Category: Statistics

Mol Oncol. 2022 Mar 1. doi: 10.1002/1878-0261.13204. Online ahead of print.

ABSTRACT

Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed Whole Exome Sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy-naïve and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC.

PMID:35231161 | DOI:10.1002/1878-0261.13204

Clin Infect Dis. 2022 Mar 1:ciac168. doi: 10.1093/cid/ciac168. Online ahead of print.

ABSTRACT

BACKGROUND: Although human case numbers of variant influenza viruses have increased worldwide, the epidemiology of human cases and human-to-human transmissibility of different variant viruses remain uncertain.

METHODS: We used descriptive statistics to summarize the epidemiologic characteristics of variant virus infections. The hospitalization rate, case-fatality and hospitalization-fatality risks were used to assess disease severity. Transmissibility of variant viruses between humans was determined by the effective reproductive number (Re) and probability of infection following exposure to human cases.

RESULTS: We identified 707 cases of variant viruses from 1959-2021, and their spatiotemporal/demographic characteristics changed across subtypes. The clinical severity of cases of variant viruses was generally mild; cases older than 18 years with underlying conditions were associated with hospitalization. Of 69 clusters of human infections with variant viruses (median cluster size: 2), the upper limit of Re was 0.09 (H1N1v, H1N2v and H3N2v: 0.20 vs. 0.18 vs. 0.05), while it was not significantly different from the pooled estimates for avian influenza A(H7N9) and A(H5N1) viruses (0.10). Moreover, contacts of H5N1 cases (15.7%) had a significantly higher probability of infection than contacts of individuals with H7N9 (4.2%) and variant virus infections (4.2-7.2%).

CONCLUSIONS: The epidemiology of cases of variant viruses varied across time periods, geographical regions and subtypes during 1959-2021. The transmissibility of different variant viruses between humans remains limited. However, given the continuous evolution of viruses and the rapidly evolving epidemiology of cases of variant viruses, improving the surveillance systems for human variant virus infections is needed worldwide.

PMID:35231106 | DOI:10.1093/cid/ciac168

Nicotine Tob Res. 2022 Mar 1;24(4):529-535. doi: 10.1093/ntr/ntab220.

ABSTRACT

INTRODUCTION: Macroeconomic studies have shown that young individuals who smoke, and have a low socioeconomic status respond more strongly to price increases. Most of this evidence stems from research on factory-made (FM) cigarettes. With the rising popularity of roll-your-own (RYO) tobacco, there is a need for studies on cigarette demand that distinguish between both.

AIMS AND METHODS: This study examined whether individual demand differed for FM and RYO tobacco, and across age, and socioeconomic (income and education) groups. Purchase tasks for FM and RYO cigarettes were included in the 2020 International Tobacco Control (ITC) Netherlands Survey. Adults who smoke daily (n = 1620) stated how many cigarettes they would smoke in 24 hours across eight prices. Four demand indices were derived: intensity (consumption at zero costs), alpha (rate of change in elasticity), Pmax (turning point elasticity), and breakpoint (lowest price where consumption equals zero). The indices were tested for subgroup differences.

RESULTS: Individuals who smoke RYO tobacco indicated higher intensity, and greater alpha than individuals who smoke FM cigarettes. Participants aged 25-39 had lower Pmax, and 18-24 year olds displayed higher breakpoints. Participants with low income displayed higher intensity, and lower Pmax than other income groups. No associations were found with education.

CONCLUSIONS: Individuals who smoke RYO tobacco indicated higher price sensitivity than those smoking FM cigarettes, supporting the need to harmonize tobacco taxation. Taxation may be especially beneficial to reducing consumption among individuals with a low income or smoke RYO tobacco. Substantially higher prices are needed in the Netherlands to achieve the desired results.

IMPLICATIONS: Individuals who smoke daily were willing to pay substantially higher prices than the current market prices, indicating the room and need for much higher taxation levels. Demand for RYO tobacco was more sensitive to price changes than demand for FM cigarettes. Taxation should be raised at equivalent rates for FM and RYO cigarettes. Taxation appears to be especially effective in reducing consumption among people who smoke RYO tobacco and low-income individuals. It remains important to combine increased taxation with other tobacco control measures.

PMID:35231115 | DOI:10.1093/ntr/ntab220

Age Ageing. 2022 Mar 1;51(3):afac011. doi: 10.1093/ageing/afac011.

