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Nevin Manimala Statistics

Genetically predicted cortisol levels and risk of venous thromboembolism

PLoS One. 2022 Aug 19;17(8):e0272807. doi: 10.1371/journal.pone.0272807. eCollection 2022.

ABSTRACT

INTRODUCTION: In observational studies, venous thromboembolism (VTE) has been associated with Cushing’s syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization.

METHODS: Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed.

RESULTS: Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62-0.87, p<0.001). The association was stronger for deep vein thrombosis (OR 0.69, 95% CI 0.55-0.88, p = 0.003) than for pulmonary embolism which did not achieve statistical significance (OR 0.83, 95% CI 0.63-1.09, p = 0.184). Adjusting for genetically predicted systolic blood pressure inverted the direction of the point estimate for VTE, although the resulting CI was wide (OR 1.06, 95% CI 0.70-1.61, p = 0.780).

CONCLUSIONS: This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for.

PMID:35984822 | DOI:10.1371/journal.pone.0272807

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Nevin Manimala Statistics

Game statistics that discriminate winning and losing at the NBA level of basketball competition

PLoS One. 2022 Aug 19;17(8):e0273427. doi: 10.1371/journal.pone.0273427. eCollection 2022.

ABSTRACT

The purpose of the present study was to examine differences in game-related statistical parameters between National Basketball Association (NBA) regular and post-season competitive periods and to determine which variables have the greatest contribution in discriminating between winning and losing game outcomes. The data scraping technique was used to obtain publicly available NBA game-related statistics over a three-year span (2016-2019). The total number of games examined in the present investigation was 3933 (3690 regular season and 243 post-season games). Despite small to moderate effect sizes, the findings suggest that NBA teams’ style of play (i.e., tactical strategies) changes when transitioning from the regular to post-season competitive period. It becomes more conservative (i.e., fewer field goal attempts, assists, steals, turnovers, and points scored), most likely due to greater defensive pressure. Discriminant function analysis correctly classified winning and losing game outcomes during the regular and post-season competitive periods in 82.8% and 87.2% of cases, respectively. Two key game-related statistics capable of discriminating between winning and losing game outcomes were field goal percentage and defensive rebounding, accounting for 13.6% and 14.2% of the total percentage of explained variance during the regular season and 11.5% and 14.7% during post-season competitive periods. Also, overall shooting efficiency (i.e., free-throw, 2-point, and 3-point combined) accounted for 23-26% of the total percentage of explained variance.

PMID:35984813 | DOI:10.1371/journal.pone.0273427

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Nevin Manimala Statistics

Assessing the impact of Ascariasis and Trichuriasis on weight gain using a porcine model

PLoS Negl Trop Dis. 2022 Aug 19;16(8):e0010709. doi: 10.1371/journal.pntd.0010709. eCollection 2022 Aug.

ABSTRACT

BACKGROUND: Infections with Ascaris lumbricoides and Trichuris trichiura remain significant contributors to the global burden of neglected tropical diseases. Infection may in particular affect child development as they are more likely to be infected with T. trichiura and/or A. lumbricoides and to carry higher worm burdens than adults. Whilst the impact of heavy infections are clear, the effects of moderate infection intensities on the growth and development of children remain elusive. Field studies are confounded by a lack of knowledge of infection history, nutritional status, presence of co-infections and levels of exposure to infective eggs. Therefore, animal models are required. Given the physiological similarities between humans and pigs but also between the helminths that infect them; A. suum and T. suis, growing pigs provide an excellent model to investigate the direct effects of Ascaris spp. and Trichuris spp. on weight gain.

METHODS AND RESULTS: We employed a trickle infection protocol to mimic natural co-infection to assess the effect of infection intensity, determined by worm count (A. suum) or eggs per gram of faeces (A. suum and T. suis), on weight gain in a large pig population (n = 195) with variable genetic susceptibility. Pig body weights were assessed over 14 weeks. Using a post-hoc statistical approach, we found a negative association between weight gain and T. suis infection. For A. suum, this association was not significant after adjusting for other covariates in a multivariable analysis. Estimates from generalized linear mixed effects models indicated that a 1 kg increase in weight gain was associated with 4.4% (p = 0.00217) decrease in T. suis EPG and a 2.8% (p = 0.02297) or 2.2% (p = 0.0488) decrease in A. suum EPG or burden, respectively.

CONCLUSIONS: Overall this study has demonstrated a negative association between STH and weight gain in growing pigs but also that T. suis infection may be more detrimental that A. suum on growth.

