Tag: statistics

Infect Genet Evol. 2022 Apr 4:105279. doi: 10.1016/j.meegid.2022.105279. Online ahead of print.

ABSTRACT

As surges of the COVID-19 pandemic continue globally, including in Palestine, several new SARS-CoV-2 variants have been introduced. This expansion has impacted transmission, disease severity, virulence, diagnosis, therapy, and natural and vaccine-induced immunity. Here, 183 whole genome sequences (WGS) were analyzed, of which 129 were from Palestinian cases, 62 of which were collected in 11 Palestinian districts between October 2020 and April 2021and sequenced completely . A dramatic shift from the wild type to the Alpha variant (B 1.1.7) was observed within a short period of time. Cluster mapping revealed statistically significant clades in two main Palestinian cities, Al-Khalil (Monte Carlo hypothesis test-Poisson model, P = 0.00000000012) and Nablus (Monte Carlo hypothesis test-Poisson model, P = 0.014 and 0.015). The phylogenetic tree showed three main clusters of SARS-CoV-2 with high bootstrap values (>90). However, population genetics analysis showed a genetically homogenous population supported by low Wright’s F-statistic values (Fst <0.25), high gene flow (Nm > 3), and statistically insignificant Tajima’s D values (Tajima’s test, neutrality model prediction, P = 0.02). The Alpha variant, rapidly replaced the wild type, causing a major surge that peaked in April 2021, with an increased COVID-19 mortality rate, especially, in the Al-Khalil and Nablus districts. The source of introduction remains uncertain, despite the minimal genetic variation. The study substantiates the use of WGS for SARS-CoV-2 surveillance as an early warning system to track down new variants requiring effective control.

PMID:35390503 | DOI:10.1016/j.meegid.2022.105279

World Neurosurg. 2022 Apr 4:S1878-8750(22)00416-8. doi: 10.1016/j.wneu.2022.03.123. Online ahead of print.

ABSTRACT

PURPOSE: Immunotherapy has revolutionized cancer treatment in the past decade, but significant hurdles remain. Human studies with immune checkpoint inhibitors (ICIs) targeting programmed cell death protein have demonstrated suboptimal efficacy in the setting of low-grade gliomas (LGG). Identification of mechanisms leading to inadequate anti-tumor immunity is paramount. The current study evaluates and validates barriers to immunotherapy using a novel machine learning algorithm.

METHODS: We utilized The Cancer Genome Atlas (TCGA) to generate expression levels of 28 immune genes related to known immunotherapeutic targets or lymphocyte cytolytic activity. We created training and testing groups and three machine learning models to determine the genes most highly correlated to cytolytic activity (CYT). The three models were multiple regression by exhaustive selection, LASSO, and random forest. We validated computational results by comparing expression of pertinent genes in patient-derived glioma samples.

RESULTS: Our models demonstrated linearity, a low mean-squared error, and consistent results with respect to the most important variables. Expression of ICOS, IDO1, and CD40 were the most important variables in all models and demonstrated positive correlation with CYT. Other variables included TIGIT and CD137. Genetic analysis from three IDH-mutants (IDHm) and three IDH-wild type (IDHwt) patient-derived glioma samples validated TCGA data and demonstrated lower levels of CYT in IDHm gliomas compared to IDHwt.

CONCLUSION: This novel methodology has elucidated three potential targets for immunotherapy development in LGG. We also demonstrated a novel method of analyzing data using advanced statistical techniques that can be further employed in developing treatments for other diseases as well.

PMID:35390499 | DOI:10.1016/j.wneu.2022.03.123

J Clin Psychiatry. 2022 Apr 4;83(2):22f14455. doi: 10.4088/JCP.22f14455.

