Nevin Manimala

Brief Bioinform. 2021 Aug 20:bbab337. doi: 10.1093/bib/bbab337. Online ahead of print.

ABSTRACT

Intratumoral heterogeneity is a well-documented feature of human cancers and is associated with outcome and treatment resistance. However, a heterogeneous tumor transcriptome contributes an unknown level of variability to analyses of differentially expressed genes (DEGs) that may contribute to phenotypes of interest, including treatment response. Although current clinical practice and the vast majority of research studies use a single sample from each patient, decreasing costs of sequencing technologies and computing power have made repeated-measures analyses increasingly economical. Repeatedly sampling the same tumor increases the statistical power of DEG analysis, which is indispensable toward downstream analysis and also increases one’s understanding of within-tumor variance, which may affect conclusions. Here, we compared five different methods for analyzing gene expression profiles derived from repeated sampling of human prostate tumors in two separate cohorts of patients. We also benchmarked the sensitivity of generalized linear models to linear mixed models for identifying DEGs contributing to relevant prostate cancer pathways based on a ground-truth model.

PMID:34415294 | DOI:10.1093/bib/bbab337

J Neuroophthalmol. 2021 Sep 1;41(3):342-350. doi: 10.1097/WNO.0000000000001220.

ABSTRACT

BACKGROUND: Tocilizumab (Actemra) is a humanized anti-interleukin-6 receptor antibody that has been used as a steroid-sparing agent in giant cell arteritis (GCA). Although the clinical effects are well described in GCA, the cost-effectiveness of the use of tocilizumab in GCA is ill defined. The purpose of this study was to determine the cost-effectiveness of tocilizumab in GCA compared with prednisone alone.

METHODS: A retrospective study of 32 patients with biopsy-proven GCA comparing prednisone alone (16 patients) and prednisone with tocilizumab (16 patients) was performed. The cost for tocilizumab therapy for 26 weeks with mild and severe side effects (Groups 1 and 2, respectively) and for 52 weeks with mild and severe side effects (Group 3 and 4, respectively) was compared with estimated costs of mild and severe steroid-induced side effects (Groups 5 and 6, respectively). Statistical analysis between groups was conducted using independent sample t tests.

RESULTS: Three out of the 4 group combinations of tocilizumab with prednisone demonstrated a statistically significant (P < 0.05) difference in cost compared with prednisone alone for GCA. Group 2 (26-week tocilizumab therapy with severe steroid-induced side effects), with no statically significant difference in price when compared with steroid therapy alone and far fewer side effects, demonstrated the potential use of tocilizumab in GCA therapy. As expected, longer treatment duration with tocilizumab was associated with greater cost. With respect to side effect severity, the number of side effects of steroid therapy was inversely associated with difference in cost between tocilizumab therapy and steroid side effect treatment.

CONCLUSION: This study demonstrates that combination therapy of tocilizumab and prednisone is significantly more expensive than steroids alone with or without accounting for the cost of steroid-induced side effects in treated GCA. The difference in cost between the 2 therapy types is directly related to tocilizumab therapy duration and inversely related to the number or severity of steroid side effects. Patients with GCA who require a shorter duration of steroid therapy and are at risk for a high number of side effects from steroid use may be potential candidates for tocilizumab therapy, from an economic perspective.

PMID:34415267 | DOI:10.1097/WNO.0000000000001220

J Pediatr Gastroenterol Nutr. 2021 Sep 1;73(3):325-328. doi: 10.1097/MPG.0000000000003178.

ABSTRACT

OBJECTIVES: Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children. Our aim was to determine factors associated with IBP in children.

METHODS: We prospectively enrolled children undergoing outpatient colonoscopy. Quality of bowel preparation was assessed using Boston Bowel Preparation Scale (BBPS) score (range 0-9). Data collected included patient demographics, indication, and type of insurance. Patients were divided into two groups based on BBPS score-adequate (BBPS score > 5) and inadequate (BBPS score < 5) and groups were compared using Student t-test and chi-square test. Possible predictors were analyzed using multivariate logistic regression models.

RESULTS: A total of 334 children were prospectively enrolled of whom 321 were studied further (age range 2-18 years; mean age 12.4 years; 60.4% female; 85.9% Caucasian). The mean BBPS score was 6.8 (standard deviation of ±2). IBP was reported in 12.8% (41/321). Multivariable logistic regression analysis did not show statistical differences between the groups in studied patient factors including age, gender, obesity, race, insurance type, and indication for colonoscopy.

