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Nevin Manimala Statistics

A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression Among University Students: A Secondary Analysis of a Randomized Clinical Trial

JAMA Psychiatry. 2023 Jun 7. doi: 10.1001/jamapsychiatry.2023.1675. Online ahead of print.

ABSTRACT

IMPORTANCE: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT.

OBJECTIVE: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022.

INTERVENTIONS: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435).

MAIN OUTCOMES AND MEASURES: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline.

RESULTS: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P = .003) or treatment as usual (40.0% [2.7%]; P = .001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P = .007; self-guided i-CBT: 25.4% [8.8%]; P = .004; treatment as usual: 31.0% [9.4%]; P = .001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P = .14; treatment as usual: 53.0% [6.0%]; P = .25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P = .001; treatment as usual: 41.8% [3.2%]; P < .001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P = .07).

CONCLUSIONS AND RELEVANCE: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04780542.

PMID:37285133 | DOI:10.1001/jamapsychiatry.2023.1675

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Fertility Trends and Adverse Pregnancy Outcomes in Female Patients With Psoriasis in the UK

JAMA Dermatol. 2023 Jun 7. doi: 10.1001/jamadermatol.2023.1400. Online ahead of print.

ABSTRACT

IMPORTANCE: Evidence regarding fertility trends and obstetric outcomes among patients with psoriasis is limited by studies of small sample sizes, noninclusion of comparators, and the lack of accurate pregnancy records.

OBJECTIVE: To investigate fertility rates and obstetric outcomes of pregnancies in female patients with psoriasis compared with age- and general practice-matched comparators without psoriasis.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used data from 887 primary care practices that contributed to the UK Clinical Practice Research Datalink GOLD database between 1998 and 2019, linked to a pregnancy register and Hospital Episode Statistics. There were 6 223 298 patients of common childbearing ages (15-44 years), and 63 681 patients with psoriasis had at least 1 year of follow-up data prior to the diagnosis of psoriasis. For each patient with psoriasis, 5 patients were matched by age from the same general practice. The median follow-up duration was 4.1 years. Data analysis was performed in 2021.

EXPOSURES: Patients with psoriasis were identified using clinical diagnostic codes from consultations.

MAIN OUTCOMES AND MEASURES: Fertility rates were calculated as the number of pregnancies per 100 patient-years. The outcomes of each pregnancy recorded in the pregnancy register or Hospital Episode Statistics were screened to identify obstetric outcomes. A negative binomial model was used to examine the association between psoriasis and the fertility rate. Logistic regression was applied to compare the association between psoriasis and obstetric outcomes.

RESULTS: A total of 63 681 patients with psoriasis and 318 405 matched comparators were included in the analysis (median [IQR] age, 30 [22-37] years). Lower fertility rates (rate ratio, 0.75; 95% CI, 0.69-0.83) were found in patients with moderate to severe psoriasis. Compared with matched comparators without psoriasis, pregnancies in patients with psoriasis had a higher risk of loss (odds ratio, 1.06; 95% CI, 1.03-1.10); however, there was no increase in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes.

CONCLUSION AND RELEVANCE: In this cohort study, patients with moderate to severe psoriasis had a lower fertility rate, and the risk of pregnancy loss was higher than in matched comparators without psoriasis. Future research should identify the mechanism of increased risk of pregnancy loss among patients with psoriasis.

PMID:37285130 | DOI:10.1001/jamadermatol.2023.1400

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Salivary fluoride concentrations following toothbrushing with experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) filler

Clin Oral Investig. 2023 Jun 7. doi: 10.1007/s00784-023-05063-6. Online ahead of print.

ABSTRACT

BACKGROUND: Single-blind 9 case comparative studies were conducted to evaluate salivary fluoride concentrations following toothbrushing using experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) fillers. Preliminary tests were conducted in order to determine the volume of usage as well as the concentrations (wt %) of S-PRG filler. Based on the results given these experiments, we compared the salivary fluoride concentrations following toothbrushing with 0.5 g of 4 different types of toothpastes: 5 wt % S-PRG filler, 1400 ppm F AmF (amine fluoride), 1500 ppm F NaF (sodium fluoride), and MFP (monofluorophosphate) containing toothpaste.

