Hã¼ttenberg, Germany

A Study of JNJ-79635322 in Combination With Daratumumab or Pomalidomide for Multiple Myeloma

Rehablines: a Further Use Databank to (re)Use Routine Clinical Data for Scientific Research in Rehabilitation of People With Physical Disabilities and/or Chronic Diseases

A Multicenter, Multinational, Cohort Long-term Post-market Clinical Follow-up (PMCF) of the Safety and Efficacy of the Osseoanchored Prostheses for the Rehabilitation of Amputees (OPRA) Implant System When Used for Transhumeral Implantation in Amputee Patients

All subjects that will be enrolled in this investigation should have been treated with the OPRA TM Implant System for a transhumeral unilateral or bilateral amputation completed before 01-Jan-2024. This retrospective, non-interventional, clinical investigation is designed as a multicenter, multinational, cohort investigation for long-term follow-up of safety and efficacy endpoints. The investigation will also include prospective visit(s) for enrollment of subjects and collection of present data on device functionality and the use of the device. No control group or comparator will be used in this investigation. All patient reported outcome questionnaires used in the investigation will be available at the investigation site for completion by the subjects during one of the subjects' visits to the site. Depending on the subjects' preferences it will also be possible to provide those questionnaires to the subjects, through use of regular mail, email or through an electronic Patient Reported Outcome system (ePRO). It will be possible for the subjects to complete the questionnaires either on paper, electronically or over phone, depending on their preferences. Preferably, the subjects prosthesis functional tests should be performed as part of the follow-up visit at the site. The tests may also be performed remotely, depending on subjects' preferences. If done remotely, this will require the functionality test being performed during a videoconference with the test administrator. No photos or video-recordings (if conducted according to the sites normal practice) of the performed tests will be part of the investigation documentation, only the related medical record notes will be used as source data for those parameters.

A Study to Evaluate the Safety, Tolerability, and Effects on Blood and Urine Markers of Single Ascending Dose of GSK4771261 in Healthy Participants and Participants With Autosomal Dominant Polycystic Kidney Disease

A Study Protocol for the Implementation and Evaluation of a Self-management Support Program in Burns Aftercare for Burn Survivors in the Netherlands

Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)

The Dragon PLC Trial (DRAGON-PLC)

Primary liver cancer (PLC) is the third most common cause of cancer death worldwide. Surgical resection is the mainstay for a curative approach as contemporary chemotherapy and immune-based therapies only lead to a median survival of 10-14 months. A complete surgical resection increases the median survival to 42 months (range 32-52 months). However, PLC is mainly diagnosed at an advanced stage and >70% of PLC patients are ineligible for an immediate surgical approach. There are different reasons that make a patient ineligible for surgery, one important reason is the risk of liver failure after the surgery due to a small remnant liver. This study aims to improve the oncological, radiological and surgical strategy to allow more patients to undergo liver resection safely, to improve quality of life and to extend overall survival at acceptable costs. Adequate function of the future liver remnant (FLR) is a prerequisite for surgical resectability. This is necessary in order to avoid liver failure after surgery, a major cause of morbidity (38%) and mortality (27%). To mitigate this risk, regenerative strategies based on preoperative calculation of the FLR volume and function are essential. Patients with technically resectable disease but predicted insufficient FLR volume or function are referred to as primarily unresectable or potentially resectable (PU/PR). These patients can undergo strategies that capitalize on the regenerative capacity of the liver which aim to preoperatively increase the FLR volume and function in order to allow surgery. Many of the patients that are primarily unresectable due to an insufficient FLR can become ultimately and safely resectable after the induction of adequate FLR-hypertrophy by the current standard, portal vein embolisation (PVE). However, 25% of patients do not show sufficient FLR growth after PVE and are unable to safely undergo resection. A new approach has been developed to improve this. Combined portal and hepatic vein embolisation (PVE/HVE) has great promise in terms of increasing FLR growth, resection rate (RR), safety and potentially, overall survival. Establishing PVE/HVE as the new standard could result in increased survival and a better quality of life (QoL) for patients.

A Study to Learn How a Tablet Compared With an IV Infusion of the Study Medicine Called Vepdegestrant is Taken up Into the Blood in Healthy Adults

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

The Impact of a Diagnostic Strategy for Acute Appendicitis in Children with Acute Abdominal Pain in Primary Care

