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Translational Psychiatry Feb 2022Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population.... (Meta-Analysis)
Meta-Analysis
Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.
Topics: Adolescent; Adult; Brain; Child; Humans; Magnetic Resonance Imaging; Obsessive-Compulsive Disorder; Thalamus
PubMed: 35190533
DOI: 10.1038/s41398-022-01823-2 -
Journal of the Royal College of... 1995A recent development of the therapeutic trial has been the mega-trial: a large, simple randomised trial analysed on an 'intention to treat' basis. Mega-trials have... (Review)
Review
A recent development of the therapeutic trial has been the mega-trial: a large, simple randomised trial analysed on an 'intention to treat' basis. Mega-trials have advantages in terms of increased statistical power, but also raise several new questions of interpretation. In mega-trials, randomisation serves to achieve identical allocation groups in a situation where there is poor experimental control and a large measure of between-subject variation. The results of mega-trials cannot readily be generalised because their conclusions are observations, not casual hypotheses, and are therefore not testable. In this sense, mega-trials can be repeated but cannot be replicated. Basic science and clinical science both seek understanding at the level of the individual subject; but in a mega-trial, analysis is only meaningful at the group level. The non-scientific nature of mega-trials derives from their methodology, which dispenses with the scientific aim of maximum experimental control to remove or minimise bias, and instead uses randomisation to achieve an equal distribution of bias between groups.
Topics: Bias; Confounding Factors, Epidemiologic; Data Interpretation, Statistical; Humans; Random Allocation; Randomized Controlled Trials as Topic; Research Design
PubMed: 7595900
DOI: No ID Found -
European Journal of Internal Medicine Dec 2023Individuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle...
INTRODUCTION
Individuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle choices. However, the association between non-alcoholic fatty liver disease (NAFLD) and educational level remains unclear. Therefore, the aim of this study was to investigate whether there is an independent relationship between NAFLD and educational level as a surrogate marker for socioeconomic status (SES).
METHODS
This cross-sectional study included 8,727 participants from the Paracelsus 10,000 study. The association between NAFLD and educational level was assessed using multivariable logistic regression models and multivariable linear regression. The primary endpoints were NAFLD (FLI score > 60) and liver fibrosis (FIB-4 score > 1.29). Further subgroup analysis with liver stiffness measurement was done.
RESULTS
In the study, NAFLD prevalence was 23% among participants with high education, 33% among intermediate, and 40% among those with low education (p<0.01). Importantly, a significantly reduced risk of NAFLD was observed in individuals with higher education, as indicated by an adjusted relative risk of 0.52 (p < 0.01). Furthermore, higher education level was associated with significantly lower odds of NAFLD and fibrosis. Additionally, a subgroup analysis revealed that higher liver stiffness measurements were independently associated with lower levels of education.
CONCLUSION
The study's findings indicate that a lower education level increases the risk of NAFLD independent of confounding factors. Therefore, these findings highlight the potential impact of educational attainment on NAFLD risk and emphasize the need for targeted interventions in vulnerable populations.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Risk Factors; Cross-Sectional Studies; Liver Cirrhosis; Educational Status
PubMed: 37541922
DOI: 10.1016/j.ejim.2023.07.039 -
Annals of Work Exposures and Health Apr 2020In the sector of occupational safety and health only a limited amount of studies are concerned with the conversion of inhalable to respirable dust. This conversion is of...
In the sector of occupational safety and health only a limited amount of studies are concerned with the conversion of inhalable to respirable dust. This conversion is of high importance for retrospective evaluations of exposure levels or of occupational diseases. For this reason a possibility to convert inhalable into respirable dust is discussed in this study. To determine conversion functions from inhalable to respirable dust fractions, 15 120 parallel measurements in the exposure database MEGA (maintained at the Institute for Occupational Safety and Health of the German Social Accident Insurance) are investigated by regression analysis. For this purpose, the whole data set is split into the influencing factors working activity and material. Inhalable dust is the most important predictor variable and shows an adjusted coefficient of determination of 0.585 (R2 adjusted to sample size). Further improvement of the model is gained, when the data set is split into six working activities and three material groups (e.g. high temperature processing, adj. R2 = 0.668). The combination of these two variables leads to a group of data concerned with high temperature processing with metal, which gives rise to a better description than the whole data set (adj. R2 = 0.706). Although it is not possible to refine these groups further systematically, seven improved groups are formed by trial and error, with adj. R2 between 0.733 and 0.835: soldering, casting (metalworking), welding, high temperature cutting, blasting, chiseling/embossing, and wire drawing. The conversion functions for the seven groups are appropriate candidates for data reconstruction and retrospective exposure assessment. However, this is restricted to a careful analysis of the working conditions. All conversion functions are power functions with exponents between 0.454 and 0.946. Thus, the present data do not support the assumption that respirable and inhalable dust are linearly correlated in general.
