Category: Statistics

Indian Pediatr. 2022 Nov 15;59(11):863-866.

ABSTRACT

OBJECTIVE: The study was conducted to evaluate the ocular toxicity of ethambutol given in both intensive and continuation phases of treatment in children with drug-sensitive tuberculosis.

METHODS: A prospective study of 94 eyes from 47 patients receiving an ethambutol-containing regimen was conducted between 1 December, 2018 and 31 August, 2020. Visual acuity, visual field, visual evoked response (VER), contrast sensitivity, colour perception, and retinal nerve fiber layer (RNFL) thickness [using optical coherence tomography (OCT)] were tested for each patient before, during, and after the treatment.

RESULTS: On follow-up, visual acuity, color vision, contrast sensitivity, fundus, and visual fields were not affected in any of the patients. There was no statistically significant increase in the mean latency of the P(100) wave at any point in time. On OCT, no significant loss of mean RNFL thickness was detected.

CONCLUSIONS: Ethambutol is safe to use up to a dose of 20 mg/kg/day throughout the entire course of anti-tubercular therapy in children with drug-sensitive tuberculosis.

PMID:36370014

Res Synth Methods. 2022 Nov 12. doi: 10.1002/jrsm.1610. Online ahead of print.

ABSTRACT

An overview of reviews aims to collect, assess, and synthesize evidence from multiple systematic reviews (SRs) on a specific topic using rigorous and reproducible methods. An important methodological challenge in conducting an overview of reviews is the management of overlapping data due to the inclusion of the same primary studies in SRs. We present a free, open-source R package called ccaR (https://github.com/thdiakon/ccaR) that provides easy-to-use functions for assessing the degree of overlap of primary studies in an overview of reviews with the use of the corrected cover area (CCA) index. A worked example with and without consideration of chronological structural missingness is outlined, illustrating the steps involved in, calculating the CCA index and creating a publication-ready heatmap. We expect ccaR to be useful for overview authors, methodologists, and reviewers who are familiar with the basics of R and contribute to the discussion on different methodological approaches for implementing the CCA index. Future research and applications could further investigate the functionality or potential limitations of our package and other potential uses. This article is protected by copyright. All rights reserved.

PMID:36369993 | DOI:10.1002/jrsm.1610

Vet Q. 2022 Nov 12:1-18. doi: 10.1080/01652176.2022.2145619. Online ahead of print.

ABSTRACT

BACKGROUND: The complex etiopathology of retained placenta (RP) and hazards associated with it has made it crucial for researchers and clinical veterinarians to study pathogenesis, early-warning diagnosis, and treatment.

OBJECTIVES: This study aimed to screen the potential prognostic markers of RP in dairy cows using plasma metabolomics coupled with clinical laboratory indicators.

METHODS: Blood samples were collected from 260 dairy cows at 21, 14, 7, and 0 days before parturition and 7, 14, and 21 days after parturition. Consequently, 10 healthy cows and 10 cows with RP with similar parity, body condition score, and age were included in the study. The changes in clinical laboratory indicators of the enrolled cows from 21 before parturition to 21 days after parturition were assessed. After initial overview of the multivariate statistical data using PCA analysis, the data were subjected to orthogonal partial least-squares discriminant analysis.

RESULTS: Compared with cows with RP at 7 days before parturition, the levels of endothelin and 6-keto-prostaglandin F1α were increased in healthy cows while the level of estradiol and progesterone decreased. Adenine dinucleotide phosphate, hypoxanthine, guanine dinucleotide phosphate, inosine monophosphate, and L-arginine were revealed as potential prognostic markers of cows with RP at 7 days before parturition involved in the regulation of taste transduction, purine and glutathione metabolism, and autophagy.

CONCLUSIONS: The best period for the early-warning diagnosis of RP in dairy cows is 7 days before parturition, and purine metabolism and autophagy may play a vital role in the occurrence and development of RP in dairy cows.

PMID:36369933 | DOI:10.1080/01652176.2022.2145619

Hum Fertil (Camb). 2022 Nov 12:1-15. doi: 10.1080/14647273.2022.2137859. Online ahead of print.

ABSTRACT

Fertility rates in Nigeria are declining at such a modest rate, that if more proactive measures are not employed to reduce fertility, the nation may double its population before long. We empirically examined fertility behaviour as derivatives of specific subgroup social norms, and the variations in the factors responsible for different fertility behaviours, using the 2018 Nigeria Demographic and Health Survey. Descriptive bivariate, and multinomial logistic regression analyses were used to predict the contribution of demographic and sociocultural factors contributing to the fertility level, and findings were reported as odds ratios. Results revealed that age, religion and level of education are the most significant predictors of fertility level, with remarkable differences in birth rate across subgroups, whereas North-West Nigeria had the highest fertility level. Furthermore, marriage had a significantly negative effect on high fertility among North-Western women, whereas higher education significantly increased high fertility among North-Eastern women. In conclusion, subgroup social norms fertility behaviour is responsible for the persistent fertility differential outcome in Nigeria. Thus, the paper strongly advocates the need to intensify community-led, norm-based solution and not a universal approach in addressing fertility control in Nigeria.

