Nevin Manimala

Commun Biol. 2022 Aug 11;5(1):806. doi: 10.1038/s42003-022-03738-6.

ABSTRACT

Genome-wide association studies (GWAS) have made impactful discoveries for complex diseases, often by amassing very large sample sizes. Yet, GWAS of many diseases remain underpowered, especially for non-European ancestries. One cost-effective approach to increase sample size is to combine existing cohorts, which may have limited sample size or be case-only, with public controls, but this approach is limited by the need for a large overlap in variants across genotyping arrays and the scarcity of non-European controls. We developed and validated a protocol, Genotyping Array-WGS Merge (GAWMerge), for combining genotypes from arrays and whole-genome sequencing, ensuring complete variant overlap, and allowing for diverse samples like Trans-Omics for Precision Medicine to be used. Our protocol involves phasing, imputation, and filtering. We illustrated its ability to control technology driven artifacts and type-I error, as well as recover known disease-associated signals across technologies, independent datasets, and ancestries in smoking-related cohorts. GAWMerge enables genetic studies to leverage existing cohorts to validly increase sample size and enhance discovery for understudied traits and ancestries.

PMID:35953715 | DOI:10.1038/s42003-022-03738-6

Sci Rep. 2022 Aug 11;12(1):13663. doi: 10.1038/s41598-022-17813-9.

ABSTRACT

Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant. After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p = 0.009) greater. When a 70% dose volume ≥ 1 cc was used, the possibility of ITN was 5.892-fold (p < 0.001) higher. On average, meningiomas with ITN increased in volume by 128.5% at 6 months after GKRS and then decreased to 94.6% at 12 months. When performing GKRS in meningioma, a 70% dose volume ≥ 1 cc is a risk factor for ITN. At 6 months after GKRS, meningiomas with ITN may experience a transient volume expansion and PTE, which are characteristics of pseudoprogression. These characteristics typically improve at 12 months following GKRS.

PMID:35953695 | DOI:10.1038/s41598-022-17813-9

Clin Rheumatol. 2022 Aug 11. doi: 10.1007/s10067-022-06327-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Intra-articular corticosteroid injection (IACI) is generally used in the management of juvenile idiopathic arthritis (JIA) to obtain rapid relief of active synovitis and functional recovery and to prevent the need for regular systemic therapy. The aim of this study was to investigate the outcome of IACI treatment and the factors associated with remission of synovitis.

METHODS: The clinical records of JIA patients who received IACI between January 2014 and December 2020 in two pediatric rheumatology centers were reviewed. The procedure was evaluated in terms of efficacy, factors that may affect the duration of remission, procedural and drug-related complications.

RESULTS: During the study period, 134 patients received 227 injections and 37 joints were injected more than once. One hundred and six (79%) patients had persistent oligoarticular disease. At the time of injection, all patients were receiving non-steroidal anti-inflammatory drugs, 74 patients were on methotrexate, and 14 patients were on biologics. The median duration of remission without exacerbation of synovitis treated with IACI was 15 (range 1-64) months. The inactivity rate was 81% at the 6th month after the injection. It has been shown that being less than 7 years old at disease onset and low initial CRP levels were correlated with a long remission period (p < 0.05). Despite the differences were not statistically significant, the duration of remission was longer in boys, in ANA positives, in HLA-B27 negatives, in patients with concurrent methotrexate treatment and in patients not receiving biologic therapy (p > 0.05). Only two patients (1.5%, 95% CI – 0.6 to 3.5) developed cutaneous hypopigmentation and subcutaneous atrophy as side effects of injection.

CONCLUSION: Intra-articular corticosteroid injection was more effective especially in patients with low initial CRP levels and younger than 7 years of age. The duration of remission was longer in these patients. Key Points • Intra-articular corticosteroid injection is an effective method for controlling joint inflammation and achieving long-term remission without significant side effects. • Intra-articular corticosteroid injection can be preferred in all forms of juvenile idiopathic arthritis as primary therapy or to relieve the patient while waiting for the effect of systemic agents or to avoid increasing the dose of systemic drugs. • It can be recommended as a treatment option at any stage of the disease, especially in young patients and patients with low initial CRP values.

PMID:35953685 | DOI:10.1007/s10067-022-06327-4

Intensive Care Med. 2022 Aug 11. doi: 10.1007/s00134-022-06826-7. Online ahead of print.

ABSTRACT

PURPOSE: This case-control study investigated the long-term evolution of multidrug-resistant bacteria (MDRB) over a 5-year period associated with the use of selective oropharyngeal decontamination (SOD) in the intensive care unit (ICU). In addition, effects on health care-associated infections and ICU mortality were analysed.

