Category: Nevin Manimala

Lifetime Data Anal. 2022 Mar 29. doi: 10.1007/s10985-022-09550-y. Online ahead of print.

ABSTRACT

This paper discusses the fitting of the proportional hazards model to interval-censored failure time data with missing covariates. Many authors have discussed the problem when complete covariate information is available or the missing is completely at random. In contrast to this, we will focus on the situation where the missing is at random. For the problem, a sieve maximum likelihood estimation approach is proposed with the use of I-spline functions to approximate the unknown cumulative baseline hazard function in the model. For the implementation of the proposed method, we develop an EM algorithm based on a two-stage data augmentation. Furthermore, we show that the proposed estimators of regression parameters are consistent and asymptotically normal. The proposed approach is then applied to a set of the data concerning Alzheimer Disease that motivated this study.

PMID:35352270 | DOI:10.1007/s10985-022-09550-y

Pharm Res. 2022 Mar 29. doi: 10.1007/s11095-022-03244-8. Online ahead of print.

ABSTRACT

BACKGROUND: Although kinase inhibitors (KIs) are generally effective, their use has a large impact on the current health care budget. Dosing strategies to reduce treatment costs are warranted. Boosting pharmacokinetic exposure of KIs metabolized by cytochrome P450 (CYP)3A4 with ritonavir might result in lower doses needed and subsequently reduces treatment costs. This study is a proof-of-concept study to evaluate if the dose of erlotinib can be reduced by co-administration with ritonavir.

METHODS: In this open-label, cross-over study, we compared the pharmacokinetics of monotherapy erlotinib 150 mg once daily (QD) (control arm) with erlotinib 75 mg QD plus ritonavir 200 mg QD (intervention arm). Complete pharmacokinetic profiles at steady-state were taken up to 24 h after erlotinib intake for both dosing strategies.

RESULTS: Nine patients were evaluable in this study. For the control arm, the systemic exposure over 24 h, maximum plasma concentration and minimal plasma concentration of erlotinib were 29.3 μg*h/mL (coefficient of variation (CV):58%), 1.84 μg/mL (CV:60%) and 1.00 μg/mL (CV:62%), respectively, compared with 28.9 μg*h/mL (CV:116%, p = 0.545), 1.68 μg/mL (CV:68%, p = 0.500) and 1.06 μg/mL (CV:165%, p = 0.150) for the intervention arm. Exposure to the metabolites of erlotinib (OSI-413 and OSI-420) was statistically significant lower following erlotinib plus ritonavir dosing. Similar results regarding safety in both dosing strategies were observed, no grade 3 or higher adverse event was reported.

CONCLUSIONS: Pharmacokinetic exposure at a dose of 75 mg erlotinib when combined with the strong CYP3A4 inhibitor ritonavir is similar to 150 mg erlotinib. Ritonavir-boosting is a promising strategy to reduce erlotinib treatment costs and provides a rationale for other expensive therapies metabolized by CYP3A4.

PMID:35352280 | DOI:10.1007/s11095-022-03244-8

Cir Cir. 2022;90(2):236-241. doi: 10.24875/CIRU.20001199.

ABSTRACT

OBJECTIVE: To compare the ONSD measured by ultrasound and tomography in patients with a diagnosis of intracranial hypertension.

METHOD: Prospective, transversal, observational, analytical study. 105 patients were included, divided into two groups: healthy (control group) and patients presenting clinical data of intracranial hypertension (study group). ONSD was measured by ultrasound and tomography. The Kruskal-Wallis test was used to compare the ONSD between the patients, and the Spearman test was used to assess the correlation between USG and CT. A value of p <0.05 was considered statistically significant.

RESULTS: Of the 105 patients, 58.1% were men and 41.9% women. The study group included 14 patients with TBI, CVD, intracranial neoplasia, or neuroinfection. The highest median of ONSD by Ultrasound was in the CVD group, followed by TBI, neoplasia and neuroinfection and the lowest was in the control group (7.5, 7.0, 6.8, 6.8 and 5.2 mm respectively); these differences being statistically significant (p < 0.001). In the correlation analysis between Ultrasound and CT, a good statistically significant positive correlation was found (rho = 0.893, p < 0.001).

