Category: Statistics

Asian J Psychiatr. 2021 Nov 24;67:102939. doi: 10.1016/j.ajp.2021.102939. Online ahead of print.

ABSTRACT

AIM: To study the association of clozapine pharmacometabolomics and clozapine response in Asian patients with treatment-resistant schizophrenia (TRS).

METHOD: A cross-sectional study was performed on 50 consecutive TRS patients following up in psychiatry department of the tertiary care hospital. Demographic details, response assessment, were collected on the case record form. A blood sample was also collected for trough concentration assessment of drug and its metabolites. Clozapine (CLZ) the parent drug and its two major metabolites – Clozapine N oxide (CNO) and N-Desmethyl clozapine (N-DSMC) levels were assessed using a high-performance liquid chromatography method. Clozapine responders and nonresponders patients were classified based upon Andreasen criteria.

RESULTS: The average trough concentration of CNO, N-DSMC, and CLZ were 123 ± 76.04, 171.93 ± 93.24, 229.27 ± 124.25 ng/ml, respectively. The two patient subgroups did not differ for CLZ, CNO, and N-DSMC concentrations statistically. However, clozapine nonresponse was associated with a higher CLZ/N-DSMC ratio (p = 0.03) and clozapine dose (p = 0.01). The receiver operator characteristic curve showed that the cut-off CLZ/N-DSMC ratio of 1.54 with a sensitivity of 85% and a positive predictive value of 84% for identifying nonresponders.

CONCLUSION: CLZ/N-DSMC ratio and clozapine dose were identified as significant variables for future dose optimization algorithms. Pharmacometabolomics-guided clozapine therapy has the potential to revolutionize TRS management.

PMID:34844176 | DOI:10.1016/j.ajp.2021.102939

Animal. 2021 Nov 26;15(12):100397. doi: 10.1016/j.animal.2021.100397. Online ahead of print.

ABSTRACT

Bovine respiratory disease is the leading user of antibiotics (AB) in calf production. Mycoplasma (M.) bovis could lead to greater use of AB as it is a persistent and AB resistant causative agent for respiratory diseases. Two cross-sectional studies were set up to assess the effects of lot size and feeding system on M. bovis infection and the effects of M. bovis seroconversion, lot size and feeding system on AB use in calves’ feedlots. Twenty-six lots in 22 fattening farms were monitored for 41-81 days, from all-in entry of calves until three consecutive weeks without using any collective antibiotics. M. bovis spread was estimated by measuring seroconversion at entry and at the end of study period in 10-15 calves randomly sampled in each lot. All AB treatments used in the meanwhile were recorded. The lots were selected according to feeding system, i.e. individual bucket (n = 7) vs. automated milk feeder (AMF, n = 19), and lot size (30-519 calves), less than 50 calves (n = 9) vs. more than 50 calves (n = 17). Statistical analysis was performed using multivariable generalised linear models with fattening farms as random effect. M. bovis spread increased with lot size (odds ratio (OR) 2.9[1.4; 5.8] per two-fold increase in lot size). This proportion of seroconverted calves was lower in bucket-fed lots compared to lots fed with the AMF using a shared nipple (OR = 0.03[0.003; 0.41]). The main risk factor for AB use was the lot size, with an increase of 1.5[0.94; 1.98] treatments per two-fold increase in lot size. For same size lots, the use of bucket can decrease AB consumption by up to 1.03[-2.18; 0.14] treatments per calf compared to AMF. Analysis of the association between seroconversion to M. bovis and AB use was inconclusive. We found that bucket feeding in small-size lots, i.e. up to a maximum of 50 calves in the same space, limits seroconversion to M. bovis and enables lower use of AB in veal calf production.

PMID:34844188 | DOI:10.1016/j.animal.2021.100397

Eur Neuropsychopharmacol. 2021 Nov 26;55:86-95. doi: 10.1016/j.euroneuro.2021.11.005. Online ahead of print.

ABSTRACT

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p = 0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11-1.98, p = 0.007). Nominal associations were also found between MDD-PRS and non-response (p = 0.013), as well as between SCZ-PRS and non-remission (p = 0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.

