Tag: statistics

Fam Pract. 2022 Jul 18:cmac077. doi: 10.1093/fampra/cmac077. Online ahead of print.

ABSTRACT

BACKGROUND: Telephone triage is fully integrated in Dutch out-of-hours primary care (OOH-PC). Patients presenting with chest pain are initially assessed according to a standardized protocol (“Netherlands Triage Standard” [NTS]). Nevertheless, little is known about its (diagnostic) performance, nor on the impact of subsequent clinical judgements made by triage assistants and general practitioners (GPs).

OBJECTIVE: To evaluate the performance of the current NTS chest pain protocol.

METHODS: Observational, retrospective cohort study of adult patients with chest pain who contacted a regional OOH-PC facility in the Netherlands, in 2017. The clinical outcome measure involved the occurrence of a “major event,” which is a composite of all-cause mortality and urgent cardiovascular and noncardiovascular conditions, occurring ≤6 weeks of initial contact. We assessed the performance using diagnostic and discriminatory properties.

RESULTS: In total, 1,803 patients were included, median age was 54.0 and 57.5% were female. Major events occurred in 16.2% of patients with complete follow-up, including 99 (6.7%) cases of acute coronary syndrome and 22 (1.5%) fatal events. NTS urgency assessment showed moderate discriminatory abilities for predicting major events (c-statistic 0.66). Overall, NTS performance showed a sensitivity and specificity of 83.0% and 42.4% with a 17.0% underestimated major event rate. Triage assistants’ revisions hardly improved urgency allocation. Further consideration of the clinical course following OOH-PC contact did generate a more pronounced improvement with a sensitivity of 89.4% and specificity of 61.9%.

CONCLUSION: Performance of telephone triage of chest pain appears moderate at best, with acceptable safety yet limited efficiency, even after including further work-up by GPs.

PMID:35849343 | DOI:10.1093/fampra/cmac077

Nucleic Acids Res. 2022 Jul 18:gkac616. doi: 10.1093/nar/gkac616. Online ahead of print.

ABSTRACT

DNA damage response pathways rely extensively on nuclease activity to process DNA intermediates. Exonuclease 1 (EXO1) is a pleiotropic evolutionary conserved DNA exonuclease involved in various DNA repair pathways, replication, antibody diversification, and meiosis. But, whether EXO1 facilitates these DNA metabolic processes through its enzymatic or scaffolding functions remains unclear. Here, we dissect the contribution of EXO1 enzymatic versus scaffolding activity by comparing Exo1DA/DA mice expressing a proven nuclease-dead mutant form of EXO1 to entirely EXO1-deficient Exo1-/- and EXO1 wild type Exo1+/+ mice. We show that Exo1DA/DA and Exo1-/- mice are compromised in canonical DNA repair processing, suggesting that the EXO1 enzymatic role is important for error-free DNA mismatch and double-strand break repair pathways. However, in non-canonical repair pathways, EXO1 appears to have a more nuanced function. Next-generation sequencing of heavy chain V region in B cells showed the mutation spectra of Exo1DA/DA mice to be intermediate between Exo1+/+ and Exo1-/- mice, suggesting that both catalytic and scaffolding roles of EXO1 are important for somatic hypermutation. Similarly, while overall class switch recombination in Exo1DA/DA and Exo1-/- mice was comparably defective, switch junction analysis suggests that EXO1 might fulfill an additional scaffolding function downstream of class switching. In contrast to Exo1-/- mice that are infertile, meiosis progressed normally in Exo1DA/DA and Exo1+/+ cohorts, indicating that a structural but not the nuclease function of EXO1 is critical for meiosis. However, both Exo1DA/DA and Exo1-/- mice displayed similar mortality and cancer predisposition profiles. Taken together, these data demonstrate that EXO1 has both scaffolding and enzymatic functions in distinct DNA repair processes and suggest a more composite and intricate role for EXO1 in DNA metabolic processes and disease.

PMID:35849338 | DOI:10.1093/nar/gkac616

Hum Reprod. 2022 Jul 18:deac161. doi: 10.1093/humrep/deac161. Online ahead of print.

