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A clinical trial alert tool to recruit large patient samples and assess selection bias in general practice research

A clinical trial alert tool to recruit large patient samples and assess selection bias in general practice research

(2) Only one practice enrolled 200 patients into the osteoporosis survey. More importantly, many practices, especially larger practices, were poor recruiters although the CTA tool presented these practices a wealth of pos- sible study participants to enrol. Obviously, the regular and frequent presentation of possible study participants on the screen did not stimulate the practice staff to con- tact them and to start the survey, but had the opposite effect. One reason may be that the clinical trial alert simply appeared too often (e.g. in practices which iden- tified more than 1,000 patients). When the practice staff is frequently reminded about the study, the activity of disengaging or “clicking off” the reminder screen may then consume the majority of the staff’s available capa- city for participating in the study.
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A model of a randomized experiment with an application to the PROWESS clinical trial

A model of a randomized experiment with an application to the PROWESS clinical trial

Abstract I develop a model of a randomized experiment with a binary intervention and a binary outcome. Potential outcomes in the intervention and control groups give rise to four types of participants. Fixing ideas such that the outcome is mortality, some participants would live regardless, others would be saved, others would be killed, and others would die regardless. These potential outcome types are not observable. However, I use the model to develop estimators of the number of participants of each type. The model relies on the randomization within the experiment and on deductive reasoning. I apply the model to an important clinical trial, the PROWESS trial, and I perform a Monte Carlo simulation calibrated to estimates from the trial. The reduced form from the trial shows a reduction in mortality, which provided a rationale for FDA approval. However, I find that the intervention killed two participants for every three it saved.
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Value of information methods to design a clinical trial in a small population to optimise a health economic utility function

Value of information methods to design a clinical trial in a small population to optimise a health economic utility function

Regulatory agencies may prefer the use of classical frequentist methods in the evaluation of pharmaceuti- cal products. In the design of a clinical trial based on the frequentist method, the type I error rate, α, is usu- ally restricted at a one-sided 0.025 level. This value is a conventional, but arbitrary, choice, and there is some indication that in practice there may be some flexibility depending on severity and/or prevalence of the disease. Our approach involves calculating a z-score for a pri- mary clinical outcome that corresponds to maximising expected utility. It therefore allows a hypothesis testing framework to be maintained, but ensures that the error rate for that hypothesis test on the primary outcome is consistent with a utility maximisation framework. Results from Fig. 3 suggest that different α-levels are appropriate for diseases with different prevalence rates. Discussion of choice of α-level depending on prevalence and severity of disease has been considered by Montazerhodjat and Lo
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Next-generation sequencing diagnostics of bacteremia in sepsis (Next GeneSiS-Trial): Study protocol of a prospective, observational, noninterventional, multicenter, clinical trial

Next-generation sequencing diagnostics of bacteremia in sepsis (Next GeneSiS-Trial): Study protocol of a prospective, observational, noninterventional, multicenter, clinical trial

Bloodstream infections remain one of the major challenges in ICUs, leading to sepsis or even septic shock in many cases. Due to the lack of timely diagnostic approaches with sufficient sensitivity, mortality rates of sepsis are still unacceptably high. However, a prompt diagnosis of the causative microorganism is critical to signi ficantly improve outcome of bloodstream infections. Although various targeted molecular tests for blood samples are available, time-consuming blood culture-based approaches still represent the standard of care for the identi fica- tion of bacteria. With regard to these alarming figures, the current clinical trial (Next GeneSiS) is designed to investigate a new diagnostic approach, namely, NGS. The majority of the patients affected are sedated and given arti ficial ventilation. Even before sedated, affected patients sometimes need to be regarded incapable of giving consent due to the underlying severe infection, inflammatory response, and severe pain. Therefore, in these cases, informed consent to participate in Next GeneSiS needs to be given by a legal guardian until the affected patient is capable of consent. Nevertheless, especially, these critically ill patients need to be enrolled in Next GeneSiS, in order to assess the diagnostic value of the above-described NGS-based approach for the early detection of the causative microorganism in sepsis. This might help to improve outcome of patients suffering from sepsis due to an early optimization of the anti-infective treatment regime. This might especially be true for patients, where classic microbiolog- ical or molecular diagnostic approaches fail.
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Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants

Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants

The production of clinical-grade P2G12 in tobacco required the development of an entire production process from first principles, including transformation, the selection of lead events, the establishment of working practices for tobacco cultivation that satisfied the regulatory bodies in Europe, the definition of MSBs and WSBs, the development of a unique GMP-compliant down- stream processing infrastructure and finally the completion of a first-in-human clinical trial to test the product for safety. P2G12 is the first GMP-compliant plant-derived mAb to undergo clinical testing in Europe, although a cocktail of three antibodies produced by transient expression in tobacco has recently been accelerated through clinical development and GMP manufactur- ing in order to provide emergency treatments for the 2014 outbreak of Ebola virus disease in West Africa (McCarthy, 2014; Olinger et al., 2012; Qiu et al., 2014). Several nonantibody plant- derived pharmaceuticals have also been produced under GMP conditions for clinical trials (Fischer et al., 2012; Paul et al., 2013) including a recombinant form of the enzyme glucocere- brosidase produced in carrot cells which is currently the only approved product for humans developed by molecular pharming in plants.
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Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants

Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants

The production of clinical-grade P2G12 in tobacco required the development of an entire production process from first principles, including transformation, the selection of lead events, the establishment of working practices for tobacco cultivation that satisfied the regulatory bodies in Europe, the definition of MSBs and WSBs, the development of a unique GMP-compliant down- stream processing infrastructure and finally the completion of a first-in-human clinical trial to test the product for safety. P2G12 is the first GMP-compliant plant-derived mAb to undergo clinical testing in Europe, although a cocktail of three antibodies produced by transient expression in tobacco has recently been accelerated through clinical development and GMP manufactur- ing in order to provide emergency treatments for the 2014 outbreak of Ebola virus disease in West Africa (McCarthy, 2014; Olinger et al., 2012; Qiu et al., 2014). Several nonantibody plant- derived pharmaceuticals have also been produced under GMP conditions for clinical trials (Fischer et al., 2012; Paul et al., 2013) including a recombinant form of the enzyme glucocere- brosidase produced in carrot cells which is currently the only approved product for humans developed by molecular pharming in plants.
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The Evolution of Master Protocol Clinical Trial Designs: A Systematic Literature Review

The Evolution of Master Protocol Clinical Trial Designs: A Systematic Literature Review

trials conducted within the master protocol framework could remedy the problem because such trial designs allow for the evaluation of 1 investigational treatments in multiple subgroups of a study population within the same overall clinical trial structure compared with traditional randomized controlled trials, which mostly evaluate only one investigational drug in one study population. Furthermore, because of several subgroups running in parallel, the chance of patients meeting the inclusion criteria of at least one of the subgroups is increased. If inclusion and exclusion criteria are similar, sharing of patients across the whole study might be feasible (eg, by dynamic control arms). Although in practice planning and implementing a trial with a master protocol require more time to properly deal with operational and data-analytical complexities, Saville and Berry 4 found, using simulation studies, that under certain assumptions such trials can greatly reduce the time and number of patients needed to successfully identify effective treatments. In many disease areas, such as remote damage control resuscitation, 5 heart failure with preserved ejection fraction, 6 pulmonary exacerbations of cystic fibrosis, 7 colorectal cancer, 8 squamous cell carcinoma of the head and neck, 9 bladder cancer, 10 nephrology, 11e13 neonatal seizures, 14 pediatric cancer, 15 radiation oncology devices, 16 schizophrenia, 17 sepsis, 18 tuberculosis, 19 transplantation, 20 and multidrug- resistant organisms, 21 master protocol trials are being considered to satisfy needs for the evaluation of new or targeted therapies, clinically validated targets, and predictive biomarkers, as well as facilitating faster clinical testing of available compounds. Although master protocol trials can also be designed using traditional design features, such as frequentist decision rules, fixed sample size, and allocation ratios, often innovative statistical methods, such as response-adaptive randomization, adaptive and seamless adaptive designs, sharing of common control arms, and/or Bayesian decision frameworks, 22e36 are used in the design of master protocols. The debate concerning the actual benefits of some of these methods is still ongoing. 37e45 The importance of adaptive trial designs and master protocols in the context of innovative trials and precision medicine has been highlighted by many authors. 46e72 The Adaptive Platform Trials
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Transversus abdominis Plane Block for Improved Early Postoperative Pain Management after Periacetabular Osteotomy: A Randomized Clinical Trial