METHODS: Of the 12 participants, 7 participated in the preliminary study and 8 in the main study. All participants brushed their teeth using the scrubbing method for 2 min. At first, 1.0 and 0.5 g of 20 wt % S-PRG filler toothpastes were used to compare, then followed by 0.5 g of 0 (control), 1, and 5 wt % S-PRG toothpastes, respectively. The participants spat out once and rinsed with 15 mL of distilled water for 5 s. Saliva was collected for 3 min each at different time intervals of 0 (baseline), 5, 10, 15, 30, 60, 120, and 180 min after the rinsing. Fluoride concentrations were determined using a fluoride electrode, and the area under the salivary clearance – time curve (AUC: ppm‧min) of each toothpaste was calculated as the salivary fluoride retention. The main study was then conducted to evaluate the salivary fluoride concentrations as well as the AUC value using 0.5 g of 5 wt % S-PRG filler toothpaste, followed by NaF, MFP, and AmF toothpastes.

RESULTS: Since there were no statistical differences between using 1.0 and 0.5 g of 20 wt % S-PRG toothpastes in salivary fluoride concentrations as well as the AUC value throughout the 180 min measurement, the volume was set as 0.5 g for the following studies. Concentrations of 5 and 20 wt % S-PRG toothpastes retained 0.09 ppm F or more in saliva even after 180 min. No statistical differences were seen in the salivary fluoride concentrations at any time intervals as well as the AUC value between 5 and 20 wt % S-PRG toothpastes. Based on these results, the concentration of 5 wt % S-PRG toothpaste was used for the main comparative study. MFP toothpaste resulted in by far the lowest salivary fluoride concentrations (0.06 ppm F at 180 min) and the AUC value (24.6 ppm‧min), whereas 5 wt % S-PRG toothpaste (0.15 ppm F at 180 min, 92.3 ppm‧min) displayed retention on par with AmF toothpaste which appeared to result in higher values (0.17 ppm F at 180 min, 103 ppm‧min), compared to NaF toothpaste (0.12 ppm F at 180 min, 49.3 ppm‧min).

CONCLUSIONS: The salivary fluoride concentrations following toothbrushing with 0.5 g of 5 wt % S-PRG filler containing toothpaste showed retention similar to the best performing 1400 ppm F AmF toothpaste even 180 min after toothbrushing.

PMID:37285102 | DOI:10.1007/s00784-023-05063-6

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The Efficacy and Safety of Patiromer for Heart Failure Patients: A Systematic Review and Meta-Analysis

Cardiovasc Drugs Ther. 2023 Jun 7. doi: 10.1007/s10557-023-07473-w. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of patiromer, a novel potassium binder, in reducing the risk of hyperkalemia in patients with heart failure and optimizing their RAASi therapy.

DESIGN: Systematic review and meta-analyses.

METHOD: The authors conducted a systematic search in Pubmed, Embase, Web of Science, and Cochrane Library for randomized controlled trials investigating the efficacy and safety of patiromer in heart failure patients from inception to 31 January 2023 and updated on 25 March 2023. The primary outcome was the association between the reduction of hyperkalemia and patiromer compared with placebo, and the secondary outcome was the association between optimization of RAASi therapy and patiromer.

RESULTS: A total of four randomized controlled trials (n = 1163) were included in the study. Patiromer was able to reduce the risk of hyperkalemia in heart failure patients by 44% (RR 0.56, 95% CI 0.36 to 0.87; I2 = 61.9%), improve tolerance to target doses of MRA in patients with heart failure (RR 1.15, 95% CI 1.02 to 1.30; I2 = 49.4%), and decrease the proportion of all-cause discontinuation of RAASi (RR 0.49, 95% CI 0.25 to 0.98; I2 = 48.4%). However, patiromer therapy was associated with an increased risk of hypokalemia (RR 1.51, 95% CI 1.07 to 2.12; I2 = 0%), while no other statistically significant adverse events were observed.

CONCLUSION: Patiromer appears to have a considerable effect on reducing the incidence of hyperkalemia in heart failure patients and on optimizing the therapy of RAASi in those patients.

PMID:37285082 | DOI:10.1007/s10557-023-07473-w

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Nevin Manimala Statistics

Diagnostic accuracy of the Dutch version of the 4AT for delirium detection in a mixed patient population and setting

Aging Clin Exp Res. 2023 Jun 7. doi: 10.1007/s40520-023-02447-2. Online ahead of print.

ABSTRACT

BACKGROUND: Delirium is an acute disturbance in attention, awareness and cognition. Immediate detection in older adults is recommended because delirium is associated with adverse outcomes. The 4 ‘A’s Test (4AT) is a short screening instrument for delirium. The aim of this study is to evaluate diagnostic accuracy of the Dutch version of the screening tool 4AT for delirium detection in different settings.

METHODS: Prospective observational study conducted in two hospitals in patients aged ≥ 65 years in geriatric wards and the Emergency Department (ED). Each participant underwent two assessments; the index test 4AT, followed by the reference standard for delirium performed by a geriatric care specialist. The reference standard delirium is according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria.

