Category: Statistics

JAMA Psychiatry. 2024 Apr 3. doi: 10.1001/jamapsychiatry.2024.0378. Online ahead of print.

ABSTRACT

IMPORTANCE: Antidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes.

OBJECTIVE: To estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study assessed data from the Taiwan national health insurance database across entire population (N = 26 554 001) between January 2003 and December 2017. Data analysis was performed from August 2021 to April 2023. TRD was defined as having experienced at least 3 distinct antidepressant treatments in the current episode, each with adequate dose and duration, based on the prescribing records. Then, we identified the first-degree relatives of individuals with TRD (n = 34 467). A 1:4 comparison group (n = 137 868) of first-degree relatives of individuals without TRD was arranged for the comparison group, matched by birth year, sex, and kinship.

MAIN OUTCOMES AND MEASURES: Modified Poisson regression analyses were performed and adjusted relative risks (aRRs) and 95% CIs were calculated for the risk of TRD, the risk of other major psychiatric disorders, and different causes of mortality.

RESULTS: This study included 172 335 participants (88 330 male and 84 005 female; mean [SD] age at beginning of follow-up, 22.9 [18.1] years). First-degree relatives of individuals with TRD had lower incomes, more physical comorbidities, higher suicide mortality, and increased risk of developing TRD (aRR, 9.16; 95% CI, 7.21-11.63) and higher risk of other psychiatric disorders than matched control individuals, including schizophrenia (aRR, 2.36; 95% CI, 2.10-2.65), bipolar disorder (aRR, 3.74; 95% CI, 3.39-4.13), major depressive disorder (aRR, 3.65; 95% CI, 3.44-3.87), attention-deficit/hyperactivity disorders (aRR, 2.38; 95% CI, 2.20-2.58), autism spectrum disorder (aRR, 2.26; 95% CI, 1.86-2.74), anxiety disorder (aRR, 2.71; 95% CI, 2.59-2.84), and obsessive-compulsive disorder (aRR, 3.14; 95% CI, 2.70-3.66). Sensitivity and subgroup analyses validated the robustness of the findings.

CONCLUSIONS AND RELEVANCE: To our knowledge, this study is the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders. Patients with a family history of TRD had an increased risk of suicide mortality and tendency toward antidepressant resistance; therefore, more intensive treatments for depressive symptoms might be considered earlier, rather than antidepressant monotherapy.

PMID:38568605 | DOI:10.1001/jamapsychiatry.2024.0378

Neuroinformatics. 2024 Apr 3. doi: 10.1007/s12021-024-09660-y. Online ahead of print.

ABSTRACT

Multimodal neuroimaging grants a powerful in vivo window into the structure and function of the human brain. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends – or gradients – in brain structure and function, offering a framework to unify principles of brain organization across multiple scales. Strong community enthusiasm for these techniques has been instrumental in their widespread adoption and implementation to answer key questions in neuroscience. Following a brief review of current literature on this framework, this perspective paper will highlight how pragmatic steps aiming to make gradient methods more accessible to the community propelled these techniques to the forefront of neuroscientific inquiry. More specifically, we will emphasize how interest for gradient methods was catalyzed by data sharing, open-source software development, as well as the organization of dedicated workshops led by a diverse team of early career researchers. To this end, we argue that the growing excitement for brain gradients is the result of coordinated and consistent efforts to build an inclusive community and can serve as a case in point for future innovations and conceptual advances in neuroinformatics. We close this perspective paper by discussing challenges for the continuous refinement of neuroscientific theory, methodological innovation, and real-world translation to maintain our collective progress towards integrated models of brain organization.

PMID:38568476 | DOI:10.1007/s12021-024-09660-y

Heart Vessels. 2024 Apr 3. doi: 10.1007/s00380-024-02394-6. Online ahead of print.

ABSTRACT

The utility of assessment of cardiovascular calcifications for predicting stroke incidence remains unclear. This study assessed the relationship between cardiovascular calcifications including coronary artery calcification (CAC), aortic valve (AVC), and aortic root (ARC) assessed by coronary computed tomography (CT) and stroke incidence in patients with suspected CAD. In this multicenter prospective cohort study, 1187 patients suspected of CAD who underwent coronary CT were enrolled. Cardiovascular events including stroke were documented. Hazard ratio (HR) and confidence interval (CI) were assessed by Cox proportional hazard model adjusted for the Framingham risk score. C statistics for stroke incidence were also examined by models including cardiovascular calcifications. A total of 980 patients (mean age, 65 ± 7 years; females, 45.8%) were assessed by the CAC, AVC, and ARC Agatston scores. During a median follow-up of 4.0 years, 19 patients developed stroke. Cox proportional hazard model showed severe CAC (Agatston score ≥ 90th percentile [580.0 value]) and presence of AVC and ARC were associated with stroke incidence (HR; 10.33 [95% CI; 2.08-51.26], 3.08 [1.19-7.98], and 2.75 [1.03-7.30], respectively). C statistic in the model with CAC and AVC severity for predicting stroke incidence was 0.841 (95% CI; 0.761-0.920), which was superior to the model with CAC alone (0.762 [95% CI; 0.665-0.859], P < 0.01). CAC, AVC, and ARC were associated with stroke incidence in patients suspected of CAD. Assessment of both CAC and AVC may be useful for prediction of stroke incidence.

