Hematuria

The WASHOUT study is an international, multicentre prospective observational study designed to describe the management of patients with unplanned admission to hospital with haematuria. The study will utilise a collaborative methodology using the BURST model. Data on demographics, comorbidities, management practices, and outcomes will be collected using a standardised case report form and analysed using multilevel linear regression modelling. Primary outcomes include length of stay, while secondary outcomes cover diagnosis time, 90-day mortality, readmission rates, and resource use. Patient and public involvement has been integral to the study design, ensuring that outcomes reflect patient priorities and that the research addresses key areas of concern Study design and aim WASHOUT is an international, multicentre prospective observational study aiming to describe the management of haematuria emergency admissions. Objectives: Our objectives are: Establish the incidence of causative diagnoses in patients being admitted with emergency haematuria. Describe demographics, comorbidities, management and clinical outcomes of patients undergoing emergency admission to hospital with haematuria. Identify factors associated with adverse outcomes and/or increased resource use. Identify if variation in management and outcomes exists at local, regional and international levels. Assess the impact different management pathways have on clinical outcomes (in terms of length of stay, health resource utilisation, readmission, 30-day and 90-day mortality rates Provide information to design a future randomised trial, for example control group outcomes and estimates of intra-cluster correlations. Inclusion criteria Patients will be included consecutively if they are over 18 years of age and admitted to a participating secondary care centre as an emergency with haematuria under the primary or joint care of the urology team. In the UK, individual consent is not necessary as this study has been considered a service evaluation. Exclusion criteria any patients with catheter-related urethral trauma (defined as haematuria immediately after insertion of a urethral catheter without a preceding history of haematuria on this admission including traumatic catheter removal by patients), urological trauma (abdominal/pelvic) as well as patients who are in hospital less than 24 hours. Primary outcome Length of stay, measured as the number of calendar days between the day of admission in the index hospital admission episode and the day of discharge from the hospital. Secondary outcomes Time to definitive diagnosis measure, defined as the number of days between original presentation and final diagnosis. 30-day and 90-day mortality rate measured as the number of patients who died from the day of admission to the 30-day and 90-day follow-up period. 30-day and 90-day readmission rate, measured as the number of patients who were readmitted to the hospital with the same issue in the 30 days and 90-day after the date of discharge. Number of days alive and out of hospital at 90 days. Healthcare costs, measured by calculating the cost of the stay, investigations, procedures, the patient underwent during the admission and in the 90-day follow-up period including readmissions. The study will also assess current pathways that exist in hospitals, including acute care pathways and specific pathways for management of haematuria. Details will be obtained through a questionnaire distributed to each participating site. Study delivery The study will utilise the The British Urology Researchers in Surgical Training (BURST) collaborative model. The design of the current study has been supported by input from the Centre for Healthcare Randomised Trials (CHaRT) (i.e. The Urology Foundation trials unit), who will be involved in designing and conducting the next study, which we anticipate will be an implementation randomised controlled trial. Recruitment Patients will be recruited consecutively. The recruitment target for this study is based pragmatically on the prevalence of inpatient haematuria. Target recruitment per participating site is 15 patients across a 12-month period from 70 centres. The cumulative recruitment target from all sites is 1,050 patients. We want to recruit as many participants as possible during the 12-month period. The sample size is also based on the anticipated wide variation of practice and the heterogeneous nature of the presentation in terms of patient demographics and the underlying cause of the haematuria ranging from benign causes to malignant urological conditions. This sample size is also adequately powered to detect a meaningful difference in length of stay (defined as at least 1 day by study authors) using ANOVA to analyse any binary variable (spanning both clinicopathological features and management factors). This 1-day difference in length of stay is based on a calculated sample size of 1,054 patients, obtaining a power of 0.90 with a significance level of 0.05, and taking a standard deviation of length of stay as 5 days obtained from original data of a retrospective review covering this study population \[2\].