RESULTS: A total of 71 geriatric inpatients and 49 older ED patients were included. The prevalence of delirium was 11.6% in the acute geriatric ward and 6.1% in the ED. The sensitivity and specificity of the 4AT in the acute geriatric ward were 0.88 and 0.69, respectively. In the ED, the sensitivity and specificity were 0.67 and 0.83, respectively. The area under the receiver operating characteristic curve was 0.80 for the acute geriatric ward setting and 0.74 for the ED setting.

CONCLUSION: The Dutch version of the 4AT is a reliable screening tool for delirium detection in both acute geriatric wards and ED. Due to its brevity and practicality (i.e., no special training is required to administer the tool), it is useful in clinical practice.

PMID:37285074 | DOI:10.1007/s40520-023-02447-2

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Building use-inspired species distribution models: using multiple data types to examine and improve model performance

Ecol Appl. 2023 Jun 7:e2893. doi: 10.1002/eap.2893. Online ahead of print.

ABSTRACT

Species distribution models (SDMs) are becoming an important tool for marine conservation and management. Yet while there is an increasing diversity and volume of marine biodiversity data for training SDMs, little practical guidance is available on how to leverage distinct data types to build robust models. We explored the effect of different data types on the fit, performance and predictive ability of SDMs by comparing models trained with four data types for a heavily exploited pelagic fish, the blue shark (Prionace glauca), in the Northwest Atlantic: two fishery-dependent (conventional mark-recapture tags, fisheries observer records) and two fishery-independent (satellite-linked electronic tags, pop-up archival tags). We found that all four data types can result in robust models, but differences among spatial predictions highlighted the need to consider ecological realism in model selection and interpretation regardless of data type. Differences among models were primarily attributed to biases in how each data type, and the associated representation of absences, sampled the environment and summarized the resulting species distributions. Outputs from model ensembles and a model trained on all pooled data both proved effective for combining inferences across data types and provided more ecologically realistic predictions than individual models. Our results provide valuable guidance for practitioners developing SDMs. With increasing access to diverse data sources, future work should further develop truly integrative modeling approaches that can explicitly leverage strengths of individual data types while statistically accounting for limitations, such as sampling biases.

PMID:37285072 | DOI:10.1002/eap.2893

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A review of the current state of single-cell proteomics and future perspective

Anal Bioanal Chem. 2023 Jun 7. doi: 10.1007/s00216-023-04759-8. Online ahead of print.

ABSTRACT

Single-cell methodologies and technologies have started a revolution in biology which until recently has primarily been limited to deep sequencing and imaging modalities. With the advent and subsequent torrid development of single-cell proteomics over the last 5 years, despite the fact that proteins cannot be amplified like transcripts, it has now become abundantly clear that it is a worthy complement to single-cell transcriptomics. In this review, we engage in an assessment of the current state of the art of single-cell proteomics including workflow, sample preparation techniques, instrumentation, and biological applications. We investigate the challenges associated with working with very small sample volumes and the acute need for robust statistical methods for data interpretation. We delve into what we believe is a promising future for biological research at single-cell resolution and highlight some of the exciting discoveries that already have been made using single-cell proteomics, including the identification of rare cell types, characterization of cellular heterogeneity, and investigation of signaling pathways and disease mechanisms. Finally, we acknowledge that there are a number of outstanding and pressing problems that the scientific community vested in advancing this technology needs to resolve. Of prime importance is the need to set standards so that this technology becomes widely accessible allowing novel discoveries to be easily verifiable. We conclude with a plea to solve these problems rapidly so that single-cell proteomics can be part of a robust, high-throughput, and scalable single-cell multi-omics platform that can be ubiquitously applied to elucidating deep biological insights into the diagnosis and treatment of all diseases that afflict us.

PMID:37285026 | DOI:10.1007/s00216-023-04759-8

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Nevin Manimala Statistics

Paediatric ventriculoperitoneal shunt failures: 12-year experience from a Singapore children’s hospital

Childs Nerv Syst. 2023 Jun 7. doi: 10.1007/s00381-023-06007-x. Online ahead of print.

ABSTRACT

PURPOSE: Cerebrospinal fluid (CSF) shunt failures in children are devastating. The primary aims of this study are to, firstly, review our institutional series of ventriculoperitoneal shunt (VPS) insertions and identify factors associated with shunt failure.

METHODS: This is a single-institution, retrospective study conducted over a 12-year period. All patients under 18 years old with VPS inserted were included. Variables of interest such as patient characteristics, hydrocephalus aetiology, shunt implant details, and outcomes were subjected to statistical analyses.