PMID:36369930 | DOI:10.1080/14647273.2022.2137859

AIDS Care. 2022 Nov 12:1-8. doi: 10.1080/09540121.2022.2141186. Online ahead of print.

ABSTRACT

In the United States, people living with HIV (PLWH) in rural areas fare worse along the HIV care continuum than their urban counterparts; this may be due in part to limited geographic access to care. We estimated drive time to care for PLWH, focusing on urban-rural differences. Adult Medicaid enrollees living with HIV and their usual care clinicians were identified using administrative claims data from 14 states (Medicaid Analytic eXtract, 2009-2012). We used geographic network analysis to calculate one-way drive time from the enrollee’s ZIP code tabulation area centroid to their clinician’s practice address, then examined urban-rural differences using bivariate statistics. Additional analyses included altering the definition of rurality; examining subsamples based on the state of residence, services received, and clinician specialty; and adjusting for individual and county characteristics. Across n = 49,596 PLWH, median drive time to care was 12.8 min (interquartile range 26.3). Median drive time for rural enrollees (43.6 (82.0)) was nearly four times longer than for urban enrollees (11.9 (20.6) minutes, p < 0.0001), and drive times exceeded one hour for 38% of rural enrollees (versus 12% of urban, p < 0.0001). Urban-rural disparities remained in all additional analyses. Sustained efforts to circumvent limited geographic access to care are critical for rural areas.

PMID:36369925 | DOI:10.1080/09540121.2022.2141186

Cancer Sci. 2022 Nov 12. doi: 10.1111/cas.15651. Online ahead of print.

ABSTRACT

Patients with advanced cancer undergo comprehensive genomic profiling only after treatment options have been exhausted in Japan. Patients with a very poor prognosis were not able to undergo profiling tests, resulting in a selection bias called length bias, which makes accurate survival analysis impossible. The actual impact of length bias on the overall survival of patients who have undergone profiling tests is unclear, yet appropriate methods for adjusting for length bias have not been developed. To assess the length bias in overall survival, we established a simulation-based model for length bias adjustment. This study utilized clinicogenomic data of 8813 patients with advanced cancer who underwent profiling tests at hospitals throughout Japan between June 2019 and April 2022. Length bias was estimated by conditional Kendall’s τ statistics and was significantly positive for 13 of the 15 cancer subtypes, suggesting a worse prognosis for patients who underwent profiling tests in early timing. The median overall survival time in colorectal, breast, and pancreatic cancer from the initial survival-prolonging chemotherapy with adjustment for length bias was 937 (886-991), 1225 (1152-1368), and 585 (553-617) days, respectively (median; 95% credible interval). Adjusting for length bias made it possible to analyze the prognostic relevance of oncogenic mutations and treatments. In total, 12 tumor-specific oncogenic mutations correlating with poor survival were detected after adjustment. There was no difference in survival between FOLFIRINOX or Gemcitabine with nab-paclitaxel-treated groups as first-line chemotherapy for pancreatic cancer. Adjusting for length bias is an essential part of utilizing real-world clinicogenomic data.

PMID:36369895 | DOI:10.1111/cas.15651

J Obstet Gynaecol. 2022 Nov 11:1-7. doi: 10.1080/01443615.2022.2141612. Online ahead of print.

ABSTRACT

Preeclampsia (PE), affecting 5-8% of pregnancies, is a common pregnancy disease that has harmful effects on mother and foetus. It has been found that the STOX1 (Storkhead Box 1), which is a transcription factor, carries variants associated with PE. Previous studies showed that, there was a strong relationship between PE and STOX1 variants. Therefore, we hypothesised that variants in the promoter region of the gene may be related to the onset of PE. The aim of this study is to investigate the contribution of STOX1 gene promoter region variants to PE. The blood samples taken from 118 PE patients and 96 healthy pregnant women were analysed by Sanger sequencing method. Sequence analysis results showed that, there is a-922 T > C polymorphism (rs884181) in the promoter region of the STOX1 gene. This polymorphism was found to be statistically significant in individuals with early onset PE (p = 0.02) and in PE (p = 0.014) compared to the control group.IMPACT STATEMENTWhat is already known on this subject? As a result of whole-exon studies on the STOX1 gene, polymorphisms were found to disrupt the structure/expression/function of the gene and strengthen its relationship with PE and HELLP syndrome. A previous study by our team found an association between Y153H, the most common polymorphism of STOX1, and early onset PE.What do the results of this study add? In our study, it was aimed to investigate the effect of genetic modifications in STOX1 gene promoter region on PE through the maternal genotype. Because any change in the promoter region affects the expression level of the gene. Also, for the first time, sequence analysis of the promoter region of STOX1 is investigated in PE. The variations in STOX1 appear to be important in PE especially in Early Onset PE.What are the implications of these findings for clinical practice and/or further research? Although PE is a disease that occurs with pregnancy and shows its effects most during this period, women and children with a history of PE are more prone to various disorders, especially cardiovascular diseases in the following years. Therefore, understanding the pathogenesis of the disease is important for both prevention and treatment process. Variations on STOX1 appear to be important in terms of disease risk.

