Participant Laboratory Research Articles

A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease

BackgroundAmyloid beta protein (Aβ) is a treatment target in Alzheimer’s Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen, an orally administered small molecule, binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aβ. To augment human data for Posiphen, we evaluated safety, tolerability and pharmacokinetic and pharmacodynamic (PD) effects on Aβ metabolism using Stable Isotope Labeling Kinetic (SILK) analysis.MethodsDouble-blind phase 1b randomized ascending dose clinical trial, at five sites, under an IRB-approved protocol. Participants with mild cognitive impairment or mild AD (Early AD) confirmed by low CSF Aβ42/40 were randomized (within each dose arm) to Posiphen or placebo. Pretreatment assessment included lumbar puncture for CSF. Participants took Posiphen or placebo for 21–23 days, then underwent CSF catheter placement, intravenous infusion of 13C6-leucine, and CSF sampling for 36 h. Safety and tolerability were assessed through participant reports, EKG and laboratory tests. CSF SILK analysis measured Aβ40, 38 and 42 with immunoprecipitation-mass spectrometry. Baseline and day 21 CSF APP, Aβ and other biomarkers were measured with immunoassays. The Mini-Mental State Exam and ADAS-cog12 were given at baseline and day 21.ResultsFrom June 2017 to December 2021, 19 participants were enrolled, randomized within dose cohorts (5 active: 3 placebo) of 60 mg once/day and 60 mg twice/day; 1 participant was enrolled and completed 60 mg three times/day. 10 active drug and 5 placebo participants completed all study procedures. Posiphen was safe and well-tolerated. 8 participants had headaches related to CSF catheterization; 5 needed blood patches. Prespecified SILK analyses of Fractional Synthesis Rate (FSR) for CSF Aβ40 showed no significant overall or dose-dependent effects of Posiphen vs. placebo. Comprehensive multiparameter modeling of APP kinetics supported dose-dependent lowering of APP production by Posiphen. Cognitive measures and CSF biomarkers did not change significantly from baseline to 21 days in Posiphen vs. placebo groups.ConclusionsPosiphen was safe and well-tolerated in Early AD. A multicenter SILK study was feasible. Findings are limited by small sample size but provide additional supportive safety and PK data. Comprehensive modeling of biomarker dynamics using SILK data may reveal subtle drug effects.Trial registrationNCT02925650 on clinicaltrials.gov (registered on 10-24-2016).

The effects of fasting compared to eating a meal or snack during simulated night shift on changes in metabolism associated with circadian misalignment: a protocol and methods paper.

This protocol paper outlines the methods that will be used to examine the impact of altering meal timing on metabolism, cognitive performance, and mood during the simulated night shift. Participants (male and female) will be recruited according to an a priori selected sample size to complete a 7-day within and between participant's laboratory protocol. Participants will be randomly assigned to one of the three conditions: meal at night or snack at night or no meal at night. This protocol includes an 8-hour nighttime baseline sleep, followed by 4 consecutive nights of simulated nightshift (7 hours day sleep; 10:00-17:00 hours), and an 8-hour nighttime sleep (return to dayshift). During the simulated night shift, meals will be provided at ~06:30, 09:30, 14:10, and 19:00 hours (no eating at night); ~06:30, 19:00, and 00:30 hours (meal at night); or ~06:30, 14:10, 19:00, and 00:30 hours (snack at night). Meal composition will be strictly controlled throughout the study (45%-65% carbohydrates, 15%-25% protein, and 20%-35% fat per day) with daily energy provided to meet individual needs using the Harris-Benedict equation (light/sedentary activity). The primary outcome measures are serum concentrations of blood glucose, insulin, and free fatty acids area under the curve in response to the oral glucose tolerance test. Mixed-effect ANOVAs will be conducted. This protocol paper describes a methodology to describe an innovative approach to reduce the metabolic disease impact associated with shift work.

