PeerJ Preprints: Clinical Trialshttps://peerj.com/preprints/index.atom?journal=peerj&subject=3630Clinical Trials articles published in PeerJ PreprintsFracture Table vs. Lateral Positioning for Intramedullary Fixation of Femur Fractures (The FLiP Study): A protocol for a pilot randomized controlled trialhttps://peerj.com/preprints/278752019-10-222019-10-22Daniel AxelrodHerman JohalKim MaddenFrancesc MarcanoCarlos Prada
Background: Femoral Shaft fractures are devastating and life threatening injuries. Femoral shaft fractures are most commonly treated with intramedullary fixation. Malrotation of the injured limb after fixation is a common and significant complication following femoral shaft fractures. During the operation, patients can be positioned either supine or in a lateral position. Additionally, patients can be placed on a standard radiolucent operating room table, or placed on a fracture table with traction statically applied to the operative limb throughout the case. Previous case series and cohort studies have shown equivalence between study groups, but choice between positioning options remains controversial.
Methods: This represents a protocol for a randomized controlled pilot trial. We will be compared lateral positioning with use of manual traction to supine positioning with use of a fracture table. Primary outcomes will be in assessment for feasibility for a future full scale randomized trial, including evaluating patient recruitment, patient compliance with followup, contamination between treatment arms and others.
Results: The primary outcome will be feasibility for a future trial. Secondary outcomes will include malrotation as measured through postoperative computed tomography scans and gait analysis at 6 months.
Background: Femoral Shaft fractures are devastating and life threatening injuries. Femoral shaft fractures are most commonly treated with intramedullary fixation. Malrotation of the injured limb after fixation is a common and significant complication following femoral shaft fractures. During the operation, patients can be positioned either supine or in a lateral position. Additionally, patients can be placed on a standard radiolucent operating room table, or placed on a fracture table with traction statically applied to the operative limb throughout the case. Previous case series and cohort studies have shown equivalence between study groups, but choice between positioning options remains controversial.Methods: This represents a protocol for a randomized controlled pilot trial. We will be compared lateral positioning with use of manual traction to supine positioning with use of a fracture table. Primary outcomes will be in assessment for feasibility for a future full scale randomized trial, including evaluating patient recruitment, patient compliance with followup, contamination between treatment arms and others.Results: The primary outcome will be feasibility for a future trial. Secondary outcomes will include malrotation as measured through postoperative computed tomography scans and gait analysis at 6 months.A guide to applying the Good Publication Practice 3 Guidelines in the Asia-Pacific regionhttps://peerj.com/preprints/278922019-08-192019-08-19Blair HespKatsuhisa AraiMagdalene ChuStefanie ChuahJose Miguel CuramengSandeep KamatZhigang MaAndrew SakkoHazel Fernandez
Numerous recommendations and guidelines aim to improve the quality, timeliness and transparency of medical publications. However, these guidelines use ambiguous language that can be challenging to interpret, particularly for speakers of English as a second language. Cultural expectations within the Asia-Pacific region raise additional challenges. Several studies have suggested that awareness and application of ethical publication practices in the Asia-Pacific region is relatively low compared with other regions. However, guidance on applying ethical publication practice guidelines in the Asia-Pacific region is lacking. This review aims to improve publication practices in the Asia-Pacific region by providing guidance on applying the 10 principles of the Good Publication Practice 3 (GPP3) guidelines and the International Committee of Medical Journal Editors (ICMJE) criteria for authorship. Recommendations are provided for encore presentations, applying the ICMJE authorship criteria in the context of regional cultural expectations, and the role of study sponsors and professional medical writers. Ongoing barriers to compliance with guidelines are also highlighted, and additional guidance is provided to support authors submitting manuscripts for publication. The roles of regional journals, regulatory authorities and professional bodies in improving practices are also discussed.
