The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: Role of the renin angiotensin system inhibition

<p>Abstract</p> <p>Background</p> <p>Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC), to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide) in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments.</p> <p>Methods/Design</p> <p>The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older) with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control") for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP < 140 mm Hg and DBP < 90 mm Hg. Additional antihypertensives are added to achieve this goal if needed. Eligible participants are those with hypertension, defined as a blood pressure 140/90 mm Hg or greater, early cognitive impairment without dementia defined (10 or less out of 15 on the executive clock draw test or 1 standard deviation below the mean on the immediate memory subtest of the repeatable battery for the assessment of neuropsychological status and Mini-Mental-Status-exam >20 and without clinical diagnosis of dementia or Alzheimer's disease). Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives), 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory), cerebral blood flow, and carbon dioxide cerebral vasoreactivity.</p> <p>Discussion</p> <p>The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the threshold of dementia. Success of this trial will offer new therapeutic application of antihypertensives that inhibit the renin angiotensin system and new insights in the role of this system in aging.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00605072</p

Anticancer drug treatment in pediatric patients : studies on optimizing dosage and on parental guidance for improved drug handling at home

Background: Every year about 370 children are diagnosed with cancer in Sweden. The treatment includes both inpatient and outpatient care with anticancer drugs. At the clinic, the optimal anticancer drug dosage is usually derived from the patient’s body surface area (BSA). However, several formulae for calculating BSA are available and knowledge about their accuracy and precision in children is scarce. Information on the best formula to use when the height of the patient is missing or cannot be measured is also lacking. Moreover, poor access to age-appropriate drug formulations can force parents to manipulate and handle oral anticancer drugs (OADs) at home without proper drug handling knowledge and skills. Aims: The overall aim of the thesis was to increase knowledge on the adjustment of anticancer drug dosages for children in clinical practice and to optimize OAD handling procedures by parents in the home setting. The specific aims were: I. to validate Mosteller’s formula for calculating BSA; II. to test potential alternative formulae for estimating BSA using bodyweight (BW) alone; III. to observe the effects of risk-reducing strategies when handling high risk substances in the home setting; and IV. to describe parents’ experiences when handling OADs in the home setting. Methods: Different methods were used in each of the four studies. Study I was an analytical retrospective study based on measured BSA values. Study II was a retrospective cohort study based on registered data from electronic health records. In Study III, we used an observational intervention study to observe parents while they handled OADs at home. In Study IV, we used qualitative methods with semi-structured interviews to obtain parents’s views. Results: Study I showed that Mosteller’s formula underestimated BSA by 4.1 % in pediatric patients, and that inter-individual variability in the BSA measurements was most pronounced in neonates and infants. Study II showed that all three of the tested alternative formulae had good accuracy and precision for estimating BSA in children, using BW alone. Study III showed that many parents were handling OADs incorrectly at home before they were given an intervention. The intervention, which included practical training and information presented in different formats, improved the parents’ handling procedures significantly. Study IV resulted in four categories for the experiences of parents handling OADs at home: parents views on the provided information, with two subcategories: lack of, too little or contradictory information, and parents preferences for information delivery; safety over time; correct drug dosage; and drug administration. Conclusions: In Study I we found that Mosteller’s formula should be used with caution in clinical practice because it underestimates the BSA of children, especially neonates and infants. Study II showed that any of the three tested alternative equations, using only BW, can be used as a substitute for Mosteller’s formula to calculate the BSA of children, including term neonates and infants, with the best fit from the Meeh-type equation. In Study III we found that an intervention comprising practical training and information presented in different formats should be provided to parents to enable them to handle OADs correctly at home. In Study IV we concluded that parents need to be provided with timely, clear, nonconflicting and repeated info

Comparative study between various controllers for power system stabilizer using Particle Swarm Optimization

This paper compares PSS based various controller structures on a single machine connected to infinite bus system. The controllers hold the types of PID, PD, PI, and lead-lag controllers. These controllers were tuned by a technique called Particle Swarm Optimization (PSO). The PSO was undertaken for multiple operating points related to the system in order to find a global solution. The simulation results had shown that the PSO optimized the PSS based PID controller structure has achieved the best performance in stabilizing the system when a disturbance occurred. © 2012 IEEE - All Rights Reserved

Health-related articles on Syria before and after the start of armed conflict: a scoping review for The Lancet-American University of Beirut Commission on Syria

Introduction Armed conflict may influence the size and scope of research in Arab countries. We aimed to assess the impact of the 2011 Syrian conflict on health articles about Syria published in indexed journals. Methods We conducted a scoping review on Syrian health-related articles using seven electronic databases. We included clinical, biomedical, public health, or health system topics published between 1991 and 2017. We excluded animal studies and studies conducted on Syrian refugees. We used descriptive and social network analyses to assess the differences in rates, types, topics of articles, and authorship before and after 2011, the start of the Syrian conflict. Results Of 1138 articles, 826 (72.6%) were published after 2011. Articles published after 2011 were less likely to be primary research; had a greater proportion reporting on mental health (4.6% vs. 10.0%), accidents and injuries (2.3% vs. 18.8%), and conflict and health (1.7% vs. 7.8%) (all p < 0.05); and a lower proportion reporting on child and maternal health (8.1 to 3.6%, p = 0.019). The proportion of research articles reporting no funding increased from 1.1 to 14.6% (p < 0.01). While international collaborations increased over time, the number of articles with no authors affiliated to Syrian institutions overtook those with at least one author affiliation to a Syrian institution for the first time in 2015. Conclusion To our knowledge, this is the first study to examine the impact of armed conflict on health scholarship in Syria. The Syrian conflict was associated with a change in the rates, types, and topics of the health-related articles, and authors’ affiliations. Our findings have implications for the prioritization of research funding, development of inclusive research collaborations, and promoting the ethics of conducting research in complex humanitarian settings

