Category: Nevin Manimala

Pharm Stat. 2022 May;21(3):535-565. doi: 10.1002/pst.2185. Epub 2021 Dec 23.

ABSTRACT

The paper addresses estimating and testing treatment effects with multivariate outcomes in clinical trials where imperfect diagnostic devices are used to assign subjects to treatment groups. The paper focuses on the pre-post design and proposes two novel methods for estimating and testing treatment effects. In addition, methods for sample size and power calculations are developed. The methods are compared with each other and with a traditional method in a simulation study. The new methods show significant advantages in terms of power, coverage probability, and required sample size. The application of the methods is illustrated with data from electroencephalogram (EEG) recordings of alcoholic and control subjects.

PMID:35475593 | DOI:10.1002/pst.2185

Alcohol Alcohol. 2022 Apr 26:agac023. doi: 10.1093/alcalc/agac023. Online ahead of print.

ABSTRACT

AIMS: To conduct an overview and systematic evaluation of prospective cohort studies on whether alcohol intake is associated with the incidence and progression of periodontitis.

METHODS: Nine databases were searched by two independent reviewers up to November 2021 according to prespecified eligibility criteria. Risk of Bias in Systematic Reviews and Risk of Bias in Non-Randomized Studies of Interventions were used for risk of bias assessment and certainty of evidence was assessed using the GRADE approach. Random-effects pair-wise meta-analyses were performed with data from cohort studies on the effects of higher levels of alcohol intake compared with current non-drinking to determine risk ratios (RR) and confidence intervals of periodontitis.

RESULTS: The four systematic reviews were at high risk of bias and concluded that alcohol intake is associated with periodontitis regardless of the study design. Five reports from seven cohort studies contributed to the meta-analyses and no statistically significant differences were found for higher levels of consumption regarding the risk of periodontitis, except for men from countries with low- and high-middle socio-demographic index (RR = 1.30, 95% CI: 1.13-1.46), with low certainty evidence.

CONCLUSION: Higher levels of alcohol consumption seem to be part of the causal mechanism of periodontitis when cooccurring with male sex in underdeveloped countries. No conclusion can be drawn regarding alcohol use disorders or patterns of consumption.

PMID:35475575 | DOI:10.1093/alcalc/agac023

Hum Mutat. 2022 Apr 27. doi: 10.1002/humu.24392. Online ahead of print.

ABSTRACT

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome where individuals are predisposed to tumor development in the brain, adrenal gland, kidney and other organs. It is caused by pathogenic variants in the VHL tumor suppressor gene. Standardized disease information has been difficult to collect due to the rarity and diversity of VHL patients. Over 4100 unique articles published until October 2019 were screened for germline genotype-phenotype data. Patient data was translated into standardized descriptions using Human Genome Variation Society (HGVS) gene variant nomenclature and Human Phenotype Ontology (HPO) terms and has been manually curated into an open-access knowledgebase called Clinical Interpretation of Variants in Cancer (CIViC). In total, 634 unique VHL variants, 2882 patients and 1991 families from 427 papers were captured. We identified relationship trends between phenotype and genotype data using classic statistical methods and spectral clustering unsupervised learning. Our analyses reveal earlier onset of pheochromocytoma/paraganglioma and retinal angiomas, phenotype co-occurrences and genotype-phenotype correlations including hot-spots. It confirms existing VHL associations and can be used to identify new patterns and associations in VHL disease. Our database serves as an aggregate knowledge translation tool to facilitate sharing information about the pathogenicity of VHL variants. This article is protected by copyright. All rights reserved.

PMID:35475554 | DOI:10.1002/humu.24392

Mol Syst Biol. 2022 Apr;18(4):e10824. doi: 10.15252/msb.202110824.

ABSTRACT

Clinical immunity to P. falciparum malaria is non-sterilizing, with adults often experiencing asymptomatic infection. Historically, asymptomatic malaria has been viewed as beneficial and required to help maintain clinical immunity. Emerging views suggest that these infections are detrimental and constitute a parasite reservoir that perpetuates transmission. To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a T_H2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T-cell function, and CTLA-4 as a predicted regulator in these processes. As proof of concept, we demonstrated a role for CTLA-4 in the development of asymptomatic parasitemia in infection models. The results suggest that asymptomatic malaria is not innocuous and might not support the induction of immune processes to fully control parasitemia or efficiently respond to malaria vaccines.

PMID:35475529 | DOI:10.15252/msb.202110824

Curr Med Res Opin. 2022 Apr 27:1-14. doi: 10.1080/03007995.2022.2070377. Online ahead of print.

ABSTRACT

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the relationship between glaucoma and the risk of Parkinson’s disease.