Early diagnosis in children with Alport syndrome (AS) with isolated hematuria opens a "window of opportunity" for early intervention. In the Alport mouse-model, this early intervention with the ACE-inhibitor Ramipril let to a delay of kidney failure by 111%. In order to observe treatment approaches for AS in humans, this registry has been established in 2006 to collect data over several generations of Alport families across Europe. In the meantime, this registry has been expanded to "Alport XXL" via the International Alport Alliance as a global effort across all continents. Small children with AS first develop microscopic hematuria (stage 0), proceeding to microalbuminuria (stage I), overt proteinuria (stage II), impaired kidney function (stage III) and finally can end up with kidney failure (stage IV), leading to impaired quality of life and premature death (stage V). This registry uses these stages to assess if earlier initiation of medications such as ACE-inhibition at earlier stages of disease is more effective than later therapy in delaying the time to disease progression (doubeling or tripeling of albuminuria), delaying loss of estimated glomerular filtration rate (eGFR), and if therapy improves life-expectancy. Untreated children with autosomal-recessive AS, digenic AS, and boys with X-linked AS typically all develop kidney failure early in life. Untreated girls with X-linked AS have a 30-40% risk of kidney failure, typically later in life (40 years or older). Untreated heterozygous patients with COL4A3/COL4A4 variants typically have a less severe phenotype (in former times also called "familial benign hematuria" or "thin basement membrane nephropathy" (TBMN)) and a 1-2% risk of kidney failure. Several interim results of this registry have been published since 2012. Alport XXL is designed and conducted as strictly observational, non-interventional data acquisition with prospective (and in parts retrospective) data analysis. Young patients with AS in disease stages 0,I,II from all over the world are included. The renewed version from 2021 has been re-approved by the Ethics Committee of the University Medical Center Göttingen as "Alport XXL", a further development of the former European Alport Therapy Registry (AZ 10/11/06). "Alport XXL" registry and data storage are in conformity with Good Clinical Practice guidelines. ICH-GCP-conform patient information and data exchange is secured by data transfer and cooperation agreements between all international trial centers and the coordinating principal investigator at University Medical Center Goettingen. At baseline, data collection including retrospective data is performed using a standardized, ICH-GCP-conform and pseudonymized questionnaire assessing age, sex, weight, height, mode of inheritance (X-linked, autosomal, compound heterozygous/homozygous, number of missense variants), family history, albumin in 24-hour or spontaneous urine, serum-creatinine, RAS-blockade with preparation and dose. Follow-up visits include same data than baseline plus blood-pressure, smoking-status, serum-potassium, eGFR, hearing loss and eye involvement, other symptoms such as leiomyomatosis, comorbidities and adverse events (adverse events of special interest defined as hyperkalemia, cough, hypotension, acute renal failure, malignancy, death).

This is a prospective, multicenter, open-label, randomized trial comparing OAC with no OAC (1:1 ratio) in patients who develop new-onset POAF after CABG. The primary effectiveness endpoint is the composite of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism or venous thromboembolism (VTE) at 90 days after randomization. The primary safety endpoint is BARC (Bleeding Academic Research Consortium) grade 3 or 5 bleeding at 90 days after randomization. The overall intent is to evaluate the trade-off in prevention of thromboembolic events versus an increase in bleeding. Patients will be randomly assigned to the following treatment strategies: * OAC-based strategy (experimental arm): OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant (apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor) * Antiplatelet-only strategy (control arm): single antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor) The protocol-specified duration of anticoagulation is 90 days. Patients, who are randomized to the control arm and develop recurrent AF after 30 days, may be crossed-over to an OAC. Accrual is expected to take 60 months. Study follow-up visits will be performed at 90 days and phone follow-up at days 30, 60, and 180 days. Data for patients enrolled in the registry will be ascertained from the local clinical site via a review of medical records. The baseline risk profile of registry patients (i.e., patients eligible but unwilling to be randomized) will be analyzed and compared to that of patients randomized in the trial. The usage of anticoagulant and antiplatelet therapies in the registry population overall and baseline CHA2DS2-VASC ischemic stroke risk score will also be determined. Up to 500 patients will also be offered the option to participate in a digital health substudy which includes a wearable heart rhythm monitor device for 30 days post discharge.

