Category: Statistics

Fam Pract. 2021 Dec 6:cmab155. doi: 10.1093/fampra/cmab155. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: New Zealand (NZ) has high rates of colorectal cancer (CRC) but low rates of early detection. The majority of CRC is diagnosed through general practice, where lengthy diagnostic intervals are common. We investigated factors contributing to diagnostic delay in a cohort of patients newly diagnosed with CRC.

METHODS: Patients were recruited from the Midland region and interviewed about their diagnostic experience using a questionnaire based on a modified Model of Pathways to Treatment framework and SYMPTOM questionnaire. Descriptive statistics were used to describe the population characteristics. Chi-square analysis and logistic regression were used to analyse factors influencing diagnostic intervals.

RESULTS: Data from 176 patients were analysed, of which 65 (36.9%) experienced a general practitioner (GP) diagnostic interval of >120 days and 96 (54.5%) experienced a total diagnostic interval (TDI) > 120 days. Patients reporting rectal bleeding were less likely to experience a long TDI (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.14-0.78) and appraisal/help-seeking interval (OR, 0.19, 95% CI: 0.06-0.59). Patients <60 were more likely to report a longer appraisal/help-seeking interval (OR, 3.32, 95% CI: 1.17-9.46). Female (OR, 2.19, 95% CI: 1.08-4.44) and Māori patients (OR, 3.18, 95% CI: 1.04-9.78) were more likely to experience a long GP diagnostic interval.

CONCLUSION: NZ patients with CRC can experience long diagnostic intervals, attributed to patient and health system factors. Young patients, Māori, females, and patients experiencing change of bowel habit may be at particular risk. We need to increase symptom awareness of CRC for patients and GPs. Concentrated efforts are needed to ensure equity for Māori in access to screening, diagnostics, and treatment.

PMID:34871389 | DOI:10.1093/fampra/cmab155

Eur J Prev Cardiol. 2021 Dec 6:zwab208. doi: 10.1093/eurjpc/zwab208. Online ahead of print.

ABSTRACT

AIMS: As the potential impact of statins on cognitive decline and dementia is still debated, we conducted a meta-analysis of observational studies to examine the effect of statin use on the risk of Alzheimer’s disease (AD) and dementia.

METHODS AND RESULTS: PubMed, Cochrane, and EMBASE were searched since inception to January 2021. Inclusion criteria were: (i) cohort or case-control studies; (ii) statin users compared to non-users; and (iii) AD and/or dementia risk as outcome. Estimates from original studies were pooled using restricted maximum-likelihood random-effect model. Measure of effects were reported as odds ratio (OR) and 95% confidence intervals (CIs). In the pooled analyses, statins were associated with a decreased risk of dementia [36 studies, OR 0.80 (CI 0.75-0.86)] and of AD [21 studies, OR 0.68 (CI 0.56-0.81)]. In the stratified analysis by sex, no difference was observed in the risk reduction of dementia between men [OR 0.86 (CI 0.81-0.92)] and women [OR 0.86 (CI 0.81-0.92)]. Similar risks were observed for lipophilic and hydrophilic statins for both dementia and AD, while high-potency statins showed a 20% reduction of dementia risk compared with a 16% risk reduction associated with low-potency statins, suggesting a greater efficacy of the former, although a borderline statistical significance (P = 0.05) for the heterogeneity between estimates.

CONCLUSION: These results confirm the absence of a neurocognitive risk associated with statin treatment and suggest a potential favourable role of statins. Randomized clinical trials with an ad hoc design are needed to explore this potential neuroprotective effect.

PMID:34871380 | DOI:10.1093/eurjpc/zwab208

Am J Clin Pathol. 2021 Dec 6:aqab196. doi: 10.1093/ajcp/aqab196. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to evaluate the effects of hemoglobin (Hb) variants prevalent in China on HbA1c measurements and to identify them during HbA1c measurements.

METHODS: We evaluated a cation-exchange high-performance liquid chromatography (HPLC) method (Bio-Rad D-100), a capillary electrophoresis (CE) method (Capillarys 3 TERA), an immunoassay (Cobas c501), and a boronate affinity method (Premier Hb9210, as a comparative method) for HbA1c measurements in the presence of Hb variants prevalent in China.

