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Nevin Manimala Statistics

Associations between insomnia and pregnancy and perinatal outcomes: Evidence from mendelian randomization and multivariable regression analyses

PLoS Med. 2022 Sep 6;19(9):e1004090. doi: 10.1371/journal.pmed.1004090. Online ahead of print.

ABSTRACT

BACKGROUND: Insomnia is common and associated with adverse pregnancy and perinatal outcomes in observational studies. However, those associations could be vulnerable to residual confounding or reverse causality. Our aim was to estimate the association of insomnia with stillbirth, miscarriage, gestational diabetes (GD), hypertensive disorders of pregnancy (HDP), perinatal depression, preterm birth (PTB), and low/high offspring birthweight (LBW/HBW).

METHODS AND FINDINGS: We used 2-sample mendelian randomization (MR) with 81 single-nucleotide polymorphisms (SNPs) instrumenting for a lifelong predisposition to insomnia. Our outcomes included ever experiencing stillbirth, ever experiencing miscarriage, GD, HDP, perinatal depression, PTB (gestational age <37 completed weeks), LBW (<2,500 grams), and HBW (>4,500 grams). We used data from women of European descent (N = 356,069, mean ages at delivery 25.5 to 30.0 years) from UK Biobank (UKB), FinnGen, Avon Longitudinal Study of Parents and Children (ALSPAC), Born in Bradford (BiB), and the Norwegian Mother, Father and Child Cohort (MoBa). Main MR analyses used inverse variance weighting (IVW), with weighted median and MR-Egger as sensitivity analyses. We compared MR estimates with multivariable regression of insomnia in pregnancy on outcomes in ALSPAC (N = 11,745). IVW showed evidence of an association of genetic susceptibility to insomnia with miscarriage (odds ratio (OR): 1.60, 95% confidence interval (CI): 1.18, 2.17, p = 0.002), perinatal depression (OR 3.56, 95% CI: 1.49, 8.54, p = 0.004), and LBW (OR 3.17, 95% CI: 1.69, 5.96, p < 0.001). IVW results did not support associations of insomnia with stillbirth, GD, HDP, PTB, and HBW, with wide CIs including the null. Associations of genetic susceptibility to insomnia with miscarriage, perinatal depression, and LBW were not observed in weighted median or MR-Egger analyses. Results from these sensitivity analyses were directionally consistent with IVW results for all outcomes, with the exception of GD, perinatal depression, and PTB in MR-Egger. Multivariable regression showed associations of insomnia at 18 weeks of gestation with perinatal depression (OR 2.96, 95% CI: 2.42, 3.63, p < 0.001), but not with LBW (OR 0.92, 95% CI: 0.69, 1.24, p = 0.60). Multivariable regression with miscarriage and stillbirth was not possible due to small numbers in index pregnancies. Key limitations are potential horizontal pleiotropy (particularly for perinatal depression) and low statistical power in MR, and residual confounding in multivariable regression.

CONCLUSIONS: In this study, we observed some evidence in support of a possible causal relationship between genetically predicted insomnia and miscarriage, perinatal depression, and LBW. Our study also found observational evidence in support of an association between insomnia in pregnancy and perinatal depression, with no clear multivariable evidence of an association with LBW. Our findings highlight the importance of healthy sleep in women of reproductive age, though replication in larger studies, including with genetic instruments specific to insomnia in pregnancy are important.

PMID:36067251 | DOI:10.1371/journal.pmed.1004090

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Nevin Manimala Statistics

A Mobile Application for Symptom Management in Patients With Breast Cancer

Oncol Nurs Forum. 2022 Aug 18;49(5):409-420. doi: 10.1188/22.ONF.409-420.

ABSTRACT

OBJECTIVES: To evaluate the effect of a symptom management mobile application on quality of life and symptom severity in women with breast cancer undergoing chemotherapy.

SAMPLE &AMP; SETTING: This parallel randomized pilot study consisted of women with breast cancer admitted to oncology outpatient clinics between November 2019 and January 2021 in Turkey.