Transversus abdominis Plane Block for Improved Early Postoperative Pain Management after Periacetabular Osteotomy: A Randomized Clinical Trial

Conflicts of Interest: The authors have no conflict of interest to declare. References 1. Rafi, A.N. Abdominal field block: A new approach via the lumbar triangle. Anaesthesia 2001, 56, 1024–1026. [ CrossRef ] 2. Brogi, E.; Kazan, R.; Cyr, S.; Giunta, F.; Hemmerling, T.M. Transversus abdominal plane block for postoperative analgesia: A systematic review and meta-analysis of randomized-controlled trials. Can. J. Anaesth. 2016, 63, 1184–1196. [ CrossRef ] [ PubMed ] 3. Covotta, M.; Claroni, C.; Costantini, M.; Torregiani, G.; Pelagalli, L.; Zinilli, A.; Forastiere, E. The Effects of Ultrasound-Guided Transversus Abdominis Plane Block on Acute and Chronic Postsurgical Pain After Robotic Partial Nephrectomy: A Prospective Randomized Clinical Trial. Pain Med. 2019. [ CrossRef ] [ PubMed ]
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Multicenter randomized clinical trial of lateral-trendelenburg vs. semi recumbent position for the prevention of ventilatorassociated pneumonia - the gravity-VAP trial

Multicenter randomized clinical trial of lateral-trendelenburg vs. semi recumbent position for the prevention of ventilatorassociated pneumonia - the gravity-VAP trial

ClinicalTrials.gov ID: NCT01138540. The study was endorsed by ECCRN/ESICM. Funding by 2013 ECCRN Clinical Trial Award and Hill-Rom A24 The effects of oral rinse with 0.2 % and 2 % chlorhexidine on oropharyngeal colonization and ventilator associated pneumonia in adults' intensive care units

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Xenon for the prevention of postoperative delirium in cardiac surgery: study protocol for a randomized controlled clinical trial

Xenon for the prevention of postoperative delirium in cardiac surgery: study protocol for a randomized controlled clinical trial

Our clinical trial will assess the efficacy of xenon for the prevention of POD in cardiac surgery. Due to its scarcity, xenon is extremely costly. These expenses will only be justified when the promising observations with xenon in preclinical experiments can be translated into a better outcome for the geriatric population. POD has been demonstrated to be associated with important short-term and long-term complications and occurs par- ticularly frequently in patients older than 65 years. Our study will, therefore, focus on an extremely vulnerable population. We will employ well-validated methods for delirium screening and also assess long-term neurocog- nitive function.
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Effect of Alirocumab on Mortality After Acute Coronary Syndromes : An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Effect of Alirocumab on Mortality After Acute Coronary Syndromes : An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Sources of Funding The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosures Dr Steg: research grants from Bayer, Merck, Sanofi, and Servier; speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Merck, Novartis, Novo-Nordisk, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi, and Servier. Dr Szarek: consultant/ advisory board for CiVi, Resverlogix, Baxter, and Regeneron Pharmaceuticals, Inc. Dr Bhatt: advisory board: Cardax, Elsevier Practice Update Cardiology, Med- scape Cardiology, PhaseBio, Regado Biosciences; board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; chair: American Heart Association Quality Oversight Committee; data monitoring committees: Baim Institute for Clinical Research (formerly Harvard Clinical Re- search Institute, for the PORTICO trial, funded by St Jude Medical, now Ab- bott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; honoraria: American College of Cardiology (Senior Associate Editor, Clinical Tri- als and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Insti- tute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research In- stitute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Interven- tion), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Com- mittee (Chair); research funding: Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Labora- tories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron,
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Effect of early palliative care for patients with glioblastoma (EPCOG): a randomised phase III clinical trial protocol