CONCLUSIONS: The ultrasound evaluation of ONSD has proven to be a reliable test for the diagnosis and non-invasive monitoring of intracranial hypertension.

PMID:35350061 | DOI:10.24875/CIRU.20001199

J Natl Cancer Inst. 2022 Mar 29:djac042. doi: 10.1093/jnci/djac042. Online ahead of print.

ABSTRACT

BACKGROUND: The ongoing debate of whether use of cellular telephones increases the risk of developing a brain tumor was recently fueled by the launch of the fifth generation of wireless technologies. Here, we update follow-up of a large-scale prospective study on the association between cellular telephone use and brain tumors.

METHODS: During 1996-2001, 1.3 million women born in 1935-1950 were recruited into the study. Questions on cellular telephone use were first asked in median year 2001 and again in median year 2011. All study participants were followed via record linkage to National Health Services databases on deaths and cancer registrations (including nonmalignant brain tumors).

RESULTS: During 14 years follow-up of 776 156 women who completed the 2001 questionnaire, a total of 3268 incident brain tumors were registered. Adjusted relative risks for ever vs never cellular telephone use were 0.97 (95% confidence interval = 0.90 to 1.04) for all brain tumors, 0.89 (95% confidence interval = 0.80 to 0.99) for glioma, and not statistically significantly different to 1.0 for meningioma, pituitary tumors, and acoustic neuroma. Compared with never-users, no statistically significant associations were found, overall or by tumor subtype, for daily cellular telephone use or for having used cellular telephones for at least 10 years. Taking use in 2011 as baseline, there were no statistically significant associations with talking for at least 20 minutes per week or with at least 10 years use. For gliomas occurring in the temporal and parietal lobes, the parts of the brain most likely to be exposed to radiofrequency electromagnetic fields from cellular telephones, relative risks were slightly below 1.0.

CONCLUSION: Our findings support the accumulating evidence that cellular telephone use under usual conditions does not increase brain tumor incidence.

PMID:35350069 | DOI:10.1093/jnci/djac042

Public Health Genomics. 2022 Mar 29:1-9. doi: 10.1159/000521971. Online ahead of print.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder characterized by chronic anovulation, infertility, polycystic ovaries, and hyperandrogenic signs.

OBJECTIVE: The aim of this study was to determine the association of luteinizing hormone/chorionic gonadotropin hormone receptor LHCGR polymorphism (rs2293275) with oligomenorrhea, amenorrhea, hirsutism, acne, infertility, LH, LH/FSH ratio, and body mass index (BMI) among PCOS females.

METHODS: This genetic case-control study recruited 55 PCOS and 55 control females, diagnosed based on the Rotterdam criteria. LH and FSH were measured by the Roche cobas c 502 automated analyzer. Genotypic analysis was carried out using the polymerase chain reaction-restriction fragment length polymorphism and restriction endonuclease digestion.

RESULTS: BMI was higher for PCOS patients (28.5 ± 6.59) compared to controls (25.1 ± 5.77), and ovulatory dysfunction was seen among 90% of PCOS females. Oligomenorrhea was common in PCOS (73%), and hirsutism and acne were detected in PCOS (80% and 40%; respectively). LH ≥10 were recoded among 51%, while LH/FSH ≥1.5 was recorded among 33% PCOS females. There is a statistical difference between rs2293275 polymorphism in the AG genotype between PCOS patients and controls. PCOS patients have a significantly higher mean LH level compared to controls (8.36 ± 4.86 and 5.67 ± 2.51, respectively) and showed higher LH/FSH value (1.46 ± 0.81) compared to (0.87 ± 0.30) controls. GG and AG genotypes of LHCGR showed statistically significant higher LH (8.22 ± 4.11; 9.02 ± 3.87) and LH/FSH values (1.57 ± 0.56; 1.64 ± 0.89) compared to controls.

CONCLUSION: LHCGR (rs2293275) GA and GG genetic variants could modulate the hormonal levels of PCOS LH levels and the LH/FSH ratio and associated with hirsutism, oligomenorrhea, BMI, and LH/FSH ratio as risk factors.

PMID:35350019 | DOI:10.1159/000521971

Cir Cir. 2022;90(2):242-247. doi: 10.24875/CIRU.20001237.