METHODS &AMP; VARIABLES: Participants (N = 40) were randomly assigned to the intervention (n = 20) or control group (n = 20). The intervention group used the mobile application in conjunction with usual care. The control group received usual care. Participants were assessed during the first, third, and last chemotherapy cycles. Data were collected using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 and the Edmonton Symptom Assessment System.

RESULTS: During the study, the decrease in general health and physical functioning and the increase in the severity of depression/sadness in the intervention group were statistically lower than in the control group.

IMPLICATIONS FOR NURSING: The use of a mobile application for symptom management may promote general well-being and physical function and may alleviate symptoms of depression/sadness in women with breast cancer undergoing chemotherapy. Further studies are needed to evaluate the application in clinical settings with larger groups.

PMID:36067241 | DOI:10.1188/22.ONF.409-420

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Nevin Manimala Statistics

MouseNet: A biologically constrained convolutional neural network model for the mouse visual cortex

PLoS Comput Biol. 2022 Sep 6;18(9):e1010427. doi: 10.1371/journal.pcbi.1010427. Online ahead of print.

ABSTRACT

Convolutional neural networks trained on object recognition derive inspiration from the neural architecture of the visual system in mammals, and have been used as models of the feedforward computation performed in the primate ventral stream. In contrast to the deep hierarchical organization of primates, the visual system of the mouse has a shallower arrangement. Since mice and primates are both capable of visually guided behavior, this raises questions about the role of architecture in neural computation. In this work, we introduce a novel framework for building a biologically constrained convolutional neural network model of the mouse visual cortex. The architecture and structural parameters of the network are derived from experimental measurements, specifically the 100-micrometer resolution interareal connectome, the estimates of numbers of neurons in each area and cortical layer, and the statistics of connections between cortical layers. This network is constructed to support detailed task-optimized models of mouse visual cortex, with neural populations that can be compared to specific corresponding populations in the mouse brain. Using a well-studied image classification task as our working example, we demonstrate the computational capability of this mouse-sized network. Given its relatively small size, MouseNet achieves roughly 2/3rds the performance level on ImageNet as VGG16. In combination with the large scale Allen Brain Observatory Visual Coding dataset, we use representational similarity analysis to quantify the extent to which MouseNet recapitulates the neural representation in mouse visual cortex. Importantly, we provide evidence that optimizing for task performance does not improve similarity to the corresponding biological system beyond a certain point. We demonstrate that the distributions of some physiological quantities are closer to the observed distributions in the mouse brain after task training. We encourage the use of the MouseNet architecture by making the code freely available.

PMID:36067234 | DOI:10.1371/journal.pcbi.1010427

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Nevin Manimala Statistics

CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018

Neuro Oncol. 2022 Sep 6;24(Supplement_3):iii1-iii38. doi: 10.1093/neuonc/noac161.

ABSTRACT

The CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and other CNS tumors in children and adolescents ages 0-19 years, collected and reported by central cancer registries covering approximately 100% of the United States population. Overall, brain and other CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in children and adolescents ages 0-19 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.

PMID:36066969 | DOI:10.1093/neuonc/noac161

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Nevin Manimala Statistics

Transdiagnostic Internet-Delivered Cognitive Behavioral Therapy for Symptoms of Postpartum Anxiety and Depression: Feasibility Randomized Controlled Trial

JMIR Form Res. 2022 Sep 6;6(9):e37216. doi: 10.2196/37216.

ABSTRACT

BACKGROUND: Postpartum depression (PPD) and postpartum anxiety (PPA) are often comorbid and are associated with significant personal and economic costs. Fewer than half of the mothers experiencing PPD or PPA symptoms receive face-to-face treatment, suggesting a need for alternative delivery formats such as internet-delivered cognitive behavioral therapy (ICBT).

OBJECTIVE: This pilot study aimed to examine the impact of a therapist-assisted, transdiagnostic ICBT program on symptoms of PPD and PPA, as there is only one previous study on transdiagnostic ICBT with this population, which did not include therapist assistance.