ABSTRACT

BACKGROUND: ad hoc approaches are used to create composite indexes of intrinsic capacity (IC) based on five domains recommended by the World Health Organization for healthy ageing. We examined how combinations of domain-specific measures determine measurement performances of composite IC indexes.

METHODS: in this population-based prospective cohort study, community-dwelling older persons (N = 2,906) aged 55 years and above were recruited. We used 12 domain-specific measures: cognition (Mini-Mental State Examination, MMSE), psychological (Geriatric Depression Scale, GDS), locomotion (Timed Up-and Go [TUG], GV, Knee Extension Strength, Performance Orientated Mobility Assessment), sensory (logarithm of the Minimum Angle of Resolution [LogMAR] vision and Whisper Test hearing) and vitality (forced expiratory volume in 1 second pulmonary function, Elderly Nutritional Indicators for Geriatric Malnutrition Assessment [ENIGMA], Nutritional Screening Initiative) to derive 144 composite 2- to 5-domain functional health indexes (FHI), and evaluated their abilities to predict 9-year mortality and their associations with health determinants.

RESULTS: with 5-domain FHI, TUG, logMAR and MMSE showed the largest factor loadings (0.65-0.75). All single-domain FHI were significantly associated with mortality risks. Area under the receiver operating characteristic curve (AUC) values of mortality prediction increased with the number of domains (from mean 0.615 for single-domain FHI to mean 0.705 for 5-domain FHI), but the difference between 3-domain versus 4-domain FHI (P = 0.082) or versus 5-domain FHI (P = 0.109) was not statistically significant. Highest AUCs (P < 0.001) of best performing FHI were single-domain TUG: 0.735; 2-domain TUG + ENIGMA: 0.743; 3-domain TUG + LogMAR + ENIGMA: 0.762; 4-domain TUG + MMSE + LogMAR + ENIGMA: 0.757; 5-domain TUG + MMSE + GDS + LogMAR + ENIGMA: 0.751. FHI showed excellent construct validity based on correlations with known health determinants.

CONCLUSIONS: among Singaporean older adults, cognition, sensory and locomotion are predominant IC domains. A multi-domain IC index performs better with more domain measures, but a minimalist 3-domain index performs just as robustly as a 4- or 5-domain index.

PMID:35231090 | DOI:10.1093/ageing/afac011

PLoS One. 2022 Mar 1;17(3):e0264653. doi: 10.1371/journal.pone.0264653. eCollection 2022.

ABSTRACT

BACKGROUND: Pancreatic cancer is associated with a high thromboembolism risk. We investigated the significance of early venous thromboembolism (VTE) detection in patients with unresectable metastatic pancreatic cancer (UR-MPC) who received first-line chemotherapy with gemcitabine plus nab-paclitaxel (GnP).

METHODS: This single-center retrospective study enrolled 174 patients with UR-MPC who underwent GnP as a first-line chemotherapy from April 2017 to March 2020. The early detection of VTE (deep venous thrombosis and pulmonary thromboembolism) was defined as diagnosis by the first follow-up CT scan after the initiation of chemotherapy. We compared the patients with early detection of VTE (VTE (+) group) with the others (VTE (-) group). We examined overall survival (OS), progress free survival (PFS), severe adverse events, and predictors associated with OS using the Cox proportional hazards model.

RESULTS: Early detection of VTE was observed in 17 patients (9.8%). Thirteen patients were diagnosed with VTE at treatment initiation, and four patients were diagnosed after treatment initiation. The median time to diagnosis after treatment initiation was 55 days (range: 31-71 days). Only 3 patients were symptomatic. The VTE (+) group exhibited worse OS and PFS than the VTE (-) group (OS: 259 days vs. 400 days, P < 0.001; PFS: 120 days vs. 162 days, P = 0.008). The frequency of grade 3-4 adverse events was not significantly different. Although the performance status was poorer in the VTE (+) group, VTE was identified as a statistically significant independent predictor for OS in multivariate analyses (HR, 1.87; 95% CI, 1.02-3.44; P = 0.041).

CONCLUSIONS: Early VTE detection is a predictor of a poor prognosis in UR-MPC patients who receive GnP as first-line chemotherapy, suggesting that screening VTE for patients with UR-MPC is crucial, even if patients are asymptomatic.