Topics: Air Pollutants, Occupational; Dust; Environmental Monitoring; Humans; Inhalation Exposure; Occupational Exposure; Retrospective Studies
PubMed: 32112076
DOI: 10.1093/annweh/wxaa016 -
Journal of Clinical Medicine Feb 2023To evaluate the efficacy and safety of medical expulsive therapy (MET) for ureteral stones in pediatric patients, Cochrane, PubMed, Web of Science, Scopus, and the... (Review)
Review
To evaluate the efficacy and safety of medical expulsive therapy (MET) for ureteral stones in pediatric patients, Cochrane, PubMed, Web of Science, Scopus, and the reference list of retrieved studies were searched up to September 2022 to identify RCTs on the efficacy of MET. The protocol was prospectively registered at PROSPERO (CRD42022339093). Articles were reviewed, data were extracted by two reviewers, and the differences were resolved by the third reviewer. The risk of bias was assessed using the RoB2. The outcomes, including the stone expulsion rate (SER), stone expulsion time (SET), episode of pain, analgesic consumption, and adverse effects, were evaluated. Six RCTs enrolling 415 patients were included in the meta-analysis. The duration of MET ranged from 19 to 28 days. The investigated medications included tamsulosin, silodosin, and doxazosin. The stone-free rate after 4 weeks in the MET group was 1.42 times that of the control group (RR: 1.42; 95% CI: 1.26-1.61, < 0.001). The stone expulsion time also decreased by an average of 5.18 days (95% CI: -8.46/-1.89, = 0.002). Adverse effects were more commonly observed in the MET group (RR: 2.18; 95% CI: 1.28-3.69, = 0.004). The subgroup analysis evaluating the influence of the type of medication, the stone size, and the age of patients failed to reveal any impact of the aforementioned factors on the stone expulsion rate or stone expulsion time. Alpha-blockers as medical expulsive therapy among pediatric patients are efficient and safe. They increase the stone expulsion rate and decrease the stone expulsion time; however, this included a higher rate of adverse effects, which include headache, dizziness, or nasal congestion.
PubMed: 36835945
DOI: 10.3390/jcm12041410 -
Ontario Health Technology Assessment... 2013As Ontario's population ages, chronic diseases are becoming increasingly common. There is growing interest in services and care models designed to optimize the... (Review)
Review
BACKGROUND
As Ontario's population ages, chronic diseases are becoming increasingly common. There is growing interest in services and care models designed to optimize the management of chronic disease.
OBJECTIVE
To evaluate the cost-effectiveness and expected budget impact of interventions in chronic disease cohorts evaluated as part of the Optimizing Chronic Disease Management mega-analysis.
DATA SOURCES
Sector-specific costs, disease incidence, and mortality were calculated for each condition using administrative databases from the Institute for Clinical Evaluative Sciences. Intervention outcomes were based on literature identified in the evidence-based analyses. Quality-of-life and disease prevalence data were obtained from the literature.
METHODS
Analyses were restricted to interventions that showed significant benefit for resource use or mortality from the evidence-based analyses. An Ontario cohort of patients with each chronic disease was constructed and followed over 5 years (2006-2011). A phase-based approach was used to estimate costs across all sectors of the health care system. Utility values identified in the literature and effect estimates for resource use and mortality obtained from the evidence-based analyses were applied to calculate incremental costs and quality-adjusted life-years (QALYs). Given uncertainty about how many patients would benefit from each intervention, a system-wide budget impact was not determined. Instead, the difference in lifetime cost between an individual-administered intervention and no intervention was presented.
RESULTS
Of 70 potential cost-effectiveness analyses, 8 met our inclusion criteria. All were found to result in QALY gains and cost savings compared with usual care. The models were robust to the majority of sensitivity analyses undertaken, but due to structural limitations and time constraints, few sensitivity analyses were conducted. Incremental cost savings per patient who received intervention ranged between $15 per diabetic patient with specialized nursing to $10,665 per patient wth congestive heart failure receiving in-home care.
LIMITATIONS
Evidence used to inform estimates of effect was often limited to a single trial with limited generalizability across populations, interventions, and health care systems. Because of the low clinical fidelity of health administrative data sets, intermediate clinical outcomes could not be included. Cohort costs included an average of all health care costs and were not restricted to costs associated with the disease. Intervention costs were based on resource use specified in clinical trials.
CONCLUSIONS
Applying estimates of effect from the evidence-based analyses to real-world resource use resulted in cost savings for all interventions. On the basis of quality-of-life data identified in the literature, all interventions were found to result in a greater QALY gain than usual care would. Implementation of all interventions could offer significant cost reductions. However, this analysis was subject to important limitations.
PLAIN LANGUAGE SUMMARY
Chronic diseases are the leading cause of death and disability in Ontario. They account for a third of direct health care costs across the province. This study aims to evaluate the cost-effectiveness of health care interventions that might improve the management of chronic diseases. The evaluated interventions led to lower costs and better quality of life than usual care. Offering these options could reduce costs per patient. However, the studies used in this analysis were of medium to very low quality, and the methods had many limitations.