RESULTS: The Bio-Rad D-100 and Capillarys 3 TERA gave specific retention times and numeric migration positions for each Hb variant, respectively, showing excellent interindividual reproducibility. All methods showed statistically significant differences (P < .01) for several variants. Clinically significant effects were observed for the Bio-Rad D-100 (Hb New York and Hb J-Bangkok), Capillarys 3 TERA (Hb New York and Hb J-Bangkok), and Cobas c501 (Hb New York). Among 297 samples with Hb variants, there were 75 (25.3%) unacceptable results for Bio-Rad D-100, 28 (9.4%) for Capillarys 3 TERA, and 19 (6.4%) for Cobas c501 compared with the results from Premier Hb9210.

CONCLUSIONS: Some Hb variants prevalent in China affect HbA1c measurements. The HPLC retention time and CE migration position can aid in the presumptive identification of Hb variants.

PMID:34871348 | DOI:10.1093/ajcp/aqab196

Arch Pathol Lab Med. 2021 Dec 6. doi: 10.5858/arpa.2021-0175-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: Despite continued surveillance and intravesical therapy, a significant subset of patients with lamina propria-invasive bladder cancer (T1) will progress to muscle-invasive disease or metastases.

OBJECTIVE.—: To analyze the value of pathologic subcategorization of T1 disease in predicting progression.

DESIGN.—: Six substaging methods were applied to a retrospective cohort of 73 patients, with pT1 urothelial carcinoma diagnosed on biopsy/transurethral resection. Additionally, the immunohistochemistry for GATA3 and cytokeratin 5/6 (CK5/6) was performed to study the prognostic value of stratifying T1 cancers into luminal or basal phenotypes.

RESULTS.—: On follow-up (mean, 46 months), 21 (29%) experienced at least 1 recurrence without progression, and 16 (22%) had progression to muscle-invasive disease and/or distant metastasis. No differences were noted between progressors and nonprogressors with regard to sex, age, treatment status, medical history, tumor grade, and presence of carcinoma in situ. Substaging using depth of invasion (cutoff ≥1.4 mm), largest invasive focus (≥3.6 mm), aggregate linear length of invasion (≥8.9 mm), and number of invasive foci (≥3 foci) correlated significantly with progression and reduced progression-free survival, whereas invasion into muscularis mucosa or vascular plexus, or focal versus extensive invasion (focal when ≤2 foci, each <1 mm) failed. Patients with luminal tumors had higher incidence of progression than those with nonluminal tumors (27% versus 11%), although the difference was statistically insignificant (P = .14).

CONCLUSIONS.—: Substaging of T1 bladder cancers should be attempted in pathology reports. Quantifying the number of invasive foci (≥3) and/or measuring the largest contiguous focus of invasive carcinoma (≥3.6 mm) are practical tools for prognostic substaging of T1 cancers.

PMID:34871364 | DOI:10.5858/arpa.2021-0175-OA

PLoS Pathog. 2021 Dec 6;17(12):e1010123. doi: 10.1371/journal.ppat.1010123. Online ahead of print.

ABSTRACT

RSK1, a downstream kinase of the MAPK pathway, has been shown to regulate multiple cellular processes and is essential for lytic replication of a variety of viruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV). Besides phosphorylation, it is not known whether other post-translational modifications play an important role in regulating RSK1 function. We demonstrate that RSK1 undergoes robust SUMOylation during KSHV lytic replication at lysine residues K110, K335, and K421. SUMO modification does not alter RSK1 activation and kinase activity upon KSHV ORF45 co-expression, but affects RSK1 downstream substrate phosphorylation. Compared to wild-type RSK1, the overall phosphorylation level of RxRxxS*/T* motif is significantly declined in RSK1K110/335/421R expressing cells. Specifically, SUMOylation deficient RSK1 cannot efficiently phosphorylate eIF4B. Sequence analysis showed that eIF4B has one SUMO-interacting motif (SIM) between the amino acid position 166 and 170 (166IRVDV170), which mediates the association between eIF4B and RSK1 through SUMO-SIM interaction. These results indicate that SUMOylation regulates the phosphorylation of RSK1 downstream substrates, which is required for efficient KSHV lytic replication.

PMID:34871326 | DOI:10.1371/journal.ppat.1010123

PLoS One. 2021 Dec 6;16(12):e0260791. doi: 10.1371/journal.pone.0260791. eCollection 2021.