PMID:35231078 | DOI:10.1371/journal.pone.0264653

PLoS One. 2022 Mar 1;17(3):e0264788. doi: 10.1371/journal.pone.0264788. eCollection 2022.

ABSTRACT

OBJECTIVE: To quantitatively study the effect of the labial inclination of the mandibular central incisors on the surrounding cortical and cancellous-bone morphology among patients with low-angle, skeletal class III malocclusion, by using cone-beam computed-tomography (CBCT) imaging.

MATERIALS AND METHODS: The CBCT images of 60 patients with low-angle, skeletal class III malocclusion were divided into lingual-inclination, upright, and labial-inclination groups. The height of the alveolar bone and the thickness and area of the cortical, cancellous, and total alveolar bone were measured separately on each side of the mandibular central incisors.

RESULTS: The thickness of the labial cortical bone from 6 mm below the cementoenamel junction (CEJ) to the root apex; the thickness of the labial cancellous bone at the root apex; the total thickness of the alveolar bone at the root apex; the area of labial cortical bone; the total area of labial alveolar bone; and the height of the labial alveolar bone were highest in the labial-inclination group (all P<0.05). All these variables were positively correlated with the labial inclination of the mandibular central incisors (all P<0.05). There were no statistical differences between the groups for any of the measurements on the lingual side of the teeth (P>0.05).

CONCLUSION: The morphology of the alveolar bone on the labial but not the lingual side of the mandibular central incisors was statistically significantly correlated with the labial inclination of those teeth in patients with low-angle, skeletal class III malocclusion.

PMID:35231080 | DOI:10.1371/journal.pone.0264788

PLoS One. 2022 Mar 1;17(3):e0264679. doi: 10.1371/journal.pone.0264679. eCollection 2022.

ABSTRACT

BACKGROUND: In association with the epidemiological, nutritional and demographic transition, many research findings showed that the number of risk factors that leads to increased prevalence of hypertension in low and middle income countries like Ethiopia is increasing. Several urban specific studies conducted in Ethiopia showed varying prevalence of hypertension. The aim of this study was to determine prevalence of hypertension and to identify factors associated with hypertension in Hawassa city administration, Southern Ethiopia.

METHODS: A community-based cross sectional study was carried out in Hawassa city administration in 2017. A multi-stage sampling technique was used to select 612 study participants. Descriptive statistics was used to describe socio-demographic, behavioral and anthropometric variables. The economic status of household, ‘wealth index’, was constructed by running principal component analysis. Binary logistic regression analysis was performed to assess factors associated with hypertension at 95%CI.

RESULTS: The overall prevalence of hypertension was 21.2% (95% CI: 18.1-24.7), (24.5% for urban and 14.7% for peri-urban). About two fifths of hypertension cases (42.3%) were newly diagnosed with elevated blood pressure during data collection. Age, occupation, wealth status, consuming vegetables and animal fat, usual mode of transport, body mass index (BMI), family history of hypertension and existence of diabetes were associated with presence of hypertension at 95%CI. The average diastolic blood pressure for urban was 2.18mmHg higher than that of peri-urban groups (p-0.01).

CONCLUSION: More than one fifth of study participants had hypertension and about two fifths of hypertension cases were newly diagnosed. Health communication should be strengthened focusing on identified risk factors and attention should be given to early detect and tackle the effects of hypertension in resource limited setting.

PMID:35231073 | DOI:10.1371/journal.pone.0264679

PLoS One. 2022 Mar 1;17(3):e0264583. doi: 10.1371/journal.pone.0264583. eCollection 2022.

ABSTRACT

OBJECTIVES: To evaluate the incidence, etiologies, and clinical outcomes of secondary postpartum hemorrhage in a hospital with a high cesarean section rate and to compare the etiologies of secondary postpartum hemorrhage following cesarean delivery versus vaginal delivery.

MATERIALS AND METHODS: This retrospective study included 123 women with secondary postpartum hemorrhage who were treated at a tertiary-level hospital between January 2004 and June 2018. Descriptive statistics and the chi-square test were used for data analysis.

RESULTS: The incidence of secondary postpartum hemorrhage was 0.21%. The median onset of bleeding was 12 days after delivery. Fifty-two percent of the deliveries were by cesarean section. The most common etiology of secondary postpartum hemorrhage was endometritis (67.5%), followed by retained placental tissue (21.1%). Women who delivered by cesarean section had a higher rate of endometritis (80.0% vs 53.4%) and a lower rate of retained placental tissue (10.8% vs. 32.8%) than those who delivered vaginally. Surgical intervention included uterine evacuation in 29.3% and hysterectomy in 8.1% of the patients. Five percent of women were treated by embolization.