PMID:35984809 | DOI:10.1371/journal.pntd.0010709

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Nevin Manimala Statistics

Histologic Cell Shape Descriptors for the Retinal Pigment Epithelium in Age-Related Macular Degeneration: A Comparison to Unaffected Eyes

Transl Vis Sci Technol. 2022 Aug 1;11(8):19. doi: 10.1167/tvst.11.8.19.

ABSTRACT

PURPOSE: Phenotype alterations of the retinal pigment epithelium (RPE) are a main characteristic of age-related macular degeneration (AMD). Individual RPE cell shape descriptors may help to delineate healthy from AMD-affected cells in early disease stages.

METHODS: Twenty-two human RPE flatmounts (7 eyes with AMD [early, 3; geographic atrophy, 1; neovascular, 3); 15 unaffected eyes [8 aged ≤51 years; 7 aged >80 years)] were imaged at the fovea, perifovea, and near periphery (predefined sample locations) using a laser-scanning confocal fluorescence microscope. RPE cell boundaries were manually marked with computer assistance. For each cell, 11 shape descriptors were calculated and correlated with donor age, cell autofluorescence (AF) intensity, and retinal location. Statistical analysis was performed using an ensemble classifier based on logistic regression.

RESULTS: In AMD, RPE was altered at all locations (most pronounced at the fovea), with area, solidity, and form factor being the most discriminatory descriptors. In the unaffected macula, aging had no significant effect on cell shape factors; however, with increasing distance to the fovea, area, solidity, and convexity increased while form factor decreased. Reduced AF in AMD was significantly associated with decreased roundness and solidity.

CONCLUSIONS: AMD results in an altered RPE with enlarged and deformed cells that could precede clinically visible lesions and thus serve as early biomarkers for AMD onset. Our data may also help guide the interpretation of RPE morphology in in vivo studies utilizing high-resolution single-cell imaging.

TRANSLATIONAL RELEVANCE: Our histologic RPE cell shape data have the ability to identify robust biomarkers for the early detection of AMD-affected cells, which also could serve as a basis for automated segmentation of RPE sheets.

PMID:35984669 | DOI:10.1167/tvst.11.8.19

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Nevin Manimala Statistics

Assessment of Adherence to Reporting Guidelines by Commonly Used Clinical Prediction Models From a Single Vendor: A Systematic Review

JAMA Netw Open. 2022 Aug 1;5(8):e2227779. doi: 10.1001/jamanetworkopen.2022.27779.

ABSTRACT

IMPORTANCE: Various model reporting guidelines have been proposed to ensure clinical prediction models are reliable and fair. However, no consensus exists about which model details are essential to report, and commonalities and differences among reporting guidelines have not been characterized. Furthermore, how well documentation of deployed models adheres to these guidelines has not been studied.

OBJECTIVES: To assess information requested by model reporting guidelines and whether the documentation for commonly used machine learning models developed by a single vendor provides the information requested.

EVIDENCE REVIEW: MEDLINE was queried using machine learning model card and reporting machine learning from November 4 to December 6, 2020. References were reviewed to find additional publications, and publications without specific reporting recommendations were excluded. Similar elements requested for reporting were merged into representative items. Four independent reviewers and 1 adjudicator assessed how often documentation for the most commonly used models developed by a single vendor reported the items.

FINDINGS: From 15 model reporting guidelines, 220 unique items were identified that represented the collective reporting requirements. Although 12 items were commonly requested (requested by 10 or more guidelines), 77 items were requested by just 1 guideline. Documentation for 12 commonly used models from a single vendor reported a median of 39% (IQR, 37%-43%; range, 31%-47%) of items from the collective reporting requirements. Many of the commonly requested items had 100% reporting rates, including items concerning outcome definition, area under the receiver operating characteristics curve, internal validation, and intended clinical use. Several items reported half the time or less related to reliability, such as external validation, uncertainty measures, and strategy for handling missing data. Other frequently unreported items related to fairness (summary statistics and subgroup analyses, including for race and ethnicity or sex).

CONCLUSIONS AND RELEVANCE: These findings suggest that consistent reporting recommendations for clinical predictive models are needed for model developers to share necessary information for model deployment. The many published guidelines would, collectively, require reporting more than 200 items. Model documentation from 1 vendor reported the most commonly requested items from model reporting guidelines. However, areas for improvement were identified in reporting items related to model reliability and fairness. This analysis led to feedback to the vendor, which motivated updates to the documentation for future users.