ABSTRACT

Selective serotonin reuptake inhibitors (SSRIs) may predispose to postpartum hemorrhage (PPH) by interfering with platelet-mediated hemostasis and serotonin-mediated myometrial contractility. A meta-analysis of 8 observational studies found that, regardless of drug class, gestational exposure to antidepressants was associated with a small (odds ratio, 1.25) but statistically significantly increased risk of PPH; however, this finding was true only when antidepressant exposure was proximal to the date of delivery. A recent, moderately large, nationally representative, Swedish observational study also found that gestational exposure to SSRIs was associated with a significantly increased risk of PPH; the crude number needed to harm was 48. For reasons related to the methodology employed, it is possible that the risk was underestimated in this study. The findings of the meta-analysis and of the observational study are examined with a view to help readers understand how to critically read and interpret the research literature in the field. A reasonable viewpoint is that the increase in risk of PPH associated with gestational exposure to SSRIs is smaller than the increase in risk associated with obstetric risk factors for PPH; nevertheless, following precautionary measures would be wise. Such measures would include the routine administration of a uterotonic agent immediately after delivery to all women who have received serotonin reuptake inhibitor treatment during the month preceding delivery; the choice of uterotonic agent would depend on local hospital protocols. Women at risk should also be closely monitored for continued blood loss during the first 24 hours after delivery.

PMID:35390232 | DOI:10.4088/JCP.22f14455

Dent Traumatol. 2022 Apr 7. doi: 10.1111/edt.12750. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Approximately 20% of patients with maxillofacial trauma are women, but few articles have analysed this. The aim of this multicentric, prospective, epidemiological study was to analyse the characteristics of maxillofacial fractures in the female population managed in 14 maxillofacial surgery departments on five continents over a 1-year period.

METHODS: The following data were collected: age (0-18, 19-64, or ≥65 years), cause and mechanism of the maxillofacial fracture, alcohol and/or drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score, associated injury, day of trauma, timing and type of treatment, and length of hospitalization.

RESULTS: Between 30 September 2019 and 4 October 2020, 562 of 2387 patients hospitalized with maxillofacial trauma were females (24%; M: F ratio, 3.2:1) aged between 1 and 96 years (median age, 37 years). Most fractures occurred in patients aged 20-39 years. The main causes were falls (43% [median age, 60.5 years]), which were more common in Australian, European and American units (p < .001). They were followed by road traffic accidents (35% [median age, 29.5 years]). Assaults (15% [median age, 31.5 years]) were statistically associated with alcohol and/or drug abuse (p < .001). Of all patients, 39% underwent open reduction and internal fixation, 36% did not receive surgical treatment, and 25% underwent closed reduction.

CONCLUSION: Falls were the main cause of maxillofacial injury in the female population in countries with ageing populations, while road traffic accidents were the main cause in African and some Asian centres, especially in patients ≤65 years. Assaults remain a significant cause of trauma, primarily in patients aged 19-64 years, and they are related to alcohol use.

PMID:35390219 | DOI:10.1111/edt.12750

J Cosmet Dermatol. 2022 Apr 7. doi: 10.1111/jocd.14978. Online ahead of print.

ABSTRACT

BACKGROUND: Onychomycosis, the most prevailing affliction of the nail, accounts for approximately 90% of the toenail infection worldwide. Owing to this infection, the affected patients experience reduced quality of their life as its awful appearance undermines their daily activities and social interactions. Onychomycosis is notoriously strenuous to cure. Systemic therapy, though effective, possess severe complication of toxicities, contra-indication, and drug-drug interaction. Albeit topical therapy is favorable to its localized effect, its potency relates to the effective concentration of the antifungal drugs achieved at the infection site. An approach to accomplish this goal would be acquiring benefits from the terpenes as penetration enhancers from natural sources. This investigation aimed to study the effectiveness of six terpenes, namely safranal, lavandulol, rose oxide, 3-methyl-2-butene-1-ol, linalool, and limonene, as potential penetration enhancers for improved nail permeation of fluconazole through the human nail.

METHODS: Ex vivo permeation experiments were carried out by soaking the nail clippings of human volunteers in control and working solutions containing fluconazole (5 mg/ml) per se and fluconazole (5 mg/ml) with 6% of each terpene, including safranal, lavandulol, rose oxide, 3-methyl-2-butene-1-ol, linalool, and limonene, respectively, for 48 hours. The amount of fluconazole in nail clippings was quantified using an HPLC method.

