Category: Statistics

Neurogastroenterol Motil. 2021 Jun 13:e14185. doi: 10.1111/nmo.14185. Online ahead of print.

ABSTRACT

BACKGROUND: In children with functional dyspepsia (FD), genes involved in pain modulation may be differentially expressed contributing to chronic pain.

METHODS: Children with suspected FD (cases) and known eosinophilic esophagitis (controls) undergoing esophagogastroduodenoscopy completed the Rome IV Diagnostic, Pain Burden and Frequency Severity-Duration questionnaires. Two antral and two duodenal biopsies were collected and relative fold differences in gene expression for 84 pain-associated genes compared to pain-free controls were calculated.

RESULTS: Sixty-six subjects with FD (postprandial distress syndrome = 34, epigastric pain syndrome = 7, both = 25; 65% female; mean age 13.7 years) and 13 pain-free controls (8% female; mean age 12.7) were studied. There were no significant differences in antral and duodenal eosinophilic counts or distribution between the pain and pain-free groups. Pain severity and burden did not differ significantly between FD subgroups and neither measure significantly correlated with eosinophil counts in the antrum or duodenum. Analysis of 47 antral and 39 duodenal biospecimens revealed 5 candidate genes significantly associated with pain burden: antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A (p < 0.01). Subsequent stringent statistical analysis comparing those with significant pain versus no pain revealed antral PTGES3 and duodenal SCN3A were the highest priority candidate genes (p < 0.001).

CONCLUSIONS: Pain burden in pediatric FD may be linked to antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A differential expression. These genes are known to be involved in pain conduction, modulation, and neurotransmission, suggesting potential therapeutic targets for managing pain in FD.

PMID:34120385 | DOI:10.1111/nmo.14185

Alcohol Clin Exp Res. 2021 Jun 12. doi: 10.1111/acer.14649. Online ahead of print.

ABSTRACT

BACKGROUND: Posttraumatic Stress Disorder (PTSD) often co-occurs with increased alcohol consumption (AC) and alcohol use disorder (AUD), however it is unknown whether the same etiologic influences underlying PTSD-AUD comorbidity are those underlying PTSD and AC.

METHODS: This study used large-scale genome wide association study (GWAS) data to test if PTSD and drinks per week [DPW]/AUD are causally related to one another, and if so, if PTSD precedes DPW/AUD and/or vice versa, using Mendelian Randomization on European ancestry GWAS summary statistics from the Psychiatric Genomics Consortia (PGC; PTSD), GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN; DPW), and Million Veteran Program (MVP; AUD).

RESULTS: PTSD exerted a potentially causal effect on AUD (beta= 0.039, se= 0.014, p= 0.005), but not on DPW (beta= 0.002, se= 0.003, p= 0.414). Additionally, neither DPW (beta= 0.019, se= 0.041, p= 0.637) nor AUD (beta= 8.87×10^-4 , se= 0.001, p= 0.441) exerted a causal effect on PTSD.

CONCLUSIONS: These findings are consistent with the self-medication model, in which individuals misuse alcohol as a way of coping with aversive trauma-related symptoms. These findings extend latent and molecular findings of shared and correlated risk between PTSD and alcohol phenotypes. Given the health behaviors associated with these phenotypes, these findings are important in that they suggest groups on which to prioritize prevention efforts. Further, they provide a rationale for future pre-clinical and clinical studies examining the biological mechanisms by which PTSD may impact AUD.

PMID:34120358 | DOI:10.1111/acer.14649

APMIS. 2021 Jun 12. doi: 10.1111/apm.13163. Online ahead of print.

ABSTRACT

BACKGROUND: Research on biofilms is predominantly made in in vitro contexts. However, in vivo observation of biofilms in human chronic infections shows distinct differences compared to in vitro biofilm growth. This could imply the use of an inadequate mental model both in research and healthcare practices. Drawing on knowledge from the cognitive sciences, we hypothesise that the predominance of in vitro research on biofilms is skewed toward a mental model promoting wrong inferences for researchers and healthcare professionals (HCPs) in the in vivo context.

METHODS: To explore the prevalence of such a mental model, we carried out a qualitative image analysis in which biofilm illustrations from a Google image search were coded for typical in vitro or in vivo characteristics. Further, to investigate potential misinformed and unhelpful clinical interventions related to biofilms, we conducted a quantitative questionnaire among HCPs. The questions were designed to test whether knowledge about in vitro biofilms was used in an in vivo context. This questionnaire was analysed through a chi-squared test.

RESULTS: Most biofilm illustrations were consistent with the in vitro model. A statistical analysis of survey responses revealed that HCPs have adequate knowledge about biofilm but often respond incorrectly when asked to apply their knowledge to in vivo contexts.