PMID:35984654 | DOI:10.1001/jamanetworkopen.2022.27779

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Nevin Manimala Statistics

Patient Understanding of Oncologic Radiology Reports: Is Access to Electronic Medical Records Helpful?

J Cancer Educ. 2022 Aug 19. doi: 10.1007/s13187-022-02204-5. Online ahead of print.

ABSTRACT

Access to electronic medical record (EMR) patient portals made it easier for patients to quickly acquire the results of their radiology studies. However, there is little research on how well oncology patients understand the findings of radiology reports presented in the online portal without patient-physician discussion. This study assessed oncology patients’ confidence and accuracy in interpreting radiology reports either with or without layman translations. A survey based on a radiology report was administered to oncology patients and caregivers. Two versions of the radiological report were randomly distributed, either a standard report or one with layman translations to evaluate participant understanding and accuracy of interpreting radiological results. Among 85 participants, a majority (67.8%) reported wanting patient portal access to radiological reports, yet less than a quarter (21.2%) felt confident in reading and interpreting radiological reports. Univariate binary logistic regression models showed that participants who read the lay report were 8 times more likely to find the radiology report easy to read. This research demonstrated that the inclusion of layman translation of standard radiology reports improves oncology patients’ and caregivers’ understanding of such reports with statistically significant and clinically meaningful increases in readability.

PMID:35984630 | DOI:10.1007/s13187-022-02204-5

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High Tolerability, Favorable Safety, and Subjects’ Preference for a Single 200 mg/2 mL Tildrakizumab Injection: A Phase I, Open-Label, Randomized Crossover Trial in Healthy Volunteers

Dermatol Ther (Heidelb). 2022 Aug 19. doi: 10.1007/s13555-022-00789-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Tildrakizumab 200 mg/2 mL pre-filled syringe is a new preparation of tildrakizumab that is developed to facilitate patients’ compliance. This phase I clinical trial compares the local tolerability, safety, and subjects’ preferred method of administration of tildrakizumab when administered as a new single 200 mg/2 mL subcutaneous injection or as two 100 mg/1 mL subcutaneous injections in healthy subjects.

METHODS: Visual analogue scores were used to self-assess injection site pain immediately (< 1 min) after each administration and at 1 h and 48 h after each administration. Treatment injection site reactions were assessed at 1 h and 48 h after each administration. Treatment safety was monitored throughout the study period. Subjects’ preferred method of administration was assessed 4 weeks after the last administration (day 56).

RESULTS: No statistically significant difference in visual analogue scores and injection site reactions was detected between the two treatments. Treatment-emergent adverse events were mild, and there were no deaths or serious adverse events. Most subjects (61.5%) preferred the treatment when administered as a single 200 mg/2 mL subcutaneous injection rather than as two 100 mg/mL subcutaneous injections.

CONCLUSIONS: Administration of 200 mg tildrakizumab as a single 2 mL subcutaneous injection was safe, well tolerated, and preferred over two separate 100 mg/1 mL subcutaneous injections by healthy subjects. Eudract No. 2020-000183-37.

PMID:35984626 | DOI:10.1007/s13555-022-00789-9

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Text validation: Overlooking consistency effect discrepancies

Mem Cognit. 2022 Aug 19. doi: 10.3758/s13421-022-01351-w. Online ahead of print.

ABSTRACT

The consistency effect, prevalent in the text comprehension literature, comprises longer reading times for inconsistent than equivalent consistent text continuations. It is widely interpreted as reflecting readers’ effective “validation” of text coherence. However, there are also numerous phenomena of readers’ deficient validation, sometimes collectively labelled “misinformation effects.” This study asked whether readers become consciously aware of the text discrepancies diagnosed by the consistency effect. Experiment 1 scrutinized (a) conspicuous conceptual inconsistencies and (b) character-trait inconsistencies. It replicated the consistency effect both at a critical target sentence and at a subsequent sentence (spillover). Experiment 2 replaced self-paced reading with consistency judgments about the target sentences. The subjects overlooked almost half of the inconsistencies, thus denying that readers reliably become aware of consistency-effect discrepancies. In Experiment 3, the former target sentences were reframed as explicit questions. Accuracy for inconsistencies was statistically indistinguishable from accuracy for consistent targets, favoring the interpretation that Experiment 2 subjects overlooked known, encoded discrepancies. The results are interpreted with reference to Kintsch’s (Psychological Review, 95, 163-182, Kintsch, 1988; Comprehension. New York: Cambridge University Press, Kintsch, 1998) construction-integration model, a refinement of which adds an immediate, passive stage of validation processing to construction and integration. It is proposed that passive validation affords the detection of text inconsistencies that do not reach the level of readers’ conscious awareness.