Numerous recommendations and guidelines aim to improve the quality, timeliness and transparency of medical publications. However, these guidelines use ambiguous language that can be challenging to interpret, particularly for speakers of English as a second language. Cultural expectations within the Asia-Pacific region raise additional challenges. Several studies have suggested that awareness and application of ethical publication practices in the Asia-Pacific region is relatively low compared with other regions. However, guidance on applying ethical publication practice guidelines in the Asia-Pacific region is lacking. This review aims to improve publication practices in the Asia-Pacific region by providing guidance on applying the 10 principles of the Good Publication Practice 3 (GPP3) guidelines and the International Committee of Medical Journal Editors (ICMJE) criteria for authorship. Recommendations are provided for encore presentations, applying the ICMJE authorship criteria in the context of regional cultural expectations, and the role of study sponsors and professional medical writers. Ongoing barriers to compliance with guidelines are also highlighted, and additional guidance is provided to support authors submitting manuscripts for publication. The roles of regional journals, regulatory authorities and professional bodies in improving practices are also discussed.Practical considerations for collaborative research between the pharmaceutical industry and external investigatorshttps://peerj.com/preprints/277852019-06-052019-06-05Maureen LloydCynthia K BarbitschMary Voehl HirschAntonia PanayiEric Southam
Traditionally, clinical research has been conducted via either industry sponsored studies or non-industry investigator sponsored studies. Collaborative Research provides a relatively new mechanism for industry and non-industry partners to work together in the pursuit of effective and safe treatments for the patient. The aims of this article are to provide both industry and non-industry investigators with a greater insight into the complex processes that are currently employed by industry when entering into Collaborative Research agreements, and to encourage consistency and transparency in approach across companies.
In Collaborative Research, instead of being limited to providing funding and/or product, the industry partner contributes expertise complementary to that of the non-industry partner, who is the sponsor of the study. Collaborative Research may be conducted before, during or after regulatory approval of a drug or medical device, and may be interventional, observational or preclinical.
A collaboration requires appropriate process and governance frameworks to be established in order to be successful. Important considerations include the routes for submitting a request, the review and approval process, due diligence criteria, budgeting and contracting processes, permissible interactions during the execution of the research, the closing out of the research, and dispute resolution. It is also necessary to have in place an agreed communication strategy and a risk control framework. Clear and specific contract language around roles and responsibilities, intellectual property, rights to data, registration and disclosure of publications, and an understanding of adverse event reporting procedures are other critical facets of Collaborative Research that are essential to avoid delays and disputes.
With no global standards for Collaborative Research, it is important that partners establish practical procedures, good ongoing communication, alignment of goals, and transparent interactions and disclosure to jointly advance the science of new, safe and effective therapies.
Traditionally, clinical research has been conducted via either industry sponsored studies or non-industry investigator sponsored studies. Collaborative Research provides a relatively new mechanism for industry and non-industry partners to work together in the pursuit of effective and safe treatments for the patient. The aims of this article are to provide both industry and non-industry investigators with a greater insight into the complex processes that are currently employed by industry when entering into Collaborative Research agreements, and to encourage consistency and transparency in approach across companies.In Collaborative Research, instead of being limited to providing funding and/or product, the industry partner contributes expertise complementary to that of the non-industry partner, who is the sponsor of the study. Collaborative Research may be conducted before, during or after regulatory approval of a drug or medical device, and may be interventional, observational or preclinical.A collaboration requires appropriate process and governance frameworks to be established in order to be successful. Important considerations include the routes for submitting a request, the review and approval process, due diligence criteria, budgeting and contracting processes, permissible interactions during the execution of the research, the closing out of the research, and dispute resolution. It is also necessary to have in place an agreed communication strategy and a risk control framework. Clear and specific contract language around roles and responsibilities, intellectual property, rights to data, registration and disclosure of publications, and an understanding of adverse event reporting procedures are other critical facets of Collaborative Research that are essential to avoid delays and disputes.With no global standards for Collaborative Research, it is important that partners establish practical procedures, good ongoing communication, alignment of goals, and transparent interactions and disclosure to jointly advance the science of new, safe and effective therapies.Catheter ablation vs antiarrhythmic medication in atrial fibrillationhttps://peerj.com/preprints/277692019-05-302019-05-30Eric W ManheimerMartin MayerBrian S Alper
The CABANA and CAPTAF trials report more data on the effects of catheter ablation vs. antiarrhythmic medication on quality of life for patients with atrial fibrillation than previously available systematic reviews. However, these publications do not report data for all-cause mortality and cardiac hospitalization in a form that can be integrated into recent meta-analyses.