Incidence of post ERCP biliary Ascariasis diagnosed on ultrasound

Ascaris lumbricoides are familiar with the roundworm that causes biliary infections in humans. Nevertheless, ascariasis is primarily found in the jejunum and transferred in numerous body parts with the intake of Ascaris lumbricoides present in food and water. These study methods were implemented at the Saidu Teaching Hospital Radiology department from December 2021 to January 2023. This study includes the participants suffering from biliary ascariasis admitted or visited Saidu Teaching hospital in that time frame. Clinical assessment of the participants was done based on the appearance of signs and symptoms present in them. The participant's laboratory test was done to determine the level of basic body parameters, after that ultrasonography was used to diagnose the presence and appearance of worms. Endoscopic retrograde cholangiopancreatography (ERCP) was used to extract worm from biliary channels, and the incidence of post-ERCP biliary ascariasis was accessed with ultrasonography. This study's results show the presence of numerous types of worms in biliary channels of patients. Also, the level of body parameters, for instance, neutrophil, hemoglobin, and others were compared at the time of admission, and at the time of discharge from the hospital. Furthermore, the incidence of post-ERCP biliary ascariasis was reported as 4% in females, and 1% in males respectively.

An evaluation of a healthy participant laboratory model of epidural hyperthermia: a physiological study

BackgroundHyperthermia complicates 21% of cases of intrapartum epidural analgesia, but the mechanism is unclear. One hypothesis is that blockade of cholinergic sympathetic nerves prevents active vasodilation and sweating, thus limiting heat loss. Because labour increases heat production, this could create a situation in which heat production exceeds loss, causing body temperature to rise. This physiological study tested a novel laboratory model of epidural-related hyperthermia, using exercise to simulate the increased heat production of labour and surface insulation to simulate the effect of epidural analgesia. MethodsTwelve healthy non-pregnant participants (six female) cycled an ergometer for two hours at 20 Watts (W) on two occasions: once with surface insulation (intervention) and once without (control). Core temperature, skin temperature (eight sites), and heat loss (eight sites) were recorded. Mean body temperature and heat production were calculated. Values are mean (SD). ResultsExercise increased heat production on both visits (intervention 38 (18) W; control 37 (31) W; P = 0.94). Total heat loss was less on the intervention visit (intervention 115 (19) W; control 129 (23) W; P = 0.002). Core temperature increased on both visits (intervention 0.21 (0.37)°C; control 0.19 (0.27)°C; P < 0.001). The increase in mean body temperature was greater on the intervention visit (intervention 0.47 (0.41)°C; control 0.25 (0.19)°C; P = 0.007). ConclusionsThis laboratory model predicts that labour epidural analgesia limits heat loss by >14 W. Once the model is validated, it could be used to test the efficacy of potential interventions to prevent and treat epidural-related maternal hyperthermia.

Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank. Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex. Among the 363313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)]. Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.

CCT-K7.2021: CIPM key comparison of water-triple-point cells

Main textThis is the final report of CCT-K7.2021 key comparison of water-triple-point (TPW) cells. The primary objective of CCT-K7.2021 was a comparison of the participant national realizations of the TPW temperature. Each participant laboratory selected one of its TPW cells for use as a transfer cell, directly compared it against its national reference and delivered it to the pilot (NRC). The pilot then compared all transfer cells against two NRC reference cells and, finally, each participant laboratory retrieved its transfer cell and directly re-compared it against its TPW national reference. The initial measurements at the participant laboratories were started in April 2021. The final measurements at the participants' laboratories were completed in September 2022. The final report was approved by the CCT WG-KC in April 2023. The adaptive weighted average procedure was adopted to compute the Key Comparison Reference Value (KCRV) and the degrees of equivalence (DoEs) were reported for the participant laboratories. The maximum difference between two transfer cells was 92 μK with a standard deviation of 26 µK (almost a factor of two improvement compared to CCT-K7 results (2002-2004). The maximum difference between two TPW national realizations was 111 µK, with a standard deviation of 28 µK (improvement similar to the one reported for the transfer cells). While the pooled distribution of CCT-K7 results was bimodal, indicating the presence of two different sub-populations (the population of laboratories that referred to ocean water definition and the population of laboratories that did not consider it), the pooled distribution of CCT-K7.2021 results was no longer bimodal, but slightly asymmetrical, indicating a more harmonized approach to water isotopic corrections.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Inflammatory Biomarkers in Rosacea Patients