METHODS: Clients endorsing the symptoms of PPD or PPA (N=63) were randomized to an 8-week transdiagnostic ICBT course (Wellbeing Course for New Moms) or to treatment as usual (TAU). Clients completed measures of depression, anxiety, stress, postnatal bonding, and relationship satisfaction, as well as measures of treatment satisfaction and therapeutic alliance, before treatment, after treatment, and at the 1-month follow-up. Outcome measures were also completed at the 6-month follow-up for clients who completed the ICBT course.

RESULTS: Both the ICBT and TAU groups experienced statistically significant improvements over time. The ICBT group experienced larger improvements after treatment and at the 1-month follow-up on more measures than the TAU group, with medium between-group Cohen d effects on primary outcome measures for anxiety (Cohen d=0.65, 95% CI 0.13-1.17), PPD (Cohen d=0.52, 95% CI 0.01-1.04), and depression (Cohen d=0.56, 95% CI 0.05-1.08), and on secondary outcome measures of overall distress (Cohen d=0.69, 95% CI 0.17-1.21), anxiety (Cohen d=0.59, 95% CI 0.07-1.11), and stress (Cohen d=0.76, 95% CI 0.23-1.28). Time-by-group interactions for proportional reductions between groups over time were only significant after treatment and at the 1-month follow-up for the primary anxiety measure (P=.006). This study was underpowered for detecting small or medium effects. Overall, clients perceived the treatment as credible, and 95% (21/22) of the clients were satisfied with the treatment content and therapist support.

CONCLUSIONS: Findings from this pilot study provide preliminary support for transdiagnostic ICBT in treating PPD and PPA symptoms to improve access to psychological treatments.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04012580; https://clinicaltrials.gov/ct2/show/NCT04012580.

PMID:36066958 | DOI:10.2196/37216

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Nevin Manimala Statistics

Feasibility and Acceptability of Delivering Pivotal Response Treatment for Autism Spectrum Disorder via Telehealth: Pilot Pre-Post Study

JMIR Pediatr Parent. 2022 Sep 6;5(3):e32520. doi: 10.2196/32520.

ABSTRACT

BACKGROUND: Pivotal response treatment (PRT), an evidence-based and parent-delivered intervention, is designed to improve social communication in autistic individuals.

OBJECTIVE: The aim of this study was to assess the feasibility, acceptability, and clinical effects of an online model of PRT delivered via MindNest Health, a telehealth platform that aims to provide self-directed and engaging online modules, real-time coaching and feedback, and accessible stepped-care to large populations of parents seeking resources for their autistic children.

METHODS: Male and female autistic children, aged 2-7 years with single-word to phrase-level speech, and their parents were eligible to participate in the study. Families were randomized to the online parent training condition or control condition. The online component of the intervention consisted of eight 20-minute online courses of content describing parent training principles in PRT. Four 1-hour videoconferences were held after course 1, course 3, course 5, and course 8. Parents were given 1-2 weeks to complete each course. Parents completed the Client Credibility Questionnaire (CCQ) at week 2 and at the study endpoint, as well as the Behavioral Intervention Rating Scale (BIRS) at the study endpoint to assess parental expectancies, and treatment acceptability and effectiveness.

RESULTS: Nine of 14 participants completed the study curriculum in the online parent training condition, and 6 of 12 participants completed the control condition. Thus, a total of 58% (15/26) participants across both groups completed the study curriculum by study closure. Within the online parent training condition, there was a significant increase in mean CCQ total scores, from 25.38 (SD 3.25) at baseline to 27.5 (SD 3.74) at study endpoint (P=.04); mean CCQ confidence scores, from 6.0 (SD 1.07) at baseline to 6.75 (SD 0.89) at study endpoint (P=.02); and mean CCQ other improvement scores, from 5.25 (SD 0.89) at baseline to 6.25 (SD 1.28) at study endpoint (P=.009). Within the control condition, a modest increase in mean CCQ scores was noted (Confidence, difference=+0.25; Recommend, difference=+0.25; Total Score, difference=+0.50), but the differences were not statistically significant (Confidence P=.38, Recommend P=.36, Total Score P=.43). Among the 11 parents who completed the BIRS at the study endpoint, 82% (n=9) endorsed that they slightly agree or agree with over 93% of the Acceptability factor items on the BIRS.