Objective: To study the safety and efficacy of an anti-platelet-free antithrombotic regimen in patients with advanced heart failure who are chronically supported with the HeartMate 3 LVAD. Hypothesis: The withdrawal of aspirin from the antithrombotic regimen of HeartMate3 LVAD patients will not adversely affect safety and efficacy and may reduce non-surgical bleeding. Clinical Investigation Design: This is a prospective, randomized, controlled clinical investigation of advanced heart failure patients who are chronically supported with the HeartMate 3 LVAD. The study will compare two different antithrombotic regimens: VKA with aspirin versus VKA without aspirin. End points: Primary end point: * Composite of Survival free of any major hemocompatibility related adverse event at 1-year post randomization. 1. Major Hemocompatibility Related Adverse Event: Stroke, Pump Thrombosis (suspected or confirmed), major non surgical Bleeding (moderate or severe) (including intracranial bleeds that do not meet the stroke definition), Arterial Peripheral Thromboembolism Secondary end point: * Non-surgical Major Hemorrhagic Events * Non-surgical Major Thrombotic Events * Survival * Stroke Rates * Pump Thrombosis Rates * Bleeding Rates, including: * Non-surgical Bleeding * Moderate Bleeding * Severe Bleeding * Fatal Bleeding * GI Bleeding Descriptive endpoints * Hemocompatibility score: a tiered hierarchal score that weighs each hemocompatibility related adverse event by its escalating clinical relevance⁸ * Rehospitalizations * Economic Cost Implications * Subgroup analysis (patients with increased bleeding/thrombotic risk (i.e prior HRAE events) Number of Subjects Required for Inclusion in Clinical Investigation: Based on ARIES results, 58 patients will need to be enrolled in each arm (116 total) to achieve 80% power to prove that the non-aspirin group is non-inferior to the aspirin group using a non-inferiority margin of 15% with the Farrington-Manning risk difference approach to non-inferiority at a one-sided alpha = 0.05. To account for an expected 10% dropout rate, up to 128 patients will be randomized in the trial.

Deep vein thrombosis and pulmonary embolism - collectively known as venous thromboembolism VTE - and major bleeding are serious surgical complications leading to poorer patient-reported quality of life and mortality. Pharmacological thromboprophylaxis is an established strategy for reducing VTE risk but balancing it with increased bleeding, particularly after major surgery, poses challenges. Guidelines typically recommend pharmacological thromboprophylaxis for patients at higher, but not lower risk of VTE, without clearly defining procedure or patient selection. There is particular uncertainty regarding the balance of potential benefits and harms of pharmacological thromboprophylaxis in patients who are at a lower estimated risk of VTE postoperatively, in patients with a baseline VTE risk in the range of 2%. In these patients, the risk of major bleeding may be similar to or could potentially outweigh the relatively lower risk of VTE complications, such that the net clinical benefit of routine pharmacological thromboprophylaxis remains unclear. "Avoiding Risks of Thrombosis and Bleeding in Surgery (ARTS)" is a large, randomized, multicenter study, comparing a direct oral anticoagulant (DOAC) called apixaban in patients undergoing abdominal and pelvic surgeries. Half of the 5436 patients will be randomized to receive apixaban after surgery for 28 days with standard of care mechanical prophylaxis - to a control group with no anticoagulation but with standard of care mechanical prophylaxis. ARTS trial will be the first to compare anticoagulation with DOACs (apixaban) versus no anticoagulation in a population of urologic, gynecologic and abdominal surgical patients. Any of the possible outcomes of 1) A clear net benefit in favor of apixaban or 2) A clear net benefit to not using prophylaxis or 3) a sufficiently close tradeoff that predictive factors and patients' values and preferences regarding bleeding versus thrombosis determines the decision, will substantially enhance evidence-based peri-operative care.

