Reporting characteristics of nonsurgical periodontal therapy trials registered in ClinicalTrials.gov: an observational study.

Aim: To evaluate the completeness of the description of nonsurgical periodontal therapy interventions in clinical trials registered in ClinicalTrials.gov and correspondence of registered information for trial participants and outcome measures with published articles. Materials & methods: We retrieved data from ClinicalTrials.gov and corresponding publications. The completeness of intervention reporting was assessed using the Template for Intervention Description and Replication (TIDieR) checklist for oral hygiene instructions (OHI), professional mechanical plaque removal (PMPR), and subgingival instrumentation, antiseptics and antibiotics. The completeness of registration of trial protocol information was assessed according to the WHO Trial Registration DataSet for participant information (enrollment, sample size calculation, age, gender, condition) and primary/secondary outcome measures. Results: 79 included trials involved OHI (n = 38 trials, 48.1%), PMPR (n = 19, 24.1%), antiseptics (n = 11, 12.7%), or antibiotics (n = 11, 12.7%). There was a great variety in the terms used to describe these interventions. Most of the analyzed trials (93.7%) were completed and did not provide any data on study phase (74.7%). The description of intervention in the registry in ClinicalTrials.gov was inadequate for all analyzed interventions, with description inconsistencies in matching publications. There were also discrepancies in registered and published outcomes: for 39 trials with published results, 18 had different registered and reported primary outcomes, and 29 different registered and reported secondary outcomes. Conclusion: The completeness of the description of nonsurgical therapy of periodontitis in clinical trials is unsatisfactory, reducing the quality of translation of the new evidence and procedures into clinical practice. Significant discrepancy in registered and reported trial outcomes calls into question the validity of reported results and relevance for practice.

Effects of Moderate Consumption of Red Wine on Hepcidin Levels in Patients with Type 2 Diabetes Mellitus.

Iron overload is often associated with type 2 diabetes (T2D), indicating that hepcidin, the master regulator of iron homeostasis, might be involved in diabetes pathogenesis. Alcohol consumption may also result in increased body iron stores. However, the moderate consumption of wine with meals might be beneficial in T2D. This effect has been mainly attributed to both the ethanol and the polyphenolic compounds in wine. Therefore, we examined the effects of red wine on hepcidin in T2D patients and non-diabetic controls. The diabetic patients (n = 18) and age- and BMI-matched apparently healthy controls (n = 13) were men, aged 40−65 years, non-smoking, with BMI < 35 kg/m2. Following a 2-week alcohol-free period, both groups consumed 300 mL of red wine for 3 weeks. The blood samples for the iron status analysis were taken at the end of each period. The red wine intake resulted in a decrease in serum hepcidin in both the diabetic subjects (p = 0.045) and controls (p = 0.001). The levels of serum ferritin also decreased after wine in both groups, reaching statistical significance only in the control subjects (p = 0.017). No significant alterations in serum iron, transferrin saturation, or soluble transferrin receptors were found. The suppression of hepcidin, a crucial iron-regulatory hormone and acute-phase protein, in T2D patients and healthy controls, is a novel biological effect of red wine. This may deepen our understanding of the mechanisms of the cardiometabolic effects of wine in T2D.

Inadequate reporting quality of registered genome editing trials: an observational study.

BACKGROUND: To assess registration completeness and safety data of trials on human genome editing (HGE) reported in primary registries and published in journals, as HGE has safety and ethical problems, including the risk of undesirable and unpredictable outcomes. Registration transparency has not been evaluated for clinical trials using these novel and revolutionary techniques in human participants. METHODS: Observational study of trials involving engineered site-specific nucleases and long-term follow-up observations, identified from the WHO ICTRP HGE Registry in November 2020 and two comprehensive reviews published in the same year. Registration and adverse events (AEs) information were collected from public registries and matching publications. Published data were extracted in May 2021. RESULTS: Among 81 eligible trials, most were recruiting (51.9%) phase 1 trials (45.7%). Five trials were withdrawn. Most trials investigated CAR T cells therapies (45.7%) and used CRISPR/Cas9 (35.8%) ex vivo (88.9%). Among 12 trials with protocols both registered and published, eligibility criteria, sample size, and secondary outcome measures were consistently reported for less than a half. Three trials posted results in ClinicalTrials.gov, and one reported serious AEs. CONCLUSIONS: Incomplete registration and published data give emphasis to the need to increase the transparency of HGE trials. Further improvements in registration requirements, including phase 1 trials, and a more controlled publication procedure, are needed to augment the implementation of this promising technology.

