Is a placebo-controlled surgical trial an oxymoron?

Within the context of the new medical methodology of evidence-based medicine, the ethical issues of making the randomized, placebo-controlled, clinical trial part of the matrix of surgical procedure evaluation are discussed. Surgical trials with alternative research design less rigorous than the double-blind, placebo-controlled, randomized trial leave the alternative: implementing surgical procedures based on anecdotal evidence and weaker scientific research. The conundrum of these clinical trials, as it relates to the evaluation of surgical procedures, is that it appears to confound some of the fundamental ethical principles of beneficence and nonbeneficence. The placebo effect with surgery is so strong that "sham surgery" within the clinical trial context is essential and an appropriate component of the ethics of clinical research. A discussion of these issues is presented.     

THE INTRARENAL PRESSURE DURING EXPERIMENTAL RENAL HYPERTENSION

The intrarenal interstitial pressure was measured during the course of experimental renal hypertension in dogs. In perinephritic hypertension, produced by wrapping the kidney in a cellophane bag, the intrarenal pressure rose slowly from the normal value of 25 mm. Hg to a final level of about 60 mm. Hg. Strong pressure pulsations were observed in the renal parenchyma during this type of hypertension. In the hypertension following partial occlusion of the renal artery, the intrarenal pressure remained approximately normal, except in malignant hypertension when it tended to decline to about 9 mm. Hg. The hypertension of perinephritis is interpreted as a consequence of renal ischemia, the high intrarenal pressure, produced by the constricting fibrotic hull, acting to reduce the effective perfusion pressure of the kidney. The two experimental hypertensions herein examined are considered as examples of influent resistance hypertensions and effluent resistance hypertensions, the former being due to renal arterial or arteriolar resistance and the latter due to renal venous resistance, specifically at the arcuate-interlobar junction. The application of this concept to renal hypertensive disease in man is discussed.     

Oxidative Balance Score during Pregnancy Is Associated with Oxidative Stress in the CANDLE Study

The objective of this study was to calculate an oxidative balance score (OBS) utilizing diet and lifestyle information collected from 1322 women during the second trimester of pregnancy in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. An energy-adjusted OBS was calculated using nutrient information from a Food Frequency Questionnaire (FFQ), lifestyle measures, and plasma folate and vitamin D levels. Using the least absolute shrinkage and selection operator method, 91 food items from the FFQ were selected and they accounted for 82% of the variance in the OBS, with cruciferous vegetables, citrus fruits, fruit juice, and coffee being among the highest anti-oxidant predictors, and red meats and alcohol among the highest pro-oxidant contributors. Urinary F₂-isoprostane, an objective indicator of oxidative stress, was lower with increasing OBS quintiles in a stairstep manner (p for trend = 0.0003), suggesting the possible utility of the OBS as an indicator of oxidative stress. The OBS was moderately correlated with the Healthy Eating Index (correlation coefficient = 0.6076), suggesting it provides a distinct measure of a healthy diet. In conclusion, the OBS may serve as a valid reflective indicator of urinary F₂-isoprostanes and an epidemiological tool to inform intervention studies, in order to minimize oxidative stress during pregnancy.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.     

Effects of Ambient Coarse,Fine, and Ultrafine Particles and Their Biological Constituents on Systemic Biomarkers: A Controlled Human Exposure Study

Background

Ambient coarse, fine, and ultrafine particles have been associated with mortality and morbidity. Few studies have compared how various particle size fractions affect systemic biomarkers.

Objectives

We examined changes of blood and urinary biomarkers following exposures to three particle sizes.

Methods

Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse (2.5–10 μm; mean, 213 μg/m³) and fine (0.15–2.5 μm; mean, 238 μg/m³) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (< 0.3 μm; mean, 136 μg/m³) and filtered medical air. Exposures lasted 130 min, separated by ≥ 2 weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr postexposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF; vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model regressions assessed pre- and postexposure differences.

Results

One hour postexposure, for every 100-μg/m³ increase, coarse CAP was associated with increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O_3, fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95% CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was significantly associated with biomarker changes similar to those found with CAPs.

Conclusions

Ambient particles with various sizes/constituents may influence systemic biomarkers differently. Endotoxin in ambient particles may contribute to vascular mediator changes and oxidative stress.

Citation

Liu L, Urch B, Poon R, Szyszkowicz M, Speck M, Gold DR, Wheeler AJ, Scott JA, Brook JR, Thorne PS, Silverman FS. 2015. Effects of ambient coarse, fine, and ultrafine particles and their biological constituents on systemic biomarkers: a controlled human exposure study. Environ Health Perspect 123:534–540; http://dx.doi.org/10.1289/ehp.1408387     

Interpreting declines in HIV test positivity: an analysis of routine data from Zimbabwe's national sex work programme, 2009–2019

IntroductionEarly diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe.MethodsWe analysed HIV test data from Zimbabwe''s nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV‐positive test after at least one HIV‐negative test in the programme. We used logistic regression to analyse test positivity over three time‐periods: 2009–2013, 2014–2017 and 2018–2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time‐periods.ResultsDuring the 10‐year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018–2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009–2013 (aOR 6.08 95% CI 5.52–6.70) and 18.8% for 2014–2017 (aOR 2.17 95% CI 2.06–2.28). Adjusting for time since last test reduced effect estimates for 2009–2013 (aOR 4.03 95% CI 3.64–4.45) and 2014–2017 (aOR 1.97 95% CI 1.86–2.09) compared to 2018–2019. Among 7573 women with an initial HIV‐negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5–4.2).ConclusionsTest positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance.     

Prediction of the Uric Acid Component in Nephrolithiasis Using Simple Clinical Information about Metabolic Disorder and Obesity: A Machine Learning-Based Model

There is a great need for a diagnostic tool using simple clinical information collected from patients to diagnose uric acid (UA) stones in nephrolithiasis. We built a predictive model making use of machine learning (ML) methodologies entering simple parameters easily obtained at the initial clinical visit. Socio-demographic, health, and clinical data from two cohorts (A and B), both diagnosed with nephrolithiasis, one between 2012 and 2016 and the other between June and December 2020, were collected before nephrolithiasis treatment. A ML-based model for predicting UA stones in nephrolithiasis was developed using eight simple parameters—sex, age, gout, diabetes mellitus, body mass index, estimated glomerular filtration rate, bacteriuria, and urine pH. Data from Cohort A were used for model training and validation (ratio 3:2), while data from Cohort B were used only for validation. One hundred and forty-six (13.3%) out of 1098 patients in Cohort A and 3 (4.23%) out of 71 patients in Cohort B had pure UA stones. For Cohort A, our model achieved a validation AUC (area under ROC curve) of 0.842, with 0.8475 sensitivity and 0.748 specificity. For Cohort B, our model achieved 0.936 AUC, with 1.0 sensitivity, and 0.912 specificity. This ML-based model provides a convenient and reliable method for diagnosing urolithiasis. Using only eight readily available clinical parameters, including information about metabolic disorder and obesity, it distinguished pure uric acid stones from other stones before treatment.