PMID:35984623 | DOI:10.3758/s13421-022-01351-w

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Nevin Manimala Statistics

Impact of surgical factors on delayed hyponatremia in patients with nonfunctioning pituitary adenoma after endonasal endoscopic transsphenoidal procedure

Endocrine. 2022 Aug 19. doi: 10.1007/s12020-022-03164-y. Online ahead of print.

ABSTRACT

PURPOSE: Delayed hyponatremia can occur after pituitary surgery, resulting in prolonged hospitalization. However, the influence of surgical factors after such a procedure has not been well established. The impact of surgery and related factors on delayed hyponatremia was investigated.

METHODS: This was a retrospective analysis of 137 consecutive patients who underwent transsphenoidal surgery for a nonfunctioning pituitary adenoma between 2008 and 2019. Preoperative (demographics, comorbidities), intraoperative (resection extent, operation time, blood loss volume, cerebrospinal fluid leak, tumor consistency), and postoperative [hematoma, meningitis, diabetes insipidus (DI), hormonal assessment] data were collected, with statistical analysis of each factor performed.

RESULTS: Among the 137 patients, delayed hyponatremia occurred in 31 (22.6%). Multivariate analysis revealed that those with hypertension had a significantly higher likelihood of avoiding delayed hyponatremia (p = 0.004). Although no correlations of direct surgical factors with delayed hyponatremia were found, multivariate analysis of indirect surgical factors showed that presence of a firm tumor, transient DI, and meningitis were significantly associated with delayed hyponatremia (p = 0.014, 0.001, and 0.047, respectively). There was also a significant association of severe hyponatremia with appearance of symptoms (p = 0.002).

CONCLUSION: There was a tendency for hypertension to be associated with delayed hyponatremia avoidance, with indirect surgical factors including tumor consistency, transient DI, and meningitis found to have an influence on delayed hyponatremia. It was concluded that attention should be given to non-hypertensive patients with a firm tumor, transient DI, or meningitis after pituitary surgery, as delayed hyponatremia may occur.

PMID:35984619 | DOI:10.1007/s12020-022-03164-y

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Nevin Manimala Statistics

Direct anterior approach in total hip arthroplasty: influence of stem length on clinical and radiological outcomes at medium-term follow-up

Musculoskelet Surg. 2022 Aug 19. doi: 10.1007/s12306-022-00758-7. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the influence of short versus long stems implanted through a Direct Anterior Approach (DAA) on clinical and radiological outcomes in THA at medium-term follow-up (average follow-up of 44.8 months).

METHODS: 167 consecutive total hip arthroplasties treating patients affected by primary hip osteoarthritis were retrospectively evaluated. A standard-length stem (H-MAXs) was used in 70 patients, while a short metaphyseal-fitting femoral stem (MINIMA) was used in 97 patients. The Harris Hip Score (HHS) and Forgotten Joint Score-12 (FJS) were used as outcomes measurements. Post-operatively, Engh’s score and Brooker classification were analyzed at 6 months, 1 year and every 2 years until the final FU. The correct size of the implant was evaluated determining the canal fill index (CFI), and all undersized stems were classified according to Magra classification.

RESULTS: The average HHS was 83 ± 13.4 in the standard stems group and 87 ± 14.1 for short stems group (p = 0.148). The average FJS was 87.9 ± 15.2 for patients in the standard stems group and 84.5 ± 17.7 with no significant differences (p = 0.327). None of the stems showed radiographic signs of instability (standard stems mean Engh’s score: 19.25 versus short stems mean Engh’s score: 19.50-p = 0.41). According to Brooker classification, no significant difference in severity was found using different stems (p = 0.715). A high rate of undersized stems was found (standard stems 24%-short stems 25%) but without statistical difference between groups (p = 0.078), while a different trend in malposition following the recent classification proposed by Magra et al. was observed evaluating all undersized stems (p = 0.0387).

CONCLUSIONS: Both groups achieved good and comparable patient-reported outcome measurements (PROMs) and radiographic stability with fixation observed by bone ingrowth. A high rate of undersized stems was found with a correlation between femoral stem length and specific pattern of malposition. Malalignment in Varus was frequent in shorter stems in contact proximally with medial calcar and distally with lateral cortex, while a uniform undersizing was observed for longer ones with a continuous margin around the stem. However, the stems never presented progressive radiolucent lines over the whole surface of the stem.

PMID:35984610 | DOI:10.1007/s12306-022-00758-7