RESULTS: Statistical analysis showed that fluconazole transungual permeation was influenced by the studied terpenes in the following order: safranal > lavandulol acetate > limonene > rose oxide (P-value > 0.05) while the other terpenes showed no significant difference with the control group and safranal represents as the most effective permeation enhancer for the transungual delivery of fluconazole.

CONCLUSION: It is concluded that the safranal can be successfully used as a safe and potential permeation enhancer to enhance the transungual delivery of fluconazole for the treatment of onychomycosis.

PMID:35390220 | DOI:10.1111/jocd.14978

J Adolesc. 2022 Apr;94(3):422-434. doi: 10.1002/jad.12037. Epub 2022 Mar 7.

ABSTRACT

INTRODUCTION: While several studies have documented a declining-with-age trend in life satisfaction in adolescence, cross-national and nationally representative longitudinal evidence is needed to establish the normative trajectory of life satisfaction during this critical developmental period.

METHODS: The Health Behaviour in School-Aged Children (HBSC) study of 10-16-year-olds included the Cantril Ladder life satisfaction measure in surveys of 43 countries between 2001 and 2014 (N = 752,620, 51% females). The UK Household Longitudinal Study (UKHLS) was used to assess within-person changes in life satisfaction from age 10 to 15 years among young people sampled between 2009 and 2018 (N = 8952, Obs. = 30,278).

RESULTS: Life satisfaction decreased by 0.61 SDs on average from ages 10 to 16 in the HBSC sample. A statistically significant decreasing-with-age trend was observed in each of the 43 countries examined. Females experienced a more pronounced decline in life satisfaction than males (0.75 SD vs. 0.46) on average, and a significantly larger decrease in life satisfaction among females was identified in 38 of 43 countries examined. Longitudinal analysis of adolescents from the UKHLS sample replicated this pattern: life satisfaction declined significantly by 0.5 SD between the ages of 10 and 15 and this decline was found to be steeper for females (0.76 SD) than for males (0.23SD).

CONCLUSIONS: The study findings enhance our understanding of the lifespan dynamics of life satisfaction and point to a potential universal decline in life satisfaction in adolescence. Understanding the developmental processes underlying this phenomenon will now be crucial.

PMID:35390206 | DOI:10.1002/jad.12037

BJS Open. 2022 Mar 8;6(2):zrac018. doi: 10.1093/bjsopen/zrac018.

ABSTRACT

BACKGROUND: External rectal prolapse (ERP) is a debilitating condition in which surgery plays an important role. The aim of this study was to evaluate the outcomes of abdominal approaches (AA) and perineal approaches (PA) to ERP.

METHODS: This was a PRISMA-compliant systematic review with meta-analysis. Studies published between 1990 and 2021 were retrieved. The primary endpoint was recurrence at the last available follow-up. Secondary endpoints included factors associated with recurrence and function. All studies were assessed for bias using the Newcastle-Ottawa Scale and Cochrane tool.

RESULTS: Fifteen studies involving 1611 patients (AA = 817; PA = 794) treated for ERP were included, three of which were randomized controlled trials (RCTs; 114 patients (AA = 54; PA = 60)). Duration of follow-up ranged from 12 to 82 months. Recurrence in non-randomized studies was 7.7 per cent in AA versus 20.1 per cent in PA (odds ratio (OR) 0.29, 95 per cent confidence interval (c.i.) 0.17 to 0.50; P < 0.001, I2 = 45 per cent). In RCTs, there was no significant difference (9.8 per cent versus 16.3 per cent, AA versus PA (OR 0.82, 95 per cent c.i. 0.29 to 2.37; P = 0.72, I2 = 0.0 per cent)). Age at surgery and duration of follow-up were risk factors for recurrence. Following AA, the recurrence rates were 10.1 per cent and 6.2 per cent in patients aged 65 years and older and less than 65 years of age, respectively (effect size [e.s.] 7.7, 95 per cent c.i. 4.5 to 11.5). Following PA, rates were 27 per cent and 16.3 per cent (e.s. 20.1, 95 per cent c.i. 13 to 28.2). Extending follow-up to at least 40 months increased the likelihood of recurrence. The median duration of hospital stay was 4.9 days after PA versus 7.2 days after AA. Overall, incontinence was less likely after AA (OR 0.32), but constipation occurred more frequently (OR 1.68). Most studies were retrospective, and several outcomes from RCTs were not consistent with those observed in non-RCTs.