PMID:38568474 | DOI:10.1007/s00380-024-02394-6

Mol Neurobiol. 2024 Apr 3. doi: 10.1007/s12035-024-04103-w. Online ahead of print.

ABSTRACT

Parkinson’s disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99 m ([^99mTc]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography-mass spectrometry (LC-MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [^99mTc]Tc radiolabeled compounds ([^99mTc]Tc-MA, [^99mTc]Tc-MA-L-DOPA, [^99mTc]Tc-MA-PLGA and [^99mTc]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague-Dawley rats and a Parkinson’s disease experimental model to evaluate the compounds’ bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [^99mTc]Tc-L-DOPA-PLGA were above 95% and had stability over 6 h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [99mTc]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [^99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research.

PMID:38568418 | DOI:10.1007/s12035-024-04103-w

Int J Cancer. 2024 Apr 3. doi: 10.1002/ijc.34942. Online ahead of print.

ABSTRACT

In sub-Saharan Africa, colorectal cancer (CRC) has historically been considered a rare disease, although some previous studies have suggested that the incidence is increasing. We examine time trends in the incidence of CRC using data from 12 population-based cancer registries in 11 countries of sub-Saharan Africa that were able to provide time series data for periods of 12 or more years, or with earlier data with which recent rates may be compared. Age-standardized incidence rates were highest in the higher-income countries, and were increasing in all of the populations studied, and these increases were statistically significant in all but three. Current evidence has suggested a link between the increased adoption of western lifestyle habits with colorectal cancer, and along with increasing urbanization of African populations, there is an increase in body weight, as well as evidence of increasing consumption of meat, sugars, and alcohol.

PMID:38568397 | DOI:10.1002/ijc.34942

Folia Microbiol (Praha). 2024 Apr 3. doi: 10.1007/s12223-024-01159-y. Online ahead of print.

ABSTRACT

The adherence of bladder uroepithelial cells, subsequent expression, and regulation of type 1 fimbrial genes (key mediator of attachment) in clinical multidrug-resistant uropathogenic Escherichia coli (MDR-UPECs) isolated from individuals with asymptomatic bacteriuria (ABU) remain unexplored till date. Therefore, this study aimed to investigate the underlying molecular mechanisms associated with the adherence of clinical MDR-ABU-UPECs to human a uroepithelial cell line (HTB-4), both in the absence and presence of D-Mannose. These investigations focused on phase variation, expression, and regulation of type 1 fimbriae and were compared to a prototype ABU-strain (E. coli 83972) and symptomatic MDR-UPECs. Discordant to the ABU prototype strain, MDR-ABU-UPECs exhibited remarkable adhesive capacity that was significantly reduced after D-mannose exposure, fairly like the MDR symptomatic UPECs. The type 1 fimbrial phase variation, determined by the fim switch analysis, asserted the statistically significant incidence of “both OFF and ON” orientation among the adherent MDR-ABU-UPECs with a significant reduction in phase-ON colonies post-D-mannose exposure, akin to the symptomatic ones. This was indicative of an operative and alternating type 1 fimbrial phase switch. The q-PCR assay revealed a coordinated action of the regulatory factors; H-NS, IHF, and Lrp on the expression of FimB and FimE recombinases, which further controlled the function of fimH and fimA genes in ABU-UPECs, similar to symptomatic strains. Therefore, this study is the first of its kind to provide an insight into the regulatory crosstalk of different cellular factors guiding the adhesion of ABU-UPECs to the host. Additionally, it also advocated for the need to accurately characterize ABU-UPECs.

PMID:38568394 | DOI:10.1007/s12223-024-01159-y

J Immigr Minor Health. 2024 Apr 3. doi: 10.1007/s10903-024-01588-4. Online ahead of print.

ABSTRACT

We tested the hypothesis that children in New York City (NYC) with an immigrant parent were more likely to lack health insurance and report poorer parent-rated health compared to those of US-born parents in this serial, cross-sectional study using existing data from 2009 to 2017 among children age < 12 years in two NYC health surveys. Main outcomes were parent-reported responses for (1) child insurance coverage and (2) child general health status. In multivariable logistic regression models, we estimated likelihood of outcomes for children of immigrants compared to those of US-born parents, adjusting for child, parent, and household characteristics. We included 2,637 children in 2009 and 7,042 in 2017 in NYC. In 2017, children of immigrant parents were more likely to experience uninsurance than children of US-born parents [adjusted odds ratio (AOR) 2.36 (95% CI: 1.05-5.31)]. Compared to children of US-born parents, children with an immigrant parent were more likely to have a gap in insurance coverage in both 2009 (AOR 1.88; 95% CI: 1.08-3.27) and 2017 (AOR 1.60; 95% CI: 1.06-2.41). Although more children of immigrants had poor/fair health than those of US-born parents in both years, differences were not statistically significant after adjusting for covariates. Our findings among a sample of children eligible for health insurance suggest policies intended to expand child health care access did not equitably reach children of immigrants despite their eligibility for health insurance. Tailored interventions for children of immigrants are needed to mitigate disparities in health insurance coverage.