Aims: Rosacea is a chronic inflammatory skin disease characterized by telangiectasia, papules and pustules associated with immune response. Several factors, especially inflammatory factors, have been investigated in its etiopathogenesis. The Systemic Immune Inflammation Index (SII) is a novel inflammation marker. It has recently been used to evaluate the inflammatory and immune status of the patients. Also, several studies investigated other inflammation markers such as neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios. The present study aims to investigate the correlation between rosacea, an inflammatory disease, and inflammatory markers such as platelet (PLT), lymphocyte (LYM), neutrophil (NEU), NLR, PLR, and especially SII. Methods:The study was conducted with 100 papulopustular rosacea patients and 100 healthy controls. The patient and control groups were similar in age and gender. Participant data and laboratory results were obtained retrospectively from the patient files. Results: Seventy-eight of the rosacea patients were female and 22 were male. The mean participant age was 47.97. There was no significant difference between rosacea patients and the control group based on age and gender. The PLT and LYM markers were significantly lower in the patient group when compared to the control group, and NLR, PLR and SII markers were significantly higher in the patient group (p&lt;0.05). Conclusion: The significant difference between the investigated inflammatory parameters suggested that rosacea could be a systemic inflammatory disease rather than a simple skin inflammation. More comprehensive studies are required to clarify this premise and the correlation between rosacea and systemic inflammation.

The Spectrum of Erythema Migrans in Early Lyme Disease: Can We Improve Its Recognition?

Background and objective Diagnosis of early Lyme disease (LD) often relies on clinical recognition of the skin lesion, erythema migrans (EM), a diagnostic sign of disease when laboratory testing is insensitive.Because EM can present in morphologically distinct forms, its recognitionby clinicians can be challenging.This study aimed to characterize the clinical spectrum of lesions in patients presenting with suspected early LD in an ambulatory care setting to identify features that might help clinicians to be better prepared to recognize EM lesions. Methods Images of lesions from 69 participants suspected to have early LD were retrospectively evaluated by a dermatologist and a family practitioner with expertise in early LD.Reviewers made determinations on the diagnoses and morphological features of lesions.Agreement between reviewers and associations among lesion types and participant demographics, symptomology, and laboratory evidence of infection were examined using the kappa statistic and contingency tables, respectively. Results Challenges in diagnosing EM were evident in our study:initial concordance between reviewers was moderate [kappa statistic (95% CI): 0.45 (0.245 - 0.657)]. The final classification included 35 lesions (51%) that were agreed to be EM; 23 lesions (30%) were considered to be possible early EM or tick bite reactions, and 11 (16%) were thought notto be EM, but rather other diagnoses, including ringworm, allergic contact dermatitis, and mosquito bites.Only two lesions (6%) were observed with a classic bull's eye or ring-within-a-ring pattern.Most EM lesions were uniform (51%), pink (74%), oval lesions (63%), with well-demarcated borders (92%).Early EM or tick bite reactions were typically <5 cm in size (74%), red (52%), round lesions (61%), with a punctum present (100%).Lesions thought notto be EM also tended to be pink or red (64%), round (55%), or uniform (45%) lesions, but also had raised (25%) or irregular borders (33%), which were not commonly observed in the reviewer-classified EM or tick bite reaction lesions.Participants with lesions classified as EM reported that they had the lesions for more days (p = 0.043) and reported more symptoms (p = 0.017) than participants with other lesions.Only 14 (20%) participants overall had positive laboratory evidence for LD; these included 13 (37%) of the participants with EM-classified lesions. Conclusions EM commonly occurs in forms that are not the classic bull's eye.Patients often present with lesions that may represent the very early stage of EM or tick bite reactions, and most patients will test negative on currently available laboratory tests, challenging clinicians in making an LD diagnosis or treatment decisions.Additional studies to further characterize the morphological features of EM and how variation in skin lesions may be perceived among clinicians would be helpful for developing guidelines onimproving clinician recognition of EM.

Application and Inspiration of Information System used in National Health and Nutrition Examination Survey of America

The National Health and Nutrition Examination Survey (NHANES) of America has been running for more than 60 years and has achieved many significant achievements with international influence. The application of modern information technologies in NHANES provides a supplementary tool for the project's high quality and refined implementation. This paper introduces the information system of NHANES from seven aspects: project management, survey participant interview, physical examination, laboratory examination, field follow-up, data sharing, and social services. The construction and application prospects of the China National Health Survey Information System, suitable for China's native conditions, are also discussed in this article.

Pediatric Cardiopulmonary Exercise Testing: Interoperability Through Domain Analysis Modeling and a National Survey.