METHODS: A systematic search of databases including MEDLINE, EMBASE, and CINAHL were conducted. Grey literature search, including Dissertations and Theses databases and conference abstracts, was performed. Duplicates were removed, and two independent reviewers conducted the screening. We included any primary observational studies that examined the relationship between glaucoma and Parkinson’s disease. Study characteristics along with relevant outcome measurements such as hazard ratio (HR), odds ratio (OR), and prevalence were extracted. Meta-analysis using STATA 15.0 was performed, and the presence of heterogeneity was determined using I² statistics, Z-test, and p-value.

RESULTS: A total of 746 citations were found through the databases and grey literature searches. After screening, five studies met the inclusion criteria, and three studies were included in the meta-analysis. There was a non-significant hazard of developing Parkinson’s disease (Hazard Ratio =1.13, 95% CI:[0.99, 1.29]) in patients with glaucoma compared to controls.

DISCUSSION: The hazard of developing Parkinson’s disease was non-significantly different for those with glaucoma compared to controls; however, there were not enough studies available to draw definitive conclusions.

PMID:35475495 | DOI:10.1080/03007995.2022.2070377

Cogn Behav Ther. 2022 Apr 27:1-14. doi: 10.1080/16506073.2022.2058996. Online ahead of print.

ABSTRACT

Cognitive processing therapy (CPT) and prolonged exposure therapy (PE) are effective psychotherapies for post-traumatic stress disorder (PTSD). However, these treatments also have high rates of dropout and non-response. Therefore, patients may need a second course of treatment. We compared outcomes for patients who switched between CPT/PE and those who repeated CPT/PE during a second course of treatment. We collected data from Iraq and Afghanistan war veterans (n = 2,958) who received a second course of CPT/PE in the Veterans Health Administration from 2001 to 2017 and had symptom outcomes (PTSD checklist; PCL). We measured the association between treatment sequence and change in PCL score over the second course of treatment using hierarchical Bayesian regression, adjusted for sociodemographic and clinical characteristics. All treatment sequences showed a significant reduction in PCL score over time (β = -4.80; HDI₉₅: -5.74, -3.86). Veterans who switched from CPT to PE had modestly greater PCL reductions during the second course than those who repeated CPT. However, no significant difference in PCL change during the second course was observed between veterans who repeated PE and those who switched from PE to CPT. Veterans participating in a second course of CPT/PE can benefit, and switching treatment may be slightly more beneficial following CPT.

PMID:35475499 | DOI:10.1080/16506073.2022.2058996

Kardiol Pol. 2022 Apr 27. doi: 10.33963/KP.a2022.0110. Online ahead of print.

ABSTRACT

BACKGROUND: The implantable cardioverter-defibrillator (ICD) and subcutaneous cardioverter-defibrillator (S-ICD) are well-accepted life-saving devices for potentially lethal ventricular arrhythmia but little is known about quality of life (QoL) in patients with S-ICD and ICD.

AIMS: The aim of our study was to compare QoL of patients with S-ICD and ICD.

METHODS: All consecutive patients who have had S-ICD implanted between October 2015 and September 2021 were included to the study. A cohort of TV-ICD patients was matched to S-ICD subjects by sex, age, indications for the device, and type of prevention. All patients were requested to fulfill two standardized questionnaires to assess QoL: 36-Item Short Form Health Survey (SF-36) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) 6 months after device implantation.

RESULTS: Patients with S-ICD (n = 49) and TV-ICD (n = 49) did not differ regarding baseline characteristics. There were no statistically significant differences between S-ICD and TV-ICD subgroup, both for mental and physical QoL assessed in SF-36 and MLHFQ (all P = NS). The median MLHFQ total score was 24 (9-41) for S-ICD and 28 (14-43) for TV-ICD (P = 0.83). The median total score for the SF-36 questionnaire was 62.5 (29-86) vs. 59 (38-77) for S-ICD and TV-ICD, respectively (P = 0.78).

CONCLUSIONS: Quality of life after device implantation does not differ significantly between a group of patients with subcutaneous and conventional implantable cardioverter-defibrillator.

PMID:35475461 | DOI:10.33963/KP.a2022.0110

Br J Nutr. 2022 Apr 27:1-15. doi: 10.1017/S0007114522001295. Online ahead of print.