Recent meta-analysis estimates for the effect of catheter ablation on all-cause mortality suggest a reduction in patients with comorbid heart failure with reduced ejection fraction (HFrEF) (risk ratio [RR] 0.52, 95% CI 0.33 to 0.81, n=732, 5 trials) and an unclear effect in patients without comorbid HFrEF (RR 0.88, 95% CI 0.29 to 2.61, n=710, 4 trials).
CABANA (n = 2,204) reported mortality for all patients combined (hazard ratio 0.86, 95% CI 0.65 to 1.15), and subgroup analyses by presence or absence of HFrEF would be useful to determine consistency with other trials and, if consistent, increase precision of pooled effect estimates. CAPTAF (n = 155) (which included almost exclusively patients without comorbid heart failure) did not report the mortality outcome data.
Both trials collected data on cardiac hospitalization. A recent meta-analysis suggests a reduction in cardiac hospitalization in patients with comorbid HFrEF (RR 0.63, 95% CI 0.46 to 0.87, n=632, 3 trials) and in patients without comorbid HFrEF (RR 0.32, 95% CI 0.23 to 0.45, n=629, 4 trials). Again, however, the CABANA and CAPTAF trials did not report these data in a way that would allow them to be integrated into existing meta-analyses or did not report these data at all. Reporting key clinical outcomes from these trials with subgrouping by comorbid HFrEF could provide substantially more data than the prior body of evidence and inform best current estimates for this comparison.
The CABANA and CAPTAF trials report more data on the effects of catheter ablation vs. antiarrhythmic medication on quality of life for patients with atrial fibrillation than previously available systematic reviews. However, these publications do not report data for all-cause mortality and cardiac hospitalization in a form that can be integrated into recent meta-analyses.Recent meta-analysis estimates for the effect of catheter ablation on all-cause mortality suggest a reduction in patients with comorbid heart failure with reduced ejection fraction (HFrEF) (risk ratio [RR] 0.52, 95% CI 0.33 to 0.81, n=732, 5 trials) and an unclear effect in patients without comorbid HFrEF (RR 0.88, 95% CI 0.29 to 2.61, n=710, 4 trials).CABANA (n = 2,204) reported mortality for all patients combined (hazard ratio 0.86, 95% CI 0.65 to 1.15), and subgroup analyses by presence or absence of HFrEF would be useful to determine consistency with other trials and, if consistent, increase precision of pooled effect estimates. CAPTAF (n = 155) (which included almost exclusively patients without comorbid heart failure) did not report the mortality outcome data.Both trials collected data on cardiac hospitalization. A recent meta-analysis suggests a reduction in cardiac hospitalization in patients with comorbid HFrEF (RR 0.63, 95% CI 0.46 to 0.87, n=632, 3 trials) and in patients without comorbid HFrEF (RR 0.32, 95% CI 0.23 to 0.45, n=629, 4 trials). Again, however, the CABANA and CAPTAF trials did not report these data in a way that would allow them to be integrated into existing meta-analysesor did not report these data at all. Reporting key clinical outcomes from these trials with subgrouping by comorbid HFrEF could provide substantially more data than the prior body of evidence and inform best current estimates for this comparison.Bayesian meta-analysis of studies with rare events: Do the choice of prior distributions and the exclusion of studies without events in both arms matter?https://peerj.com/preprints/277322019-05-152019-05-15Soheila AghlmandiPeter JüniJames CarpenterMarcel Zwahlen
Randomized controlled trials (RCTs) analyzing serious adverse events often observe low incidence and might even observe zero events in either or both of the treatment and control arms. In the meta-analysis of RCTs of adverse events, it is unclear whether trials with zero events in both arms provide any information for the summary risk ratio (RR) or odds ratio (OR). Studies with zero events in both arms are usually excluded in both frequentist and Bayesian meta-analysis. We used a fully probabilistic approach—a Bayesian framework—for the meta-analysis of studies with rare events, and systematically assessed whether exclusion of studies with no events in both arms produced different results compared to keeping all studies in the meta-analysis. We did this by conducting a simulation study in which we assessed the bias in the point estimate of the log(OR) and the coverage of the 95% posterior interval for the log(OR) for different analytical decisions and choices in fixed effect and random effects meta-analysis. We used simulated data generated from a known fixed effect or random effects data scenario (each scenario with a 1000 meta-analysis data-set). We found that the uniform and Jeffrey’s prior on the baseline risk in the control group leads to biased results and a reduced coverage, and that setting the prior distribution on the log(odds) scale worked better. We also found nearly identical results regardless of whether studies with no events in both arms were excluded or not.