Effect of early palliative care for patients with glioblastoma (EPCOG): a randomised phase III clinical trial protocol

In spite of the positive results of EIPC in systemic cancer 12–18 we do not know how EIPC affects GBM patients, if such an effect will be sustainable and when to integrate PC in the care of this patient group. There- fore, our proposed design involves a wide range of GBM patients (initial diagnosis, recurrence, rural and urban areas) for a long period of time (12 months interven- tion, 12 months follow- up), in most cases, probably until death (median survival of GBM patients is between 15 and 17 months). 25–27 This means that EIPC effects on this patient group will be studied comprehensively and will answer our study questions using a prospective clinical study design. What justifies a confirmatory clinical trial at this time point? Following the Medical Research Council (UK)in its current version from 2008, 28 we believe that the development phase of our complex intervention can be based on numerous studies including own modelling work identifying the specific needs of GBM patients and their caregivers 1–11 and also the efficacy of EIPC. 12–18 A potential intervention for GBM patients can be modelled on this existing evidence and our clinical experience. We have conducted two feasibility studies on prospec- tive ongoing patient- reported outcome measurement (PROM) data collection from diagnosis to death 2 and on assessing PC needs of GBM patients and caregiver burden. 3 Our results demonstrated that prospective ongoing PROM data collection is feasible but that the importance of caregivers’ external assessment increases 2 3 with disease progression and that this did not bias our results significantly. 2 Therefore, in this trial, we will involve proxies in the assessment, if patients should be unable to participate themselves. Our previous studies also demon- strated the challenges of recruitment and attrition in this patient group with a recruitment rate of almost 30% of all GBM patients in the field and a considerably high attri- tion rate of 10%–79% 2 3 depending on the presence of assessment personnel. High attrition in PC trials is well- known, 29–31 thus to assure sufficient recruitment rates, a study nurse will at least partly be engaged at the neuro- surgery/neuro- oncological departments at each site
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How to do a clinical trial? Recommendations from the aerobiological point of view

How to do a clinical trial? Recommendations from the aerobiological point of view

The forward shift of ten days for the long-term pollen forecast at the start of the pollen season is a safety measure necessary for a clinical trial in order not to begin too late, and is explained as follows. Anticipation effects are observed for several locations and different pollen seasons, and show the reaction of pollen allergy sufferers before relevant pollen concentrations are in the air. 23 There is more than one plausible reason for this phenomenon, although it has not been clarified until now. Following reasons could explain this outcome: 1) pollen concentrations are point measurements and could miss very local exposure, as known for Alnus x spaethii, 32 2) cross-reactivity, 3) pollen information preparing the population for exposure soon and psychological reasons, 4) lower thresholds after a period of relief (all discussed in Ref. 23 ), and 5) allergen release apart from pollen release 33–36 and/or connections with air pollution including increased allergenicity, inflammatory effects, and interaction with microscopic particles. 37–39
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Survival and Complications of Single Dental Implants in the Edentulous Mandible Following Immediate or Delayed Loading : A Randomized Controlled Clinical Trial

Survival and Complications of Single Dental Implants in the Edentulous Mandible Following Immediate or Delayed Loading : A Randomized Controlled Clinical Trial

Introduction A single implant to retain a complete denture in the mandible was firstly introduced by Cordioli et al. in the 1990s (Cordioli 1993; Cordioli et al. 1997). In this first clinical trial, 21 patients received 1 mandibular midline implant that was used to retain an existing mandibular denture with an O-ring attachment. A submerged healing protocol was chosen, and implants were loaded 4 mo after implant placement. After 5 y of observation, all implants survived, and remarkable improvements of all parameters of oral comfort and prostheses function were observed. Since then, different clinical investigations with varying study designs have been conducted, mostly with a small number of participants over a short- to midterm observa- tion period (Kern 2012; Passia and Kern 2014).
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Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized, Placebo-Controlled, Double-Blind Clinical Trial in Healthy Volunteers

Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized, Placebo-Controlled, Double-Blind Clinical Trial in Healthy Volunteers

Usually, such products are mainly thought to exert ra- ther non-specific effects via either improving the supply of vitamins, or the presence of antioxidants. Despite the fact that in the CA juice tested in this clinical trial surely considerable amount of vitamins and antioxidants (such as polyphenols, flavonoids, etc.) are present, it would be inadequate to assume that these alone could have caused the changes observed during this study. For example, other constituents are well-known for their effects on im- mune cells, such as docohexaenoic acid (DHA) from Shi- zochytrium sp. [23], selenium [24], L-carnitine [25], zinc [26], etc. Multi-component mixtures of biologically ac- tive constituents, like CA, must indeed be expected to potentially generate more complex interactions with hu- man physiology. Each constituent may show effects on different sub-systems of the human body (e.g. on mucos- al secretions, the mucosal epithelial cells, various organs, immune cells, the neuro-endocrine system, but also—last, but surely not least—the intestinal microbiota, which again can generate additional secondary effects). Thus, the more complex such mixtures, the less likely it will be possible to trace back certain effects to just one of these ingredients. In the end, preparations like CA can only be judged by their net effects on certain physiological func- tions in vivo. It was therefore the purpose of this clinical investigation to examine possible shifts in immune cell activation as a measure of what the ingestion of CA may change with regards to defense reactions or inflammatory processes.
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Relationship between polyunsaturated fatty acids and psychopathology in the NEURAPRO clinical trial

Relationship between polyunsaturated fatty acids and psychopathology in the NEURAPRO clinical trial

The study cohort consisted of 285 of 304 (94%) participants in the NEURAPRO study who provided consent for additional biomarker analysis. NEURAPRO was a double-blind  placebo- controlled randomized clinical trial of fish oil (1.4 g fish oil/ day) in people at UHR for psychosis ( 21 ) (ANZCTR identifier: 12608000475347) with 10 study sites (Amsterdam, Basel, Copenhagen, Jena, Hong Kong, Melbourne, Singapore, Sydney, Vienna, and Zurich). The intervention was administered in addition to cognitive behavioral case management (CBCM) for 6 months followed by a 6-month follow-up period. Help- seeking individuals attending UHR services in the trial centers were eligible if they were aged 13–40 years and met UHR criteria ( 24 , 25 ). Exclusion criteria were a previous psychotic episode, acute intoxication, organic brain disease, serious developmental disorder, abnormal coagulation profile or thyroid function, physical illness with a psychotropic effect, current treatment with mood stabilizers, past neuroleptic exposure to a total lifetime haloperidol equivalent dose of more than 50 mg, IQ of less than 70, dangerous behavior, aggression or suicidality, pregnancy, or current supplementation with n-3 PUFA ( 25 ). All participants provided written informed consent (parent/guardian consent for participants aged <17 years). The NEURAPRO study was approved by the local human research ethics committees of the study centers.
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The RESOLVE Trial for people with chronic low back pain : protocol for a randomised clinical trial

The RESOLVE Trial for people with chronic low back pain : protocol for a randomised clinical trial