ABSTRACT

OBJECTIVE: Bull-horn injuries (BHI) are unique and there is reduced published literature about it. We present an analysis of a 11-year BHI case series.

METHOD: Study of 138 cases developed during a 11-year period with hospitalization admission greater than 24 hours with diagnosis of BHI/contusion. We classified patients in two groups: group A, patients undergoing procedures under general anaesthesia and group B undergoing procedures under local anaesthesia. Variables: age, sex, date, hospitalization length, main region affected, Comprehensive complication index (CCI, ISS, intensive care unit (ICU) admission, stay and mortality. Statistical analysis: t-Student test, ANOVA, χ² and linear or logistic regression.

RESULTS AND CONCLUSIONS: ISS was related to hospital stay, CCI, ICU admission and type of treatment applied. The comparative statistical analysis of variables between both groups determined a significant difference in age, ISS and hospitalization length, being greater in those belonging to group A. There is a more risk of undergoing surgery by increasing age, ISS and presenting the wounds in thorax-abdomen-pelvis area. CCI may be a good method of quantifying postoperatory morbidity in polytraumatized patients or in other areas besides the abdomen.

PMID:35350059 | DOI:10.24875/CIRU.20001237

J Phys Act Health. 2022 Mar 29:1-11. doi: 10.1123/jpah.2021-0305. Online ahead of print.

ABSTRACT

BACKGROUND: The long-term parallel changes of physical activity and body mass index (BMI) in the adult population are still unclear. The present study assessed the association between physical activity and BMI over time, considering obesity risk trajectory groups and sex strata.

METHODS: Total sample of 6897 adults was followed for an average of 12 years. The reliable and validated Iranian version of the Modifiable Activity Questionnaire measured physical activity. After determining the risk clusters in each reexamination using a 2-step cluster analysis, the latent growth curve modeling was used to identify distinct subgroups of individuals following a similar change of risk cluster over time. Latent growth curve modeling estimated the parameters of cross-sectional, prospective, and parallel associations.

RESULTS: Three trajectories were identified, including stable low risk, unstable risk, and stable high risk. The results showed significant increases in BMI (kg/m2/year) for the stable low-risk trajectory group 0.478 (95% confidence interval [CI] 0.444 to 0.513), unstable risk 0.360 (95% CI, 0.324 to 0.396), and those in the stable high-risk trajectory group 0.255 (95% CI, 0.221 to 0.289). In cross-sectional -0.483 kg/m2 (95% CI, -0.836 to -0.129) and parallel -0.93 kg/m2 (95% CI, -1.862 to 0.00) estimations, significant statistical associations were observed in the stable high-risk trajectory group.

CONCLUSIONS: The current results showed that changes in physical activity could slightly affect BMI only in stable high-risk adults.

PMID:35349978 | DOI:10.1123/jpah.2021-0305

Ultramicroscopy. 2022 Mar 10;236:113493. doi: 10.1016/j.ultramic.2022.113493. Online ahead of print.

ABSTRACT

When the Al-Mg-Si(-Cu) alloy system is subjected to age hardening, different types of precipitates nucleate depending on the composition and thermomechanical treatment. The main hardening precipitates extend as needles, laths or rods along the <100> directions in the aluminium matrix. It has been found that the structures of all metastable precipitates may be generalized as stacks of <100> columns, where most of these columns are replaced by solute elements. In the precipitates, a column relates to neighbour columns by a set of simple structural principles, which allows identification of species and relative longitudinal displacement over the (100) cross-section. Aberration-corrected high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) is an important tool for studying such precipitates. With the goal of analysing atomic resolution HAADF-STEM images of precipitate cross-sections in the Al-Mg-Si(-Cu) system, we have developed the stand-alone software AutomAl 6000, which features a column characterization algorithm based on the symbiosis of a statistical model and the structural principles formulated in a digraph-like framework. The software can semi-autonomously determine the 3D column positions in the image, as well as column species. In turn, AutomAl 6000 can then display, analyse and/or export the structure data. This paper describes the methodology of AutomAl 6000 and applies it on three different HAADF-STEM images, which demonstrate the methodology. The software, as well as other resources, are available at http://automal.org. The source code is also directly available from https://github.com/Haawk666/AutomAl-6000.