The electronic health record, data science advances, and dynamic environmental and infectious threats to child health highlight the need for harmonized and interoperable approaches to pediatric cardiopulmonary exercise testing (CPET). Accordingly, we developed a terminology harmonization in exercise medicine and exercise science domain analysis model (THEMES DAM) to structure CPET data elements. THEMES DAM identified 114 data elements, including participant information, calibration, equipment, protocols, laboratory personnel, encouragement strategies, and analysis procedures. We used the THEMES DAM, vetted by the international data standards organization HL7, to construct a current-state survey of pediatric CPET centers in the United States. Forty-eight of 101 centers responded to a questionnaire covering seven major topic areas (38 items). Centers predominantly performed between 100 and 500 tests annually. Cardiac disease represented 55% of referrals. Almost all centers calibrated gas concentrations and flow daily, but 42% never calibrated their treadmill or cycle ergometers. All centers measured V̇O2peakbut calculated differently. Centers used a variety of protocols (e.g., for treadmill: 61%, Bruce; 43%, modified Bruce; 59%, other); 44% calculated CPET slopes from submaximal portions of CPET (e.g., V̇O2-HR). All centers verbally encouraged participants, but only 40% used a standardized approach. The interpretation of CPET was done by physicians (60%), exercise physiologists (25%), exercise technicians (10%), nurses (1%), or others (4%). Ninety-one percent would agree to collaborate in multicenter research, 89% to establish dynamic reference values, and 83% to better interpret CPET. The survey data and the implementation of THEMES DAM could accelerate interoperability across multiple centers. This would facilitate a nimble approach to create pediatric reference values responsive to the constantly changing health environment and stimulate novel approaches to CPET research and clinical application.

An International Survey of Glucose-6-Phosphate Dehydrogenase Laboratory Reporting Practices.

Glucose-6-phosphate dehydrogenase (G6PD) activity is used in the evaluation of hemolysis risk in patients being assessed for G6PD deficiency. A long-acting 8-aminoquinoline drug (tafenoquine) used in malaria treatment is contraindicated in patients with G6PD deficiency (<70% normal G6PD activity). The current state of G6PD reporting practices to support clinical eligibility assessment is poorly understood. To assess clinical laboratory reporting practices for G6PD testing. In October 2019 and October 2020, voluntary questionnaires were distributed to 327 and 324 laboratories participating in the College of American Pathologists G6PD proficiency testing (PT). Two hundred fifty-seven and 119 laboratories responded to the 2019 and 2020 questionnaires, respectively. Few laboratories have received clinical questions about average normal G6PD activity (US/Canada, 2.0% [3 of 149]; international, 8.4% [9 of 107]), whereas slightly more have determined the average normal G6PD activity for their own assay and patient populations (US/Canada, 6.7% [10 of 149]; international, 19.4% [21 of 108]). Few laboratories report G6PD activity in percent of normal format (US/Canada, 2.7% [4 of 149]; international, 8.3% [9 of 108]). The most common unit of measurement in use for quantitative G6PD reporting is unit per gram of hemoglobin. Reference intervals vary based on assay, reaction temperature, and participant laboratory and demonstrate moderate correlation (r = .46-.51) to G6PD activity measured from a "normal" PT challenge specimen. Nearly half of participants (47.8% [85 of 178]) categorized a quantitatively "intermediate" G6PD PT challenge as "normal" when using qualitative assays. Percent of normal G6PD activity reporting would facilitate patient eligibility assessment for drugs, such as tafenoquine. Quantitative assays are better able to differentiate "intermediate" specimens than qualitative assays.

Report on the AFRIMETS.M. F-S1 supplementary force comparison for 10 kN and 100 kN

Main textThis bilateral comparison of Force Standard Machines (FSM) named AFRIMETS.M. F-S1 was carried out in the force range from 1 kN to 100 kN between Physikalisch-Technische Bundesanstalt (PTB) of Germany as the pilot laboratory and Kenya Bureau of Standards (KEBS) of Kenya as the participant laboratory. KEBS had already participated in the APMP.M. F-K2 key comparison where measurements were made only at 50 kN and 100 kN force steps. Therefore, this bilateral comparison was planned to thoroughly compare the KEBS FSM and the PTB Deadweight Machines in wider force steps than those of the APMP.M. F-K2 key comparison and thus it had no corresponding key-comparisons values to be linked to at that time. PTB provided two force transducers for the supplementary comparison with 10 kN and 100 kN nominal capacities. The comparison method called "DKD" procedure was used. This procedure has already been used in several comparisons in Germany and other countries. The purpose to this comparison is to give support to the uncertainty claims for KEBS and will be used to determine the Calibration and Measurement Capability (CMC). In addition, this comparison will provide metrological proof of the application for a CMC entry in the BIPM Key Comparison Database (KCDB). This report describes the scheme and results of the comparison.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Electrophysiological findings in patients with restless legs syndrome

