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Perspectives in Clinical Research 2016Deviations from the approved trial protocol are common during clinical trials. They have been conventionally classified as deviations or violations, depending on their...
INTRODUCTION
Deviations from the approved trial protocol are common during clinical trials. They have been conventionally classified as deviations or violations, depending on their impact on the trial.
METHODS
A new method has been proposed by which deviations are classified in five grades from 1 to 5. A deviation of Grade 1 has no impact on the subjects' well-being or on the quality of data. At the maximum, a deviation Grade 5 leads to the death of the subject. This method of classification was applied to deviations noted in the center over the last 3 years.
RESULTS
It was observed that most deviations were of Grades 1 and 2, with fewer falling in Grades 3 and 4. There were no deviations that led to the death of the subject (Grade 5).
DISCUSSION
This method of classification would help trial managers decide on the action to be taken on the occurrence of deviations, which would be based on their impact.
PubMed: 27453830
DOI: 10.4103/2229-3485.184817 -
Chest Nov 2021Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no...
BACKGROUND
Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no prospective studies have compared weaning strategies for liberation from ECMO.
RESEARCH QUESTION
Is a protocolized daily assessment of readiness to liberate from venovenous ECMO safe and feasible?
STUDY DESIGN AND METHODS
We conducted a prospective, single-arm safety and feasibility study of a protocol for daily assessment of readiness to liberate from venovenous ECMO among consecutive adult patients receiving venovenous ECMO across four ICUs at a single center between June 20, 2020, and November 24, 2020. The ECMO-free protocol included three phases: (1) the safety screening, (2) non-ECMO Fio titration, and (3) the ECMO-free trial. Enrollment, interventions, and data collection were performed prospectively by trained study staff.
RESULTS
Twenty-six patients received the ECMO-free protocol on 385 patient-days. The safety screening was passed during a total of 59 ECMO-free daily assessments (15.3%) among 20 patients. Every passed safety screening proceeded to an ECMO-free trial. Twenty-eight passed ECMO-free trials (47.5%) occurred among 16 patients (61.5%). No missed safety screenings, protocol deviations, or adverse events occurred. Of the 16 patients who passed an ECMO-free trial, 14 patients (87.5%) were decannulated. Among decannulated patients, 12 patients (85.7%) were decannulated on the same day as a passed ECMO-free trial, 6 patients (42.9%) were decannulated on the first day that they passed an ECMO-free trial, and 6 patients (42.9%) passed an ECMO-free trial at least twice consecutively before decannulation. The median time from first passed ECMO-free trial to decannulation was 2 days (interquartile range, 0-3 days).
INTERPRETATION
The ECMO-free protocol is feasible and may identify patients for decannulation earlier than gradual approaches to weaning.
Topics: Clinical Protocols; Critical Care; Duration of Therapy; Extracorporeal Membrane Oxygenation; Feasibility Studies; Female; Humans; Male; Middle Aged; Outcome and Process Assessment, Health Care; Patient Safety; Pilot Projects; Prospective Studies; Risk Adjustment; Symptom Assessment; Withholding Treatment
PubMed: 34166644
DOI: 10.1016/j.chest.2021.05.066 -
Gait & Posture Sep 2022Objective gait analysis that fully captures the multi-segmental foot movement of a clubfoot may help in early identification of a relapse clubfoot. Unfortunately, this...
BACKGROUND
Objective gait analysis that fully captures the multi-segmental foot movement of a clubfoot may help in early identification of a relapse clubfoot. Unfortunately, this type of objective measure is still lacking in a clinical setting and it is unknown how it relates to clinical assessment.
RESEARCH QUESTION
The aim of this study was to identify differences in total gait and foot deviations between clubfoot patients with and without a relapse clubfoot and to evaluate their relationship with clinical status.
METHODS
In this study, Ponseti-treated idiopathic clubfoot patients were included and divided into clubfoot patients with and without a relapse. Objective gait analysis was done resulting in total gait and foot scores and clinical assessment was performed using the Clubfoot Assessment Protocol (CAP). Additionally, a new clubfoot specific foot score, the clubFoot Deviation Index (cFDI*), was calculated to better capture foot kinematics of clubfoot patients.