PMID:35349939 | DOI:10.1016/j.ultramic.2022.113493

Drug Alcohol Depend. 2022 Mar 5;234:109396. doi: 10.1016/j.drugalcdep.2022.109396. Online ahead of print.

ABSTRACT

BACKGROUND: A large HIV outbreak in People Who Inject Drugs (PWID) occurred in Athens, Greece in 2011-2013. In response, opioid substitution treatment (OST) and needle and syringe programs (NSP) were scaled-up and a seek-test-treat program was introduced in mid-2012. We aim to assess the impact of these interventions.

METHODS: A mathematical model of HIV transmission among PWID was calibrated to data available over time (2009-2013) on HIV prevalence, NSP/antiretroviral treatment (ART) coverage and high-risk injection. A combined interventions scenario, including decrease in high-risk injection through linkage to OST and modification of risk behaviours and access to NSP and ART, was compared to a counterfactual scenario (no improvement at the levels of these interventions), with HIV incidence being the main outcome.

RESULTS: HIV incidence increased from <0.1 new cases/100 person-years (in 2099) to 11.0 new cases/100 person-years (in 2012). Under both models, a subsequent decline was projected following early 2012, with incidence at the end of 2013 in the combined interventions scenario being lower by 77% compared to the counterfactual. The projected reduction in incidence under the intervention scenario was in agreement with empirical data. HIV prevalence would have escalated to 20.4% (95% CrI: 16.9%, 23.6%) in 2013 under the counterfactual scenario (vs. 16.8% (95% CrI: 11.2%, 23.0%) under the combined interventions scenario). In total, 31.4% of HIV cases (392) were averted over 2012-2013.

CONCLUSION: These results underline the importance of high-coverage harm reduction programs and of community-based interventions to rapidly reach PWID most in need.

PMID:35349919 | DOI:10.1016/j.drugalcdep.2022.109396

Acta Psychol (Amst). 2022 Mar 26;226:103577. doi: 10.1016/j.actpsy.2022.103577. Online ahead of print.

ABSTRACT

INTRODUCTION: China emerged from the first wave of COVID-19 in a short period of time and returned to normal economic and living order nationwide, making China’s entry into the post-COVID-19 epidemic period since April 2020. However, the COVID-19 epidemic had a great impact on young adults’ psychological status and may continue into the post-epidemic period. The enormous economic, employment and entrepreneurship pressures of this period may exacerbate this negative impact. This study investigated the depression status of the young adults and put forward the suggestions on how to strengthen the psychological crisis intervention and social security to cultivate the resilience of the young adults after major public health emergencies.

METHODS: This study conducted a questionnaire survey to identify the prevalence of depressive symptoms and explore the associated factors of depressive symptoms among 1069 young adults in X City, Hubei province in September 2020. And the multistage stratified random sampling method was used for sampling. Depressive symptoms were measured using the 10-item version of the Center for Epidemiological Studies Depression Scale (CES-D-10). Descriptive statistics and logistic regression analysis were adopted for statistical analysis.

RESULTS: 1069 respondents (67.68% male; mean age = 28.87 ± 4.18 years; age range = 18-35 years) were included in final analyses. About 25.9% of the respondents reported depressive symptoms (CES-D-10 score = 7.28 ± 3.85). Age, marital status, employment status, monthly disposable income, the cognition, experience and social relationship of the COVID-19 epidemic, and regional discrimination were significantly associated with depressive symptoms. Being male (P = 0.025), age of 25-29 years (P = 0.011), having a household size with 4-5 (P = 0.01) and more than 8 (P = 0.012) family members, a little pessimism about the prospect of COVID-19 epidemic prevention and control (P = 0.044), often (P = 0.018) or always (P = 0.009) participation in anti-epidemic volunteer work were likely to lead to depressive symptoms.

CONCLUSIONS: In the post-COVID-19 epidemic period, the psychological status of young people is generally stable, but some of them are depressed. Life, work and mental stress affect the generation of depressive symptoms among the young adults.

PMID:35349926 | DOI:10.1016/j.actpsy.2022.103577