BackgroundRestless legs syndrome (RLS) manifests as an urge to move the body to relieve the discomfortable sensations, primarily when resting, sitting, laying down, or sleeping. Diagnosis of RLS relies on clinical criteria, and the immobilization test was the only instrumental tool with equivocal results. ObjectivesTo assess different electrophysiological findings in patients with RLS, and compare the diagnostic values of these parameters in the diagnosis of RLS. Methods30 patients with primary RLS and 30 controls who were matched for age and gender were studied. Participant's demographics, laboratory findings, and electrophysiological test, namely nerve conduction studies (NCS), cutaneous silent period (CSP), H reflex and sympathetic skin response (SSR), F-wave latency, amplitude, F-wave duration (FWD), and the ratio between FWD and duration of the corresponding compound muscle action potential (FWD/CMAPD) were analyzed. ResultsNone of the patients showed altered NCS data. FWD of upper (12.37 ± 2.77 ms) and lower limb (21.71 ± 5.24 ms) were significantly longer in patients. Also, FWD/CMAP duration of the upper (1.03 ± 0.2) and lower limb (2.02 ± 0.55) was longer in patients. Likewise, they exhibited delayed CSP latency from TA (110.62 ± 13.73 ms) and APB (77.35 ± 12.16 ms) whereas the CSP duration from TA and APB was decreased (37.36 ± 11.59 ms; 42.55 ± 7.97 ms, respectively). The SSR latency was not different, and right-sided H reflex amplitude (5.07 ± 3.98 mV) and H/M ratio (0.65 ± 1.81) were significantly increased in the patient group. ConclusionThe data suggest that there may be a dysfunction of the inhibitory/excitatory circuits at a spinal level; and no pathology in the peripheral nerves. The unilateral difference of H reflex amplitude and H/M ratio may suggest asymmetrical central inhibitory dysfunction. Further prospective studies with larger cohorts are now needed to evaluate the pathophysiology of RLS with different neurophysiological assessment tools.

Incidences and factors associated with viral suppression or rebound among HIV patients on combination antiretroviral therapy from three counties in Kenya

BackgroundLimited data are available on the incidence and factors associated with viral rebound following viral suppression among HIV-infected individuals taking antiretroviral therapy (ART) in Kenya. Furthermore, the durability of viral suppression among HIV individuals taking ART is unknown. Information on incidence rates and factors associated with HIV viral load rebound and the durability of viral suppression (undetectable HIV copies in plasma) among HIV-infected individuals taking ART, will help improve the long-term management of HIV-infected individuals and explore approaches to long-term HIV remission or complete cure. ObjectivesThe objectives of this study were to investigate the incidence rates of viral rebound following viral suppression, factors associated with viral rebound, and the durability of viral suppression among HIV-infected individuals on ART from Kilifi, Meru, and Nakuru counties in Kenya. MethodsThis was a retrospective study involving 600 HIV-infected individuals taking combination ART (cART) and enrolled in comprehensive care centers (CCCs) at Malindi Sub-county Hospital, Nakuru Level 5 Hospital, and Meru Level 5 Hospital in Kenya. The medical files were inspected and medical history records abstracted for the selected participants. Participant laboratory data including HIV viral loads, types and history of ART, and treatment history of any opportunistic infections were abstracted using an abstraction checklist. Participants were grouped into those who achieved HIV viral suppression, with viral loads lower than the detection limit (LDL) (viral suppression), and those who experienced one or more detectable viral load measurements >40 copies/ml following the initial LDL (viral rebound). Durable viral suppression was defined as all viral load values at LDL over the 2-year period (2017–2019). Univariate and multivariate Poisson regression analyses were performed to assess the rates of viral rebound, as well as to investigate factors associated with it. ResultsOut of 549 HIV-positive patients, 324/549 (59%) achieved HIV viral suppression (Meru 159/194 (82%), Nakuru 21/178 (12%), and Malindi 144/177 (81%)). The overall viral rebound rate was 41%, with site-specific viral rebound of 88.2%, 18.6%, and 18.0% in Nakuru, Malindi, and Meru, respectively. There was an overall rate of first viral rebound of 3.9 (95% confidence interval (CI) 6.9–14.4), 0.7 (95% CI 0.5–1.0), and 0.89 (95% CI 0.64–1.24) per 100 person-months in Nakuru, Malindi, and Meru, respectively. Good ART adherence (p = 0.0002), widow status (p = 0.0062), and World Health Organization (WHO) stage I (p = 0.0002) were associated with viral suppression, while poor ART adherence (p < 0.0001), WHO stage II (p = 0.0024), and duration on ART of 36 months (p = 0.0350) were associated with viral rebound. ConclusionsThe rate of viral suppression in patients on cART in the CCCs fell short of the WHO target. However, the study provides proof of evidence of undetectable viral load levels for more than 2 years, a sign that the United Nation’s 2030 objective of controlling the risk of HIV transmission could be achieved.