Steroids are used routinely aiming to reduce pain and nausea, especially in surgery with high levels of postoperative pain. The majority of international studies on tonsillectomy (TE) are performed on dexamethasone which is used in large parts of the world. Use of steroids when TE is performed on children are also more studied on than on adults. Islam et al 2011 demonstrated in a study that dexamethasone (8 mg) reduced postoperative nausea for 24 hours in a study population of both children and adults. Mc Kean et al 2006 studied the effect of 10 mg dexamethasone on nausea in adults after TE during a seven-day period. Effect was seen during the first 24 hours but not the remaining days. With regard to postoperative pain, the research results differ in terms of what effect steroids have at TE. Mc Kean et al 2006 showed significantly lower estimated pain on surgery day and day 4 to 7 after a single dose of dexamethasone peroperatively. Stewart et al 2002 has shown that, by means of preoperatively given dexamethasone (8 mg) and in decreasing dose over an 8 day period postoperative \[2mgx2 for 4 days and then 2mgx1 for 4 days\], the patient's estimated pain and consumption of additional pain relievers were reduced. Michele et al 1999, on the other hand, found no effect on pain over a 10 day period despite a relatively high peroperatively dose of dexamethasone (20 mg). There are, however, studies on children, suggesting that there is a dose-dependent relationship between dexamethasone and postoperative bleeding after TE in children. In a study by Czarnetzki et al 2008, 0.05, 0.15 and 0.5 mg / kg dexamethasone were used peroperatively. In this study it was seen that 0.5 mg / kg dexamethasone increased the risk of bleeding from 4% to 24%, which led to a premature termination of the study due to the bleeding risk. In 2012, a meta-analysis of the steroid effect on bleeding after tonsillectomy was conducted by Plante et al. Both studies on children and adults were included. No significant increase in the overall frequency of bleeding after tonsillectomy was seen. On the other hand, a significant increase in the number of haemorrhages that required operative action was noted. This could be interpreted as that the severity of bleedings was increased. It was recommended that systemic steroids should be used with caution until further studies have been performed. The investigators conducted a retrospective study on children with TE in Gällivare with and without betamethasone (69 patients in total) and found no evidence of increased bleeding risk, but also no effect on PONV. However, a significant effect on pain was found during the first 24 hours postoperative with the average dose of 0.15 mg / kg. When comparing different cortisone preparations, 8 mg of betamethasone corresponds to approximately 10 mg of dexamethasone. Bellis et al., 2014 performed a meta-analysis of dexamethasone and postoperative bleeding at TE in children, but considered that more studies are needed to determine the bleeding risk before any safe conclusions can be drawn. Thus, there are uncertainties with regard to the cortisone effect, both when it comes to the size of the dose and whether there really is an effect on PONV and / or postoperative pain or not. On the other hand one does not want to use high doses with risks of postoperative bleeding. Betamethasone has not been studied to the same extent as dexamethasone, and in Sweden betamethasone is preferably used preoperatively to counteract PONV and pain associated with certain operations. The results of previous studies are however not conclusive and there is no consensus of what doses that should be used. In Sweden 4 mg of betamethasone, given intravenously during the surgery, is routine at tonsillectomy surgery. However, in the literature there is very weak evidence that such a small dose have any effect. On the other hand, there are studies signaling that dexamethasone doses of 20 mg (= 16 mg betamethasone) reduced PONV, but increased postoperative hemorrhages after TE surgery. Glucocorticoids may act via the following mechanisms: (1) anti-inflammatory effect; (2) direct central action at the solitary tract nucleus, (3) interaction with the neurotransmitter serotonin, and receptor proteins tachykinin NK1 and NK2, alpha-adrenaline, etc.; (4) maintaining the normal physiological functions of organs and systems; (5) regulation of the hypothalamic-pituitary-adrenal axis; and (6) reducing pain and the concomitant use of opioids, which in turn reduces opioid-related nausea and vomiting. 