ABSTRACT

In the most recent version of the ‘WHO Laboratory Manual For The Examination And Processing Of Human Semen’, the updated target population used to infer reference values included 3589 fertile subjects, representative of 12 countries and 5 continents, and 10 studies. We have critically evaluated the newly proposed distribution of semen examination results using an approach borrowed from clinical chemistry laboratories and based on the recommendations of the International Federation of Clinical Chemistry for estimation of reference intervals. Surprisingly, most prerequisites to produce common reference intervals through multicentric data were not met. Moreover, when we assessed with the bootstrap method the descriptive reference values obtained from raw data of the 10 individual studies for sperm concentration, sperm number, motility and normal forms, we found that none of the populations was completely correctly described by the reference centiles. We concluded that aggregated data used to build the reference distribution cannot be considered to originate from the same population, and this can result from real differences among individuals or different methodological approaches used in the various studies. Transferability conditions across studies did not seem to have been met. Our findings strengthen the relevance of concerns regarding the use of reference populations in the World Health Organization manual to discriminate between fertile and infertile men.

PMID:35849333 | DOI:10.1093/humrep/deac161

Adv Ther. 2022 Jul 17. doi: 10.1007/s12325-022-02231-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β₂-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD.

METHODS: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV₁), annualized rate of combined moderate and severe exacerbations, St George’s Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible).

RESULTS: The NMA was informed by five trials reporting FEV₁ at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV₁ (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6).

CONCLUSION: The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.

PMID:35849317 | DOI:10.1007/s12325-022-02231-0

Radiol Med. 2022 Jul 18. doi: 10.1007/s11547-022-01524-2. Online ahead of print.

ABSTRACT

BACKGROUND: There is an unmet need for new biomarkers able to predict both the outcomes of up-front therapy and the compliance of elderly patients diagnosed with glioblastoma. For this purpose, temporal muscle thickness is a promising tool to be investigated.

METHODS: Data from 52 glioblastoma patients older than 65 years, treated with post-operative radio or radio-chemotherapy and referred to Pisa University Hospital, were retrieved. The thickness of temporal muscle (TMT) was divided into quartiles and correlated with overall survival (Our primary endpoint). Survival curves were calculated using Kaplan-Meier method, and log-rank test was used to evaluate the differences between curves.

RESULTS: Patients in the lower quartile of TMT, with TMT thinner than 7 mm, have survived longer; both univariate and multivariate analyses showed a statistically significant correlation between TMT and overall survival (P = 0.012 and P = 0.003, respectively).

CONCLUSION: Future prospective and more extensive studies focused on elderly glioblastoma patients are needed to confirm the role of TMT as prognostic value on OS and to help explaining this association.

PMID:35849309 | DOI:10.1007/s11547-022-01524-2

Ann Surg Oncol. 2022 Jul 18. doi: 10.1245/s10434-022-12245-1. Online ahead of print.

NO ABSTRACT

PMID:35849286 | DOI:10.1245/s10434-022-12245-1

Indian J Pediatr. 2022 Jul 18. doi: 10.1007/s12098-022-04289-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether magnesium sulfate and therapeutic hypothermia in combination decreases mortality and/or major neurodevelopmental disability at 1 y of age among term neonates with hypoxic-ischemic encephalopathy.

METHODS: A total of 134 term neonates were randomized to receive intravenous magnesium sulfate at a dose of 250 mg/kg (at 8 mg/kg/min) once daily for 3 d starting within 6 h after birth along with therapeutic hypothermia in the intervention group and therapeutic hypothermia alone in the comparator group. The primary outcome was the composite outcome of mortality and/or major neurodevelopmental disability (Developmental Assessment Scale for Indian Infants score < 70) at 1 y of age.

RESULTS: A total of 115 infants were included in the primary analysis. The composite primary outcome occurred in 14 (24%) infants in the intervention group and 19 (33%) infants in the comparator group, and the difference was not statistically significant (p = 0.30; relative risk 0.72; 95% confidence interval 0.40-1.30). The secondary outcomes including neonatal mortality, major neurodevelopmental disability at 1 y of age, neurological status at discharge, level of oxidative stress markers, and adverse effects including hypotension and respiratory depression requiring support were also comparable between the groups.