Introduction: Low back pain is the leading worldwide cause of disability, and results in significant personal hardship. Most available treatments, when tested in high-quality randomised, controlled trials [32_TD$DIFF], achieve only modest improvements in pain, at best. Recently, treatments that target central nervous system function have been developed and tested in small studies. Combining treatments that target central nervous system function with traditional treatments directed towards functioning of the back is a promising approach that has yet to be tested in adequately powered, prospectively registered [33_TD$DIFF], clinical trials. The RESOLVE trial will be the first high-quality assessment of two treatment programs that combine central nervous system-directed and traditional interventions in order to improve chronic low back pain. Aim: To compare the effectiveness of two treatment programs that combine central nervous system-directed and traditional interventions at reducing pain intensity at 18 weeks post randomisation in a randomised clinical trial of people with chronic low back pain. Design: Two-group, [34_TD$DIFF]randomised, [35_TD$DIFF]clinical [36_TD$DIFF]trial [37_TD$DIFF]with [38_TD$DIFF]blinding [39_TD$DIFF]of [40_TD$DIFF]participants and assessors. Participants and [41_TD$DIFF]setting: Two hundred and seventy [42_TD$DIFF]-five participants with chronic low back pain that has persisted longer than 3 months and no specific spinal pathology will be recruited from the community and primary care in Sydney, Australia. Interventions: Both of the interventions contain treat- ments that target central nervous system function combined with treatments directed towards functioning of the back. Adherence to the intervention will be monitored using an individual treatment diary and adverse events recorded through passive capture. Participants are informed prior to providing informed consent that some of the treatments are not active. Blinding is maintained by not disclosing any further information. Complete disclosure of the contents of the intervention has been made with the UNSW HREC (HC15357) and an embargoed project registration has been made on the Open Science Framework to meet the Declaration of Helsinki requirement for transparent reporting of trial methods a priori [2_TD$DIFF]. Intervention A: Participants randomised to Intervention A will receive a 12-session treatment program delivered as 60-minute sessions, scheduled approximately weekly, over a period of 12 to 18 weeks. All treatment sessions are one-on-one. The program includes a home treatment component of 30 minutes, five times per week. The intervention comprises discussion of the participant’s low back pain experience, graded sensory training, graded motor
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Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy

Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy

ized, open, phase II, two-arm trial, with six participating tertiary-care centres in Austria specialized in pancreatic surgery, each of which had an annual frequency of more than 20 pancreatic resections. The first patient entered the study on 5 September 2013 and the final patient com- pleted the study on 22 March 2015. Local ethics committee approval was received (1169/2013) and the study was reg- istered in the European Clinical Trials register (EudraCT number 2013-000639-29).

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Clinical trial design enabling E-optimal treatment rules

Clinical trial design enabling E-optimal treatment rules

Spiegelhalter, Freedman, and Parmar (1994). The controversy suggests that inability to express a credible prior is common in actual decision settings. In these circumstances, the decision maker faces a problem of choice under ambiguity (Ellsberg, 1961). In past research, we have studied the use of trial data to make treatment decisions under ambiguity. To address the problem, we have utilized and extended the Wald (1950) development of frequentist statistical decision theory. Wald considered the broad problem of using sample data to make decisions under uncertainty. He posed the task as choice of a statistical decision function, which maps potential data into a choice among the feasible actions. He recommended ex ante evaluation of statistical decision functions as procedures, specifying how a decision maker would use whatever data may be realized. Expressing the objective as minimization of a loss function, he proposed that the decision maker evaluate a statistical decision function by the distribution of loss that it yields across realizations of the sampling process. He focused attention on mean sampling performance, which he termed risk.
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Alternative Caries Management Options for Primary Molars: 2.5-Year Outcomes of a Randomised Clinical Trial

Alternative Caries Management Options for Primary Molars: 2.5-Year Outcomes of a Randomised Clinical Trial

Even with good access to dental treatment, the stan- dard approach to treating cavitated primary tooth carious lesions has shown limited effectiveness in controlling the carious process [Kidd, 2012]. Less invasive alternatives to the “drill and fill” approach to manage carious lesions have been advocated [Kidd, 2011; Innes and Evans, 2013; Kuzmina and Ekstrand, 2015]. Non-restorative caries treatment (NRCT; recently called non-restorative cavity control [Innes et al., 2016a]), involving no caries removal, opening up the carious lesion to make it cleansable, effec- tive plaque removal instruction, and fluoride application in individual patient-based scenarios, has shown encour- aging results within an efficacy framework (under ide- al and controlled circumstances) [Gruythuysen, 2010]. However, there are limited long-term investigations in- to its effectiveness (performance in a more “real-world” situation). Additionally, sealing carious lesions with no tooth or biofilm removal as with the Hall Technique (HT) [Innes et al., 2011] or conventional fillings for permanent teeth [Mertz-Fairhurst et al., 1998] have shown potential for the management of teeth with carious lesions into dentine in long-term clinical trials.
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