CONCLUSION: Contrary to several adult studies, the results of our prospective study did not show any relationship between examined patient factors and IBP in children. Interestingly, IBP was less prevalent in our pediatric study compared to published adult data (12.8% vs 20-40%).

PMID:34415261 | DOI:10.1097/MPG.0000000000003178

Adv Skin Wound Care. 2021 Sep 1;34(9):473-480. doi: 10.1097/01.ASW.0000767332.40833.28.

ABSTRACT

OBJECTIVES: To assess the knowledge and attitudes of student nurses regarding evidence-based guidelines for preventing pressure injuries.

METHODS: This study used a descriptive research design. The participants included second-, third-, and fourth-year nursing students completing their bachelor’s degrees at a faculty of nursing in Turkey. Data collection forms consisted of a student nurse information form, the Pressure Ulcer Prevention Knowledge Assessment Instrument, and the Attitude Towards Pressure Ulcer Prevention Instrument.

RESULTS: The overall mean score for knowledge was 49.9% (11.7/26). The highest scores for the instrument’s subthemes were for nutrition (72%), and the lowest were for etiology and development (40.1%). The overall mean attitude score was 42.20 ± 2.40, although a statistically significant difference among grades was found (P < .001). The highest mean scores showed agreement among students that pressure injury prevention should be a priority (10.50 ± 1.43). A significant difference was found in the competence subscale according to the number of dressing changes observed and sense of competence in pressure injury care (P = .003). A weak but statistically significant positive relationship was found between knowledge and attitude scores (r = 0.158; 95% confidence interval, .040-.269; P < .001).

CONCLUSIONS: This study revealed that certain revisions are needed in the nursing curriculum to improve the knowledge and attitudes of nursing students toward the prevention and care of pressure injuries. More details should be covered in the classroom and laboratories through simulation or clinical practice for improved management of pressure injuries.

PMID:34415251 | DOI:10.1097/01.ASW.0000767332.40833.28

Int J Circumpolar Health. 2021 Dec;80(1):1969745. doi: 10.1080/22423982.2021.1969745.

ABSTRACT

The primary aim of this study was to determine if self-reported occupational noise exposure was associated with Raynaud’s phenomenon. In northern Sweden, a nested case-control study was performed on subjects reporting Raynaud’s phenomenon (N=461), and controls (N=763) matched by age, sex and geographical location. The response rate to the exposure questionnaire was 79.2%. The study showed no statistically significant association between occupational noise exposure and reporting Raynaud’s phenomenon (OR 1.10; 95% CI 0.83-1.46) in simple analyses. However, there was a trend towards increasing OR for Raynaud’s phenomenon with increasing noise exposure, although not statistically significant. Also, there was a significant association between noise exposure and hearing loss (OR 2.76; 95% CI 2.00-3.81), and hearing loss was associated with reporting Raynaud’s phenomenon (OR 1.52; 95% CI 1.03-2.23) in a multiple regression model. In conclusion, self-reported occupational noise exposure was not statistically significantly associated with Raynaud’s phenomenon, but there was a dose-effect trend. In addition, the multiple model showed a robust association between hearing loss and Raynaud’s phenomenon. These findings offer some support for a common pathophysiological background for Raynaud’s phenomenon and hearing loss among noise-exposed workers, possibly through noise-induced vasoconstriction.

PMID:34415235 | DOI:10.1080/22423982.2021.1969745

J Obstet Gynaecol. 2021 Aug 20:1-7. doi: 10.1080/01443615.2021.1929116. Online ahead of print.

ABSTRACT

This study examines the relationship between the age at menarche and gestational diabetes mellitus (GDM). This retrospective study included subjects who were diagnosed with GDM at a pregnancy polyclinic in Kocaeli, Turkey between 2014 and 2018. The mean ages at menarche were 12.6 and 13.03 years in the GDM group and control group, respectively. The analysis results showed that pre-pregnancy cycle duration, age at menarche and pre-pregnancy BMI are statistically significant in terms of the development of gestational diabetes. (p < .05).In our study showed that the risk of GDM was found to be 2.3 times higher in pregnant women with a menarche age of <12 years. If the pre-pregnancy BMI value is more than 25 kg/cm², the risk of GDM was found to be approximately 2 times higher. The study indicated that age at menarche, cycle duration, and BMI were risk factors for GDM. IMPACT STATEMENTWhat is already known on this subject? GDM has a lasting health impact on both the mother and the foetus. While several risk factors have previously been identified for GDM such as family history, obesity, advanced maternal age, significant gaps remain in our understanding of the risk factor and pathogenesis. Recent studies suggested that earlier menarche was significantly associated with an increased risk of GDM.What do the results of this study add? There might be ethnic differences on the relationship between the GDM and menarche age. There is no study examining the relationship between the age of menarche and GDM in Turkey. In presented study, we determined the risk factors of GDM including the age of menarche, cycle duration and BMI.What are the implications of these findings for clinical practice and / or further research? Therefore, a comprehensive evaluation of the menstrual history by healthcare professionals is important for future pregnancy risks. It is important to understand risk factors for GDM and to establish preventive strategies among high-risk populations. In addition, this study will shed light on future epidemiological and cohort studies.

