Tag: statistics

PLoS One. 2022 Dec 29;17(12):e0276726. doi: 10.1371/journal.pone.0276726. eCollection 2022.

ABSTRACT

Identification of small objects in fluorescence microscopy is a non-trivial task burdened by parameter-sensitive algorithms, for which there is a clear need for an approach that adapts dynamically to changing imaging conditions. Here, we introduce an adaptive object detection method that, given a microscopy image and an image level label, uses kurtosis-based matching of the distribution of the image differential to express operator intent in terms of recall or precision. We show how a theoretical upper bound of the statistical distance in feature space enables application of belief theory to obtain statistical support for each detected object, capturing those aspects of the image that support the label, and to what extent. We validate our method on 2 datasets: distinguishing sub-diffraction limit caveolae and scaffold by stimulated emission depletion (STED) super-resolution microscopy; and detecting amyloid-β deposits in confocal microscopy retinal cross-sections of neuropathologically confirmed Alzheimer’s disease donor tissue. Our results are consistent with biological ground truth and with previous subcellular object classification results, and add insight into more nuanced class transition dynamics. We illustrate the novel application of belief theory to object detection in heterogeneous microscopy datasets and the quantification of conflict of evidence in a joint belief function. By applying our method successfully to diffraction-limited confocal imaging of tissue sections and super-resolution microscopy of subcellular structures, we demonstrate multi-scale applicability.

PMID:36580473 | DOI:10.1371/journal.pone.0276726

PLoS One. 2022 Dec 29;17(12):e0279580. doi: 10.1371/journal.pone.0279580. eCollection 2022.

ABSTRACT

INTRODUCTION: Metabolic syndrome is a group of metabolic risk factors which are associated with an increased risk of cardiovascular disease and type2 diabetes. Nowadays, several studies have shown that the burden of metabolic syndrome is increasing among epileptic patients, and leads to MS-associated complications, including cardiovascular disease. However, getting published documents has been limited in Ethiopia and the study area. Therefore, we aimed to analyze the magnitude and associated factors of metabolic syndrome among epileptic patients in Dessie Comprehensive Specialized Hospital in compression with respective controls.

METHODS: Hospital-based comparative cross-sectional study design was implemented from June 25 to August 20, 2021. A total of 204 participants with an equal number of cases and controls (n = 102 each) were included. The data was collected through face-to-face interviews and biochemical analyses such as fasting blood glucose and lipid profiles were done through the enzymatic technique. The magnitude of metabolic syndrome was determined using both National Cholesterol Education Program Adult Treatment Panel III and International Diabetes Federation definition criteria. The STATA version 14 was used for statistical data analysis, and a comparison of categorical and continuous variables was done with χ2 and an independent t-test, respectively. The multivariable binary logistic regression analysis was used to identify factors associated with metabolic syndrome, and variables having a P-value of <0.05 were considered statistically significant.

RESULT: The prevalence of metabolic syndrome among the epileptic group was (25.5% in National Cholesterol Education Program Adult Treatment Panel III and 23.5% in International Diabetes Federation criteria), whereas it was 13.7% in National Cholesterol Education Program Adult Treatment Panel III and 14.7% in International Diabetes Federation criteria among control groups. According to the International Diabetes Federation criteria, low physical activity (adjusted odds ratio = 4.73, 95% CI: 1.08-20.68), taking multiple antiepileptic drugs (adjusted odds ratio = 8.08, 95% CI: 1.52-42.74), having a total cholesterol level of ≥ 200 mg/dl (adjusted odds ratio = 5.81, 95%: 1.32-41.13) and body mass index (adjusted odds ratio = 1.57, 95% CI = 1.16-2.11) were significantly associated with metabolic syndrome among epileptic participants. Applying National Cholesterol Education Program Adult Treatment Panel III criteria, taking multiple antiepileptic drugs (adjusted odds ratio = 6.81, 95% CI: 1.29-35.92), having a total cholesterol level > 200 mg/dl (adjusted odds ratio = 7.37, 95% CI: 1.32-41.13) and body mass index (adjusted odds ratio = 1.53, 96% CI: 1.16-2.01) were also significantly associated.

CONCLUSION: The prevalence of metabolic syndrome among epileptic patients was higher than that of control groups and reaches statistically significant by National Cholesterol Education Program Adult Treatment Panel III. Being on multiple antiepileptic drugs, body mass index, having low physical activity and raised total cholesterol were significantly associated with metabolic syndrome among the epileptic group. Therefore, it is better to focus on controlling weight, having sufficient physical exercise, and regular monitoring of total cholesterol levels in epileptic patients.