2.2. Risk/Benefit evaluation One of the main problems after tonsillectomy is PONV and especially postoperative pain that can persist up to 10-14 days after the surgery. This long period of postoperative pain leads to weakness and dehydration due to difficulties to eat and drink after the operation. Sometimes hemorrhage after TE can be fatal, but normally the bleeding can be stopped with local anaesthesia or diathermy during general anaesthesia. Normally this type of bleeding occurs in 8-10% after TE. After TE the patients normally go home the same day as the surgery. In northern Sweden the distances from the Hospital with an ear, nose and throat (ENT) emergency unit to the home of the patients could be as far as 3-400 kilometers. In this situation it is not advisory to give additional medications, which increases the risk of lethal hemorrhage. Benefits of 8 mg betamethasone: * Reduced PONV * Reduced pain =\> Less NSAID pain killers =\> Less risk of hemorrhage * Reduced pain =\> Increased ability to eat and drink =\> less risk of postoperative infection =\> less risk of bleeding * Reduced pain =\> Shorter sick leave =\> Socioeconomic benefits Risks of 8 mg betamethasone: * Increased bleeding risk =\> more patients comes back to the hospital due to hemorrhage =\> more patients need re-surgery with diathermy of the bleeding * Patients with gastric ulcers have an increased risk of gastric bleeding A previous retrospective study showed a reduced pain postoperatively with 8 mg betamethasone, without any sign of increased postoperative hemorrhage. There are no studies that have showed an increased postoperative risk of hemorrhage with 10 mg of dexamethasone given to adults at TE surgery. On the other hand lower doses of dexamethasone, as for example 5 mg (= 4 mg of betamethasone), does not seem to have any clinical benefits. The aim of the present study is to evaluate if it is possible to register a beneficial effect of 8 mg betamethasone, given as a premedication orally, without increasing side effects as increased bleeding. In conclusion, the side effects are mild and probably very infrequent, while the positive effects are visible in almost all patients with less pain and a shorter recovery period after the surgery. 3\. STUDY OBJECTIVES AND ENDPOINTS 3.1. Primary objective The primary objective of this study is to verify if 8 mg of betamethasone at adolescents and adult TE operations can significantly reduce PONV. 3.2. Secondary objective(s) The secondary objective is to verify that 8 mg of betamethasone in adolescents and adult TE operations reduces postoperative pain but does not increase the postoperative bleeding risks. 4\. STUDY DESIGN AND PROCEDURES 4.1. Overall study design and flow chart The study is a double-blind, placebo-controlled, randomized study in 100 volunteered patients over 12 years of age selected for elective tonsillectomy at the ENT clinic in Norrbotten. Patients fulfilling all of the inclusion and none of the exclusion criterias will be included. Enrollment will be continued until the required sample size is achieved (100 subjects). Once informed consent is obtained, screening data will be collected to determine each subject´s eligibility for study participation. The total expected duration of the subject participation is maximum 95 days, from screening visit to end of follow-up. The active participation is 5 days (surgery at visit 2 and phone calls, 1 and 5 days after day of surgery). The study pharmaceutical (betamethasone) is a well-known substance and has been used in humans for many years for the same indications as in the present study. Thus it will be regarded as a phase IV study.

Bladder cancer is the 4th most common cancer in men and 6th most common cancer overall with over 80,000 new cases in the US per year. The most common causes of bladder cancer are smoking and it is usually found in patients over the age of 50. By the time it is diagnosed, the disease is often advanced since there are few warning signs other than seeing blood in the urine. Screening is currently accepted practice for colon, cervical, and breast cancer. However, there is not an accepted screening methodology for bladder cancer. Bladder cancer is currently detected in 2-5% of patients who have microhematuria on routine urinalysis, a cheap, non-invasive test obtained by many primary care physicians. Bladder cancer diagnosed by microscopic blood on urinalysis is often lower stage than patients diagnosed with visible blood. Urine testing, therefore, offers a simple screening mechanism that can be tailored to patients at higher risk for bladder cancer based on age, tobacco exposure and other risk factors. In conjunction with routine traditional urinalysis testing, there are advances in urine molecular markers which utilize protein and genetic alterations resulting in a higher sensitivity and specificity for the detection of bladder cancer. Markers have not been evaluated for screening in high-risk populations, and there is a gap in knowledge of the most accurate screening method. Early detection of bladder cancer has the potential to identify disease at an earlier stage resulting in a lower burden of treatment, improved quality of life, and improved survival. This study will prospectively screen patients at high risk for the development of bladder cancer at bi-annual intervals with a commonly available urinalysis test that assess for microhematuria and urine based molecular markers. This is a single arm study. The outcomes from the experimental arm will be compared to a historical control (bladder cancer detected by standard of care using SEER registries).

The goal of this observational study is to further validate the sensitivity and specificity of Bladder EpiCheck in primary detection of urothelial carcinoma in participants aged 45 years or older presenting with haematuria, compared to cystoscopy and pathology, if performed. Participants will provide a voided urine sample, and data from standard of care haematuria work-up will be collected.