PMID:36369889 | DOI:10.1080/01443615.2022.2141612

Cancer Sci. 2022 Nov 11. doi: 10.1111/cas.15646. Online ahead of print.

ABSTRACT

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) gefitinib and erlotinib were approved for metastatic or relapsed non-small cell lung cancer (NSCLC) in Japan in 2002 and 2007, respectively. EGFR mutation testing was also approved in 2007. Although clinical trials showed efficacy in NSCLC patients harboring activating EGFR mutations, these effects have rarely been reported in real-world practice. We evaluated changes in survival in NSCLC patients following introduction of these agents and EGFR mutation testing by extracting patients diagnosed with NSCLC from 1993 through 2011 from six prefectural population-based cancer registries in Japan. Relative survival (RS) was calculated by sex, histological subtype, and cancer stage. We conducted interrupted time series analysis to assess survival changes following introduction of EGFR-TKIs and EGFR mutation testing. 120,068 patients with NSCLC were analyzed. One- and 3-year RS gradually increased in overall NSCLC for men and women. For adenocarcinoma, among men, slopes of 1- and 3-year RS increased steeply in patients diagnosed from 2007 through 2011; among women, significant level increases were seen in 1-year RS in patients diagnosed in 2002 (4.55% [95% confidence interval: 1.76-7.33]) and 2007 (3.40% [95% CI: 1.27-5.52]). These significant level increases were particularly obvious in women with adenocarcinoma at an advanced stage. Our results suggest that recent improvements in survival in men and women with adenocarcinoma are due at least partly to introduction of EGFR-TKIs into real-world practice, and to prescription based on appropriate patient selection following introduction of EGFR mutation testing into real-world practice in Japan.

PMID:36369880 | DOI:10.1111/cas.15646

Clin Transl Sci. 2022 Nov 11. doi: 10.1111/cts.13454. Online ahead of print.

ABSTRACT

In prior clinical studies, levocetirizine (LEVO) has demonstrated no effect on ventricular repolarization (QTc intervals), therefore it is a relevant negative control to assess in nonclinical assays to define low proarrhythmic risk. LEVO was tested in beagle dog and cynomolgus monkey (NHP) telemetry models to understand the nonclinical-clinical translation of this negative control. One oral dose of vehicle, LEVO (10 mg/kg/species) or moxifloxacin (MOXI: 30 mg/kg/dog; 80 mg/kg/NHP) was administered to instrumented animals (N=8/species) using a cross-over dosing design; MOXI was the in-study positive control. Corrected QT values (QTcI) were calculated using an individual animal correction factor. Blood samples were taken for drug exposure during telemetry and for pharmacokinetic (PK) analysis (same animals; different day) for exposure-response (C-QTc) modeling. Statistical analysis of QTc-by-timepoint data showed that LEVO treatment was consistent with vehicle, thus no effect on ventricular repolarization was observed over 24 hr in both species. PK analysis indicated that LEVO-Cmax levels in dog (range: 12300-20100 ng/ml) and NHP (range: 4090-12700 ng/ml) were ≥ 4-fold higher than supra-therapeutic drug levels in clinical QTc studies. Slope analysis values in dog (0.00019 ms/ng/mL) and NHP (0.00016 ms/ng/mL) were similar to the human C-QTc relationship and indicated no relationship between QTc intervals and plasma levels of LEVO. MOXI treatment caused QTc interval prolongation (dog: 18 ms; NHP: 29 ms). The characterization of LEVO in these non-rodent telemetry studies further demonstrates the value and impact of the in vivo QTc assay to define a “no QTc effect” profile and support clinical safety assessment.

PMID:36369797 | DOI:10.1111/cts.13454

Acta Otolaryngol. 2022 Nov 11:1-5. doi: 10.1080/00016489.2022.2138968. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with Meniere’s disease (MD) receive treatment to reduce vertigo.

PURPOSE: To explore the fluctuation of vertigo symptoms and the changes in endolymphatic hydrops (EHs) in MD patients during long-term regular medication.

MATERIALS AND METHODS: We enrolled MD patients who had received two magnetic resonance imaging with intravenous contrast agents.

RESULTS: Of the 42 patients in the study, 18(42.9%) had progressive EHs and 3(7.1%) had remission. The change value of the signal intensity ratio (SIR; cochlear perilymph/cerebellum) on the affected side (1.2) was larger than that on the healthy side (0.9), but there was no statistical difference. Among the 30 patients followed up, two patients had complete control of vertigo, two patients had substantial control, and three patients had worse control. The other 23 patients had insignificant control of vertigo symptoms before and after treatment. The correlation between the progression of cochlear and vestibular hydrops and the improvement of vertigo symptoms in MD patients was not significant.

CONCLUSIONS AND SIGNIFICANCE: In treated patients with MD, EHs may progress or relieve over the long course of the disease. But there was no correlation between the development of EHs and changes in vertigo symptoms.

PMID:36369788 | DOI:10.1080/00016489.2022.2138968