BACKGROUND About 10% of pediatric general practitioner (GP) consultations are for acute abdominal pain of which about 5% have acute appendicitis (AA). Delaying a diagnosis of AA and subsequent appendectomy increases the short and long-term morbidity. AA in an early stage is difficult to distinguish from other (self-limiting) causes of acute abdominal pain (e.g. urinary tract infection, constipation and gastroenteritis), resulting in missing 19% of children with AA at first presentation in primary care and 70% non-AA cases among referrals, which has a negative impact on the child and parents, such as anxiety and psychological distress. As urgent illnesses other than AA are very rare in children with acute abdominal pain, the yield of referrals in terms of detecting other conditions than AA that need urgent specialist care is low. An evidence based diagnostic strategy for AA referral could help the GP in the diagnostic process, thereby reducing non-AA referrals without missing children with AA. OBJECTIVE AND HYPOTHESIS The objective of this study is to evaluate the impact of a diagnostic strategy for AA, consisting of an externally validated cPR based on seven signs and symptoms, selectively followed by a CRP-POCT in the medium-risk group, on referral efficiency in children with acute abdominal pain in primary care, as compared with usual care. The hypothesis is that the diagnostic strategy will decrease the proportion of non-AA referrals, without delaying the diagnosis of AA. STUDY DESIGN A pragmatic cluster RCT will be conducted with 1:1 permuted-block randomization of general practices to the intervention or control group using randomly varying block size. Stratification will be based on the GP practice size (greater or smaller than 5000 patients). Follow-up is 30 days for the primary outcome (efficiency) and 30 days and 3 months for secondary outcomes (7). Alongside the trial, a process evaluation will be performed according to the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance). STUDY POPULATION Inclusion criteria are: children, 4 to 18 years, presenting with acute abdominal pain (onset ≤ 7 days) in primary care. Exclusion criteria are: a history of appendectomy, pregnancy, traumatic cause of abdominal pain. INTERVENTION The intervention in this study is a diagnostic strategy for AA referral using an externally validated cPR selectively followed by a CRP POCT in the medium risk group. By using the diagnostic strategy, GPs will evaluate a set of signs and symptoms on a structural basis and get guidance for indication and interpretation of CRP POCT, for which current practice is very heterogeneous. The cPR includes seven signs and symptoms of AA: sex (2 points), duration of symptoms (< 24 hrs= 1 point, 24-48 hrs= 2 points), nausea or vomiting (2 points), elevated temperature (≥ 37.3 °C) (1 point), tenderness of the right lower quadrant (5 points), peritoneal irritation (4 points), and abnormal bowel sounds (1 point). For children in the low-risk group (score 0-7; mean probability AA 0.5%) safety netting advice should be provided. In the high-risk group (score ≥14; mean probability AA 41.0%), the GP should refer the patient to the emergency department. In the medium-risk group (score 8-13; mean probability AA 7.5%), GPs should perform CRP POCT according to Dutch laboratory quality standards. CRP values <10mg/l (mean probability AA 1.3%) imply safety netting advice and for CRP >50 mg/l a referral is needed (mean probability AA 41.8%). In case of a CRP value between 10 and 50 mg/l (mean probability AA 16.8%), the GP will discuss the following two management options with the patient: 1) a reconsultation later the same day or the next day; or 2) immediate referral. The cPR will be made available electronically for GPs, by a link integrated in the GP registry. USUAL CARE Care provided as usual is according to the recommendations of the Dutch College of GPs guideline 'abdominal pain in children', which states that AA could be suspected when a child presents with pain and tenderness in the right lower quadrant and fever. Children with peritonitis signs and abnormal bowel sounds need to be referred. In case of doubt, GPs should perform safety netting and/or plan reassessment. CRP testing is not recommended, because lack of evidence for added diagnostic value in primary care. The GPs in the control group receive a leaflet with a summary of the NHG guideline 'abdominal pain in children'. SAMPLE SIZE CALCULATION Results from previous studies show that the cut-off for the high-risk group based on the cPR had a specificity of 97% and that CRP value of ≥50 mg/l in children in the medium risk group had a specificity of 94%. As the weighted mean of these is a specificity (efficiency) of at least 95%, an improvement of efficiency from 88% (current care) to 95% is expected. In order to detect this difference, with 80% power, using a two-sided 5% significance level, and expecting 10% loss to follow-up, a randomized controlled trial would need to include 566 children (283 per group). The researchers assume to recruit on average 4 children per practice in 2 years and that 10 practices will not recruit any children. Therefore, 150 practices will be recruited which each recruit children for 2 years. STATISTICAL ANALYSIS The primary outcome will be evaluated on an intention-to-treat basis. Children will be analyzed in the intervention or control group based on the GP practice in which they are registered, irrespective of the actual care received. In addition, a per protocol analysis will be done. In the intervention group according to the per protocol analysis, only children who received the intended diagnostic strategy and CRP-POCT testing in the prescribed way will be included. In the control group, we will only include children who did not undergo CRP POCT testing. Separately in both randomized groups, characteristics of children will be compared in the intention-to-treat and per-protocol analysis. A multilevel logistic regression model will be used to analyze the primary outcome, accounting for clustering of observations within GP practices and adjusting for the stratification variable (practice size) and, if necessary, for baseline differences. Exploratory analyses will assess subgroups by age and sex. For secondary outcomes, multilevel logistic (dichotomous variables) or linear regression (continuous variables) will be used, as appropriate. In addition, adverse health outcomes (e.g. complications in AA cases and non-AA cases, missed other emergency diseases) will be described without statistical evaluation. COST-EFFECTIVENESS ANALYSIS Cost-effectiveness will be calculated from societal and healthcare perspective with a time horizon of 30 days. Secondary analyses will address a 3-month time horizon. Efficiency will be the primary effect parameter. Cost-utility will be calculated based on the EQ-5D-(Y)-3L. Bootstrap re-sampling will be performed on the costs, and on costs and effect pairs (cost-effectiveness and cost-utility analyses) in order to calculate confidence intervals. Furthermore, both cost-effectiveness and cost-utility planes will be plotted, along with acceptability curves.