The outcomes of severe COVID-19 pneumonia managed with supportive care in Palestine: an experience from a developing country

INTRODUCTION: About 14% of COVID-19 patients experience severe symptoms and require hospitalization. Managing these patients could be challenging for limited-resource countries, such as Palestine. This study aimed to evaluate hospitalized severe COVID-19 patients' treatment outcomes managed with supportive care and steroids. METHODOLOGY: This was a single-center observational retrospective cohort study that enrolled COVID-19 patients admitted to the “Martyrs medical military complex- COVID Hospital” in Palestine. The managing physicians manually collected data through chart reviews, including patients' characteristics, complications, outcomes, and different management modalities. Continuous and categorical variables between those who were discharged alive and who died were compared using t-test and Chi-squares test, respectively. RESULTS: Overall, 334 patients were included in this study. Median (IQR) age was 62(11) years, 49.1% were males, and 29.6% were ICU status patients. The median (IQR) PaO2/FiO2 ratio was 76 (67), and 67.6% of these patients had moderate to severe acute respiratory distress syndrome, and 4.8% of the patients received invasive mechanical ventilation. Most of the patients (78.7%) had at least one comorbidity, and 18.3% developed at least one complication. The overall mortality was 12.3% (95% CI 8.9-16.2%), and the median (IQR) length of hospital stay was 11 (8) days. Age (aOR 1.05, p = 0.08), smoking (aOR 4.12, p = 0.019), IMV (aOR 27.4, p &lt; 0.001) and PaO2/FiO2 ratio (aOR 1.03, p &lt; 0.001) were found to predict higher mortality. CONCLUSIONS: Supportive care for patients with severe COVID-19 pneumonia in a Palestinian hospital with limited resources was associated with in-hospital mortality of 12.3%

DataSheet1_DHRS7 is an immune-related prognostic biomarker of KIRC and pan-cancer.docx

Renal clear cell carcinoma (KIRC) is one malignancy whose development and prognosis have been associated with aberrant DHRS7 expression. However, the catalytic activity and pathophysiology of KIRC are poorly understood, and no sensitive tumor biomarkers have yet been discovered. In our study, we examined the significant influence of DHRS7 on the tumor microenvironment (TME) and tumor progression using an overall predictable and prognostic evaluation approach. We found novel cancer staging, particularly in KIRC, as well as potential therapeutic drugs out of 27 drug sensitivity tests. Using Perl scripts, it was possible to determine the number of somatic mutations present in 33 tumors, as well as the relative scores of 22 immune cells using CIBERSORT, the relationship between immune infiltration and differential expression using TCGA data, and the immune microenvironment score using the estimate technique. Our results show that DHRS7 is abnormally expressed in pan-cancer patients, which influences their survival. Low DHRS7 expression was associated with late clinical stages and a low survival rate in KIRC patients, suggesting a poor prognosis and course of treatment, in HNSG, MESO, and KIRC patients. We also found that DHRS7 was associated with TMB and MSI in certain tumors. Using KIRC as an example, we discovered a negative correlation between DHRS7 expression and immunological assessments, suggesting that this substance might be used as a tumor biomarker.</p

68Ga-PSMA PET/CT in early relapsed prostate cancer patients after radical therapy

Abstract Biochemical recurrence (BCR) of prostate cancer (PCa) occurs in about 25% of patients treated with radical prostatectomy (RP) and up to 45% in patients who receive external beam radiotherapy (RT). Early diagnosis of PCa recurrence is of high importance for successful salvage therapy. The aim of the present study is to analyze the efficacy of 68 Ga-PSMA PET/CT in detecting the presence of local and/or systemic disease in patients with a history of PCa who have BCR. A total of 52 PCa patients with BCR referred for 68 Ga-PSMA PET/CT were recruited from the American University of Beirut Medical Center between November 2017 and December 2019. We compared the performance of PSMA PET/CT to the results and clinical factors based on follow up: PSA, PSA kinetics, primary treatment, and Gleason score. The relationship between the PET/CT findings and clinical indicators of disease were assessed by univariate and multivariate logistic regression. From a total of 52 patients, 34 (65.4%) had positive PSMA-PET/CT scans. Among those, 8/34 (23.5%) received primary RT. For all patients with a positive PSMA-PET: the detection rate was 2/4 (50%) for PSA < 0.2, 5/10 (50%) for PSA 0.2–0.49, 3/6 (50%) for PSA 0.5–0.99, 6/12 (50%) for PSA 1–1.99, 8/9 (88.9%) for PSA 2–3.99, and 10/11 (90.9%) for PSA 4–10. PSMA-PET/CT positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score and TNM staging. However, it did not show a significant correlation with radiotherapy as primary treatment, ongoing androgen deprivation therapy (ADT), time to relapse, and initial PSA before therapy. In our single center prospective trial, 68 Ga-PSMA PET/CT successfully detected the recurrence of PCa in patients with BCR. Scan positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score, and TNM staging. PSMA- PET/CT is a highly promising modality in the work up of patients with PCa in the setting of BCR for earlier detection of disease recurrence