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Biology of Blood and Marrow... Mar 2015The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease...
National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report.
The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity and more accurately measures the global burden of disease attributed to GVHD, and it will facilitate biomarker association studies.
Topics: Biomarkers; Chronic Disease; Clinical Trials as Topic; Consensus; Consensus Development Conferences, NIH as Topic; Female; Graft vs Host Disease; Humans; Male; Organ Specificity; Practice Guidelines as Topic; United States
PubMed: 25529383
DOI: 10.1016/j.bbmt.2014.12.001 -
Infectious Disease Clinics of North... Mar 2019Diagnostic advances in visceral leishmaniasis include the development of the rK39 and rK28 rapid diagnostic test. The direct agglutination test is also increasingly... (Review)
Review
Diagnostic advances in visceral leishmaniasis include the development of the rK39 and rK28 rapid diagnostic test. The direct agglutination test is also increasingly used, as well as conventional and real-time polymerase chain reaction, which also performs well on peripheral blood. The choice of treatment for visceral leishmaniasis depends on the geographic region where the infection is acquired. Liposomal amphotericin B is generally found to be safe and effective in most endemic regions of the world; antimonials still remain to be the most effective in eastern Africa despite its high toxicity. Combination therapy is increasingly explored. Immunosuppressed patients require adapted diagnostic and therapeutic strategies.
Topics: Amphotericin B; Antiprotozoal Agents; Clinical Trials as Topic; Humans; Leishmaniasis, Visceral; Molecular Diagnostic Techniques
PubMed: 30712769
DOI: 10.1016/j.idc.2018.10.005 -
The New England Journal of Medicine Aug 2016
Topics: Follow-Up Studies; Humans; Patient Selection; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27518663
DOI: 10.1056/NEJMra1510059 -
Frontiers in Public Health 2022Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19... (Review)
Review
Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19 pandemic has caused a significant increase in DCT: a survey shows that 76% of pharmaceutical companies, device manufacturers, and Contract Research Organizations adopted decentralized techniques during the early phase of the pandemic. The implementation of DCTs relies on the use of digital tools such as e-consent, apps, wearable devices, Electronic Patient-Reported Outcomes (ePRO), telemedicine, as well as on moving trial activities to the patient's home (e.g., drug delivery) or to local healthcare settings (i.e., community-based diagnosis and care facilities). DCTs adapt to patients' routines, allow patients to participate regardless of where they live by removing logistical barriers, offer better access to the study and the investigational product, and permit the inclusion of more diverse and more representative populations. The feasibility and quality of DCTs depends on several requirements including dedicated infrastructures and staff, an adequate regulatory framework, and partnerships between research sites, patients and sponsors. The evaluation of Ethics Committees (ECs) is crucial to the process of innovating and digitalizing clinical trials: adequate assessment tools and a suitable regulatory framework are needed for evaluation by ECs. DCTs also raise issues, many of which are of considerable ethical significance. These include the implications for the relationship between patients and healthcare staff, for the social dimension of the patient, for data integrity (at the source, during transmission, in the analysis phase), for personal data protection, and for the possible risks to health and safety. Despite their considerable growth, DCTs have only received little attention from bioethicists. This paper offers a review on some ethical implications and requirements of DCTs in order to encourage further ethical reflection on this rapidly emerging field.
Topics: Humans; COVID-19; Delivery of Health Care; Pandemics; Telemedicine; Clinical Trials as Topic
PubMed: 36590004
DOI: 10.3389/fpubh.2022.1081150 -
Diabetes Care Mar 2019This study evaluated the association of time in range (TIR) of 70-180 mg/dL (3.9-10 mmol/L) with the development or progression of retinopathy and development of...
OBJECTIVE
This study evaluated the association of time in range (TIR) of 70-180 mg/dL (3.9-10 mmol/L) with the development or progression of retinopathy and development of microalbuminuria using the Diabetes Control and Complications Trial (DCCT) data set in order to validate the use of TIR as an outcome measure for clinical trials.
RESEARCH DESIGN AND METHODS
In the DCCT, blood glucose concentrations were measured at a central laboratory from seven fingerstick samples (seven-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. Retinopathy progression was assessed every 6 months and urinary microalbuminuria development every 12 months. Proportional hazards models were used to assess the association of TIR and other glycemic metrics, computed from the seven-point fingerstick data, with the rate of development of microvascular complications.
RESULTS
Mean TIR of seven-point profiles for the 1,440 participants was 41 ± 16%. The hazard rate of development of retinopathy progression was increased by 64% (95% CI 51-78), and development of the microalbuminuria outcome was increased by 40% (95% CI 25-56), for each 10 percentage points lower TIR ( < 0.001 for each). Results were similar for mean glucose and hyperglycemia metrics.
CONCLUSIONS
Based on these results, a compelling case can be made that TIR is strongly associated with the risk of microvascular complications and should be an acceptable end point for clinical trials. Although hemoglobin A remains a valuable outcome metric in clinical trials, TIR and other glycemic metrics-especially when measured with continuous glucose monitoring-add value as outcome measures in many studies.
Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Disease Progression; Female; Glycated Hemoglobin; Humans; Longitudinal Studies; Male; Middle Aged; Outcome Assessment, Health Care; Patient Care Planning; Prognosis; Research Design; Time Factors; Treatment Outcome
PubMed: 30352896
DOI: 10.2337/dc18-1444 -
Psychiatry Research Oct 2019The traditional research pipeline that encourages a staged approach to moving an intervention from efficacy trials to the real world can take a long time. To address...
The traditional research pipeline that encourages a staged approach to moving an intervention from efficacy trials to the real world can take a long time. To address this issue, hybrid effectiveness-implementation designs were codified to promote examination of both effectiveness and implementation outcomes within a study. There are three types of hybrid designs and they vary based on their primary focus and the amount of emphasis on effectiveness versus implementation outcomes. A type 1 hybrid focuses primarily on the effectiveness outcomes of an intervention while exploring the "implementability" of the intervention. A type 2 hybrid has a dual focus on effectiveness and implementation outcomes; these designs allow for the simultaneous testing or piloting of implementation strategies during an effectiveness trial. A type 3 hybrid focuses primarily on implementation outcomes while also collecting effectiveness outcomes as they relate to uptake or fidelity of the intervention. This paper provides an introduction to these designs and describes each of the three types, design considerations, and examples for each.
Topics: Biomedical Research; Clinical Trials as Topic; Humans; Research Design; Treatment Outcome
PubMed: 31434011
DOI: 10.1016/j.psychres.2019.112513 -
Seizure Jan 2017Status epilepticus (SE) requires not only urgent symptomatic treatment with antiepileptic drugs but also rapid identification and treatment of its cause. This narrative... (Review)
Review
PURPOSE
Status epilepticus (SE) requires not only urgent symptomatic treatment with antiepileptic drugs but also rapid identification and treatment of its cause. This narrative review summarizes the most important advances in classification and treatment of SE.
METHOD
Data sources included MEDLINE, EMBASE, ClinicalTrials.gov, and back tracking of references in pertinent studies, reviews, and books.
RESULTS
SE is now defined as "a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures." A new diagnostic classification system of SE introduces four axes: semiology, aetiology, EEG correlates, and age. For the acute treatment intravenous benzodiazepines (lorazepam, diazepam, clonazepam) and intramuscular midazolam appear as most effective treatments for early SE. In children, buccal or intranasal midazolam are useful alternatives. In established SE intravenous antiepileptic drugs (phenytoin, valproate, levetiracetam, phenobarbital, and lacosamide) are in use. Treatment options in refractory SE are intravenous anaesthetics; ketamine, magnesium, steroids and other drugs have been used in super-refractory SE with variable outcomes.
CONCLUSION
Over the past 25 years major advances in definition, classification and understanding of its mechanisms have been achieved. Despite this up to 40% of patients in early status cannot be controlled with first line drugs. The treatment of super-refractory status is still an almost evidence free zone.
Topics: Clinical Trials as Topic; Databases, Factual; Electroencephalography; History, 20th Century; History, 21st Century; Humans; Status Epilepticus
PubMed: 27890484
DOI: 10.1016/j.seizure.2016.11.001 -
Stroke Jul 2017
Review
Topics: Clinical Trials as Topic; Humans; Stroke; Treatment Outcome
PubMed: 28626052
DOI: 10.1161/STROKEAHA.117.017866 -
Transactions of the American Clinical... 2018Efficacy trials, which assess treatments in optimally selected patients under advantageous conditions for relatively short time periods, are necessary to gain regulatory...
Efficacy trials, which assess treatments in optimally selected patients under advantageous conditions for relatively short time periods, are necessary to gain regulatory approval for marketing. In contrast, effectiveness trials, which test treatments across a spectrum of patients in real-world conditions with follow-up periods that match typical treatment regimens, provide critical information on drug effects in those patients who may ultimately receive the treatment. We previously proposed a study design that integrates efficacy and effectiveness trials into a 2-component "efficacy-to-effectiveness (E2E) trial," in which if the initial efficacy trial component is positive, then the trial immediately and seamlessly transitions to the effectiveness trial component. However, we believe that total study duration could be even further shortened by simultaneously addressing efficacy and effectiveness too (EE2). An EE2 trial rigorously demonstrates efficacy, but uses broad inclusion characteristics of effectiveness trials. An example of a study using EE2 design, the IMMEDIATE (Immediate Myocardial Metabolic enhancement During Initial Assessment and Treatment in Emergency Care) trial, is provided.
Topics: Acute Coronary Syndrome; Administration, Intravenous; Clinical Trials as Topic; Drug Administration Schedule; Drug Approval; Endpoint Determination; Glucose; Humans; Insulin; Potassium; Research Design; Time Factors; Treatment Outcome
PubMed: 30166723
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Aug 2018Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available;...
BACKGROUND
Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD.
AIM
To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease.
METHODS
An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting.
RESULTS
Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials.
CONCLUSIONS
Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.
Topics: Catheterization; Clinical Trials as Topic; Colon; Consensus; Constriction, Pathologic; Crohn Disease; Dilatation; Endoscopy; Expert Testimony; Fibrosis; Humans; Intestinal Obstruction; Intestine, Small; Practice Guidelines as Topic; Reference Standards
PubMed: 29920726
DOI: 10.1111/apt.14853