CONCLUSION: The overall risk of recurrence of ERP appears to be higher with PA versus AA. Incontinence is less frequent after AA but at the cost of increased constipation. Age at surgery and duration of follow-up are associated with increased risk of recurrence, which warrants adequate reporting of future studies on this topic.

PMID:35390136 | DOI:10.1093/bjsopen/zrac018

Ann Work Expo Health. 2022 Apr 7;66(Supplement_1):i3-i22. doi: 10.1093/annweh/wxab107.

ABSTRACT

The GuLF Study is investigating adverse health effects from work on the response and clean-up after the Deepwater Horizon explosion and oil release. An essential and necessary component of that study was the exposure assessment. Bayesian statistical methods and over 135 000 measurements of total hydrocarbons (THC), benzene, ethylbenzene, toluene, xylene, and n-hexane (BTEX-H) were used to estimate inhalation exposures to these chemicals for >3400 exposure groups (EGs) formed from three exposure determinants: job/activity/task, location, and time period. Recognized deterministic models were used to estimate airborne exposures to particulate matter sized 2.5 µm or less (PM2.5) and dispersant aerosols and vapors. Dermal exposures were estimated for these same oil-related substances using a model modified especially for this study from a previously published model. Exposures to oil mist were assessed using professional judgment. Estimated daily THC arithmetic means (AMs) were in the low ppm range (<25 ppm), whereas BTEX-H exposures estimates were generally <1000 ppb. Potential 1-h PM2.5 air concentrations experienced by some workers may have been as high as 550 µg m-3. Dispersant aerosol air concentrations were very low (maximum predicted 1-h concentrations were generally <50 µg m-3), but vapor concentrations may have exceeded occupational exposure excursion guidelines for 2-butoxyethanol under certain circumstances. The daily AMs of dermal exposure estimates showed large contrasts among the study participants. The estimates are being used to evaluate exposure-response relationships in the GuLF Study.

PMID:35390131 | DOI:10.1093/annweh/wxab107

Am J Hypertens. 2022 Apr 7:hpac045. doi: 10.1093/ajh/hpac045. Online ahead of print.

ABSTRACT

Epidemiologic studies have consistently identified a strong, progressive relationship between blood pressure and cardiovascular disease events, in a range of systolic blood pressure (SBP) from as low as 90 mm Hg to as high as 180 mm Hg. Clinical trials have demonstrated greater prevention of cardiovascular disease with more compared to less intensive antihypertensive drug treatment. Meta-analyses of randomized controlled trials provides strong evidence for more intensive antihypertensive drug therapy down to an SBP of 130 mm Hg, and to an SBP 120-124 mm Hg in the meta-analysis with the greatest statistical power. In the Systolic Blood Pressure Intervention Trial (SPRINT) randomization to an SBP treatment goal of <120 mm Hg compared to <140 mm Hg in persons with high cardiovascular disease risk not only reduced the rate of cardiovascular disease but also all-cause mortality. These benefits were noted in all of the pre-stated subgroups of interest, including those ≥65 years of age at baseline. In addition, cognitive impairment was less common in those randomized to the intensive compared to standard treatment. Most clinical practice guidelines recommend an SBP treatment target <130 mm Hg in adults with a high risk of CVD, which is the norm for many patients seen in clinical practice, especially those who are older, have diabetes mellitus, or chronic kidney disease.

PMID:35390116 | DOI:10.1093/ajh/hpac045