PMID:36580471 | DOI:10.1371/journal.pone.0279580

PLoS One. 2022 Dec 29;17(12):e0278906. doi: 10.1371/journal.pone.0278906. eCollection 2022.

ABSTRACT

There is limited knowledge on the association between different health complaints and the development of persistent musculoskeletal pain in adolescents. The aims of this study were to assess whether specific health complaints, and an accumulation of health complaints, in the first year of upper-secondary school, were associated with persistent musculoskeletal pain 2 years later. We used data from a population-based cohort study (the Fit Futures Study in Norway), including 551 adolescents without persistent musculoskeletal pain at baseline. The outcome was persistent musculoskeletal pain (≥3 months) 2 years after inclusion. The following self-reported health complaints were investigated as individual exposures at baseline: asthma, allergic rhinitis, atopic eczema, headache, abdominal pain and psychological distress. We also investigated the association between the accumulated number of self-reported health complaints and persistent musculoskeletal pain 2 years later. Logistic regression analyses estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs). At the 2-year follow-up, 13.8% (95% CI [11.2-16.9]) reported persistent musculoskeletal pain. Baseline abdominal pain was associated with persistent musculoskeletal pain 2 years later (OR 2.33, 95% CI [1.29-4.19], p = 0.01). Our analyses showed no statistically significant associations between asthma, allergic rhinitis, atopic eczema, headache or psychological distress and persistent musculoskeletal pain at the 2-year follow-up. For the accumulated number of health complaints, a higher odds of persistent musculoskeletal pain at the 2-year follow-up was observed for each additional health complaint at baseline (OR 1.33, 95% CI [1.07-1.66], p = 0.01). Health care providers might need to take preventive actions in adolescents with abdominal pain and in adolescents with an accumulation of health complaints to prevent development of persistent musculoskeletal pain. The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research to understand the underlying patterns of persistent pain conditions in adolescents.

PMID:36580469 | DOI:10.1371/journal.pone.0278906

PLoS One. 2022 Dec 29;17(12):e0279381. doi: 10.1371/journal.pone.0279381. eCollection 2022.

ABSTRACT

Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues, notably the brain, and genetic variation in the PCSK9 locus has recently been shown to be associated with mood disorder-related traits. We investigated whether PCSK9 inhibition, proxied by a genetic reduction in expression of PCSK9 mRNA, might have a causal adverse effect on mood disorder-related traits. We used genetic variants in the PCSK9 locus associated with reduced PCSK9 expression (eQTLs) in the European population from GTEx v8 and examined the effect on PCSK9 protein levels and three mood disorder-related traits (major depressive disorder, mood instability, and neuroticism), using summary statistics from the largest European ancestry genome-wide association studies. We conducted summary-based Mendelian randomization analyses to estimate the causal effects, and attempted replication using data from eQTLGen, Brain-eMETA, and the CAGE consortium. We found that genetically reduced PCSK9 gene-expression levels were significantly associated with reduced PCSK9 protein levels but not with increased risk of mood disorder-related traits. Further investigation of nearby genes demonstrated that reduced USP24 gene-expression levels was significantly associated with increased risk of mood instability (p-value range = 5.2×10-5-0.03), and neuroticism score (p-value range = 2.9×10-5-0.02), but not with PCSK9 protein levels. Our results suggest that genetic variation in this region acts on mood disorders through a PCSK9-independent pathway, and therefore PCSK9-inhibitors are unlikely to have an adverse impact on mood disorder-related traits.

PMID:36580462 | DOI:10.1371/journal.pone.0279381

PLoS One. 2022 Dec 29;17(12):e0265783. doi: 10.1371/journal.pone.0265783. eCollection 2022.

ABSTRACT

Parental age at conception often influences offspring’s longevity, a phenomenon referred as the “Lansing effect” described in large variety of organisms. But, the majority of the results refer to the survival of juveniles, mainly explained by an inadequate parental care by the elderly parents, mostly the mothers. Studies on the effect of parental age on offspring’s longevity in adulthood remain few, except in humans for whom effects of parental age vary according to statistical models or socioeconomic environments. In a small primate in which the longevity reaches up to 13 years, we investigated the effects of parental age at conception on the longevity of offspring (N = 278) issued from parents with known longevity. None of the postnatal parameters (body mass at 30 and 60 days after birth, size and composition of the litter) influenced offspring’s longevity. Mothers’ age at conception negatively affected offspring’s longevity in males but not in females. By contrast, fathers’ age at conception did not influence offspring’s longevity. Finally, the longevity of female offspring was significantly positively related to the longevity of both parents. Compared with current studies, the surprisingly minor effect of fathers ‘age was related to the high seasonal reproduction and the particular telomere biology of mouse lemurs.