Drug-drug interaction trials incompletely described drug interventions in ClinicalTrials.gov and published articles: an observational study.

OBJECTIVES: The aim of the study was to evaluate the completeness of intervention description in ClinicalTrials.gov and corresponding journal articles for registered and published drug-drug interaction (DDI) trials because complete and transparent description of interventions is particularly important for DDI. STUDY DESIGN AND SETTING: Observational study of completed interventional trials on DDIs with up to two drugs within the Intervention registration element in ClinicalTrials.gov until October 2015. We used the Template for Intervention Description and Replication items to assess the quality of intervention description in both ClinicalTrials.gov Descriptive Information section and matching publications. Corresponding articles were identified in March 2019. RESULTS: The description of 1,180 drug interventions registered for 642 DDI trials mostly lacked information on the intervention provider (99.7%), adherence strategies (99.2%), procedure (83.8%), location (71.3%), and dosage form (60.7%). Generic name (82.5%), dose (70.8%), and duration of administration (65.6%) were most frequently reported. Among 51 trials that had data reported both in ClinicalTrials.gov and publication, 60.8% were in phase 1. Less than half of 96 interventions had clear and matching description of dosage form, procedure, and route of administration in both sources. CONCLUSION: DDI trials did not sufficiently report components required for complete intervention description. Further improvements in ClinicalTrials.gov registration requirements, including phase 1 trials, and more stringent publishing requirements for essential data on drug interventions, are needed to prevent patient risk in clinical practice regarding concomitant medication use.

Expression of Leukocytes Following Myocardial Infarction in Rats is Modulated by Moderate White Wine Consumption.

How moderate white wine consumption modulates inflammatory cells infiltration of the ischemic myocardium following permanent coronary ligation was the key question addressed in this study. Male Sprague-Dawley rats were given either a combination of different white wines or water only for 28 days. Three peri-infarct/border zones and a control/nonischemic zone were analysed to determine the expression of myeloperoxidase (MPO) and cluster of differentiation 68 (CD68). Smaller expressions for both MPO and CD68 were found in all three peri-infarct zones of wine drinking animals (p < 0.001). There was no difference in the expression of leukocyte markers between animals drinking standard and polyphenol-rich white wine, although for CD68, a nonsignificant attenuation was noticed. In sham animals, a subepicardial MPO/CD68 immunoreactive "inflammatory ring" is described. Standard white wine consumption caused attenuation of the expression of MPO but not of CD68 in these animals. We conclude that white wine consumption positively modulates peri-infarct inflammatory infiltration.

Effectiveness of treatment of newly diagnosed hypertension in family medicine practices in South Croatia.