CONCLUSIONS: Endometritis was the most common cause of secondary postpartum hemorrhage. Women who delivered by cesarean section were less likely to have retained placental tissue but were at higher risk for endometritis and uterine pseudoaneurysm than those who delivered vaginally.

PMID:35231065 | DOI:10.1371/journal.pone.0264583

PLoS One. 2022 Mar 1;17(3):e0264733. doi: 10.1371/journal.pone.0264733. eCollection 2022.

ABSTRACT

OBJECTIVE: Trophoblast inclusions-cross sections of abnormal trophoblast bilayer infoldings-have previously been associated with aneuploidy, placenta accreta, and prematurity. This study was conducted to establish the relationship between trophoblast inclusions and a range of placental, pregnancy, and birth outcomes in a patient population with high smoking and alcohol exposure. Specifically, we sought to evaluate the association between the presence of trophoblast inclusions and 1) three primary birth outcomes: full-term birth, preterm birth, and stillbirth; 2) gestational age at delivery; and 3) specific placental pathologies.

METHODS: Two slides containing chorionic villi were evaluated from 589 placentas that were collected from Stellenbosch University in Cape Town, South Africa as part of the prospective, multicenter cohort Safe Passage Study of the Prenatal Alcohol and SIDS and Stillbirth Network. The subsample included 307 full-term live births, 212 preterm live births, and 70 stillbirths.

RESULTS: We found that the odds of identifying at least one trophoblast inclusion across two slides of chorionic villi was significantly higher for placentas from preterm compared to term liveborn deliveries (OR = 1.74; 95% CI: 1.22, 2.49, p = 0.002), with an even greater odds ratio for placentas from stillborn compared to term liveborn deliveries (OR = 4.95; 95% CI: 2.78, 8.80, p < 0.001). Gestational age at delivery was inversely associated with trophoblast inclusion frequency. Trophoblast inclusions were significantly associated with small for gestational age birthweight, induction of labor, villous edema, placental infarction, and inflammation of the chorionic plate.

CONCLUSIONS: The novel associations that we report warrant further investigation in order to understand the complex network of biological mechanisms through which the factors that lead to trophoblast inclusions may influence or reflect the trajectory and health of a pregnancy. Ultimately, this line of research may provide critical insights that could inform both clinical and research applications.

PMID:35231069 | DOI:10.1371/journal.pone.0264733

PLoS One. 2022 Mar 1;17(3):e0264740. doi: 10.1371/journal.pone.0264740. eCollection 2022.

ABSTRACT

INTRODUCTION: Analytic approaches to clinical validation of results from preclinical models are important in assessment of their relevance to human disease. This systematic review examined consistency in reporting of glioblastoma cohorts from The Cancer Genome Atlas (TCGA) or Chinese Glioma Genome Atlas (CGGA) and assessed whether studies included patient characteristics in their survival analyses.

METHODS: We searched Embase and Medline on 02Feb21 for studies using preclinical models of glioblastoma published after Jan2008 that used data from TCGA or CGGA to validate the association between at least one molecular marker and overall survival in adult patients with glioblastoma. Main data items included cohort characteristics, statistical significance of the survival analysis, and model covariates.

RESULTS: There were 58 eligible studies from 1,751 non-duplicate records investigating 126 individual molecular markers. In 14 studies published between 2017 and 2020 using TCGA RNA microarray data that should have the same cohort, the median number of patients was 464.5 (interquartile range 220.5-525). Of the 15 molecular markers that underwent more than one univariable or multivariable survival analyses, five had discrepancies between studies. Covariates used in the 17 studies that used multivariable survival analyses were age (76.5%), pre-operative functional status (35.3%), sex (29.4%) MGMT promoter methylation (29.4%), radiotherapy (23.5%), chemotherapy (17.6%), IDH mutation (17.6%) and extent of resection (5.9%).

CONCLUSION: Preclinical glioblastoma studies that used TCGA for validation did not provide sufficient information about their cohort selection and there were inconsistent results. Transparency in reporting and the use of analytic approaches that adjust for clinical variables can improve the reproducibility between studies.

PMID:35231064 | DOI:10.1371/journal.pone.0264740