Topics: Advanced Practice Nursing; Ambulatory Care; Chronic Disease; Continuity of Patient Care; Cost Savings; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Disease Management; Evidence-Based Medicine; Health Expenditures; Heart Diseases; Home Care Services; Humans; Information Dissemination; Ontario; Patient Discharge; Pulmonary Disease, Chronic Obstructive; Quality of Health Care; Quality of Life; Survival Analysis
PubMed: 24228076
DOI: No ID Found -
NMR in Biomedicine Apr 2020The aim of this work was to develop simultaneous edited MRS of γ-aminobutyric acid (GABA), glutathione (GSH), and ethanol (EtOH) using Hadamard encoding and... (Clinical Trial)
Clinical Trial
The aim of this work was to develop simultaneous edited MRS of γ-aminobutyric acid (GABA), glutathione (GSH), and ethanol (EtOH) using Hadamard encoding and reconstruction of MEGA-edited spectroscopy (HERMES) at 3T. Density-matrix simulations of HERMES were carried out and compared with phantom experiments. In vivo experiments were performed in six healthy volunteers about 30 min after alcohol consumption. Simulations of HERMES showed GABA-, GSH-, and EtOH-edited spectra with low levels of crosstalk and excellent agreement with phantom spectra. In vivo experiments showed well edited GABA signals at 3.0 ppm, GSH at 2.95 ppm, and EtOH at 1.18 ppm in the respective Hadamard combination spectra. Measured integral ratios were 0.082 ± 0.012 for GABA/Cr, 0.037 ± 0.006 for GSH/Cr, and 0.305 ± 0.129 for EtOH/Cr. Simulated, phantom, and in vivo measurements of HERMES show excellent separation of GABA-, GSH-, and EtOH-edited signals with negligible levels of crosstalk. HERMES allows a threefold acceleration of editing while maintaining spectral quality compared with sequentially acquired MEGA-PRESS measurements.
Topics: Adult; Computer Simulation; Ethanol; Female; Glutathione; Humans; Magnetic Resonance Spectroscopy; Male; Phantoms, Imaging; gamma-Aminobutyric Acid
PubMed: 31943424
DOI: 10.1002/nbm.4227 -
British Journal of Cancer Jun 1999
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Helicobacter Infections; Helicobacter pylori; Humans; Odds Ratio; Research Design; Stomach Neoplasms
PubMed: 10362097
DOI: 10.1038/sj.bjc.6690444 -
Blood Pressure Dec 2022Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol... (Review)
Review
Diverse pharmacological properties, trial results, comorbidity prescribing and neural pathophysiology suggest European hypertension guideline downgrading of beta-blockers is not justified.
Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trials. Hypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rate. Beta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic properties. This position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failure. Analogous differences in beta-blocker efficacy is also likely in hypertension. Beta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blocker first choices in clinical practice. Thus, beta-blockers should be regarded as relevant first choices for hypertension in clinical practice, particularly if characterised by a long half-life, highly selective beta-1 blocking activity and no intrinsic agonist properties.SUMMARYBeta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trialsHypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rateBeta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic propertiesThis position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failureAnalogous differences in beta-blocker efficacy is also likely in hypertensionBeta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blockers first choices in clinical practiceThese observations, in totality, inform our opinion that beta-blockers are relevant first choices for hypertension in clinical practice and this fact needs highlightingFurther, these arguments suggest European hypertension guideline downgrading of beta-blockers is not justified.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Atenolol; Cardiovascular Diseases; Comorbidity; Heart Failure; Humans; Hypertension; Metoprolol; Oxprenolol; Propranolol
PubMed: 36029011
DOI: 10.1080/08037051.2022.2110858 -
Advances in Therapy Jun 2022Unmet expectations are a major cause of perceived treatment failure and discontinuation of treatment. To enable evidence-based counselling of patients on realistic...
INTRODUCTION
Unmet expectations are a major cause of perceived treatment failure and discontinuation of treatment. To enable evidence-based counselling of patients on realistic expectations, we determined the chance of patients with overactive bladder becoming free of a given symptom upon treatment with a muscarinic antagonist in a non-interventional setting.
METHODS
Two non-interventional studies included 1335 and 745 patients, respectively, who received 30 or 45 mg q.d. propiverine ER for 12 weeks. They were monitored for becoming free of urgency, urinary incontinence, frequency, or nocturia. Analyses were also performed in subgroups defined by basal symptom severity, age, and gender. Categorical data are shown as a percentage of the respective population. Continuous data are expressed as means or as median depending on whether the variability was considered to exhibit a normal distribution.
RESULTS
The probability of becoming symptom-free was largest for incontinence and frequency (about 50%), but lesser for urgency (about 20%) and nocturia (about 10%). Greater basal severity of a symptom reduced the chance to become free of that symptom upon treatment, but the chance to become free of incontinence and frequency was still considerable. Age and gender had only minor if any effects on the chance of becoming symptom-free. These findings are in line with those of a limited number of randomized controlled trials.
CONCLUSION
These data provide an evidence base for the counselling of patients with overactive bladder on realistic expectations of treatment outcomes. We propose that realistic expectations can lead to greater long-term adherence.
Topics: Benzilates; Humans; Motivation; Nocturia; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence
PubMed: 35325367
DOI: 10.1007/s12325-022-02114-4