Randomized controlled trials (RCTs) analyzing serious adverse events often observe low incidence and might even observe zero events in either or both of the treatment and control arms. In the meta-analysis of RCTs of adverse events, it is unclear whether trials with zero events in both arms provide any information for the summary risk ratio (RR) or odds ratio (OR). Studies with zero events in both arms are usually excluded in both frequentist and Bayesian meta-analysis. We used a fully probabilistic approach—a Bayesian framework—for the meta-analysis of studies with rare events, and systematically assessed whether exclusion of studies with no events in both arms produced different results compared to keeping all studies in the meta-analysis. We did this by conducting a simulation study in which we assessed the bias in the point estimate of the log(OR) and the coverage of the 95% posterior interval for the log(OR) for different analytical decisions and choices in fixed effect and random effects meta-analysis. We used simulated data generated from a known fixed effect or random effects data scenario (each scenario with a 1000 meta-analysis data-set). We found that the uniform and Jeffrey’s prior on the baseline risk in the control group leads to biased results and a reduced coverage, and that setting the prior distribution on the log(odds) scale worked better. We also found nearly identical results regardless of whether studies with no events in both arms were excluded or not.Characteristics of effective home-based resistance training exercise in patients with chronic disease: a scoping review protocolhttps://peerj.com/preprints/276792019-04-242019-04-24Thomas WilkinsonRoseanne BillanyCourtney J LightfootMatthew Graham-BrownAlice C Smith
Regular exercise, principally resistance training, is an effective method to promote muscle hypertrophy and attenuate muscle atrophy during various atrophic conditions . There is growing interest in the evaluation of home-based resistance training programmes. These programmes have the potential to overcome common barriers to participation, such as accessibility and affordability. The objective of the scoping review is to map the available evidence to provide an overview of what characteristics, principles, and components are required for an effective home-based resistance training programme in patients with chronic disease. The four specific objectives of the scoping review will be to: 1) conduct a systematic search of the published and grey literature for studies reporting on home-based resistance training in patients with chronic disease; 2) map out the characteristics and range of methodologies (including exercise protocols and outcome measures) used in effective home-based resistance training; 3) examine reported challenges and limitations of home-based resistance training; and 4) propose recommendations for optimizing home-based resistance training protocols in this population.
Regular exercise, principally resistance training, is an effective method to promote muscle hypertrophy and attenuate muscle atrophy during various atrophic conditions . There is growing interest in the evaluation of home-based resistance training programmes. These programmes have the potential to overcome common barriers to participation, such as accessibility and affordability. The objective of the scoping review is to map the available evidence to provide an overview of what characteristics, principles, and components are required for an effective home-based resistance training programme in patients with chronic disease. The four specific objectives of the scoping review will be to: 1) conduct a systematic search of the published and grey literature for studies reporting on home-based resistance training in patients with chronic disease; 2) map out the characteristics and range of methodologies (including exercise protocols and outcome measures) used in effective home-based resistance training; 3) examine reported challenges and limitations of home-based resistance training; and 4) propose recommendations for optimizing home-based resistance training protocols in this population.Attribution of non-ClinicalTrials.gov registries among WHO International Clinical Trials Registry Platform-registered trials from 2014 to 2018: A protocol for a meta-epidemiological studyhttps://peerj.com/preprints/272982019-03-182019-03-18Masahiro BannoYasushi TsujimotoYuki Kataoka
Background. The attribution of non-ClinicalTrials.gov registries among registered trials of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) had increased until 2013. However, the attribution after 2013 is unknown. Moreover, no study has investigated the usage of non-ClinicalTrials.gov registries after 2015 or compared the characteristics of trials under non-ClinicalTrials.gov and ClinicalTrials.gov registries. Methods. This will be a meta-epidemiological study. It will include all trials registered on the ICTRP from January 1, 2014, to December 31, 2018. First, we will describe the total attribution of non-ClinicalTrials.gov registries among the ICTRP-registered trials for each year and each registry worldwide. Second, we will compare the recruitment status, target sample size, study type, countries, retrospective registration, funding, and study phase of the trials on