CONCLUSIONS: The outcome of this research points to a prevalent and consolidated mental model derived from in vitro observations. This model has likely been made dominant by HCPs’ frequent exposure to visual depictions in articles and presentations. The prevalence of the in vitro model sets up the possibility of erroneous claims when the in vitro model is inadequately applied to in vivo contexts. This has potential implications for HCPs working in fields involving biofilm, such as wound care treatment.

PMID:34120370 | DOI:10.1111/apm.13163

J Cancer Educ. 2021 Jun 12. doi: 10.1007/s13187-021-02052-9. Online ahead of print.

ABSTRACT

In 2018, we conducted a survey among a convenience sample of men (n = 205) living in a resource-poor, semi-urban community in South Africa. We aimed to describe what they know about cancer by asking questions about cancer-related knowledge and understanding, and health-seeking behavior. We also investigated possible relationships between the variables. We used a researcher-administered questionnaire to collect the data and descriptive statistics and quantitative content analyses for the analysis. Chi-square was used to examine the relationships. The mean age of the sample was 35 years, and 49.8% (n = 102) attended 11 or 12 years of school. One-third (32.7%; n = 67) indicated they knew what cancer was, but only 28.8% (n = 59) gave an explanation: “very dangerous/a killer/worse than HIV” were the most common explanations. Only 24.9% (n = 51) were able to identify a possible warning sign, and “feeling very sick” was the most common. However, more than 60% considered six of the seven warning signs of cancer as serious. When suspecting they might have cancer, most (77%; n = 159) indicated they would tell the preferred person within 1 week, while 5.9% (n = 12) would tell “nobody.” Although the majority (52.2%; n = 107) felt their partners and families motivated them to seek healthcare when sick, 28.3% (n = 58) needed permission to consult a professional. Educating the community about cancer in a culturally sensitive manner, irrespective of their educational level and perceived knowledge of cancer, could improve knowledge and understanding and lead to seeking healthcare timely.

PMID:34120328 | DOI:10.1007/s13187-021-02052-9

Andrologia. 2021 Jun 12:e14139. doi: 10.1111/and.14139. Online ahead of print.

ABSTRACT

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%-30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.

PMID:34120353 | DOI:10.1111/and.14139

Stat Med. 2021 Jun 13. doi: 10.1002/sim.9094. Online ahead of print.

ABSTRACT

In sequential analysis, hypothesis testing is performed repeatedly in a prospective manner as data accrue over time to quickly arrive at an accurate conclusion or decision. In this tutorial paper, detailed explanations are given for both designing and operating sequential testing. We describe the calculation of exact thresholds for stopping or signaling, statistical power, expected time to signal, and expected sample sizes for sequential analysis with Poisson and binary type data. The calculations are run using the package Sequential, constructed in R language. Real data examples are inspired on clinical trials practice, such as the current efforts to develop treatments to face the COVID-19 pandemic, and the comparison of treatments of osteoporosis. In addition, we mimic the monitoring of adverse events following influenza vaccination and Pediarix vaccination.

PMID:34120357 | DOI:10.1002/sim.9094

Oncol Ther. 2021 Jun 13. doi: 10.1007/s40487-021-00156-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Dacomitinib and gefitinib are irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) indicated for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Pharmacokinetic (PK) studies in healthy volunteers suggested that acid-reducing drugs such as proton pump inhibitors (PPI) decreased dacomitinib and gefitinib exposure by limiting the pH-dependent absorption. This analysis retrospectively evaluates the effect of concomitant PPI use on dacomitinib exposure and on progression-free survival (PFS) and overall survival (OS) in patients treated with dacomitinib 45 mg QD or gefitinib 250 mg QD in a 1:1 randomized phase 3 study (ARCHER 1050).

METHODS: The analysis grouped all patients (n = 452) treated in each arm of the study as non-PPI users, PPI users, or extensive PPI users. PFS and OS data were presented by Kaplan-Meier plots and analyzed using Cox proportional hazards models. Dacomitinib exposure was compared using a linear mixed-effects model.

RESULTS: Results showed that dacomitinib PFS and OS did not differ significantly when comparing PPI users (N = 59) to non-PPI users (N = 152), while extensive PPI users (N = 24) had shorter PFS [hazard ratio (HR): 1.94, p = 0.011] and OS (HR: 1.77, p = 0.027) when compared to non-PPI users. For patients treated with gefitinib, PFS did not differ significantly when comparing PPI users (N = 51) and extensive PPI users (N = 19) to non-PPI users (N = 159); however, both PPI users (HR: 1.65, p = 0.007) and extensive PPI users (HR: 1.70, p = 0.050) had shorter OS when compared to non-PPI users. Further analysis by adjusting potential confounders indicated no statistically significant differences in PFS or OS between any PPI user vs. non-PPI user groups in the dacomitinib and gefitinib arms. PPI use did not appear to affect dacomitinib exposure.

CONCLUSION: In conclusion, PPI use in patients with NSCLC likely has minimal impact on dacomitinib or gefitinib efficacy despite decreased absorption of these drugs observed in PK studies.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01774721.

