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D M Jensen

Publications and source records attributed to D M Jensen.

At least 19 recordsLinked to original sources

Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin.

We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon-alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities.

Adult↗

A comparison of hepatitis C treatment and outcomes at academic, private and Veterans' Affairs treatment centres.

BACKGROUND: Currently, there is a lack of published data examining hepatitis C treatment practices in different care settings. AIM: To provide data describing treatment practices for patients with hepatitis C virus infection in actual clinical practice, and to examine clinical outcomes in patients treated with interferon alpha-2b/ribavirin combination therapy in academically affiliated centres, private treatment centres and Veterans' Affairs treatment centres. METHODS: This multi-centre, retrospective, cohort study of 231 patients examined hepatitis C virus treatment practices in patients receiving interferon alpha-2b from January 1997 to May 2001 and explored outcomes in academically affiliated, private and Veterans' Affairs centres. RESULTS: Differences in treatment practice and use of diagnostic procedures were found. Genotype testing was under-utilized in non-academic sites (academic centres, 79.2%; private centres, 33.7%; Veterans' Affairs centres, 35.9%; P<0.001). Liver biopsies were performed less often in private sites (academic centres, 95.8%; private centres, 80.0%; Veterans' Affairs centres, 92.2%; P<0.01). End-of-treatment viral response (academic centres, 40.0%; private centres, 31.3%; Veterans' Affairs centres, 17.2%; P<0.05) was lower than that found in published trial data. Multivariate analysis revealed genotype 1 as the single significant predictor of treatment failure (P<0.01). CONCLUSIONS: Outside of the academic setting, there is significantly less diagnostic work-up performed prior to the initiation of hepatitis C virus therapy. This suggests a need for a standardization of care across treatment settings.

Academic Medical Centers↗

Endoscopic treatment outcomes in watermelon stomach patients with and without portal hypertension.

BACKGROUND AND STUDY AIMS: Watermelon stomach is a source of recurrent gastrointestinal hemorrhage and anemia. The aims of this study were to describe the endoscopic appearance and treatment outcomes in watermelon stomach patients with and without portal hypertension. PATIENTS AND METHODS: All patients with watermelon stomach enrolled in a hemostasis research group's prospective studies from 1991 to 1999 were identified. Investigators collected data using standardized forms. Comparisons were made using the chi-squared test, Wilcoxon rank-sum test, and Wilcoxon signed-rank test. RESULTS: Twenty-six of 744 (4 %) consecutively enrolled patients with nonvariceal upper gastrointestinal hemorrhage had watermelon stomach as the cause. Eight of these 26 patients (31 %) also had portal hypertension. These patients had diffuse antral angiomas, as opposed to the classic linear arrays seen in those without portal hypertension. The demographic data and clinical presentations of the two groups were otherwise similar. Palliative endoscopic treatment was associated with a significant rise in hematocrit and a decrease in the need for blood transfusion or hospitalization in watermelon stomach patients with and without portal hypertension. CONCLUSIONS: Watermelon stomach patients with and without portal hypertension had similar clinical presentations. The endoscopic findings differed in that those with portal hypertension had more diffuse gastric angiomas. Bleeding was effectively palliated by endoscopic treatment, regardless of the presence of portal hypertension.

Aged↗

Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C.

BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-naïve adults with CHC.

Antiviral Agents↗

First phase hepatitis c viral kinetics in previous nonresponders patients.