RESULTS: A total of 214 VPS patients were selected for this study. The mean age at VPS insertion was 6 months with a mean follow-up duration of 44 months. The most common type of hydrocephalus was obstructive (n = 142, 66.4%), and the most frequent aetiology was tumour-related (n = 66, 30.8%). The 30-day shunt failure rate was 9.3%: 9 infections (4.2%), 7 occlusions (3.3%), and 4 others (1.9%). After multivariable analysis, only recent central nervous system (CNS) infection prior to VPS insertion remained significant (OR 15.4 (1.3-175), p = 0.028).

CONCLUSION: This is the first, large-scale local study focused on the shunt failure in Singaporean children. Significant findings in our study demonstrate that recently treated CNS infection is a factor associated with 30-day shunt failure while the values of CSF constituents were not contributory.

PMID:37284980 | DOI:10.1007/s00381-023-06007-x

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Geometric Reliability of Super-Resolution Reconstructed Images from Clinical Fetal MRI in the Second Trimester

Neuroinformatics. 2023 Jun 7. doi: 10.1007/s12021-023-09635-5. Online ahead of print.

ABSTRACT

Fetal Magnetic Resonance Imaging (MRI) is an important noninvasive diagnostic tool to characterize the central nervous system (CNS) development, significantly contributing to pregnancy management. In clinical practice, fetal MRI of the brain includes the acquisition of fast anatomical sequences over different planes on which several biometric measurements are manually extracted. Recently, modern toolkits use the acquired two-dimensional (2D) images to reconstruct a Super-Resolution (SR) isotropic volume of the brain, enabling three-dimensional (3D) analysis of the fetal CNS.We analyzed 17 fetal MR exams performed in the second trimester, including orthogonal T2-weighted (T2w) Turbo Spin Echo (TSE) and balanced Fast Field Echo (b-FFE) sequences. For each subject and type of sequence, three distinct high-resolution volumes were reconstructed via NiftyMIC, MIALSRTK, and SVRTK toolkits. Fifteen biometric measurements were assessed both on the acquired 2D images and SR reconstructed volumes, and compared using Passing-Bablok regression, Bland-Altman plot analysis, and statistical tests.Results indicate that NiftyMIC and MIALSRTK provide reliable SR reconstructed volumes, suitable for biometric assessments. NiftyMIC also improves the operator intraclass correlation coefficient on the quantitative biometric measures with respect to the acquired 2D images. In addition, TSE sequences lead to more robust fetal brain reconstructions against intensity artifacts compared to b-FFE sequences, despite the latter exhibiting more defined anatomical details.Our findings strengthen the adoption of automatic toolkits for fetal brain reconstructions to perform biometry evaluations of fetal brain development over common clinical MR at an early pregnancy stage.

PMID:37284977 | DOI:10.1007/s12021-023-09635-5

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The causal effects of inflammatory bowel disease on primary biliary cholangitis: A bidirectional two-sample Mendelian randomization study

Liver Int. 2023 Jun 7. doi: 10.1111/liv.15616. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies have indicated that the incidence of primary biliary cholangitis (PBC) is higher in inflammatory bowel disease (IBD) patients than that in healthy people. However, whether the correlation is causal remains unclear.

METHODS: The genetic associations with IBD were obtained from publicly available genome-wide association studies (GWAS) of European ancestry with 31 665 cases and 33 977 controls, consisting of 17 897 Crohn’s disease (CD) and 13 768 ulcerative colitis (UC) cases. The genetic associations with PBC were obtained from a European GWAS with 2764 cases and 10 475 controls. A bidirectional two-sample Mendelian randomization (MR) design was implemented to determine the causal relationship between IBD and PBC. In the forward MR, the IBD was treated as the exposure while the PBC was the exposure in the reverse MR. The inverse-variance-weighted (IVW) method was utilized as the main statistic method, and a series of sensitivity analyses were performed to detect heterogeneity and horizontal pleiotropy.

RESULTS: A total of 99 valid instrumental variables (IVs) were selected for IBD and the number of IVs for PBC was 18. The forward MR analysis indicated that genetically predicted IBD (UC and CD) was significantly associated with an increased risk of PBC (IVW OR = 1.343; 95% CI: 1.220-1.466). Similar casual associations were observed in UC (IVW OR = 1.244; 95% CI: 1.057-1.430) and CD (IVW OR = 1.269; 95% CI: 1.159-1.379). Such results were still consistent in multiple MR methods. The reverse MR analysis implicated that genetic susceptibility to PBC might not alter the risk of IBD (IVW OR = 1.070; 95% CI: 0.984-1.164).

CONCLUSION: Our study found that genetically predicted IBD can increase the risk of PBC while not vice versa in the European population, which may enlighten the aetiology of PBC, together with the IBD patient management.

PMID:37283182 | DOI:10.1111/liv.15616