PMID:34844152 | DOI:10.1016/j.euroneuro.2021.11.005

Gait Posture. 2021 Nov 18;92:123-128. doi: 10.1016/j.gaitpost.2021.11.017. Online ahead of print.

ABSTRACT

BACKGROUND: Voluntary movement such as lifting a foot in preparation to stepping acts as a self-initiated perturbation that disturbs postural equilibrium. To maintain and restore equilibrium, humans utilize early, anticipatory, and compensatory postural adjustments. Despite technological progress in accessible virtual reality (VR) devices, little is known on the usage of VR in control and maintenance of balance while standing.

RESEARCH QUESTION: How does VR modulate early, anticipatory, and compensatory postural adjustments during a dynamic task of leg lifting while avoiding an obstacle?

METHODS: First, the postural adjustments in a single-leg obstacle avoidance were compared between real and VR settings, where a statistical reanalysis was performed with data subsets that minimize the difference of foot elevation speed. Second, the effect of simple foot elevation was examined to identify the fundamental nature of leg lifting motion as a self-initiated perturbation. Lastly, perceptual distortion in VR was assessed by evaluating how the spatial scale of the virtual scene used in the single-leg obstacle avoidance experiment was recognized by participants.

RESULTS: The VR setting reduced the activities of lower leg muscles on the supporting side not only in the compensatory phase but also in the preparatory early and anticipatory phases. On the other hand, simple foot elevation resulted in a significant increase of muscle activities with lifting height only found in the compensatory phase. Furthermore, it is suggested that the VR induced perceptual distortion in estimating the sizes of the virtual objects.

SIGNIFICANCE: The findings provide more definitive evidence that VR presentation modulates the components of postural adjustments for maintaining upright stance while being perturbed. One of the potential psychophysical factors is perceptual distortion in VR, and this provides critical information for further development of VR based training system.

PMID:34844150 | DOI:10.1016/j.gaitpost.2021.11.017

Gait Posture. 2021 Nov 18;92:129-134. doi: 10.1016/j.gaitpost.2021.11.012. Online ahead of print.

ABSTRACT

BACKGROUND: There is a range of magneto-inertial measurement unit (MIMU) systems commercially available, however sensor specifications and fusion methods vary considerably between manufacturers. Such variability can influence the concurrent validity of MIMUs relative to reference standard measurement devices. Different MIMUs have been compared during static or low-velocity conditions, with higher-velocity movements assessed in robotic-based studies. However, there is a need for the concurrent validity of higher-velocity movements to be established in human-based studies.

RESEARCH QUESTION: This study aimed to assess the concurrent validity of two commercial MIMU systems (Noraxon and Xsens), relative to a ‘gold-standard’ retro-reflective motion capture system, when measuring trunk angles during uni-planar range of motion (ROM) and cricket bowling, which involves high-speed, multi-planar movements.

METHODS: For this criterion-based validity study, both MIMU systems incorporated comparable sensor specifications and employed Kalman filter sensor fusion algorithms. The MIMU based angles were compared with angles derived from concurrently captured three-dimensional retro-reflective data for 10 fast-medium bowlers. Statistical parametric mapping and root mean squared differences (RMSD) were computed for both MIMU systems.

RESULTS: One-dimensional statistical parametric mapping showed no significant differences for angles from both MIMU systems when compared with retro-reflective based angle outputs. The MIMU systems produced ROM RMSDs between 1.4 ± 1.0° and 2.6 ± 1.5°. One system displayed RMSDs between 4.6 ± 1.4° and 7.4 ± 1.9° during bowling, indicating functionally relevant differences to retro-reflective derived angles. There were some small but statistically significant differences in RMSDs between the MIMU systems.

SIGNIFICANCE: MIMU-based angle accuracy is poorer during high-speed, multi-planar movement than uni-planar tasks. Comparable MIMU systems can produce varying measurements during ROM and bowling tasks. It is likely that varying sample rates and sensor fusion algorithm parameters contributed to the differences.