PMID:34415226 | DOI:10.1080/01443615.2021.1929116

J Neurointerv Surg. 2021 Aug 19:neurintsurg-2021-017867. doi: 10.1136/neurintsurg-2021-017867. Online ahead of print.

ABSTRACT

BACKGROUND: Despite constant improvements in recent years, sufficient reperfusion after mechanical thrombectomy (MT) is not reached in up to 15% of patients with large vessel occlusion stroke (LVOS). The outcome of patients with unsuccessful reperfusion after MT especially after intravenous thrombolysis (IVT) use is not known. We investigated the influence of initial IVT in this particular group of patients with failed intracranial recanalization.

METHODS: We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry from January 2015 to December 2019. Patients presenting with LVOS of the anterior circulation and final modified Thrombolysis in Cerebral Infarction score (mTICI) of 0, 1 or 2a were included. Posterior circulation, isolated cervical carotid occlusions and successful reperfusions (mTICI 2b, 2c or 3) were excluded. The primary endpoint was favorable outcome (modified Rankin Scale score of 0-2) after 3 months. Secondary endpoints were safety outcomes including mortality, any intracranial hemorrhage (ICH), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) rates.

RESULTS: Among 5076 patients with LVOS treated with MT, 524 patients with insufficient recanalization met inclusion criteria, of which 242 received IVT and 282 did not. Functional outcome was improved in the MT+IVT group compared with the MT alone group, although the difference did not reach statistical significance (23.0% vs 12.9%; adjusted OR=1.82; 95% CI 0.98 to 3.38; p=0.058). However, 3 month mRS shift analysis showed a significant benefit of IVT (adjusted OR=1.68; 95% CI 1.56 to 6.54). ICH and sICH rates were similar in both groups, although PH rate was higher in the MT+IVT group (adjusted OR=3.20; 95% CI 1.56 to 6.54).

CONCLUSIONS: Among patients with LVOS in the anterior circulation and unsuccessful MT, IVT was associated with improved functional outcome even after unsuccessful MT. Despite recent trials questioning the place of IVT in the LVOS reperfusion strategy, these findings emphasize a subgroup of patients still benefiting from IVT.

PMID:34413246 | DOI:10.1136/neurintsurg-2021-017867

Proc Natl Acad Sci U S A. 2021 Aug 24;118(34):e2100761118. doi: 10.1073/pnas.2100761118.

ABSTRACT

Binary classification is one of the central problems in machine-learning research and, as such, investigations of its general statistical properties are of interest. We studied the ranking statistics of items in binary classification problems and observed that there is a formal and surprising relationship between the probability of a sample belonging to one of the two classes and the Fermi-Dirac distribution determining the probability that a fermion occupies a given single-particle quantum state in a physical system of noninteracting fermions. Using this equivalence, it is possible to compute a calibrated probabilistic output for binary classifiers. We show that the area under the receiver operating characteristics curve (AUC) in a classification problem is related to the temperature of an equivalent physical system. In a similar manner, the optimal decision threshold between the two classes is associated with the chemical potential of an equivalent physical system. Using our framework, we also derive a closed-form expression to calculate the variance for the AUC of a classifier. Finally, we introduce FiDEL (Fermi-Dirac-based ensemble learning), an ensemble learning algorithm that uses the calibrated nature of the classifier’s output probability to combine possibly very different classifiers.

PMID:34413191 | DOI:10.1073/pnas.2100761118

Postgrad Med J. 2021 Aug 19:postgradmedj-2021-140852. doi: 10.1136/postgradmedj-2021-140852. Online ahead of print.

NO ABSTRACT

PMID:34413176 | DOI:10.1136/postgradmedj-2021-140852

Eur Respir J. 2021 Aug 19:2101796. doi: 10.1183/13993003.01796-2021. Online ahead of print.

NO ABSTRACT

PMID:34413149 | DOI:10.1183/13993003.01796-2021