Burc Aydin

Evidence-based clinical practice: Overview of threats to the validity of evidence and how to minimise them

Using the best quality of clinical research evidence is essential for choosing the right treatment for patients. How to identify the best research evidence is, however, difficult. In this narrative review we summarise these threats and describe how to minimise them. Pertinent literature was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment represent the highest level of evidence. Even though systematic reviews are trust worthier than other types of evidence, all levels of the evidence hierarchy are under threats from systematic errors (bias); design errors (abuse of surrogate outcomes, composite outcomes, etc.); and random errors (play of chance). Clinical research infrastructures may help in providing larger and better conducted trials. Trial Sequential Analysis may help in deciding when there is sufficient evidence in meta-analyses. If threats to the validity of clinical research are carefully considered and minimised, research results will be more valid and this will benefit patients and heath care systems.

Trait-related alterations of N-acetylaspartate in euthymic bipolar patients: A longitudinal proton magnetic resonance spectroscopy study

BACKGROUND Neurochemical changes are responsible for bipolar disorder (BD) pathophysiology. Despite current progress in BD research, mood- and trait-related alterations in BD continue to elicit further investigation. METHODS In this study, we report a longitudinal proton magnetic resonance spectroscopy study evaluating dorsomedial prefrontal cortex (DMPFC) metabolites N-acetylaspartate (NAA), creatine plus phosphocreatine (total creatine [tCr]), phosphorylcholine plus glycerophosphocholine, myo-inositol, and glutamate plus glutamine levels of manic and euthymic adult BD type I patients (n=48) treated with standard antimanic medicines, compared to matching healthy controls (n=44). RESULTS DMPFC NAA values and NAA/tCr ratio were significantly lower in euthymic BD patients when compared with healthy controls with similar levels of other metabolites in all groups, indicating a trait-related NAA abnormality in euthymic BD patients. LIMITATIONS of our study include a relatively low (1.5T) magnetic resonance field strength and variable drugs administered to achieve euthymia despite the best efforts to standardize the open fashion treatment. CONCLUSIONS Our study contributes to the integrating models of trait-related metabolite alterations observed in euthymia since NAA is considered as a marker of neuronal viability and mitochondrial energy metabolism. In light of supporting and conflicting results reported previously, future studies with longitudinal designs and larger patient groups are warranted to better define both state- and trait-related cerebral metabolic alterations associated with BD pathophysiology.

Clinical Research Infrastructure in Turkey: a Pilot Strengths, Weaknesses, Opportunities, Threats Analysis

Objective: The purpose of the study was to evaluate the infrastructure facilities of clinical trial units in Turkey to create descriptive information and perform a pilot strengths, weaknesses, opportunities, and threats (SWOT) analysis that describes the strengths to match them with the opportunities and aims to reduce weaknesses and threats. Methods: This study was conducted using the data provided by nine clinical trial units within the scope of a collaboration agreement signed with Turkish Clinical Research Infrastructure Network between April 2013 and December 2016, using a survey created and applied with Google Forms application. Descriptive statistics was used to summarize infrastructure and capacity questions. Mean and median were calculated to interpret the current data. A pilot SWOT analysis was performed to evaluate the clinical research environment in Turkey. Results: The number of clinical trials conducted varied over a wide range among the units. Most trials were conducted in the area of pediatrics, with the least number of trials being conducted in the area of endocrinology. Most units conducted national singlecenter trials with public funds. Physicians were mostly involved in clinical trials, and the number of nonprofessional healthcare personnel was limited. Application to the Ethics Committees and MoH was the most provided service among clinical trials units, where monitoring was the least provided service. None of the units had quality certification. A wide range of evaluations and suggestions concerning the clinical trial environment in Turkey was provided in this pilot SWOT analysis. Conclusion: As these weaknesses and threats with the data, provided by the units, are consistent with the concerns expressed by the national policy makers, suggestions expressed in the survey to improve the clinical research capacity and environment in Turkey should be considered for future actions.