PMID:34844151 | DOI:10.1016/j.gaitpost.2021.11.012

Epilepsy Res. 2021 Nov 19;178:106814. doi: 10.1016/j.eplepsyres.2021.106814. Online ahead of print.

ABSTRACT

Despite the best possible medication and treatment protocols, one-third of epilepsy patients have drug resistance which is associated with an elevated risk of mortality and debilitating psychological consequences. P-glycogen encoded by ABCB1 is major drug transporter for a wide variety of AED. To evaluate the complex haplotypic association, genetic and allelic frequency distribution of rs1128503, rs1045642, and rs2032582 polymorphisms of ABCB1 gene with drug resistance in Pakistani pediatric epilepsy patients, we performed this study. A total of 337 individuals including 100 healthy control, 110 drug-resistant patients, and 127 drug-responsive patients were enrolled and genotyped for three polymorphisms. PCR and direct sequencing of DNA were done for genotyping. All the studied SNPs showed a statistically significant association with drug-resistant epilepsy at p < 0.01. In addition, we identified a novel variant at c 0.2678C > A (SCV001712095) position. The haplotype analysis indicated strong linkage disequilibrium between three SNPs. The in-silico analysis indicated that rs2032582 polymorphism at c 0.2677T > A is benign while c 0.2677T > G and c 0.2678C > A are possibly damaging. Our findings showed that pharmacogenetic variants play a key role in disease. Our findings shed light on the pharmacogenomic association of ABCB1 with epilepsy which might facilitate study on pharmacokinetics concerning ethnology.

PMID:34844091 | DOI:10.1016/j.eplepsyres.2021.106814

Prev Vet Med. 2021 Nov 3;198:105532. doi: 10.1016/j.prevetmed.2021.105532. Online ahead of print.

ABSTRACT

In the Qinghai-Tibet Plateau of China, the yak is an animal of particular economic interest, which provides protein and income for herders in daily life. Brucellosis is a bacterial disease that can infect humans and animals, including yaks. It can damage the yak reproductive system, causing miscarriage and orchitis. At the same time, brucellosis threatens the health of herders. We performed this meta-analysis using R software to explore the combined prevalence and risk factors of brucellosis in yak in China. Variability was assessed by the I² statistic and Cochran Q statistic. We identified 52 publications of related research from four databases (Wanfang Data, VIP Chinese Journal Database, China National Knowledge Infrastructure, and of PubMed). The pooled prevalence of yak brucellosis was 8.39 %. Prevalence was highest in Southwestern China (11.1 %). The point estimate of brucellosis in yak from 2012 to 2016 was the highest (11.47 %). The point estimate of age ≤ 12 months (1.44 %) was lower than that of age > 12 months (15.6 %). This study shows that yak brucellosis is serious, and its incidence is higher than before 2012. We recommend carrying out large-scale yak brucellosis investigations in Western China and conducting comprehensive testing planning. The detection of brucellosis in adult animals should be strengthened to reduce the economic loss caused by brucellosis to herders and to improve public health.

PMID:34844124 | DOI:10.1016/j.prevetmed.2021.105532

J Surg Res. 2021 Nov 26;271:67-72. doi: 10.1016/j.jss.2021.10.004. Online ahead of print.

ABSTRACT

PURPOSE: Surgical management of pediatric ovarian torsion includes total oophorectomy (TO) or ovarian preservation surgery (OPS). This study sought to identify factors contributing to surgical management and readmission outcomes for ovarian torsion.

METHODS: The Nationwide Readmission Database from 2010-2014 was used to identify patients < 18 years admitted with ovarian torsion. Patient factors, hospital characteristics, and readmission outcomes were compared by TO and OPS. Standard statistical analysis was performed and results were weighted for national estimates.