ClinicalTrials.gov and other registries from 2014 to 2018. Third, we will report on the distribution of primary registries of trials from the top five countries in order of the quantity of registered trials on the ICTRP. We will separately report the results from interventional and other studies. Inclusion criteria for interventional studies will be studies that include the word “intervention” or “interventional” in “study type” of the data set. Other studies will refer to studies other than interventional studies such as cohort, case-control, and cross-sectional studies. Ethics & Dissemination. Ethics approval is not required for this study. This protocol has been registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR). The findings will be published in a peer-reviewed journal and may be presented at conferences. Trial Registration Number. UMIN000034401
Background. The attribution of non-ClinicalTrials.gov registries among registered trials of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) had increased until 2013. However, the attribution after 2013 is unknown. Moreover, no study has investigated the usage of non-ClinicalTrials.gov registries after 2015 or compared the characteristics of trials under non-ClinicalTrials.gov and ClinicalTrials.gov registries. Methods. This will be a meta-epidemiological study. It will include all trials registered on the ICTRP from January 1, 2014, to December 31, 2018. First, we will describe the total attribution of non-ClinicalTrials.gov registries among the ICTRP-registered trials for each year and each registry worldwide. Second, we will compare the recruitment status, target sample size, study type, countries, retrospective registration, funding, and study phase of the trials on ClinicalTrials.gov and other registries from 2014 to 2018. Third, we will report on the distribution of primary registries of trials from the top five countries in order of the quantity of registered trials on the ICTRP. We will separately report the results from interventional and other studies. Inclusion criteria for interventional studies will be studies that include the word “intervention” or “interventional” in “study type” of the data set. Other studies will refer to studies other than interventional studies such as cohort, case-control, and cross-sectional studies. Ethics & Dissemination. Ethics approval is not required for this study. This protocol has been registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR). The findings will be published in a peer-reviewed journal and may be presented at conferences. Trial Registration Number. UMIN000034401Method to collect ground truth data for walking speed in real-world environments: description and validationhttps://peerj.com/preprints/275582019-02-282019-02-28Gerhard AignerBernd GrimmChristian LedererMartin Daumer
Background. Physical activity (PA) is increasingly being recognized as a major factor related to the development or prevention of many diseases, as an intervention to cure or delay disease and for patient assessment in diagnostics, as a clinical outcome measure or clinical trial endpoint. Thus, wearable sensors and signal algorithms to monitor PA in the free-living environment (real-world) are becoming popular in medicine and clinical research. This is especially true for walking speed, a parameter of PA behaviour with increasing evidence to serve as a patient outcome and clinical trial endpoint in many diseases. The development and validation of sensor signal algorithms for PA classification, in particular walking, and deriving specific PA parameters, such as real world walking speed depends on the availability of large reference data sets with ground truth values. In this study a novel, reliable, scalable (high throughput), user-friendly device and method to generate such ground truth data for real world walking speed, other physical activity types and further gait-related parameters in a real-world environment is described and validated.
Methods. A surveyor’s wheel was instrumented with a rotating 3D accelerometer (actibelt). A signal processing algorithm is described to derive distance and speed values. In addition, a high-resolution camera was attached via an active gimbal to video record context and detail. Validation was performed in the following main parts: 1) walking distance measurement is compared to the wheel’s built-in mechanical counter, 2) walking speed measurement is analysed on a treadmill at various speed settings, 3) speed measurement accuracy is analysed by an independent certified calibration laboratory - accreditation by DAkkS applying standardised test procedures.
Results: The mean relative error for distance measurements between our method and the built-in counter was 0.12%. Comparison of the speed values algorithmically extracted from accelerometry data and true treadmill speed revealed a mean adjusted absolute error of 0.01 m/s (relative error: 0.71 %). The calibration laboratory found a mean relative error between values algorithmically extracted from accelerometry data and laboratory gold standard of 0.36% (0.17-0.64 min/max), which is below the resolution of the laboratory. An official certificate was issued.
Discussion. Error values were a magnitude smaller than the any clinically important difference for walking speed.