CONCLUSIONS: The combination of magnesium sulfate and therapeutic hypothermia did not improve the composite outcome of neonatal mortality and/or major neurodevelopmental disability at 1 y of age.

TRAIL REGISTRATION: Clinical Trials Registry of India (CTRI/2018/06/014594), prospectively registered.

PMID:35849276 | DOI:10.1007/s12098-022-04289-8

Neurochem Res. 2022 Jul 18. doi: 10.1007/s11064-022-03679-w. Online ahead of print.

ABSTRACT

Glioblastoma (GBM) is one of the most common malignancies among primary brain tumors in adults, featuring a poor prognosis and a high recurrence rate. Eukaryotic elongation factor 2 kinase (eEF2K) is a calcium/calmodulin-dependent protein kinase that is involved in promoting tumor cell proliferation, migration, invasion, and survival. However, its expression level in GBM, its prognostic impact and correlation with immune infiltration are not yet known. In this study, we used The Cancer Genome Atlas (TCGA) database to explore the potential molecular mechanisms of eEF2K in GBM development and clinical prognosis in terms of gene expression, survival status, immune infiltration, and associated cellular pathways. We found that eEF2K expression levels were elevated in GBM, but eEF2K was not associated with the prognosis of GBM patients; eEF2K expression in GBM was associated with multiple immune cell infiltrations. These results show a statistical correlation between eEF2K expression and the development of GBM and immune cell infiltration, which helps us to understand the roles of eEF2K in GBM from different perspectives.

PMID:35849271 | DOI:10.1007/s11064-022-03679-w

Insights Imaging. 2022 Jul 18;13(1):120. doi: 10.1186/s13244-022-01258-9.

ABSTRACT

BACKGROUND: Online summative assessment has emerged during the COVID-19 pandemic as an alternative to traditional examinations, bringing opportunities and challenges. The study aims to evaluate the feasibility and effectiveness of online structured oral examination (SOE) in radiology clerkships. The study identifies measures taken to successfully implement online SOE and minimize chances of cheating. It also discusses the challenges encountered and how they were addressed.

METHODS: SOE percent scores of fourth-year medical students from two institutions were correlated with students’ grade point average (GPA). The scores were compared among different institutions, students’ genders, students’ batches, examination versions, and examiners with different experience levels. Students’ perceived satisfaction and concerns were captured using anonymous self-administered questionnaire. Technical problems and success rate of SOE implementation were recorded. Results were analyzed using descriptive and inferential statistics.

RESULTS: A total of 79 students participated in the study, out of which 81.0% (n = 64) responded to the survey. SOE scores showed poor positive correlation with the students’ GPAs (r = 0.22, and p = .09). Scores showed no significant difference between the two institutions or genders. Scores were also not significantly different between students who were examined by junior or senior examiners. All but one version of examination showed no significant difference in students’ scores. No significant difference was observed in students’ scores between each two subsequent batches who were exposed to the same examination version.

CONCLUSION: Online summative SOE is a feasible alternative whenever face-to-face SOE could not be implemented provided that appropriate measures are taken to ensure its successful execution.

PMID:35849259 | DOI:10.1186/s13244-022-01258-9

Eur Arch Otorhinolaryngol. 2022 Jul 18. doi: 10.1007/s00405-022-07544-y. Online ahead of print.

ABSTRACT

OBJECTIVES: To comprehensively analyse the disease presentation and mortality of COVID-associated rhino-orbito-cerebral mucormycosis.

METHODS: A retrospective analysis of the demographics, clinical and radiographic findings was performed. A binary logistic regression analysis was performed to examine the survival of patients with mucormycosis from hypothesised predictors.

RESULTS: A total of 202 patients were included in this study. Statistical significance was demonstrated in the predilection to the male gender, recent history of SARS-COV-2, history of use of corticosteroid and hyperglycemia in this cohort of CAM. The mortality rate was 18.31%. Advanced age, raised HbA1c and intra-orbital extension were found to be predictors adversely affecting survival.

CONCLUSION: Early diagnosis, aggressive surgical therapy, early and appropriate medical therapy can help improve outcomes.

LEVEL OF EVIDENCE: Level 4.

PMID:35849188 | DOI:10.1007/s00405-022-07544-y