Association between liver diffusion-weighted imaging apparent diffusion coefficient values and other measures of liver disease in pediatric autoimmune liver disease patients

Multiple quantitative magnetic resonance imaging (MRI) methods have been described to noninvasively detect and characterize liver fibrosis, including diffusion-weighted imaging (DWI). To evaluate associations between liver MRI DWI apparent diffusion coefficient (ADC) values and clinical factors and other quantitative liver MRI metrics in pediatric patients with autoimmune liver disease (AILD). Fifty-seven research liver MRI examinations performed from January 2017 to August 2018 for pediatric AILD registry participants were evaluated. Liver DWI ADC values, liver and spleen stiffness (kPa), and iron-corrected T1 (cT1; Perspectum Diagnostics) were measured at four anatomic levels. Participant age, sex, and laboratory data (alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, gamma-glutamyl transferase [GGT]) were recorded. Spearman's rank-order correlation (rho) and multiple linear regression were used to evaluate the associations between liver ADC values and predictor variables. Mean (SD) participant age was 14.8 (4.0) years, 45.6% (26/57) were girls. Mean liver DWI ADC value was 1.34 (0.14 × 10-3) mm2/s. Liver ADC values showed weak to moderate correlations with liver stiffness (r = - 0.42, p = 0.001), spleen stiffness (r = - 0.34; p = 0.015), whole-liver mean cT1 (r = - 0.39; p = 0.007), ALT (r = - 0.50; p = 0.0001), and GGT (r = - 0.48; p = 0.0004). Multiple linear regression showed liver stiffness (p = 0.0009) and sex (p = 0.023) to be independent predictors of liver ADC values. Liver DWI ADC values are significantly associated with liver and spleen stiffnesses, liver cT1, ALT, GGT, and participant sex, with liver stiffness and sex remaining significant at multivariable regression. Liver ADC ultimately may play a role in multi-parametric prediction of chronic liver disease/fibrosis severity.

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. ClinicalTrials.gov Identifier: NCT04323527.

Development of ethylene glycol Samples in silicone tubes and their application in inter-laboratory comparison

Objective: To development of ethylene glycol samples in silicone tubes, and the samples were applied to inter-laboratory comparison, through it to evaluate the detection capacity of occupational health testing laboratories. Methods: Three content levels of ethylene glycol samples in silicone tubes were prepared, and the homogeneity and stability of samples were investigated, the results were statistically analyzed. A robust statistical four-point distance method was used to calculate the results submitted by each participant laboratory and the test capability of the laboratory was assessed by the z-score method. Results: The statistic of the homogeneity of ethylene glycol samples in silicone tubes were less than the critical value (P>0.05) , and the samples were stable at room temperature for one month. The satisfactory rate of comparison between 204 laboratories was 88.24%. Conclusion: The homogeneity and stability of the ethylene glycol samples in the silicone tubes can meet the requirements of proficiency testing and can be used for laboratory comparison. Most of the laboratories that participated in the comparison had the ability to detect ethylene glycol.

Comparisons between protocols and publications of case-control studies: analysis of potential causes of non-reproducibility and recommendations for enhancing the quality of personalization in healthcare.