ABSTRACT

Studying the dynamic patterns of dietary changes or stability (otherwise known as dietary trajectories) across the life course can provide important information about when and in whom to intervene with nutritional interventions. This article reviews evidence from longitudinal studies that describe dietary trajectories through the different life stages, covering early life, adolescence to young adulthood and from mid to late adulthood. Current findings suggest that the establishment of diet patterns likely occurs before 3 years of age and allude to other potential ‘windows of change’ in the life course such as the period 7 – 9 years of age and during the period of adolescence and early adulthood. Examining diets using various diet parameters appears to be valuable in elucidating different aspects of the diet that can be changed to potentially alter trajectories. In adults, examining long-term diet trends at a population level can reveal shifts in eating patterns as countries undergo epidemiological and nutrition transitions, and elucidate the longer-term impact of adherence to particular diets on the development of chronic diseases. While challenges such as the availability of adequate diet data points, consistency in the dietary assessment tools used and the limitations of statistical methods for trajectory modelling remain, integrating diet data with other lifestyle behaviours, high-dimensional biomarkers and genetics data into pattern analyses and examining them from a longitudinal approach opens up potential opportunities to gain deeper insights into diet-disease relationships and support the development of more holistic lifestyle-disease prevention recommendations stratified for population groups.

PMID:35475441 | DOI:10.1017/S0007114522001295

Gynecol Endocrinol. 2022 Apr 27:1-5. doi: 10.1080/09513590.2022.2068521. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the changes in CRH concentrations in the blood serum of pregnant women and in the placenta of patients after the 41st week of gestation, and to determine its influence on the effectiveness of inducing labor and its progress.

MATERIALS AND METHODS: The study group comprised pregnant patients who did not deliver until the 41 week of gestation (n = 114). The control group was divided into two subgroups: patients in whom delivery started spontaneously before the 41st week of gestation (n = 24) and pregnant patients in whom delivery started spontaneously after the 41st week of gestation (n = 23). Blood serum and placenta were obtained from the patients. Corticoliberin originating from blood serum was assessed with the use of ELISA Kit. Parts of the placenta were stained with monoclonal antibodies for the presence of corticoliberin, corticoliberin receptors 1 and 2.

RESULTS: No statistically significant differences were found with regard to corticoliberin concentrations in the blood or during a qualitative assessment of the number of CRH R1 in the placenta between the research groups. However, corticoliberin receptor 2 had a statistically higher expression rate in the control group in which the delivery started spontaneously before the 41st week of gestation.

CONCLUSION: In post-term pregnancy, the up-regulation of CRH R2 receptor is disturbed with no change in CRH R1 expression, which complicates the initiation of labor despite correct corticoliberin levels in both blood serum and the placenta. Pregnancy duration over 41 weeks and the effectiveness of preinducing or inducing labor do not depend on corticoliberin concentrations.

PMID:35475389 | DOI:10.1080/09513590.2022.2068521

Hypertens Pregnancy. 2022 Apr 27:1-14. doi: 10.1080/10641955.2022.2066119. Online ahead of print.

ABSTRACT

The angiogenic factors sFlt-1 and PlGF play an established role in the detection of preeclampsia (PE). Recent data suggest that sEng might contribute to the pathogenesis of PE. However, only a few studies so far have addressed its role.This monocentric cross-sectional study of high-risk pregnancies aims to compare the levels of sFlt-1/PlGF ratio and sEng depending on different placental-related adverse pregnancy outcomes. The statistical analysis takes into account Pearson’s correlation coefficient between angiogenic factors, the area under the curve estimates (AUCs) for detection, and adjusted odds ratios (aOR) with 95% confidence intervals (95%-CIs). The analysis included 206 patients: 60 controls, 90 PE (59 EOPE, 35 LOPE), 94 FGR, and 35 HELLP cases. Some outcomes overlapped because FGR commonly complicated PE and HELLP syndrome. Serum levels of sFlt-1/PlGF and sEng correlated with each other. Higher levels were observed in HELLP syndrome and EOPE cases. AUCs for sFlt-1/PlGF ratio and sEng were, respectively, 0.915 (95%-Cl 0.87-0.96) and 0.872 (95%-Cl 0.81-0.93) in PE, 0.895 (95%-Cl 0.83-0.96) and 0.878 (95%-Cl 0.81-0.95) in HELLP syndrome, 0.891 (95%-Cl 0.84-0.94), and 0.856 (95%-Cl 0.79-0.92) in FGR.aORsfor sFlt-1/PlGF ratio and sEng were, respectively: 2.69 (95%-Cl 1.86-3.9) and 2.33 (95%-Cl 1.59-3.48) in PE, 2.38 (95%-Cl 1.64-3.44) and 2.28 (95%-Cl 1.55-3.4) in FGR, and 2.10 (95%-Cl 1.45-3.05) and 1.88 (95%-Cl 1.31-2.69) in HELLP syndrome. In addition, the aORs between sFlt-1/PlGF and sEng were very similar but higher for PE and FGR than HELLP syndrome.In conclusion,sEng performed similarly to sFlt-1/PlGF to detect placental dysfunctions.

PMID:35475405 | DOI:10.1080/10641955.2022.2066119