CONCLUSIONS: The feasibility of this online treatment is endorsed by the high rate of online module completion and attendance to videoconferences within the online parent training group. Acceptability of treatment is supported by strong ratings on the CCQ and significant improvements in scores, as well as strong ratings on the BIRS. This study’s small sample size limits the conclusions that can be drawn; however, the PRT MindNest Health platform holds promise to support parents of autistic children who are unable to access traditional, in-person parent-mediated interventions for their child.

PMID:36066927 | DOI:10.2196/32520

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Nevin Manimala Statistics

Coronary and extra-coronary artery calcium scores as predictors of cardiovascular events and mortality in chronic kidney disease stages 1-5: a prospective cohort study

Nephrol Dial Transplant. 2022 Sep 6:gfac252. doi: 10.1093/ndt/gfac252. Online ahead of print.

ABSTRACT

BACKGROUND: Vascular calcification is a known risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, since there is a lack of studies examining several arterial regions at a time, we aimed to evaluate the risk of major adverse cardiovascular events (MACE) and all-cause mortality according to calcium scores in five major arterial sites.

METHODS: This was a prospective study of 580 patients from the Copenhagen CKD Cohort. Multidetector computed tomography of the coronary and carotid arteries, the thoracic aorta, the abdominal aorta, and the iliac arteries was used to determine vascular calcification at baseline. Calcium scores were divided into categories: 0, 1-100, 101-400, and > 400.

RESULTS: During the follow-up period of 4.1 years a total of 59 cardiovascular events and 64 all-cause deaths occurred. In Cox proportional hazards models adjusted for age, sex, eGFR, hypertension, diabetes mellitus, hypercholesterolemia, and smoking, only the coronary and carotid arteries, and the thoracic aorta were independent predictors of the designated endpoints. When examining the potential of calcification in the five arterial sites for predicting MACE, the difference in C-statistic was also most pronounced in these three sites, 0.21 (95% CI 0.16%-0.26%, P < 0.001), 0.26 (95% CI 0.22%-0.3%, P < 0.001), and 0.20 (95% CI 0.16%-0.24%, P < 0.001), respectively. This trend also applied to all-cause mortality.

CONCLUSIONS: The overall results, including data on specificity, suggest that calcium scores of the coronary and carotid arteries have the most potential for identifying patients with CKD at high cardiovascular risk and for evaluating new therapies.

PMID:36066908 | DOI:10.1093/ndt/gfac252

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Nevin Manimala Statistics

The absence of the Queuosine tRNA modification leads to pleiotropic phenotypes revealing perturbations of metal and oxidative stress homeostasis in Escherichia coli K12

Metallomics. 2022 Sep 6:mfac065. doi: 10.1093/mtomcs/mfac065. Online ahead of print.

ABSTRACT

Queuosine (Q) is a conserved hypermodification of the wobble base of tRNA containing GUN anticodons but the physiological consequences of Q deficiency are poorly understood in bacteria. This work combines transcriptomic, proteomic and physiological studies to characterize a Q-deficient Escherichia coli K12 MG1655 mutant. The absence of Q led to increased resistance to nickel and cobalt, and to increased sensitivity to cadmium, compared to the wild-type (WT) strain. Transcriptomic analysis of the WT and Q-deficient strains, grown in the presence and absence of nickel, revealed that the nickel transporter genes (nikABCDE) are down-regulated in the Q- mutant, even when nickel is not added. This mutant is therefore primed to resist to high nickel levels. Downstream analysis of the transcriptomic data suggested that the absence of Q triggers an atypical oxidative stress response, confirmed by the detection of slightly elevated ROS levels in the mutant, increased sensitivity to hydrogen peroxide and paraquat, and a subtle growth phenotype in a strain prone to accumulation of ROS.