A large proportion of patients fails to respond to treatment for hepatitis C. Initiation of interferon therapy is associated with a rapid first phase decline in viremia, reflecting inhibition of viral production or release from infected cells. We characterized first phase viral kinetics in previous nonresponder patients and compared the antiviral efficacy of interferon in nonresponders to that observed in naive patients. Twenty nonresponders with genotype 1 infection were evaluated. Ten received a single 15 mcg dose of interferon alfacon-1 and ten were given a 30 mcg dose. Viral kinetic data from previously untreated historical control patients with genotype 1 infection who received 9 mcg (n = 12) or 15 mcg (n = 13) of interferon alfacon-1 provided a basis for comparison. Antiviral efficacy was evaluated by calculating the reduction in HCV RNA levels during the first 24 h after interferon administration (log effectiveness). Hepatitis C virus levels decreased exponentially in previous nonresponder patients. Non-responders treated with 30 mcg of interferon alfacon-1 exhibited a greater log drop than non-responders receiving 15 mcg (P = 0.01). The log effectiveness of 15 mcg of interferon alfacon-1 in nonresponders was similar to 9 mcg in naives and was significantly < 15 mcg (P = 0.04) in naïve patients. The 30 mcg dose provided similar log effectiveness in nonresponders compared with 15 mcg in naive patients and exceeded the log effectiveness of 9 mcg in previously untreated patients (P = 0.035). Nonresponders who had greater than a 50% decrease in HCV RNA level from baseline at the end of previous treatment had a larger reduction in viral load at 24 h compared with those who had not achieved that level of response with prior therapy (P = 0.04). In conclusion, the log effectiveness of interferon was lower in nonresponders compared with treatment naive patients. The difference in antiviral effectiveness in previous nonresponders was overcome by higher interferon doses.

Adult↗

Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women.

AIMS: To study if established diagnostic threshold values for gestational diabetes based on a 75-g, 2-h oral glucose tolerance test can be supported by maternal and perinatal outcomes. METHODS: Historical cohort study of 3260 pregnant women examined for gestational diabetes on the basis of risk indicators. Information on oral glucose tolerance test results and clinical outcomes were collected from medical records. RESULTS: There was an increased risk of delivering a macrosomic infant in women with 2-h capillary blood glucose of 7.8-8.9 mmol/l compared with women with 2-h glucose < 7.8 mmol/l. Despite treatment, 2-h glucose of 9.0-11.0 mmol/l and > or = 11.1 mmol/l were both associated with increased rates of macrosomia, spontaneous preterm delivery, hypertensive complications, and neonatal hypoglycaemia. Adverse outcomes tended to be more frequent in women with 2-h glucose > or = 11.1 mmol/l than in women with 2-h glucose of 9.0-11.0 mmol/l. CONCLUSIONS: The risk for several maternal and perinatal complications increased with the diagnostic threshold for 2-h glucose. Large-scale blinded studies are needed to clarify the question of a clinically meaningful diagnosis of gestational diabetes mellitus. Until these results are available, a 2-h threshold level of 9.0 mmol/l after a 75-g oral glucose tolerance test seems acceptable.

Adult↗

Push enteroscopy for recurrent gastrointestinal hemorrhage due to jejunal anastomotic varices: a case report and review of the literature.

Small-bowel anastomotic and adhesion-related varices can form within adhesions in the setting of mesenteric venous hypertension, arising from either mesenteric venous obstruction or portal hypertension. In evaluating gastrointestinal bleeding in patients who have had previous abdominal surgery and mesenteric venous hypertension, small-bowel anastomotic varices and adhesion-related varices should be considered. For patients with recurrent, severe melena or hematochezia, we recommend that the initial diagnostic work-up should include push enteroscopy in patients with previous small-bowel surgery. Retrograde ileoscopy should also be considered these patients to look for distal small-bowel varices. Potentially, such small-bowel varices can be identified by wireless capsule endoscopy. We report a case of recurrent gastrointestinal bleeding caused by jejunal anastomotic varices which were secondary to superior mesenteric vein occlusion following an abdominal gunshot wound. Although the treatment of segmental varices has been surgical resection, for patients with overt systemic portal hypertension, a transjugular intrahepatic portal-systemic shunt or a decompressive shunting procedure are recommended.

Adult↗

Physicians' preference values for hepatitis C health states and antiviral therapy: a survey.