PMID:36580457 | DOI:10.1371/journal.pone.0265783

PLoS Med. 2022 Dec 29;19(12):e1004141. doi: 10.1371/journal.pmed.1004141. eCollection 2022 Dec.

ABSTRACT

BACKGROUND: Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.

METHODS AND FINDINGS: The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.

CONCLUSIONS: Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.

PMID:36580444 | DOI:10.1371/journal.pmed.1004141

Neuropsychol Rehabil. 2022 Dec 29:1-21. doi: 10.1080/09602011.2022.2157446. Online ahead of print.

ABSTRACT

OBJECTIVES: The growing population of survivors of childhood brain tumors present the challenge of long-term quality of survival. The domains most affected by tumor and treatment are those implicated in development of typical intellectual functions: attention, working memory, and processing speed, with consequent effects upon function and quality of life. In this paper we present service evaluation data on the 12-month effect upon processing speed, visual and auditory attentional domains in 29 patients receiving methylphenidate aged 5-16 years (Mean=10.6).

METHODS: Patients received immediate-release methylphenidate and were converted to modified-release as appropriate. Mean optimal dose of immediate-release methylphenidate was 0.34 mg/kg per dose (range 0.2-0.67).

RESULTS: Patients showed a significant positive impact of methylphenidate on attention in all tests of selective visual attention from the Test of Everyday Attention for Children 2. A significant improvement was also shown on response time. Significant change was not found on psychometric measures of sustained auditory or visual attention, or selective auditory attention. Ratings of Health-Related Quality of Life showed a positive benefit of methylphenidate at 12 months. Side effects were minimal and not statistically significant.

CONCLUSIONS: Survivors of childhood brain tumor with attentional and processing speed deficit show clinical benefit from methylphenidate.

PMID:36580420 | DOI:10.1080/09602011.2022.2157446

Int J Neurosci. 2022 Dec 29:1-6. doi: 10.1080/00207454.2022.2158825. Online ahead of print.

ABSTRACT

BACKGROUND: The etiology of Alzheimer’s disease (AD) is multifactorial. The most important challenge of research is the identification of potential biomarkers associated with AD pathogenesis that may significantly contribute to early diagnosis of the disease. We aim to explore an eventual association of the C677T and A1298C genetic polymorphisms in the MTHFR gene with AD risk in an Algerian population.

METHODS: This case-control study involved comparing a group of 106 patients that had developed AD to another group of 104 non-demented individuals. The MTHFR genotypes were determined using PCR-RFLP method. Additionally, the homocysteine level was evaluated.

RESULTS: Genotypes analysis did not show an association for both MTHFR677CT and 677TT variants with AD risk (OR = 1.12; p = 0.66; OR = 1.76; p = 0.09) respectively. As expected, the 677CC wild type genotype showed a protective role against AD (OR = 0.52; p = 0.03). For 1298AC MTHFR variant, the distribution of different genotypes did not show a statistical significant difference between the two cohorts. However the silmutaneous carrier, CT/AC presented association with AD (OR = 5.96; p = 0.05). On the other hand, carrier-state of MTHFR T allele showed a relationship with AD (OR = 1.98; p = 0.02). Additionally, hyperhomocysteinemia seems to be a risk factor for AD (OR = 1.08; p = 0.02).

CONCLUSION: Our exploration reveals that the silmutaneous carrier, CT/AC, carrier-state of MTHFR T allele, and hyperhomocysteinemia seem to be risk factors for AD.

PMID:36580407 | DOI:10.1080/00207454.2022.2158825

JMIR Res Protoc. 2022 Dec 29;11(12):e42526. doi: 10.2196/42526.

