The inverse starving test is not a suitable provocation test for Gilbert's syndrome

<p>Abstract</p> <p>Background</p> <p>Introduction</p> <p>The aim of this study was to evaluate a simple diagnostic test for Gilbert's syndrome (GS), which avoids hospitalization and exposure to toxic test substrates. GS is the most frequent cause of isolated unconjugated hyperbilirubinemia. The nicotinic acid test and the starving test are established approaches to diagnose GS. However, these tests cause considerable side effects or require hospital admission. In single GS patients, we observed rapid serum bilirubin normalization after a standard European lunch (the "inverse starving test").</p> <p>Findings</p> <p>At two consecutive days, 18 profoundly characterized GS patients (7 females, 11 males, median age 34.5 years, range 21–58 years) were investigated with the nicotinic acid test and the inverse starving test. Unconjugated serum bilirubin (UCB) levels were measured before and hourly up to four hours after lunch (median 645 kcal), and after the ingestion of 170 milligrams nicotinic acid, respectively. Patients who consulted their physicians with jaundice were significantly more likely to undergo invasive diagnostic procedures than patients with an incidental finding of elevated UCB, despite UCB levels were indifferent in both groups. Two hours after nicotinic acid ingestion, relative UCB exceeded 1.7 fold the fasting levels (median, range 0.9–2.4 fold, sensitivity 83%). In the inverse starving test, UCB remained almost unchanged three hours after lunch (median 1.0; range: 0.8–1.2 fold). Molecular analysis established the genotype of the TATAA box of the UGT1A1 gene; all patients carried an UGT1A1 promotor polymorphism.</p> <p>Conclusion</p> <p>The inverse starving test is not an appropriate provocation test for patients with suspected GS. The 100% prevalence of the UGT1A1 polymorphism in our cohort underlines that the diagnosis of GS may be substantiated with this simple molecular test in patients with an uncertain diagnosis of GS.</p

Decrease of CA 19–9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer

Chemotherapy with gemcitabine has been shown to be an effective regimen in advanced or metastatic pancreatic cancer with improvement of both quality of life and survival time. The response of the tumour marker CA 19–9 to chemotherapy with gemcitabine was studied in order to find out whether it is related to survival time of patients. Forty-three consecutive patients (median age 61 years, range 39–76 years; 20 males, 23 females) suffering from histologically proven locally advanced or metastatic pancreatic adenocarcinoma and a baseline Karnofsky-index ≥ 60 were treated with gemcitabine in a dose of 1000 mg m−2weekly × 7 followed by 1 week of rest during the first cycle and thereafter 1000 mg m−2weekly × 3 followed by 1 week of rest until progression. In 36 of 43 patients serial measurements of CA 19–9 could be performed. Patients with a decrease of > 20% of the baseline CA 19–9 level after 8 weeks of treatment (n = 25) had a significantly better median survival than patients with a rise or a decrease ≤ 20% (n = 11) (268 vs 110 days;P< 0.001). The response of CA 19–9 was the strongest independent predictor of survival (P< 0.001) in the multivariate analysis. In conclusion, a decrease of CA 19–9 > 20% during the first weeks of chemotherapy with gemcitabine is associated with a better survival of patients with locally advanced or metastatic pancreatic cancer. Serial measurements of CA 19–9 are useful to decide whether further chemotherapy after the first weeks of treatment is indicated. © 2000 Cancer Research Campaig

The Hole in the Stomach

A 57 year old woman was presented to the emergency department with upper abdominal pain and left sided chest discomfort. No cardiac or pulmonary cause could be determined and the patient underwent upper gastrointestinal endoscopy. Inversion of the scope to the fundus and subsequent fluoroscopy revealed a diaphragmatic hernia with a large herniation of the gastric fundus. Immediate laparotomy showed a 3 cm orifice of the diaphragm. The orifice was widened and a partial necrosis of the incarcerated fundus was resected. The patient recovered fully and was discharged 12 days after laparotomy

Early health technology assessment during nonalcoholic steatohepatitis drug development: a two-round, cross-country, multicriteria decision analysis