BACKGROUND: Physicians' perspectives regarding hepatitis C shape their approach to patient management. We used utility analysis to evaluate physicians' perceptions of hepatitis C-related health states (HS) and their threshold to recommend treatment. METHODS: A written questionnaire was administered to practicing physicians. They were asked to rate hepatitis C health states on a visual analog scale ranging from 0% (death) to 100% (health without hepatitis C). Physicians then judged quality of life associated with the side effects of antiviral therapy for hepatitis C and indicated the sustained virological response rate that they would require to recommend treatment. RESULTS: One hundred and thirteen physicians from five states were included. Median utility ratings for hepatitis C health states declined significantly with increasing severity of symptoms: HS1-No Symptoms, No Cirrhosis (88%; 12% reduction from good health), HS2-Mild Symptoms, No Cirrhosis (66%), HS3-Moderate Symptoms, No Cirrhosis (49%), HS4-Mild Symptoms, Cirrhosis (40%), HS5-Severe Symptoms, Cirrhosis (18%) [p < 0.001]. The median rating for life with side effects of antiviral therapy was 47%, suggesting a 53% reduction from good health. That was similar to the utility value for HS3-Moderate Symptoms, No Cirrhosis. The median threshold value for recommending treatment was a sustained response rate of 60%. CONCLUSIONS: 1) Physicians' utility ratings for hepatitis C health states were inversely related to the severity of disease manifestations described. 2) Physicians viewed side effects of therapy unfavorably and indicated that on average, they would require a 60% sustained response rate before recommending treatment, which far exceeds the efficacy of current antiviral therapy for hepatitis C in the majority of patients.

Antiviral Agents↗

Daily interferon therapy for hepatitis C virus infection in liver transplant recipients.

BACKGROUND: Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients. Standard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients. METHODS: Twelve patients, at least 7 months posttransplant, with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were randomized to interferon-alpha2a, 3 mU daily for 12 months (n=8) or no treatment (n=4). The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level, quasispecies evolution, and liver histology were studied. RESULTS: Treated patients had an improvement in histological activity index at the end of therapy relative to controls (median reduction of 2 versus median increase of 1.5) (P=0.04). Four treated patients had a virological response (all bDNA negative, one qualitative polymerase chain reaction negative) compared with none of the untreated patients. Only two of six treated patients tested had evidence of quasispecies diversification on therapy. Seven of eight patients in the treatment group required dose reduction for fatigue and/or depression. They tolerated 1.5 mU of interferon-alpha2a daily. Two treated patients developed graft dysfunction, one of who had histological evidence of rejection and subsequent graft loss. CONCLUSIONS: Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases. These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant.

Adult↗

Clots and spots on ulcers: why and how to treat.

The clinical indication for urgent endoscopy with combined diagnosis and treatment is bleeding severe enough to warrant urgent medical attention. Stigmata of ulcer hemorrhage are utilized as a guide to endoscopic therapy. Active arterial bleeding, nonbleeding visible vessels, and adherent nonbleeding clots are always treated endoscopically. In randomized trials, patients with these "major stigmata" had better outcomes from endoscopic therapies than with medical therapies alone. Flat spots, gray or black sloughs, and clean ulcer bases are not treated endoscopically, since medical therapy alone affords good outcome. The current recommendation is to treat major stigmata of hemorrhage endoscopically for the initial bleeding episode and a second time for rebleeding before considering ulcer surgery. Clinical presentation and comorbidity and the endoscopic appearance of the ulcer (i.e., stigmata of hemorrhage) of patients with UGI bleeding are used to determine the subsequent level of care (e.g., discharge or ward or intensive care).

Endoscopy, Gastrointestinal↗

Treatment of hepatitis C virus and HIV co-infections.

Hepatitis C coinfection is common in patients with HIV, particularly in injection-drug users. Hepatitis C virus levels tend to be higher in coinfected patients, and histologic progression is more rapid than in patients with HCV alone. The efficacy of interferon monotherapy in HIV patients with an adequate CD4 cell count is comparable to that observed in patients without HIV. The combination of interferon plus ribavirin and pegylated interferon will further improve response rates. Interferon therapy is associated with leukopenia and a decrease in absolute CD4 cell count. Some concern remains that ribavirin might reduce the activity of pyrimidine analogues such as zidovudine and stavudine, and HIV-RNA levels should be followed when these medications are given concurrently. It is hoped that in time, new drug development will make the multiple-drug therapeutic strategy that has been highly successful in the management of HIV feasible for the treatment of HCV.

Antiviral Agents↗

Adult living donor liver transplantation: Preferences about donation outside the medical community.