ABSTRACT

OBJECTIVES: Women in oral health science face similar societal issues and challenges as those in other STEMM careers, and gender disparities continue to exist as evidenced by fewer women represented as first and last authors in scientific publications. Pre-prints may serve as a conduit to immediately disseminating one’s work, bypassing the arduous peer review process and its associated inherent biases. Therefore, the purpose of this study was to 1] compare the gender of first and last authors in pre-print versus peer reviewed publications, 2] examine the composition of first and last author pairs as stratified by publication type, and 3] examine the correlation between woman authorship and institutional geographic location and publication metrics stratified by publication type.

METHODS: The keyword “oral health” was used to search for publications in BioRxiv and Pubmed in the years 2018 and 2019. Gender of first and last authors were determined, and its frequency was considered as the primary outcome. Additionally, the geographic location of the author’s associated institution and publication metrics measured by Altmetrics score were extracted. Data was descriptively summarized by frequencies and percentages. Chi-square analysis was conducted for categorical variables which included the relationship between gender and publication type as well as gender and region of author’s associated institution. Binomial regression analysis was conducted to analyze the relationship between gender and Altmetrics.

RESULTS: Woman first authors comprised 40.3% of pre-prints and 64.5% of peer reviewed publications [p<0.05]. Woman last authors comprised 31.3% of pre-prints and 61.5% of peer reviewed publications [p<0.05]. When analyzing the relationships between first and last author, the Man-Man pairing represented 47.7% of the pre-print publications and the Woman-Woman pairing comprised a majority of the of the peer review publications at 47.5%. All results were statistically significant with a p-value <0.05. No significant correlation was found between region of institution or Altmetrics and gender of first or last authors [p>0.05].

CONCLUSION: For the first time in oral health science, it was found that women show higher representation as first and last author positions in peer reviewed publications versus pre-prints.

PMID:34871320 | DOI:10.1371/journal.pone.0260791

PLoS Negl Trop Dis. 2021 Dec 6;15(12):e0009974. doi: 10.1371/journal.pntd.0009974. Online ahead of print.

ABSTRACT

BACKGROUND: Left ventricular systolic dysfunction (LVSD) in Chagas disease (ChD) is relatively common and its treatment using low-cost drugs can improve symptoms and reduce mortality. Recently, an artificial intelligence (AI)-enabled ECG algorithm showed excellent accuracy to detect LVSD in a general population, but its accuracy in ChD has not been tested.

OBJECTIVE: To analyze the ability of AI to recognize LVSD in patients with ChD, defined as a left ventricular ejection fraction determined by the Echocardiogram ≤ 40%.

METHODOLOGY/PRINCIPAL FINDINGS: This is a cross-sectional study of ECG obtained from a large cohort of patients with ChD named São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) Study. The digital ECGs of the participants were submitted to the analysis of the trained machine to detect LVSD. The diagnostic performance of the AI-enabled ECG to detect LVSD was tested using an echocardiogram as the gold standard to detect LVSD, defined as an ejection fraction <40%. The model was enriched with NT-proBNP plasma levels, male sex, and QRS ≥ 120ms. Among the 1,304 participants of this study, 67% were women, median age of 60; there were 93 (7.1%) individuals with LVSD. Most patients had major ECG abnormalities (59.5%). The AI algorithm identified LVSD among ChD patients with an odds ratio of 63.3 (95% CI 32.3-128.9), a sensitivity of 73%, a specificity of 83%, an overall accuracy of 83%, and a negative predictive value of 97%; the AUC was 0.839. The model adjusted for the male sex and QRS ≥ 120ms improved the AUC to 0.859. The model adjusted for the male sex and elevated NT-proBNP had a higher accuracy of 0.89 and an AUC of 0.874.

CONCLUSION: The AI analysis of the ECG of Chagas disease patients can be transformed into a powerful tool for the recognition of LVSD.

PMID:34871321 | DOI:10.1371/journal.pntd.0009974

PLoS Comput Biol. 2021 Dec 6;17(12):e1009638. doi: 10.1371/journal.pcbi.1009638. Online ahead of print.