METHODS: We investigated patients undergoing mechanical ventilation > 48 h in 11 adult ICUs located at 3 campuses of a university hospital. Administrative, clinical, and microbiological data which were routinely recorded electronically served as the basis. We analysed differences in the rates and incidence densities (ID, cases per 1000 patient-days) of MDRB associated with SOD use in all patients and stratified by patient origin (outpatient or inpatient). After propensity score matching, health-care infections and ICU mortality were compared.

RESULTS: 5034 patients were eligible for the study. 1694 patients were not given SOD. There were no differences in the incidence density of MDRB when SOD was used, except for more vancomycin-resistant Enterococcus faecium (0.72/1000 days vs. 0.31/1000 days, p < 0.01), and fewer ESBL-producing Klebsiella pneumoniae (0.22/1000 days vs. 0.56/1000 days, p < 0.01). After propensity score matching, SOD was associated with lower incidence rates of ventilator-associated pneumonia and death in the ICU but not with ICU-acquired bacteremia or urinary tract infection.

CONCLUSIONS: Comparisons of the ICU-acquired MDRB over a 5-year period revealed no differences in incidence density, except for lower rate of ESBL-producing Klebsiella pneumoniae and higher rate of vancomycin-resistant Enterococcus faecium with SOD. Incidence rates of ventilator-associated pneumonia and death in the ICU were lower in patients receiving SOD.

PMID:35953676 | DOI:10.1007/s00134-022-06826-7

J Pharmacokinet Pharmacodyn. 2022 Aug 11. doi: 10.1007/s10928-022-09811-1. Online ahead of print.

ABSTRACT

Quantitative Systems Pharmacology (QSP) modeling is increasingly applied in the pharmaceutical industry to influence decision making across a wide range of stages from early discovery to clinical development to post-marketing activities. Development of standards for how these models are constructed, assessed, and communicated is of active interest to the modeling community and regulators but is complicated by the wide variability in the structures and intended uses of the underlying models and the diverse expertise of QSP modelers. With this in mind, the IQ Consortium conducted a survey across the pharmaceutical/biotech industry to understand current practices for QSP modeling. This article presents the survey results and provides insights into current practices and methods used by QSP practitioners based on model type and the intended use at various stages of drug development. The survey also highlights key areas for future development including better integration with statistical methods, standardization of approaches towards virtual populations, and increased use of QSP models for late-stage clinical development and regulatory submissions.

PMID:35953664 | DOI:10.1007/s10928-022-09811-1

Behav Res Methods. 2022 Aug 11. doi: 10.3758/s13428-022-01932-2. Online ahead of print.

ABSTRACT

Researcher degrees of freedom can affect the results of hypothesis tests and consequently, the conclusions drawn from the data. Previous research has documented variability in accuracy, speed, and documentation of output across various statistical software packages. In the current investigation, we conducted Pearson’s chi-square test of independence, Spearman’s rank-ordered correlation, Kruskal-Wallis one-way analysis of variance, Wilcoxon Mann-Whitney U rank-sum tests, and Wilcoxon signed-rank tests, along with estimates of skewness and kurtosis, on large, medium, and small samples of real and simulated data in SPSS, SAS, Stata, and R and compared the results with those obtained through hand calculation using the raw computational formulas. Multiple inconsistencies were found in the results produced between statistical packages due to algorithmic variation, computational error, and statistical output. The most notable inconsistencies were due to algorithmic variations in the computation of Pearson’s chi-square test conducted on 2 × 2 tables, where differences in p-values reported by different software packages ranged from .005 to .162, largely as a function of sample size. We discuss how such inconsistencies may influence the conclusions drawn from the results of statistical analyses depending on the statistical software used, and we urge researchers to analyze their data across multiple packages to check for inconsistencies and report details regarding the statistical procedure used for data analysis.

PMID:35953660 | DOI:10.3758/s13428-022-01932-2

Pain Ther. 2022 Aug 11. doi: 10.1007/s40122-022-00423-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Computed tomography (CT)-guided coeliac plexus neurolysis (CPN) is considered effective at controlling pain in patients with intra-abdominal malignancies. The primary objective was to correlate pain outcomes with the spread of neurolytic solution in the coeliac area and to evaluate the predictive value for the spread of injectate for pain outcomes and side effects.

METHODS: Blinded CT scans were reviewed. The coeliac area was divided into nine quadrants. Assessors evaluated quadrants according to contrast spread, needle tip position, and the contact between the injectate and other organs and plexuses. Efficacy of CPN and complications were estimated.