Conclusion. Besides the high accuracy, the presented method can be deployed in a real world setting and allows to be integrated into the digital data flow.
Background. Physical activity (PA) is increasingly being recognized as a major factor related to the development or prevention of many diseases, as an intervention to cure or delay disease and for patient assessment in diagnostics, as a clinical outcome measure or clinical trial endpoint. Thus, wearable sensors and signal algorithms to monitor PA in the free-living environment (real-world) are becoming popular in medicine and clinical research. This is especially true for walking speed, a parameter of PA behaviour with increasing evidence to serve as a patient outcome and clinical trial endpoint in many diseases. The development and validation of sensor signal algorithms for PA classification, in particular walking, and deriving specific PA parameters, such as real world walking speed depends on the availability of large reference data sets with ground truth values. In this study a novel, reliable, scalable (high throughput), user-friendly device and method to generate such ground truth data for real world walking speed, other physical activity types and further gait-related parameters in a real-world environment is described and validated.Methods. A surveyor’s wheel was instrumented with a rotating 3D accelerometer (actibelt). A signal processing algorithm is described to derive distance and speed values. In addition, a high-resolution camera was attached via an active gimbal to video record context and detail. Validation was performed in the following main parts: 1) walking distance measurement is compared to the wheel’s built-in mechanical counter, 2) walking speed measurement is analysed on a treadmill at various speed settings, 3) speed measurement accuracy is analysed by an independent certified calibration laboratory - accreditation by DAkkS applying standardised test procedures.Results: The mean relative error for distance measurements between our method and the built-in counter was 0.12%. Comparison of the speed values algorithmically extracted from accelerometry data and true treadmill speed revealed a mean adjusted absolute error of 0.01 m/s (relative error: 0.71 %). The calibration laboratory found a mean relative error between values algorithmically extracted from accelerometry data and laboratory gold standard of 0.36% (0.17-0.64 min/max), which is below the resolution of the laboratory. An official certificate was issued.Discussion. Error values were a magnitude smaller than the any clinically important difference for walking speed.Conclusion. Besides the high accuracy, the presented method can be deployed in a real world setting and allows to be integrated into the digital data flow.Time arrow in published clinical studies/trials indexed in MEDLINE: a systematic analysis of Retrospective vs Prospective study design, from 1960 to 2017.https://peerj.com/preprints/273852018-11-272018-11-27Michele M CiullaPatrizia Vivona
Clinical studies/trials are experiments or observations on human subjects considered by the scientific community the most appropriate instrument to answer specific research questions on interventions on health outcomes. The time-line of the observations might be focused on a single time point or to follow time, backward or forward, in the so called, respectively, retrospective and prospective study design. Since the retrospective approach has been criticized for the possible sources of errors due to bias and confounding, we aimed this study to assess if there is a prevalence of retrospective vs prospective design in the clinical studies/trials by querying MEDLINE. Our results on a sample of 1,438,872 studies/trials, (yrs 1960-2017), support a prevalence of retrospective, respectively 55% vs 45%. To explain this result, arandom sub-sample of studies where the country of origin was reported (n=1576) was categorized in high and low-income based onthe nominal Gross Domestic Product (GDP) and matched with the topic of the research. As expected, the absolute majority of studies/trials are carried on by high-income countries, respectively 86% vs 14%; even if a slight prevalence of retrospective was recorded in both income groups, nonetheless the most part of prospective studies are carried out by high-GDP countries, 85% vs 15%. Finally the differences in the design of the study are understandable when considering the topic of the research.