PMID:34120312 | DOI:10.1007/s40487-021-00156-2

Endocrine. 2021 Jun 12. doi: 10.1007/s12020-021-02775-1. Online ahead of print.

ABSTRACT

PURPOSE: Type III gastric neuroendocrine neoplasms (g-NENs) have historically been regarded as aggressive tumours, hence current guidelines advocate radical surgery with lymph node dissection. Data on the roles of endoscopic or less extensive surgical resections are more limited. The aim of our study is to evaluate the clinicopathological features and long-term outcomes of patients undergoing endoscopic or limited surgical resection for localised grade 1 or 2 type III g-NENs when compared to radical surgery.

METHODS: Retrospective analysis of all patients diagnosed with a localised grade 1 or 2 type III g-NENs across six tertiary NEN centers between 2006 and 2019.

RESULTS: Forty-five patients were diagnosed with a potentially resectable grade 1 or 2 type III g-NEN of whom 36 underwent either endoscopic or surgical resection. No statistically significant differences were found between the three resection groups in terms of patient age, tumour location, grade or size. Only tumour size was found to be significantly associated with poor clinical outcome (p = 0.012) and ROC curve analysis identified tumour size >10 mm as a negative predictor (AUC:0.8030, p = 0.0021). Tumours >10 mm were also more likely to be associated with lymph node metastases on imaging and histology (p = 0.039 and p = 0.026 respectively).

CONCLUSIONS: Localised grade 1 or 2 type III g-NENs had a good prognosis in this series. Tumour size >10 mm was the most significant prognostic factor affecting patient outcome. Endoscopic resection or limited surgical resection is feasible and safe in small type III g-NENs which demonstrate favourable grade 1/2, well differentiated histology.

PMID:34120313 | DOI:10.1007/s12020-021-02775-1

Ambio. 2021 Jun 12. doi: 10.1007/s13280-021-01579-x. Online ahead of print.

ABSTRACT

Nearly three-quarters of global natural rubber production is used to produce tyres, supporting mobility around the globe. The projected increase in mobility could contribute to further expansion of rubber plantations and impact tropical ecosystems. We quantified the use of natural rubber in tyres in the European Union (EU), the corresponding land footprint, and explored drivers of tyre use using country-specific transport statistics and trade registers of rubber goods. Five percent of the world’s natural rubber is consumed in tyres used in the EU, using up to a quarter of the area under rubber plantations in some producing countries. Car use is responsible for 58% of this consumption, due to car-dependent lifestyles that are associated with economic prosperity and spatial planning paradigms. While the EU’s transport policy focuses on reducing dependence on fossil-fuels, cross-cutting policies are needed to address car-dependency and reduce the EU’s land footprint in tropical landscapes without compromising progress towards decarbonisation.

PMID:34120297 | DOI:10.1007/s13280-021-01579-x

Turk J Med Sci. 2021 Jun 13. doi: 10.3906/sag-2101-224. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Cisplatin (CIS) is an effective antineoplastic agent used in the treatment of several cancer types. Peripheral neuropathy is a major dose-limiting side-effect in cisplatin therapy. Cannabinoids may alleviate this painful side effect. This study investigated the analgesic effects of anandamide (AN) on CIS-induced peripheral neuropathy, in vitro effects of AN in CIS neurotoxicity and influence of nitric oxide (NO) in this effect.

MATERIALS AND METHODS: This study is an experimental animal study. Primary DRG cultures were prepared from one day old rats for in vitro investigations. DRG cells were incubated with CIS (100-300 mM), and AN (10, 50, 100 and 500 mikroM) was administered with the submaximal concentration of CIS. Female Sprague Dawley rats were divided into Control, CIS, CIS+AN, CIS+AN+ L-NG-nitro arginine methyl ester (L-NAME). CIS was administered 3 mg/kg ip once weekly for five weeks. AN (1 mg/kg ip) or in combination with 10 mg/kg ip L-NAME was administrated 30 min before CIS injection. Mechanical allodynia, thermal hyperalgesia and tail clip tests were performed. After intracardiac perfusion, sciatic nerves (SN) and dorsal root ganglia (DRG) were isolated and semi-thin sections were stained with toluidine blue and investigated histologically.SPSS21.0 and Sigma STAT 3.5 were used for statistical analysis. One/two way ANOVA, Kruskal Wallis, and Wilcoxon Signed Ranks tests were used. A p-value of 0.05 was accepted as significant.

RESULTS: Cisplatin caused significant mechanical allodynia. AN and AN+L-NAME significantly increased hind paw withdrawal latency in mechanical allodynia test. The degenerated axons significantly increased in cisplatin group, anandamide decreased this effect. The frequency of larger neurons seems to be higher in CIS+AN group.

CONCLUSION: Anandamide may be a therapeutic alternative for the treatment of cisplatin-induced peripheral neuropathy however its central adverse effects must be considered.

PMID:34118805 | DOI:10.3906/sag-2101-224