This is a single-center, retrospective, observational study. All adult hematologic patients receiving a central venous catheter in the department of intensive and perioperative care at Skåne University Hospital in Lund, Sweden will be eligible for inclusion. Current Swedish guidelines recommend a pre-procedural platelet transfusion trigger of 50x10\^9/L to decrease the risk of bleeding during and after the procedure. However, these guidelines are based on data from an era when the landmark technique was predominant, and the bleeding complication incidence has decreased with the widespread use of real-time ultrasound guidance. Thus, our departmental pre-procedural platelet transfusion trigger for CVC placement was lowered from 50 to 10x10\^9/L in March 2023. This corresponds to the threshold commonly used in hematologic patients to prevent spontaneous bleeding. This study is set to investigate if the incidence of grade 3-4 postprocedural bleeding events have increased after the change in platelet transfusion trigger from 50x10\^9/L to 10x10\^9/L before the insertion of a CVC in hematologic patients. Approximately 110 CVCs are placed annually in hematological patients at the current institution. Retrospective data will be extracted from the electronic charts and prospective data will be collected continuously. Intervention checkpoints will be put in place to control for grade 3-4 bleeding events: 1. The transfusion trigger will remain at 10x10\^9/L provided that the incidence of post-procedural grade 3-4 bleeding events in patients with a pre-procedural platelet count of 10-49 x10\^9 is less than three in six months, less than four in one year or less than five in two years. 2. The transfusion trigger will be increased to 30x10\^9/L if the incidence of post-procedural grade 3-4 bleeding events in patients with a pre-procedural platelet count of 10-49 x10\^9 is more than two in six months, more than three in one year or more than four in two years.

Rationale: Hemato-oncological patients treated with intensive chemotherapy receive prophylactic platelet transfusions to prevent bleeding events as soon as their platelet counts drop below 10 x109/L. This platelet count based prophylactic transfusion strategy, however, is both inefficient and often not needed. This is reflected in the high percentage of patients with bleeding despite this strategy (43%), and the high percentage of patients who do not bleed without this strategy (50%). Solely platelet count therefore is not a good predictor for bleeding. Identification of new risk factors and confirmation of already suspected risk factors is essential, and should lead to better prediction and prevention of bleeding. Patients with a high risk profile could be given more effective haemostatic treatments including more efficient transfusion strategies. On the other hand one could consider omitting prophylactic transfusions to low risk patients and conditions. Furthermore, additional knowledge about the pathophysiology of bleeding in hemato-oncology patients is needed. Objective: Identify hemato-oncology patients and conditions with a high versus a low bleeding risk and investigate the association of bleeding related biomarkers with bleeding. Study design: Case cohort study, consisting of two parts: epidemiologically research including short questionnaire (part A, eligible for all patients fulfilling inclusion criteria), and additional blood and urine sampling (part B, eligible only for included patients admitted for chemotherapy or stem cell transplantation). Study population: Adult hemato-oncology patients: 1.) who are admitted for treatment and who have or will develop thrombocytopenia and are likely to receive one or more prophylactic platelet transfusions, and 2.) patients who have received such treatments in the last year but are readmitted to the hospital for disease or treatment related adverse events. Intervention: Part A: standard available data collection, short questionnaire. Part B: sampling of blood and urine on top of routinely performed laboratory tests. Main study parameters: Part A: The presence of clinical factors and results of routinely performed laboratory tests compared between bleeding versus non-bleeding patients. Part B: Presence of markers for coagulation-, platelet- and endothelial or vascular dysfunction compared between bleeding versus non-bleeding patients. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Part A: No burden or health risks: comparison of standard available data between bleeding and non-bleeding patients makes this a non-WMO part of the study, since there is no invasive intervention. The 10-15 minutes questionnaire in this respect is not considered as a burden. Part B of the study only applies for a subgroup of the included patients and falls under the scope of the WMO. The intervention is the additional to regularly performed citrate anticoagulated blood sampling (maximum 10 samples of 10-15 cc in 4 weeks), as well as weekly urine sampling. Both are considered a minor burden for participants, and the risk of additional blood sampling at regular sampling moments is negligible. Finally, all BITE-study activities in both study parts will not have any consequences on the treatment or monitoring of patients.