BACKGROUND: Uncontrolled blood pressure remains an urgent issue in clinical practice worldwide. This study aimed to compare the characteristics and effectiveness of hypertension control in family medicine pratice in the first treatment year, in relation to the geographical position, socio-economic standard, and access to medical services and public pharmacies in urban, rural and island environments (city of Split vs. Dalmatian Hinterland vs. islands in Southern Croatia). METHODS: A historical cohort study included 213 patients diagnosed from 2008 to 2014 with essential arterial hypertension (AH) and without related complications or diabetes mellitus. Each patient was followed up for 365 days from the visit when the diagnosis of hypertension was ascertained. Normotension was defined as arterial pressure < 140/90 mmHg. The annual cost of drugs prescribed for treating newly diagnosed hypertensive patient and the total price for defined daily dose per patient were also evaluated. RESULTS: More than half patients achieved normotension within a year from the initial diagnosis in all family medicine practices (57.3%), without significant differences among the three geographic regions (P = 0.981). Higher initial systolic blood pressure was a positive predictive prognostic factor on achieveing normotension (odds ratio (OR) 0.96, 95% confidence interval 0.95-0.98). ACE inhibitors were the most commonly prescribed antihypertensive agents in monotherapy (35.1%), as well as considering overall prescriptions (25.2%). Calcium channel blockers were the most commonly prescribed initial BP-lowering single agents in urban areas (28.6%), whereas angiotensin-converting enzyme inhibitors were more common in rural (28.0%) and island areas (22.7%) (P = 0.037). The median annual antihypertensive drug cost was 169.4 (95% CI 151.5-201.8) Croatian kunas and was similar across the study sites. CONCLUSION: Multiple antihypertensive drugs, prescribed in accordance with the guidelines, lead to similar pharmacological effects. Primary care physicians seem to be able to overcome potential interfering socio-economic factors and successfully achieve normotension in newly diagnosed patients with uncomplicated AH after 1 year of treatment.

Clinical trials on drug-drug interactions registered in ClinicalTrials.gov reported incongruent safety data in published articles: an observational study.

OBJECTIVE: To assess safety data of trials on drug-drug interactions (DDIs) reported in ClinicalTrials.gov and published in journal articles, since DDIs are a growing concern. STUDY DESIGN AND SETTING: In an observational study of clinical trials retrieved by the search term "drug-drug interaction(s)," we collected the information on registration and on adverse events (AEs) from ClinicalTrials.gov and corresponding publications. Trials were included if they primarily investigated DDIs, had a National Clinical Trial identifier, and were closed and completed by October 16, 2015. Publication data were extracted until March 2017. RESULTS: Among 1,110 eligible trials, most were in phase 1 (76.8%), industry-funded (68.8%), and started before registration (56.9%). Results were not reported in the registry for 86.8% and not published for 68.1% trials. Published AE data were completely identical to the data submitted to ClinicalTrials.gov for only 15.6% trials. Among 64 trials with results reported both in ClinicalTrials.gov and publications, 34.4% published concordant number for other AEs. CONCLUSION: Discrepancies that emerge from incomplete or changed reporting of AEs in publications emphasize the need to amend and enforce regulatory requirements for timely and complete submission of results, clearer AE reporting for trials focusing on DDIs, and regular assessment of the congruence of AE data submitted to ClinicalTrials.gov and scientific journals during the publication process.

Effects of White Wine Consumption on Weight in Rats: Do Polyphenols Matter?

INTRODUCTION: Effects of white wine and the role of wine polyphenols on weight gain in rats of different age were examined in the 4-week-voluntary-consumption trial. METHODS AND MATERIALS: Biochemically characterized standard (low polyphenols, W) and macerated (high polyphenolic content, PW) white wines were compared. One- and three-month-old Sprague-Dawley male rats (n = 78) were used. Each age group was subdivided into water-only-drinking controls (C), W, and PW-drinking animals. Daily wine and total liquid consumption, food intake, and body weight were measured, and energy intake and feed efficiency index were calculated. RESULTS: In both age categories, wine-drinking animals consumed less food and gained less weight in comparison to C (181 ± 2, 179 ± 6, and 201 ± 5 in younger animals and 32 ± 5, 28 ± 6, and 47 ± 4 grams in older animals, resp.), regardless of wine type. Total energy intake was the lowest in PW-drinking animals. CONCLUSION: Wine-drinking animals gained less weight in comparison to C, regardless of the wines' polyphenol content. Although our results are indicative of the major role of nonphenolic constituents of the wines (probably ethanol), the modifying role of wine phenolics on weight gain cannot be excluded as the group consuming PW had lower total energy intake than other groups.