PMID:36066904 | DOI:10.1093/mtomcs/mfac065

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Nevin Manimala Statistics

Utilisation and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study

Nephrol Dial Transplant. 2022 Sep 6:gfac250. doi: 10.1093/ndt/gfac250. Online ahead of print.

ABSTRACT

BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilisation, survival, and function.

METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥ 2 + on dipstick testing, on kidney utilisation, early graft function, graft failure, and estimated glomerular filtration rate (eGFR).

RESULTS: Eighteen % (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% vs 82%; OR 0.70, 95% CI 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (HR 0.91, 95% CI 0.74 to 1.11). There was also no association with delayed graft function, patient survival, or eGFR at 1 or 3 years.

CONCLUSIONS: Our study suggests reluctance in the UK to utilise kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilisation without negatively impacting transplant outcomes.

PMID:36066902 | DOI:10.1093/ndt/gfac250

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Nevin Manimala Statistics

Lung Cancer Screening in Individuals With and Without Lung-Related Comorbidities

JAMA Netw Open. 2022 Sep 1;5(9):e2230146. doi: 10.1001/jamanetworkopen.2022.30146.

ABSTRACT

IMPORTANCE: Comorbidities characterize the underlying health status of individuals. In the context of lung cancer screening (LCS), lung-related comorbidities may influence the observed benefits and harms.

OBJECTIVE: To compare the characteristics of individuals undergoing LCS, the LCS examination result, the cancer detection rate (CDR), and the false-positive rate (FPR) in those with and without lung-related comorbidities.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted in 5 academic and community screening sites across North Carolina from January 1, 2014, to November 7, 2020. Participants included 611 individuals screened for lung cancer who completed a 1-page health history questionnaire.

EXPOSURES: Presence of at least 1 self-reported lung-related comorbidity, including chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma, bronchiectasis, pulmonary fibrosis, silicosis, asbestosis, sarcoidosis, and tuberculosis.

MAIN OUTCOMES AND MEASURES: The LCS examination result was determined from the radiologist’s Lung Imaging Reporting and Data System assessment (negative, 1 or 2; positive, 3 or 4). The age-adjusted CDR and FPR were calculated per 100 LCS examinations, using binary logistic regression.

RESULTS: Among the 611 individuals screened for lung cancer (308 men [50.4%]; mean [SD] age, 64 [6.2] years), 335 (54.8%) had at least 1 lung-related comorbidity. Individuals with vs without lung-related comorbidities were more likely to be female than male (180 of 335 [53.7%] vs 123 of 276 [44.6%]; P = .02), White vs non-White race (275 of 326 [84.4%] vs 193 of 272 [71.0%]; P < .001), and have high school or less education vs greater than a high school education (108 of 231 [46.7%] vs 64 of 208 [30.8%]; P = .001). There were no significant differences in the proportion of positive LCS examinations in those with vs without a lung-related comorbidity at baseline (37 [16.0%] vs 22 [11.1%]; P = .14) or subsequent (40 [12.3%] vs 23 [10.6%]; P = .54) LCS examination. Comparing individuals with vs without lung-related comorbidities, there was no statistically significant difference in the CDR (1.6 vs 1.9 per 100; P = .73) or FPR (13.0 vs 9.3 per 100; P = .16). Of the 17 individuals with lung cancer, 13 patients (76.5%) were diagnosed with stage I lung cancer.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that individuals with self-reported lung-related comorbidities undergoing LCS were more likely to be female, of White race, and have less education than those without lung-related comorbidity. Although no statistically significant differences in the proportion of positive examinations, CDR, or FPR by self-reported lung comorbidities were noted, additional studies with larger numbers of individuals undergoing screening are needed to understand LCS outcomes in those with lung-related comorbidities.

PMID:36066893 | DOI:10.1001/jamanetworkopen.2022.30146