RESULTS
Clubfoot patients with a relapse show lower total gait quality (GDI*) and lower clinical status defined by the CAP than clubfoot patients without a relapse. Abnormal cFDI* was found in relapse patients, reflected by differences in corresponding variable scores. Moderate relationships were found for the subdomains of the CAP and total gait and foot quality in all clubfoot patients.
SIGNIFICANCE
A new total foot score was introduced in this study, which was more relevant for the clubfoot population. The use of this new foot score (cFDI*) besides the GDI*, is recommended to identify gait and foot motion deviations. Along with clinical assessment, this will give an overview of the overall status of the complex, multi-segmental aspects of a (relapsed) clubfoot. The relationships found in this study suggest that clinical assessment might be indicative of a deviation in total gait and foot pattern, therefore hinting towards personalised screening for better treatment decision making.
Topics: Casts, Surgical; Clubfoot; Foot; Gait; Gait Analysis; Humans; Recurrence; Treatment Outcome
PubMed: 35995000
DOI: 10.1016/j.gaitpost.2022.07.261 -
Journal of Clinical Medicine Sep 2019Principles of treat-to-target (T2T) have been widely adopted in both multinational and regional guidelines for rheumatoid arthritis (RA). Several questionnaire studies... (Review)
Review
Principles of treat-to-target (T2T) have been widely adopted in both multinational and regional guidelines for rheumatoid arthritis (RA). Several questionnaire studies among physicians and real-world data have suggested that an evidence-practice gap exists in RA management. Investigating physician adherence to T2T, which requires a process measure, is difficult. Different practice patterns among physicians are observed, while adherence to protocolized treatment declines over time. Rheumatologist awareness, agreement, and claims of adherence to T2T guidelines are not always consistent with medical records. Comorbidities, a difficult disease course, communication barriers, and individual preferences may hinder an intensive, proactive treatment stance. Interpreting deviations from protocolized treatment/T2T guidelines requires sufficient clinical context, though higher adherence seems to improve clinical outcomes. Nonmedical constraints in routine care may consist of barriers in healthcare structure and socioeconomic factors. Therefore, strategies to improve the institution of T2T should be tailored to local healthcare. Educational interventions to improve T2T adherence among physicians may show a moderate, although beneficial effect. Meanwhile, a proportion of patients with inadequately controlled RA exists, while management decisions may not be in accordance with T2T. Physicians tend to be aware of current guidelines, but their institution in routine practice seems challenging, which warrants attention and further study.
PubMed: 31500394
DOI: 10.3390/jcm8091416 -
BMC Emergency Medicine May 2022The number of ambulance assignments and the influx of patients to the emergency departments (EDs) in Sweden have increased in recent years. This is one reason the...
BACKGROUND
The number of ambulance assignments and the influx of patients to the emergency departments (EDs) in Sweden have increased in recent years. This is one reason the protocol for prehospital emergency care was developed around referring patients for non-conveyance, either through the see-and-convey elsewhere approach or through the see-and-treat approach. However, this protocol has led to challenges in patient assessments. This study aimed to investigate the underlying causes of patient harm among those referred for the see-and-treat approach by the emergency medical services.
METHODS
This three-phase study involved a mixed-methods design. Cases of injuries, internal investigations and incident analyses of referrals for the see-and-treat approach in two regions in south eastern Sweden from 2015 to 2020 were examined using qualitative content analysis. This qualitative analysis was the basis for the quantitative analysis of the ambulance records. After the qualitative analysis was completed, a review protocol was developed; 34 variables were used to review 240 randomly selected ambulance records logged in 2020, wherein patients were referred for the see-and-treat approach. Finally, the review results were synthesised.
RESULTS
The qualitative analysis revealed three common themes: 'assessment of patients', 'guidelines' and 'environment and organisation'. These results were confirmed by a medical journal review. Shortcomings were found in the anamnesis and in the number of targeted examinations performed. The checklist for referring patients for the see-and-treat approach and the information sheet to be provided to the patients were not used. In 34% of the ambulance records examined, the EMS clinicians deviated from the current guidelines for a see-and-treat referral.