Selective reporting of results in published case-control studies has been widely suspected, but little comprehensive information on selective reporting is available with regard to case-control studies. We aimed to evaluate the concordance of findings between publications and the protocols of case-control studies and to assess the level of selective reporting of results in case-control studies. The databases of Embase, Medline, Scopus, and Web of Science were searched to identify case-control study protocols published between January 1, 1990 and December 31, 2017. The numbers and characteristics of predefined exposures (or factors) were extracted from the protocols. The reported and unreported factors were both collected from the published studies and protocols. The frequency of selective reporting of results were estimated by identifying the discrepancies of factors between the protocols and the published studies. Study sample size and the extent of selective reporting of factors were measured by a Spearman correlation analysis. Fourteen protocols with 24 published studies and 159 factors were identified, of which eight protocols (57.1%) had discrepancies between the publications and protocols. The prevalence of incomplete reporting in published case-control studies was 42.9% (6/14), with participant characteristics, anthropometric and laboratory measurement variables more likely to be unreported. A total of 16,835 cases and 56,049 controls were recruited in the 14 protocols of case-control studies (sample size ranges from 428 to 52,596 per study). Sample size had no statistical significance with selective reporting of results (P > 0.05). The study protocols should be publicly available prior to the completion of case-control studies so that the potential bias can be assessed by the readers. Our findings highlight the need for investigators, peer reviewers, and readers to exercise increased awareness and scrutiny due to the undesirable practice of selective reporting of results in medical sciences causing the loss of potentially important information, thus impacting quality of personalized attitude in healthcare in the context of the predictive, preventive, and personalized medicine.

Identification of mosquitoes (Diptera: Culicidae): an external quality assessment of medical entomology laboratories in the MediLabSecure Network

BackgroundIdentification of vectors is of prime importance in the field of medical entomology for both operational and research purposes. An external quality assessment of mosquito identification capacities was carried out within the MediLabSecure Network, which is composed of laboratories located in 19 countries close to the European Union around the Mediterranean and Black seas.MethodsA set of blind samples consisting of 7 or 8 adult mosquitoes and 4 larvae was given to each participant laboratory. In all, 138 adult mosquitoes and 76 larvae of different species were distributed for genus and species identification.ResultsAll identifications were exclusively morphology based. Overall, 81% of identifications were correct at the genus level, 64% at the species level. The results were highly varied among the 19 participating laboratories. The levels of correct identifications were: 100% (three laboratories), 90–95% (four laboratories), 50–75% (six laboratories) and < 50% (six laboratories).ConclusionsThis evaluation showed the need to maintain efforts in capacity building and quality control in the field of medical entomology and, more specifically, in the morphological identification of the Culicidae.

Epidemiology of hepatitis B, C and D in Malawi: systematic review

BackgroundViral hepatitis is an important public health issue in sub-Saharan Africa. Due to rising mortality from cirrhosis and hepatocellular carcinoma and limited implementation of screening and treatment programmes, it has been characterised as a neglected tropical disease. Synthesis of the existing evidence on the epidemiology of viral hepatitis B, C and D in Malawi is required to inform policy and identify research gaps.MethodsWe searched Pubmed, EMBASE and Scopus for studies reporting the epidemiology of viral hepatitis B, C and D in Malawi from 1990 to 2018. Articles reporting prevalence estimates were included provided they described details of participant selection, inclusion criteria and laboratory methods (detection of HBsAg, anti-HCV or anti-HDV antibody, HCV antigen or HCV RNA or HDV RNA). We assessed study quality using a prevalence assessment tool. Where appropriate, a pooled prevalence was calculated using a DerSimonian Laird random effects model.ResultsSearches identified 199 studies, 95 full text articles were reviewed and 19 articles were included. Hepatitis B surface antigen (HBsAg) seroprevalence was assessed in 14 general population cohorts. The pooled prevalence among adults was 8.1% (95% CI 6.1, 10.3). In 3 studies where HBsAg was stratified by HIV status, no effect of HIV on HBsAg prevalence was observed (OR 1.2 (95% CI: 0.8, 1.6, p = 0.80)). In a single study of HIV/HBV infected individuals, anti-hepatitis D antibody (anti-HDV) prevalence was low (1.5%). HCV antibody prevalence (anti-HCV) ranged from 0.7 to 18.0% among 12 cohorts in general populations. Among three studies which used PCR to confirm current infection, the pooled rate of HCV RNA confirmation among anti-HCV positive individuals was only 7.3% (95% CI: 0.0, 24.3).ConclusionsHepatitis B is highly prevalent in Malawi. There is a paucity of epidemiological data from rural areas where 85% of the population reside, and the Northern region. Priority research needs include large-scale representative community studies of HBV, HDV and HCV seroprevalence, assessment of children following introduction of the HBV vaccine in 2002, prevalence estimates of viral hepatitis among individuals with cirrhosis and HCC and data on HCV prevalence using PCR confirmation, to support a viral hepatitis strategy for Malawi.