ABSTRACT

BACKGROUND: Research suggests that the rapid increase in worldwide antidepressant use is mainly due to a rise in long-term and potentially inappropriate use. It has been suggested that 1 in 3 antidepressant users among general practice patients are no longer experiencing clinical benefits from their medication and should commence deprescribing. However there are many barriers to antidepressant deprescribing for both patients and clinicians, which adds to the complex nature of reducing or ceasing the medication. As such, antidepressant deprescribing does not routinely occur in clinical practice. Evidence-based supports and interventions for safe and successful antidepressant deprescribing are needed to assist patients and their doctors. Interventions should also include an understanding of how an intervention works, why it works, and whom it is for.

OBJECTIVE: This study aims to evaluate how the WiserAD approach to antidepressant deprescribing works, whom it is for, and the underlying circumstances by (1) examining the experiences and perceptions of WiserAD among antidepressant users, (2) identifying the underlying mechanisms of the WiserAD approach to antidepressant deprescribing, and (3) describing in what contexts and to what extent the underlying mechanisms of WiserAD are suited for antidepressant users.

METHODS: A mixed methods case study with realist evaluation will be conducted among participants in the WiserAD randomized controlled trial for antidepressant deprescribing. Quantitative data will be obtained from up to 12 participants from the intervention and control arms at baseline and 3-month follow-up. Baseline data will be used to characterize the sample using descriptive statistics. Paired samples t tests will also be performed to compare responses between baseline and 3-month follow-up for participant self-management, skills, confidence and knowledge, beliefs about medicines, current emotional health, and well-being symptoms. Qualitative data from the same participants will be collected via narrative interview at 3-month follow-up. Quantitative and qualitative data will be converged to form a “case,” and analysis will be conducted within each case with comparisons made across multiple cases.

RESULTS: Recruitment of participants commenced in October 2022 and will be completed by March 2023. Analysis will be completed by June 2023.

CONCLUSIONS: To our knowledge, this will be the first realist evaluation of an antidepressant deprescribing intervention in general practice. Findings from this evaluation may assist in the implementation of the WiserAD approach to antidepressant deprescribing in routine clinical practice.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/42526.

PMID:36580362 | DOI:10.2196/42526

JMIR Res Protoc. 2022 Dec 29;11(12):e39319. doi: 10.2196/39319.

ABSTRACT

BACKGROUND: The management of infected metaphyseal nonunion of the tibia is devastating, especially when associated with significant bone loss, poor soft tissues, draining sinuses, axial deformity, knee or ankle joint stiffness, limb discrepancy, and multiresisted pathogens. A systematic review, performed recently by the primary investigators but not yet published, yielded the lack of studies in the field and the huge heterogeneity of the presented results. We found several bias and controversies such as no clear definition of the exact part of the tibia where the nonunion was located, the pathogen causing the fracture-related infection, the number of previous interventions and time to presentation, and the exact type of treatment methods including the use of muscle flaps or bone grafting. Time to final union as a functional score is another important but missing data.

OBJECTIVE: The proposed study is designed to evaluate a sufficient number of patients with infected metaphyseal tibial nonunions using various general health, functional, and bone scores.

METHODS: This prospective clinical trial study, with a minimum follow-up period of 36 months, focuses on the effectiveness of the Ilizarov method after radical nonunion debridement and targeted antibiotic therapy in patients with infected metaphyseal tibial nonunions. The primary outcomes would be the definite healing of nonunion and infection-free results. Secondary outcomes would be limb alignment and discrepancy, alteration in the patient’s quality of life, and functional results. A power analysis calculated a minimum of 11 patients to obtain statistical power, but we aim to include at least 25 patients. Limb discrepancy, clinical validation of infection eradication and fracture healing, radiographic validation, and patient-reported outcome measures will be highlighted and correlated. Statistical analysis of the results will offer data missing from the literature so far. Measurements are scheduled at specific times for each patient: preoperatively, 3 and 6 months postoperatively, 1 month after Ilizarov frame removal, and once per semester afterward until the end of the follow-up period (minimum 36 months). Laboratory evaluation will be assessed once per month. Any complication will be reported and treated when it occurs.

RESULTS: The trial has already started. It was funded in June 2020. As of May 2022, 19 participants have been recruited and no major complications have been noticed yet. Data analysis will be performed after data collection ends, and results will be published afterward.

CONCLUSIONS: An infected metaphyseal tibial nonunion is a rare condition with limited treatment options and many controversies. There is no consensus in the literature about the best treatment strategy, and this lack of evidence should be fulfilled.

TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 30905788; https://www.isrctn.com/ISRCTN30905788.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39319.

PMID:36580353 | DOI:10.2196/39319