburgh Sleep Quality Index, and depressive symptoms with the short-form Depression, Anxiety and Stress Scale. Regression models of increasing complexity (linear and non-linear, with and without interactions) were compared to determine the presence of associations and statistical interactions, and to explore the best functional form for these associations and interactions. Out-of-sample R² from repeated cross-validation was used to select the final models. We found that sleep quality was associated with depressive symptoms in all final models. Sleep quality showed a linear interaction with perfectionistic concerns in relation to depressive symptoms, such that perfectionistic concerns were more strongly associated with depressive symptoms when sleep quality was poor. Loneliness, risky alcohol use and physical inactivity were non-linearly associated with depressive symptoms but did not interact with sleep quality. We concluded that out of the four examined variables, only perfectionistic concerns interacted with sleep quality in relation to depressive symptoms. This interaction was weak and explained little of the overall variance in depressive symptoms.

PMID:36217878 | DOI:10.1111/jsr.13745

Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221132035. doi: 10.1177/15330338221132035.

ABSTRACT

Purpose: This study aimed to establish a nomogram to predict overall survival in lung squamous cell carcinoma patients with metastasis for clinical decision-making. Methods: We investigated lung squamous cell carcinoma patients diagnosed with stage M1 in the Surveillance, Epidemiology, and Final Results database between 2010 and 2015. They were divided into training cohort and validation cohort. In the training cohort, statistically significant prognostic factors were identified using univariate and multivariate Cox regression analysis, and an individualized nomogram model was developed. The model was evaluated by C-index, area under the curve, calibration plot, decision curve analysis, and risk group stratification. Results: In total, 9910 patients were included in our study, including 6937 in the training cohort and 2937 in the validation cohort. Factors containing age, T stage, N stage, bone metastasis, brain metastasis, liver metastasis, surgery, chemotherapy, and radiotherapy were independent prognostic factors for overall survival and were used in the construction of the nomogram. The C-index in the training cohort and validation cohort were 0.711 (95% confidenc interval: 0.705-0.717) and 0.707 (95% confidenc interval: 0.697-0.717), respectively. The time-dependent area under the curve of both groups was higher than 0.7 within 5 years. Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 6-month, 1-year, and 2-year prognoses. Furthermore, decision curve analysis revealed that the nomogram was clinically useful and had a better discriminative ability to recognize patients at high risk than the TNM criteria-based tumor staging. And then we developed an overall survival risk classification system based on the nomogram total points for each patient, which divided all patients into a high-risk group and a low-risk group. Finally, we implemented this nomogram in a free online tool. Conclusion: We constructed a nomogram and a corresponding risk classification system predicting the overall survival of lung squamous cell carcinoma patients with metastasis. These tools can assist in patients’ counseling and guide treatment decision-making.

PMID:36217877 | DOI:10.1177/15330338221132035

S Afr Med J. 2022 May 31;112(6):413-417.

ABSTRACT

In resource-limited settings, holding regimens such as lamivudine monotherapy (LAM) have been used to manage HIV-positive children failing combination antiretroviral therapy to mitigate the risk of drug resistance developing, while adherence barriers are addressed or when access to second- or third-line regimens is restricted. South African HIV treatment guidelines previously advocated the use of LAM to manage HIV-infected children with virological failure. However, the outcomes of patients on LAM compared with those who continued on a failing regimen have not been well described. Objectives. To investigate characteristics of a large cohort of children placed on LAM and their outcomes. Methods. This was a retrospective review of children with virological failure and the documented M184V drug resistance mutation who were placed on LAM v. a control group of children who continued on a failing regimen despite persistent virological failure. Virological and immunological outcomes of LAM were compared with those in patients who remained on a failing regimen. Results. A total of 179 children were included in the analysis, with 92 in the LAM group and 87 in the control group. The median (interquartile range (IQR)) age at baseline was 9.2 (5.4 – 12) years, the median CD4 count was 384 (184 – 622) cells/μL, and the median HIV viral load was 4.7 (IQR 3.7 – 5.3) log10. Twenty-two children (25.6%) in the LAM group and 15 (17.4%) in the control group experienced immunological deterioration. There was no statistical difference between the two groups with regard to overall time to immunological deterioration (log-rank p-value 0.4810). Conclusion. Given that a higher proportion of children in the LAM group experienced immunological failure, the LAM strategy may be a useful short-term one but should be restricted to children with limited treatment options. Managing children with virological failure will continue to be a challenge until improved adherence strategies are available.

PMID:36217870

S Afr Med J. 2022 Jul 1;112(7):494-501.

ABSTRACT

BACKGROUND: Maternal mental health during the perinatal period has been of interest to many researchers, with antenatal depression and postnatal depression (PND) being a leading cause of morbidity. The adverse effects of maternal depression on the offspring throughout infancy, childhood and adolescence are well documented. Studies on the mental health of persons living with HIV have also reported a high prevalence of depression.

OBJECTIVES: To describe the prevalence of PND in a sample of HIV-positive and HIV-negative mothers delivering healthy singleton infants at one obstetric unit in KwaZulu-Natal (KZN) Province, South Africa, and the subsequent factors influencing neonatal behaviour and perceptions of caregiver competence. Correlations between the presence of PND and perceptions of caregiver competence (with the mother as caregiver), and between infant behaviour, the mother’s confidence in her competence as caregiver, and demographic and medical variables, were also examined.

METHODS: Demographic and clinical data were collected from 132 mothers at initial contact and from 32 mothers at the 6-week follow-up appointment. Mothers independently completed the Edinburgh Postnatal Depression Scale at each time point, and the Mother and Baby Scales (MABS) at the 6-week follow-up appointment.

RESULTS: The prevalence of depression among all mothers at initial contact was 72.0%, remaining high (68.8%) among the mothers who returned for follow-up. There was a statistically significant correlation between depression and employment at follow-up (p=0.013), and between depression and delivery method (p=0.030). The majority of mothers reported being ‘able to laugh and see the funny side of things’ and ‘looking forward with enjoyment to things’ at initial contact and follow-up. Thoughts of self-harm were reported by 44.7% of mothers at baseline, and by 53.1% at follow-up. Although most infants scored in the average clinical band for neonatal behavioural factors in the MABS, mothers reported lack of confidence, globally and in caring for their infant.

CONCLUSION: This study of maternal mental health of a sample of HIV-positive and HIV-negative mothers of infants in KZN revealed a higher prevalence of PND than reported in other studies. This population of mothers and infants is at risk of adverse outcomes of maternal depression, in addition to other possible risk factors.

PMID:36217860