CONCLUSIONS
The results indicated that the low adherence to guidelines and the patient assessment deviating from the protocol put patients at risk of being harmed during a see-and-treat referral. Measures are needed to guarantee a safe assessment of an increasing number of patients who are referred for the see-and-treat approach, especially the multi-sick elderly patients.
Topics: Aged; Ambulances; Emergency Medical Services; Emergency Service, Hospital; Humans; Referral and Consultation; Sweden
PubMed: 35524195
DOI: 10.1186/s12873-022-00630-8 -
Journal of Stroke and Cerebrovascular... Jan 2016Protocol deviations before and after tissue plasminogen activator (tPA) treatment for ischemic stroke are common. It is unclear if patient or hospital factors predict...
BACKGROUND
Protocol deviations before and after tissue plasminogen activator (tPA) treatment for ischemic stroke are common. It is unclear if patient or hospital factors predict protocol deviations. We examined predictors of protocol deviations and the effects of protocol violations on symptomatic intracerebral hemorrhage (sICH).
METHODS
We used data from the Increasing Stroke Treatment through Interventional Behavior Change Tactics trial, a cluster-randomized, controlled trial evaluating the efficacy of a barrier assessment and educational intervention to increase appropriate tPA use in 24 Michigan community hospitals, to review tPA treatments between 2007 and 2010. Protocol violations were defined as deviations from the standard tPA protocol, both before and after treatment. Multilevel logistic regression models were fitted to determine if patient and hospital variables were associated with pretreatment or post-treatment protocol deviations.
RESULTS
During the study, 557 patients (mean age 70, 52% male, median National Institutes of Health Stroke Scale score 12) were treated with tPA. Protocol deviations occurred in 233 (42%) patients: 16% had pretreatment deviations, 35% had post-treatment deviations, and 9% had both. The most common protocol deviations included elevated post-treatment blood pressure, antithrombotic agent use within 24 hours of treatment, and elevated pretreatment blood pressure. Protocol deviations were not associated with sICH, stroke severity, or hospital factors. Older age was associated with pretreatment protocol deviations (adjusted odds ratio [OR], .52; 95% confidence interval [CI], .30-.92). Pretreatment deviations were associated with post-treatment deviations (adjusted OR, 3.20; 95% CI, 1.91-5.35).
CONCLUSIONS
Protocol deviations were not associated with sICH. Aside from age, patient and hospital factors were not associated with protocol deviations.
Topics: Age Factors; Brain Ischemia; Cerebral Hemorrhage; Clinical Protocols; Emergency Service, Hospital; Fibrinolytic Agents; Guideline Adherence; Health Personnel; Hospitals, Community; Humans; Hypertension; Infusions, Intravenous; Logistic Models; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 26419527
DOI: 10.1016/j.jstrokecerebrovasdis.2015.08.036 -
Seminars in Cell & Developmental Biology Jul 2022Kidney organoid technology has led to a renaissance in kidney developmental biology. The complex underpinnings of mammalian kidney development have provided a framework...
Kidney organoid technology has led to a renaissance in kidney developmental biology. The complex underpinnings of mammalian kidney development have provided a framework for the generation of kidney cells and tissues from human pluripotent stem cells. Termed kidney organoids, these 3-dimensional structures contain kidney-specific cell types distributed similarly to in vivo architecture. The adult human kidney forms from the reciprocal induction of two disparate tissues, the metanephric mesenchyme (MM) and ureteric bud (UB), to form nephrons and collecting ducts, respectively. Although nephrons and collecting ducts are derived from the intermediate mesoderm (IM), their development deviates in time and space to impart distinctive inductive signaling for which separate differentiation protocols are required. Here we summarize the directed differentiation protocols which generate nephron kidney organoids and collecting duct kidney organoids, making note of similarities as much as differences. We discuss limitations of these present approaches and discuss future directions to improve kidney organoid technology, including a greater understanding of anterior IM and its derivatives to enable an improved differentiation protocol to collecting duct organoids for which historic and future developmental biology studies will be instrumental.