PMID:38568393 | DOI:10.1007/s10903-024-01588-4

Arch Orthop Trauma Surg. 2024 Apr 3. doi: 10.1007/s00402-024-05300-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Upper-tight tourniquet is widely used in Total Knee Arthroplasty in different modalities. However, it has been associated with a negative impact on post-operative muscle strength end pain. This study aimed to investigate the effect of tourniquet on post-operative pain and recovery in enhanced recovery joint surgery.

MATERIALS AND METHODS: In this prospective randomized study, we included 116 patients undergoing to TKA. Surgery was performed with a staged use of tourniquet in Group A (58 patients) and without tourniquet in Group B. In the former group a low-pressure tourniquet was deflated after bone cuts to allow hemostasis of posterior recess and re-inflated for cementation. For all patients a multimodal fast-track recovery protocol was used. Time to reach rehabilitation milestones was recorded as primary endpoint. Range of motion, pain, hemarthrosis, total blood loss, surgical field visualization, Knee Score (KS) and Oxford Knee Score (OKS) were considered as secondary outcomes.

RESULTS: . No statistically significant differences were found (group B: average 1.3 ± 0.6 day; group A: average 1.2 ± 0.5 day). Group A had a shorter mean surgical time and a clearer surgical field visualization. Group B had a larger estimated blood loss and hemoglobin drop without a statistically significant difference in the transfusion rate. No differences between the groups were seen in the KS, OKS and range of motion (ROM) and post-operative joint swelling. Pain score was similar between cohorts and recorded thigh pain was surprisingly greater in group B.

DISCUSSION: The use of tourniquet in TKA surgery helps to minimize intraoperative blood loss and improves surgical field visualization. Its application with a modern and staged protocol does not affect the functional outcomes (OKS, KSS, ROM) of the early post operative period without compromising the fast-track recovery.

PMID:38568385 | DOI:10.1007/s00402-024-05300-x

Pharm Stat. 2024 Apr 3. doi: 10.1002/pst.2381. Online ahead of print.

ABSTRACT

In several therapeutic areas, including chronic kidney disease (CKD) and immunoglobulin A nephropathy (IgAN), there is a growing interest in how best to analyze estimated glomerular filtration rate (eGFR) data over time in randomized clinical trials including how to best accommodate situations where the rate of change is not anticipated to be linear over time, often due to possible short term hemodynamic effects of certain classes of interventions. In such situations, concerns have been expressed by regulatory authorities that the common application of single slope analysis models may induce Type I error inflation. This article aims to offer practical advice and guidance, including SAS codes, on the statistical methodology to be employed in an eGFR rate of change analysis and offers guidance on trial design considerations for eGFR endpoints. A two-slope statistical model for eGFR data over time is proposed allowing for an analysis to simultaneously evaluate short term acute effects and long term chronic effects. A simulation study was conducted under a range of credible null and alternative hypotheses to evaluate the performance of the two-slope model in comparison to commonly used single slope random coefficients models as well as to non-slope based analyses of change from baseline or time normalized area under the curve (TAUC). Importantly, and contrary to preexisting concerns, these simulations demonstrate the absence of alpha inflation associated with the use of single or two-slope random coefficient models, even when such models are misspecified, and highlight that any concern regarding model misspecification relates to power and not to lack of Type I error control.

PMID:38568372 | DOI:10.1002/pst.2381

J Autism Dev Disord. 2024 Apr 3. doi: 10.1007/s10803-024-06304-7. Online ahead of print.

ABSTRACT

Autistic adults are often challenged to engage in and complete life skill tasks independently and are underrepresented in employment. No prior study has explored the perceptions of autistic individuals regarding K-12 life skills experiences and postsecondary employment. As such, the purposes of this study were to explore the association between components of life skills instruction and employment for 12 autistic individuals, and to elicit the perspectives of and experiences in K-12 education and employment of six autistic adults. As this was a mixed methods study, surveys and semi-structured interviews were conducted. Results of Fisher’s test indicated no statistically significant associations between employment and instructional components; however, the associations between employment and household chores [Cramer’s V = .60]; cooking [Cramer’s V = .66]; one-on-one instruction [Cramer’s V = .63]; and field trips [Cramer’s V = .41]) were large. The associations between employment and job site training [Cramer’s V = .33] and token boards [Cramer’s V = .33]) were moderate. Three themes and 10 subthemes emerged. Specifically, participants remembered Memorable Components from K-12 instruction: (a) job site training, (b) field trips, and (c) household chores. Participants perceived Beneficial Practices as: (a) job site training and (b) skills learned. Participants described shortcomings of K-12 instruction as need (a) for more skills training, (c) for social skills training, (d) to eliminate unnecessary instruction and (e) to carefully consider student placement. In conclusion, participants described experiences that helped them gain and attain post-secondary employment. More specific individualized programming in K-12 instruction would be beneficial to develop independence and post-secondary employment.

PMID:38568366 | DOI:10.1007/s10803-024-06304-7