Background. The assessment of value along the clinical development of new biopharmaceutical compounds is a challenging task. Complex and uncertain evidence has to be analyzed, considering a multitude of value preferences from different stakeholders. Objective. To investigate the use of multicriteria decision analysis (MCDA) to support decision making during drug development while considering payer and health technology assessment (HTA) value concerns, by applying the Advance Value Framework in nonalcoholic steatohepatitis (NASH) and testing for the consistency of the results. Design. A multiattribute value theory methodology was applied and 2 rounds of decision conferences (DCs) were organized in 3 countries (England, France, and Germany), with the participation of national key experts and stakeholders using the MACBETH questioning protocol and algorithm. A total of 51 health care professionals, patient advocates, and methodologists, including (ex-) committee members or assessors from national HTA bodies, participated in 6 DCs in the study countries. Target Population. NASH patients in fibrosis stages F2 to 3 were considered. Interventions. The value of a hypothetical product profile was assessed against 3 compounds under development using their phase 2 results. Outcome Measures. DC participants’ value preferences were elicited involving criteria selection, options scoring, and criteria weighting. Results. Highly consistent valuation rankings were observed in all DCs, always favoring the same compound. Highly consistent rankings of criteria clusters were observed, favoring therapeutic benefit criteria, followed by safety profile and innovation level criteria. Limitations. There was a lack of comparative treatment effects, early evidence on surrogate endpoints was used, and stakeholder representativeness was limited in some DCs. Conclusions. The use of MCDA is promising in supporting early HTA, illustrating high consistency in results across countries and between study rounds

Barrett's esophagus: endoscopic treatments I

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87170/1/j.1749-6632.2011.06049.x.pd

Questions and answers on iron deficiency treatment selection and the use of intravenous iron in routine clinical practice.

Iron deficiency is a common cause of morbidity and can arise as a consequence or complication from many diseases. The use of intravenous iron has increased significantly in the last decade, but concerns remain about indications and administration. Modern intravenous iron preparations can facilitate rapid iron repletion in one or two doses, both for absolute iron deficiency and, in the presence of inflammation, functional iron deficiency, where oral iron therapy is ineffective or has not worked. A multidisciplinary team of experts experienced in iron deficiency undertook a consensus review to support healthcare professionals with practical advice on managing iron deficiency in gastrointestinal, renal and cardiac disease, as well as; pregnancy, heavy menstrual bleeding, and surgery. We explain how intravenous iron may work where oral iron has not. We provide context on how and when intravenous iron should be administered, and informed opinion on potential benefits balanced with potential side-effects. We propose how intravenous iron side-effects can be anticipated in terms of what they may be and when they may occur. The aim of this consensus is to provide a practical basis for educating and preparing staff and patients on when and how iron infusions can be administered safely and efficiently. Key messages Iron deficiency treatment selection is driven by several factors, including the presence of inflammation, the time available for iron replenishment, and the anticipated risk of side-effects or intolerance. Intravenous iron preparations are indicated for the treatment of iron deficiency when oral preparations are ineffective or cannot be used, and therefore have applicability in a wide range of clinical contexts, including chronic inflammatory conditions, perioperative settings, and disorders associated with chronic blood loss. Adverse events occurring with intravenous iron can be anticipated according to when they typically occur, which provides a basis for educating and preparing staff and patients on how iron infusions can be administered safely and efficiently

ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study.

Non-adherence to medication is a challenging problem in daily clinical practice. To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. The DACH cohort had significantly different levels of adherence depending on the IMID (P &lt; 0.05) and the type of therapy (P &lt; 0.05). Based on the significant influence of concerns on treatment adherence (P &lt; 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups

Scoping review of the literature on shoulder impairments and disability after neck dissection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102688/1/hed23243.pd

Differences in bleeding behavior after endoscopic band ligation: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Endoscopic band ligation (EBL) is generally accepted as the treatment of choice for bleeding from esophageal varices. It is also used for secondary prophylaxis of esophageal variceal hemorrhage. However, there is no data or guidelines concerning endoscopic control of ligation ulcers. We conducted a retrospective study of EBL procedures analyzing bleeding complications after EBL.</p> <p>Methods</p> <p>We retrospectively analyzed data from patients who underwent EBL. We analyzed several data points, including indication for the procedure, bleeding events and the time interval between EBL and bleeding.</p> <p>Results</p> <p>255 patients and 387 ligation sessions were included in the analysis. We observed an overall bleeding rate after EBL of 7.8%. Bleeding events after elective treatment (3.9%) were significantly lower than those after treatment for acute variceal hemorrhage (12.1%). The number of bleeding events from ligation ulcers and variceal rebleeding was 14 and 15, respectively. The bleeding rate from the ligation site in the group who underwent emergency ligation was 7.1% and 0.5% in the group who underwent elective ligation. Incidence of variceal rebleeding did not vary significantly. Seventy-five percent of all bleeding episodes after elective treatment occurred within four days after EBL. 20/22 of bleeding events after emergency ligation occured within 11 days after treatment. Elective EBL has a lower risk of bleeding from treatment-induced ulceration than emergency ligation.</p> <p>Conclusions</p> <p>Patients who underwent EBL for treatment of acute variceal bleeding should be kept under medical surveillance for 11 days. After elective EBL, it may be reasonable to restrict the period of surveillance to four days or even perform the procedure in an out-patient setting.</p