An increasing number of transplant centers are performing adult living donor liver transplantation (LDLT). We evaluated peoples' perspectives on possible outcomes of living donation, thresholds for donating, and views regarding the donation process. One hundred fifty people were surveyed; half were from a medical care group serving an indigent population and half were from a private clinic. Preferences about outcomes of adult living donation were ranked and quantified on a visual analogue scale. Thresholds for donation to a loved one were quantified. Sixty percent of the respondents suggested they would prefer to donate and die and have the transplant recipient live rather than forego donation and have the potential transplant recipient die of liver failure. Participants' stated threshold for living donation was a median survival for themselves of only 79%. They would require that their loved one have a median survival of 55% with transplantation before they would agree to donate. Respondents from the medical care group reported higher survival thresholds for themselves and the transplant recipient, and race was the most statistically significant predictor of those thresholds. Sex was more predictive of threshold probabilities from the private clinic. Eighty-one percent of the respondents believed that the potential donor, not a physician, should have the final say regarding candidacy for living donation. In conclusion, the findings of this survey support the use of adult LDLT. Most respondents were willing to accept mortality rates that far exceed the estimated risk of donation and favored outcomes in which a loved one was saved.

Adult↗

Clinical impact of mild carbohydrate intolerance in pregnancy: a study of 2904 nondiabetic Danish women with risk factors for gestational diabetes mellitus.

OBJECTIVE: The objective was to study the clinical impact of mild carbohydrate intolerance in pregnant women with risk factors for gestational diabetes mellitus. STUDY DESIGN: This was a historical cohort study of 2904 pregnant women examined for gestational diabetes on the basis of risk factors. Information on oral glucose tolerance test results and clinical outcomes was collected from laboratory charts and medical records. RESULTS: The following outcomes increased significantly with increasing glucose values during the oral glucose tolerance test: shoulder dystocia, macrosomia, emergency cesarean section, assisted delivery, hypertension, and induction of labor. However, when corrections were made for other risk factors, hypertension and induction of labor were only marginally associated with glucose levels. CONCLUSION: In a group of nondiabetic pregnant women with risk factors for gestational diabetes, there was a graded increase in the frequency of shoulder dystocia and other maternal-fetal complications with increasing glucose levels during an oral glucose tolerance test.

Adult↗

An analysis of acute changes in interleukin-6 levels after treatment of hepatitis C with consensus interferon.

Cytokine production has been implicated in the antiviral response to interferon-alpha (IFN-alpha) in hepatitis C and in the development of IFN-alpha-related side effects. We characterized acute changes in serum cytokine levels following administration of a single dose of consensus IFN (IFN-con1) and during continuous treatment of chronic hepatitis C patients. Serum samples were collected at baseline, at multiple times early after IFN administration, and weekly thereafter. Viral RNA titers were assessed by RT-PCR, and viral kinetics were followed. ELISA assays were used to measure IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, and IL-16. Serum cytokine levels were low at baseline. IL-6 was detected in patients with hepatitis C but not in healthy control subjects by either ELISA or RT-PCR, indicating that low levels of circulating IL-6 were associated with hepatitis C infection. None of the cytokines measured increased significantly after IFN administration except for IL-6. IL-6 levels rose rapidly, peaked at 6-15 h in a dose-dependent manner, and returned to baseline by 48 h in both patients receiving a single dose of IFN and those receiving continuous treatment. This was confirmed by RT-PCR. Pretreatment IL-6 levels were directly correlated with area under the curve (AUC) for IL-6 during the 24 h after IFN dosing (r = 0.611, p = 0.007). Viral titers decreased within 24-48 h after a single dose of IFN-con1. Changes in hepatitis C RNA titers were not significantly associated with pretreatment IL-6 levels or with changes in IL-6 levels. In conclusion, (1) baseline serum cytokine levels, except for IL-6, were low or within the normal range in patients with hepatitis C, (2) IL-6 levels were detected in some patients with hepatitis C before treatment but not in healthy controls, (3) IL-6 levels increased acutely after a single dose of IFN-alpha, and IL-6 induction was related to baseline IL-6 level, and (4) changes in IL-6 levels did not correlate with the early virologic response to IFN.