Topics: Adult; Animals; Cell Differentiation; Humans; Kidney; Mammals; Nephrons; Organogenesis; Organoids; Pluripotent Stem Cells
PubMed: 34627669
DOI: 10.1016/j.semcdb.2021.09.017 -
International Journal of Radiation... May 2022To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent...
PURPOSE
To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy.
METHODS AND MATERIALS
Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated.
RESULTS
The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07).
CONCLUSIONS
Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines.
Topics: Gastrointestinal Diseases; Humans; Male; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Rectum; Salvage Therapy
PubMed: 34990777
DOI: 10.1016/j.ijrobp.2021.12.174 -
Resuscitation Plus Mar 2022Automated external defibrillators (AEDs) use various shock protocols with different characteristics when deployed in pediatric mode. The aim of this study is to assess...
AIM
Automated external defibrillators (AEDs) use various shock protocols with different characteristics when deployed in pediatric mode. The aim of this study is to assess and compare the safety and efficacy of different AED pediatric protocols using novel experimental approaches.
METHODS
Two defibrillation protocols (A and B) were assessed across two studies: Protocol A: escalating (50-75-90 J) defibrillation waveform with higher voltage, shorter duration and equal phase durations. Protocol B; non-escalating (50-50-50 J) defibrillation waveform with lower voltage, longer duration and unequal phase durations.Experiment 1: Isolated shock damage was assessed following shocks to 12 anesthetized pigs. Animals were randomized into two groups, receiving three shocks from Protocol A (50-75-90 J) or B (50-50-50 J). Cardiac function, cardiac troponin I (cTnI), creatine phosphokinase (CPK) and histopathology were analyzed. Experiment 2: Defibrillation safety and efficacy were assessed through shock success, ROSC, ST-segment deviation and contractility following 16 randomized shocks from protocol A or B delivered to 10 anesthetized pigs in VF.
RESULTS
Experiment 1: No clinically meaningful difference in cTnI, CPK, ST-segment deviation, ejection fraction or histopathological damage was observed following defibrillation with either protocol. No difference was observed between protocols at any timepoint. Experiment 2: all defibrillation types demonstrated shock success and ROSC ≥ 97.5%. Post-ROSC contractility was similar between protocols.
CONCLUSIONS
There is no evidence that administration of clinically relevant shock sequences, without experimental confounders, result in significant myocardial damage in this model of pediatric resuscitation. Typical variations in AED pediatric mode settings do not affect defibrillation safety and efficacy.
PubMed: 35146463
DOI: 10.1016/j.resplu.2022.100203 -
Therapeutic Innovation & Regulatory... Nov 2020When conducting clinical trials under COVID-19 pandemic, protocol deviations and/or protocol violations are inevitably encountered due to possible environment change...
When conducting clinical trials under COVID-19 pandemic, protocol deviations and/or protocol violations are inevitably encountered due to possible environment change which may have an impact on the accuracy and reliability of clinical evaluation of the test treatment under investigation. Protocol deviations and/or violations include, but are not limited to, eligibility criteria, testing procedure, dose and dose regiment, treatment duration and clinical operation of the intended trial. FDA published guidance in March 2020 to assist investigators and institutional boards (IRBs) in assuring the safety of trial participants, maintaining compliance with good clinical practice, and minimizing risks to trial integrity during the COVID-19 pandemic. The purpose of this article is to proposal methods for statistical evaluation in terms of (i) possible shift in target patient population and (ii) assessment of reproducibility of clinical studies conduct under COVID-19 pandemic environment. The proposed methods can be used to determine whether the clinical results of the intended trials are acceptable from both statistical and regulatory perspectives.
Topics: COVID-19; Clinical Protocols; Clinical Trials as Topic; Eligibility Determination; Humans; Pandemics; Reproducibility of Results; Research Design; Research Subjects; Safety
PubMed: 32583289
DOI: 10.1007/s43441-020-00182-8