RESULTS: In 54.9% there was complete spread of the neurolytic in the coeliac area with no correlation between pain relief and spread of injectate. In 85% the neurolytic had contact with viscera with no correlation with pain relief or complications. There was no correlation between needle tip position and spread of the neurolytic and contact of the neurolytic with viscera. In 71.6% the injectate was found to have spread into “other” plexuses. In 13.3% hampered spread of the injectate was observed. There was no correlation between patterns of injectate spread and pain relief, pain relief and spread of injectate in any particular quadrants, and expected and documented post-procedural pain scores.

CONCLUSIONS: Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control.

PMID:35953656 | DOI:10.1007/s40122-022-00423-8

Biol Trace Elem Res. 2022 Aug 12. doi: 10.1007/s12011-022-03358-5. Online ahead of print.

ABSTRACT

Hexavalent chromium [Cr(VI)] has emerged as a prevailing environmental and occupational contaminant over the past few decades. However, the knowledge is sparse regarding Cr(VI)-induced neurological aberrations, and its remediation through natural bioactive compounds has not been fully explored. This study intended to probe the possible invigorative effects of nutraceuticals such as coenzyme Q10 (CoQ10), biochanin A (BCA), and phloretin (PHL) on Cr(VI) intoxicated Swiss albino mice with special emphasis on Nrf2/HO-1/NQO1 gene expressions. Mice received potassium dichromate (75 ppm) through drinking water and were simultaneously co-treated intraperitoneally with CoQ10 (10 mg/kg), BCA, and PHL (50 mg/kg) each for 30-day treatment period. The statistics highlight the elevated levels of lipid peroxidation (LPO) and protein carbonyl content (PCC) with a concomitant reduction in the superoxide dismutase (SOD), glutathione-S-transferase (GST), reduced glutathione (GSH), total thiols (TT), catalase (CAT), and cholinesterase activities in the Cr(VI)-exposed mice. The collateral assessment of DNA fragmentation, DNA breakages, and induced histological alterations was in conformity with the above findings in conjugation with the dysregulation in the Nrf2 and associated downstream HO-1 and NQO1 gene expressions. Co-treatment with the selected natural compounds reversed the above-altered parameters significantly, thereby bringing cellular homeostasis in alleviating the Cr(VI)-induced conciliated impairments. Our study demonstrated that the combination of different bioactive compounds shields the brain better against Cr(VI)-induced neurotoxicity by revoking the oxidative stress-associated manifestations. These compounds may represent a new potential combination therapy due to their ability to modulate the cellular antioxidant responses by upregulating the Nrf2/HO-1/NQO1 signaling pathway against Cr(VI)-exposed population. HIGHLIGHTS: Cr(VI)-associated heavy metal exposure poses a significant threat to the environment, especially to living organisms. Cr(VI) exposure for 30 days resulted in the free radical’s generation that caused neurotoxicity in the Swiss albino mice. Natural compounds such as coenzyme Q10, biochanin A, and phloretin counteracted the neurotoxic effect due to Cr(VI) exposure in scavenging of free radicals by enhancing Nrf2/HO-1/NQO1 gene expressions in maintaining the cellular homeostasis.

PMID:35953644 | DOI:10.1007/s12011-022-03358-5

Dev Med Child Neurol. 2022 Aug 11. doi: 10.1111/dmcn.15346. Online ahead of print.

ABSTRACT

AIM: To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP).

METHOD: A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010).

RESULTS: Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included.

INTERPRETATION: The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence.

PMID:35952356 | DOI:10.1111/dmcn.15346

Psychother Res. 2022 Aug 11:1-8. doi: 10.1080/10503307.2022.2109443. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with Major Depressive Disorder (MDD) have been found to have restricted capacity for mentalization, and it is possible that this constitutes a vulnerability factor for developing depression. Due to its focus on linking depressive symptomatology to emotions and interpersonal relations, it was hypothesized that Interpersonal Psychotherapy (IPT) would improve mentalization more than Cognitive Behavioral Therapy (CBT).

METHODS: In a randomized controlled trial of 90 patients undergoing IPT and CBT for MDD, Reflective Functioning (RF) was rated from Adult Attachment and from Depression-Specific Reflective Functioning (DSRF) Interviews before and after therapy. Treatment outcome was assessed using the Beck Depression Inventory-II.

RESULTS: The interaction between time and treatment approach was statistically significant, with RF improving significantly more in IPT than in CBT. Change in RF was not correlated with change in depression. The difference in DSRF ratings before and after therapy was not statistically significant for any of the treatments.

CONCLUSIONS: IPT may improve mentalization more than CBT. However, although RF increased significantly in IPT, the mean level was still low after therapy. A limitation of the study is the large amount of post-treatment missing data. More research is needed to understand the potential role of mentalization in symptom reduction.

PMID:35952325 | DOI:10.1080/10503307.2022.2109443