Clinical studies/trials are experiments or observations on human subjects considered by the scientific community the most appropriate instrument to answer specific research questions on interventions on health outcomes. The time-line of the observations might be focused on a single time point or to follow time, backward or forward, in the so called, respectively, retrospective and prospective study design. Since the retrospective approach has been criticized for the possible sources of errors due to bias and confounding, we aimed this study to assess if there is a prevalence of retrospective vs prospective design in the clinical studies/trials by querying MEDLINE. Our results on a sample of 1,438,872 studies/trials, (yrs 1960-2017), support a prevalence of retrospective, respectively 55% vs 45%. To explain this result, arandom sub-sample of studies where the country of origin was reported (n=1576) was categorized in high and low-income based onthe nominal Gross Domestic Product (GDP) and matched with the topic of the research. As expected, the absolute majority of studies/trials are carried on by high-income countries, respectively 86% vs 14%; even if a slight prevalence of retrospective was recorded in both income groups, nonetheless the most part of prospective studies are carried out by high-GDP countries, 85% vs 15%. Finally the differences in the design of the study are understandable when considering the topic of the research.Transcranial direct current stimulation in mild cognitive impairment: methodology for a randomized controlled trialhttps://peerj.com/preprints/16102018-09-072018-09-07Aline S AlencastroDanilo A PereiraJoaquim P Brasil-NetoAline Iannone
Background: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique that has shown encouraging results regarding performance improvement of normal subjects in tests of executive functions. Moreover, when applied repeatedly in daily sessions, tDCS has shown therapeutic potential in various neuropsychiatric disorders. However, there is a need for double-blind, placebo-controlled studies to determine the true therapeutic potential of this portable, low-cost and non-invasive treatment. Mild cognitive impairment (MCI) of the amnestic subtype may evolve into Alzheimer’s dementia (AD) and pharmacological approaches have not been successful in ameliorating symptoms or halting progression to AD. Here we propose a protocol for studying a possible role for tDCS on improvement of MCI symptoms in older patients.
Methods/Design: This will be a double-blind, placebo-controlled study of the effects of anodal tDCS over the left dorsolateral prefrontal cortex of patients with MCI. Patients aged 60-90 years will be randomly assigned to either real tDCS or sham stimulation. Twenty-minute real or sham tDCS sessions, 5 days a week, will be performed over the course of two weeks. The Rivermead Behavioural Memory Test (RBMT), California Verbal Learning Test, Rey Verbal Auditory Learning Test (RVALT) and Digit Span (WAIS-IV) will be assessed at baseline, after the first and second weeks of treatment, as well as one and three months after the last tDCS session. The primary outcome will be change in test scores over time. Secondary outcomes will be self-reported memory improvement and possible side effects of tDCS.
Discussion: This study will evaluate possible therapeutic applications of tDCS for treatment of MCI. tDCS is a portable and low-cost neuromodulatory technique that has been found to increase performance of both normal subjects and patients in many cognitive tasks. It will also examine the tolerability, program adherence and possible side effects of this novel technique in this age group. The information obtained in this study should be useful in planning further studies in which tDCS could be combined with other treatment modalities, such as cognitive training.
Background: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique that has shown encouraging results regarding performance improvement of normal subjects in tests of executive functions. Moreover, when applied repeatedly in daily sessions, tDCS has shown therapeutic potential in various neuropsychiatric disorders. However, there is a need for double-blind, placebo-controlled studies to determine the true therapeutic potential of this portable, low-cost and non-invasive treatment. Mild cognitive impairment (MCI) of the amnestic subtype may evolve into Alzheimer’s dementia (AD) and pharmacological approaches have not been successful in ameliorating symptoms or halting progression to AD. Here we propose a protocol for studying a possible role for tDCS on improvement of MCI symptoms in older patients.Methods/Design: This will be a double-blind, placebo-controlled study of the effects of anodal tDCS over the left dorsolateral prefrontal cortex of patients with MCI. Patients aged 60-90 years will be randomly assigned to either real tDCS or sham stimulation. Twenty-minute real or sham tDCS sessions, 5 days a week, will be performed over the course of two weeks. The Rivermead Behavioural Memory Test (RBMT), California Verbal Learning Test, Rey Verbal Auditory Learning Test (RVALT) and Digit Span (WAIS-IV) will be assessed at baseline, after the first and second weeks of treatment, as well as one and three months after the last tDCS session. The primary outcome will be change in test scores over time. Secondary outcomes will be self-reported memory improvement and possible side effects of tDCS.Discussion: This study will evaluate possible therapeutic applications of tDCS for treatment of MCI. tDCS is a portable and low-cost neuromodulatory technique that has been found to increase performance of both normal subjects and patients in many cognitive tasks. It will also examine the tolerability, program adherence and possible side effects of this novel technique in this age group. The information obtained in this study should be useful in planning further studies in which tDCS could be combined with other treatment modalities, such as cognitive training.