Antiviral Agents↗

Patients' values for health states associated with hepatitis C and physicians' estimates of those values.

OBJECTIVES: Hepatitis C is the leading cause of chronic hepatitis in the United States. Little information is available regarding how persons with hepatitis C view health with their disease. We studied patients' perceptions about the value of hepatitis C health states and evaluated whether physicians understand their patients' perspectives about this disease. METHODS: A total of 50 consecutive persons with hepatitis C were surveyed when they presented as new patients to a hepatology practice. Subjects provided utility assessments (preference values) for five hepatitis C health states and for treatment side effects. They also stated their threshold for accepting antiviral therapy. Five hepatologists used the same scales to estimate their patients' responses. RESULTS: On average, patients believed that hepatitis C without symptoms was associated with an 11% reduction in preference value from that of life without infection, and the most serious condition (severe symptoms, cirrhosis) was believed to carry a 73% decrement. Patients judged the side effects of antiviral therapy quite unfavorably, and their median stated threshold for accepting treatment was a cure rate of 80%. Physicians' estimates were not significantly associated with patients' preference values for hepatitis C health states, treatment side effects, or with patients' thresholds for accepting treatment. In multivariate analysis, patients' stated thresholds for taking treatment were significantly associated with their decisions regarding therapy (beta = -2.72+/-1.21, p = 0.025). CONCLUSIONS: There was little agreement between patients' preference values about hepatitis C and their physicians' estimates of those values. Utility analysis could facilitate shared decision making about hepatitis C.

Adult↗

[The clinical impact of gestational diabetes mellitus].

In Denmark, gestational diabetes mellitus (GDM) develops in about 2% of all pregnant women. The discussion of GDM is complicated by lack of consensus regarding screening methods, diagnosis and treatment. Observational studies indicate that untreated GDM is associated with an increased risk of maternal and perinatal morbidity, and that the offspring of GDM mothers tend to be at increased risk of developing diabetes and adiposity as a result of an abnormal intrauterine environment. Several follow-up studies have shown that women with previous GDM run a considerable risk of developing diabetes (especially type 2 diabetes) later in life. Intervention strategies for this high risk group are suggested.

Diabetes, Gestational↗

Urgent colonoscopy for the diagnosis and treatment of severe diverticular hemorrhage.

BACKGROUND: Although endoscopy is often used to diagnose and treat acute upper gastrointestinal bleeding, its role in the management of diverticulosis and lower gastrointestinal bleeding is uncertain. METHODS: We studied the role of urgent colonoscopy in the diagnosis and treatment of 121 patients with severe hematochezia and diverticulosis. All patients were hospitalized, received blood transfusions as needed, and received a purge to rid the colon of clots, stool, and blood. Colonoscopy was performed within 6 to 12 hours after hospitalization or the diagnosis of hematochezia. Among the first 73 patients, those with continued diverticular bleeding underwent hemicolectomy. For the subsequent 48 patients, those requiring treatment received therapy, such as epinephrine injections or bipolar coagulation, through the colonoscope. RESULTS: Of the first 73 patients, 17 (23 percent) had definite signs of diverticular hemorrhage (active bleeding in 6, nonbleeding visible vessels in 4, and adherent clots in 7). Nine of the 17 had additional bleeding after colonoscopy, and 6 of these required hemicolectomy. Of the subsequent 48 patients, 10 (21 percent) had definite signs of diverticular hemorrhage (active bleeding in 5, nonbleeding visible vessels in 2, and adherent clots in 3). An additional 14 patients in this group (29 percent) were presumed to have diverticular bleeding because although they had no stigmata of diverticular hemorrhage, no other source of bleeding was identified. The other 24 patients (50 percent) had other identified sources of bleeding. All 10 patients with definite diverticular hemorrhage were treated endoscopically; none had recurrent bleeding or required surgery. CONCLUSIONS: Among patients with severe hematochezia and diverticulosis, at least one fifth have definite diverticular hemorrhage. Colonoscopic treatment of such patients with epinephrine injections, bipolar coagulation, or both may prevent recurrent bleeding and decrease the need for surgery.

Acute Disease↗