RESULTS: There were 6028 patients (age 13 ± 4 years) identified with ovarian torsion who underwent either TO (50%) or OPS (50%). Patients had secondary pathology of ovarian cyst (41%), benign mass (19%), and malignant mass (0.4%). OPS was more common in teaching hospitals (84% vs. 74% TO, P<0.001), patients < 13 years of age (41% vs. 37% TO, P = 0.001), and those from high-income households (51% vs. 41% TO, P<0.001). The overall readmission rate was 4%, with no difference between surgical approach (4.3% OPS vs. 4.4% TO, P = 0.882). Of those readmitted (n = 265), readmission diagnoses were cyst (10%), malignant mass (9%), benign mass (7%), and torsion (5%). The overall rate of recurrent torsion was 0.2%, with no difference between OPS and TO (< 0.3% vs. < 0.2%, P = 0.282).

CONCLUSION: Half of pediatric patients are undergoing TO for ovarian torsion in the U.S. and disparities exist with the utilization of OPS. There is no difference in rate of readmission or recurrent torsion between surgical approaches, and the overall rate of retorsion is lower than previously reported.

PMID:34844056 | DOI:10.1016/j.jss.2021.10.004

Addict Behav. 2021 Nov 26;126:107193. doi: 10.1016/j.addbeh.2021.107193. Online ahead of print.

ABSTRACT

Two systematic reviews have been conducted to summarize the literature on Internet Gaming Disorder (IGD) and personality. However, the data was not synthesized statistically, imposing a limit to their conclusions. The current study aimed to extend on the two reviews by conducting a series of five meta-analyses, one for each of the Big Five personality factors, to examine their relationships with IGD. A comprehensive search was conducted on the databases PsycArticles, PsycInfo, and Web of Science from inception to 29 July 2021. The data was analyzed using Meta-Essentials and the random effects model was used to obtain the pooled estimate of the effect size. A total of 12 articles were included (n = 145 to 3389). IGD was not significantly correlated with openness to experience (r = -0.05). However, IGD was negatively correlated with conscientiousness (r = -0.29), extraversion (r = -0.15), and agreeableness (r = -0.17), and positively correlated with neuroticism (r = 0.20). Age moderated the relationships between IGD and openness to experience and conscientiousness. The results were broadly consistent with the DSM-5 IGD criteria and the Big Five personality framework. Future research directions might include examining age as moderator variables, and using appropriate instruments based on the DSM-5 IGD criteria.

PMID:34844064 | DOI:10.1016/j.addbeh.2021.107193

Oral Oncol. 2021 Nov 26;124:105634. doi: 10.1016/j.oraloncology.2021.105634. Online ahead of print.

ABSTRACT

BACKGROUND: Taxane-based checkpoint inhibitor combination therapy might improve the outcome in recurrent/metastatic (R/M) head and neck cancer (HNSCC) patients. Thus, we investigated the efficacy and safety of docetaxel (DTX) plus pembrolizumab (P) in a prospective phase I/II trial.

METHODS: Platinum-resistant R/M HNSCC patients received DTX 75 mg/m^² plus P 200 mg for up to six cycles followed by P maintenance therapy. The primary endpoint was overall response rate (ORR) and safety. Secondary endpoints comprised disease control rate (DCR), overall survival (OS) and progression free survival (PFS).

RESULTS: Twenty-two patients were enrolled. Nine patients (40.9%) had a primary tumor in the oropharynx, 8 (36.4%) in the oral cavity, 3 (13.6%) in the hypopharynx and 2 (9.1%) in the larynx. The ORR was 22.7% (95% CI 10.1%-43.4%) and one (4.5%) complete response was achieved. The DCR was 54.6% (95% 34.7%-73.1%). The median PFS was 5.8 months (95% CI 2.7-11.6) and the median OS 21.3 months (95% CI 6.3-31.1). The 1-year PFS and OS rates were 27.3% and 68.2%, respectively. While the most frequent adverse event (AE) was myelosuppression, which was reported in all 22 patients, 3 (13.6%) patients experienced grade 3 febrile neutropenia. The most common immune-related AEs were grade skin rash (40.9%) and hypothyroidism (40.9%). One patient (4.5%) experienced grade 5 immune thrombocytopenia.

CONCLUSION: DXT in combination with P shows promising activity accompanied with a manageable side effect profile in pre-treated R/M HNSCC patients.

PMID:34844042 | DOI:10.1016/j.oraloncology.2021.105634