ABSTRACT

This work studies the effects of the two rounds of Whole Genome Duplication (WGD) at the origin of the vertebrate lineage on the architecture of the human gene regulatory networks. We integrate information on transcriptional regulation, miRNA regulation, and protein-protein interactions to comparatively analyse the role of WGD and Small Scale Duplications (SSD) in the structural properties of the resulting multilayer network. We show that complex network motifs, such as combinations of feed-forward loops and bifan arrays, deriving from WGD events are specifically enriched in the network. Pairs of WGD-derived proteins display a strong tendency to interact both with each other and with common partners and WGD-derived transcription factors play a prominent role in the retention of a strong regulatory redundancy. Combinatorial regulation and synergy between different regulatory layers are in general enhanced by duplication events, but the two types of duplications contribute in different ways. Overall, our findings suggest that the two WGD events played a substantial role in increasing the multi-layer complexity of the vertebrate regulatory network by enhancing its combinatorial organization, with potential consequences on its overall robustness and ability to perform high-level functions like signal integration and noise control. Lastly, we discuss in detail the RAR/RXR pathway as an illustrative example of the evolutionary impact of WGD duplications in human.

PMID:34871317 | DOI:10.1371/journal.pcbi.1009638

PLoS One. 2021 Dec 6;16(12):e0260972. doi: 10.1371/journal.pone.0260972. eCollection 2021.

ABSTRACT

BACKGROUND: Unmet family planning is one of the common causes for low contraceptive prevalence rates in developing countries, including Ethiopia. Rapid urbanization had profound effect on population health, however, little is known about the unmet need of family planning in settings where there was increased industrializations and internal migrations in Ethiopia. This study aims to determine the unmet need for family planning services among currently married women and identify factors associated with it in Bishoftu town, Eastern Ethiopia.

METHODS: Community-based cross-sectional study was conducted from 1st January to 28th February, 2021 among 847 randomly sampled currently married women of the reproductive age group. Data were collected using semi structured interviewer administered questionnaire. Multivariate logistic regression was used to identify factors associated with the outcome variable and a 95% confidence interval was used to declare the presence of statistical significance associations.

RESULTS: Eight hundred twenty-eight women were participated in the study. The prevalence of unmet need for family planning among currently married women was 26% [95% CI: 23,29]. Maternal age [AOR, 3.00, 95% CI:1.51-5.95], educational status [AOR, 2.49, 95% CI:1.22-5.07], occupational status of self-employee [AOR, 1.98, 95% CI:1.15-3.39] and housewife [AOR, 1.78, 95% CI:1.02-3.12], being visited by health care provider in the last 12 months [AOR, 1.81, 95% CI: 1.26-2.60] and desired number of children less than two [AOR, 1.53, 95% CI:1.01-2.30] were significantly associated with unmet need for family planning.

CONCLUSIONS: Unmet need for family planning was higher in the study area compared with the United Nations sphere standard of unmet need for family planning and the national average, and slightly lower than the regional average. Socio-demographic, economic, and health institution factors were determinants of the unmet need for family planning in the study area. Therefore, health education and behaviour change communication related to family planning services should be strengthened and access to family planning services should be improved.

PMID:34871318 | DOI:10.1371/journal.pone.0260972

PLoS One. 2021 Dec 6;16(12):e0260512. doi: 10.1371/journal.pone.0260512. eCollection 2021.

ABSTRACT

This research proposes a new multi-membrane search algorithm (MSA) based on cell biological behavior. Cell secretion protein behavior and cell division and fusion strategy are the main inspirations for the algorithm. In order to verify the performance of the algorithm, we used 19 benchmark functions to compare the MSA test results with MVO, GWO, MFO and ALO. The number of iterations of each algorithm on each benchmark function is 100, the population number is 10, and the running is repeated 50 times, and the average and standard deviation of the results are recorded. Tests show that the MSA is competitive in unimodal benchmark functions and multi-modal benchmark functions, and the results in composite benchmark functions are all superior to MVO, MFO, ALO, and GWO algorithms. This paper also uses MSA to solve two classic engineering problems: welded beam design and pressure vessel design. The result of welded beam design is 1.7252, and the result of pressure vessel design is 5887.7052, which is better than other comparison algorithms. Statistical experiments show that MSA is a high-performance algorithm that is competitive in unimodal and multimodal functions, and its performance in compound functions is significantly better than MVO, MFO, ALO, and GWO algorithms.

PMID:34871309 | DOI:10.1371/journal.pone.0260512