Thoracic impedance pneumography in propofol-sedated patients undergoing percutaneous endoscopic gastrostomy (PEG) placement in gastrointestinal endoscopy: A prospective, randomized trial.

STUDY OBJECTIVE: To assess the efficacy of an ECG-based method called thoracic impedance pneumography to reduce hypoxic events in endoscopy. DESIGN: This was a single center, 1:1 randomized controlled trial. SETTING: The trial was conducted during the placement of percutaneous endoscopic gastrostomy (PEG). PATIENTS: 173 patients who underwent PEG placement were enrolled in the present trial. Indication was oncological in most patients (89%). 58% of patients were ASA class II and 42% of patients ASA class III. INTERVENTIONS: Patients were randomized in the standard monitoring group (SM) with pulse oximetry and automatic blood pressure measurement or in the intervention group with additional thoracic impedance pneumography (TIM). Sedation was performed with propofol by gastroenterologists or trained nurses. MEASUREMENTS: Hypoxic episodes defined as SpO2 < 90% for >15 s were the primary endpoint. Secondary endpoints were minimal SpO2, apnea >10s/>30s and incurred costs. MAIN RESULTS: Additional use of thoracic impedance pneumography reduced hypoxic episodes (TIM: 31% vs SM: 49%; p = 0.016; OR 0.47; NNT 5.6) and elevated minimal SpO2 per procedure (TIM: 90.0% ± 8.9; SM: 84.0% ± 17.6; p = 0.007) significantly. Apnea events >10s and > 30s were significantly more often detected in TIM (43%; 7%) compared to SM (1%; 0%; p < 0.001; p = 0.014) resulting in a time advantage of 17 s before the occurrence of hypoxic events. As a result, adjustments of oxygen flow were significantly more often necessary in SM than in TIM (p = 0.034) and assisted ventilation was less often needed in TIM (2%) compared with SM (9%; p = 0.053). Calculated costs for the additional use of thoracic impedance pneumography were 0.13$ (0.12 €/0.11 £) per procedure. CONCLUSIONS: Additional thoracic impedance pneumography reduced the quantity and extent of hypoxic events with less need of assisted ventilation. Supplemental costs per procedure were negligible. KEY WORDS: thoracic impedance pneumography, capnography, sedation, monitoring, gastrointestinal endoscopy, percutaneous endoscopic gastrostomy.

Individual invitation letters lead to significant increase in attendance for screening colonoscopies: Results of a pilot study in Northern Hesse, Germany.

BACKGROUND: Colorectal cancer (CRC) is the second most common cancer in Germany. Screening colonoscopies are considered an effective tool for early detection and prevention of CRC and are recommended in Germany for citizens over the age of 55. To increase the participation rate for screening colonoscopies, an invitation procedure was initiated in parts of Germany for patients between the ages of 55 and 75 who had never undergone a screening colonoscopy before. METHODS: We examined the number of participating patients before, during, and after the invitation procedure and compared the number of the participating patients who received a cover letter with the participating patients from the control group. Additionally, we classified the findings of the colonoscopies including CRC, advanced adenomas, and polyps. RESULTS: During the invitation period, the participation rate of the invitation group increased from 220 patients to 531 patients compared to 1256 to 1693 in the control group. The increase was significantly greater in patients with cover letters (+141% vs.+35%, p < 0.0001). Also, significantly more polyps and adenomas were found in patients from the invitation letter group (254 (+102%) vs. 679 (-9%), p < 0.0001). CONCLUSIONS: Our study clearly indicates that personal invitation letters are an effective measure to increase overall participation rates in screening colonoscopies.

[Gender differences and inflammatory bowel disease]. / Geschlechtsspezifische Unterschiede in der Behandlungsrealität von Patientinnen und Patienten mit chronisch-entzündlichen Darmerkrankungen (CED).

This review focuses on the gender and sex dimorphic disease profile and treatment reality of patients suffering from inflammatory bowel diseases (IBD). It provides an overview of gender-specific differences in the disease course, medical and surgical therapy as well as psychosocial aspects of IBD.

[Integrated management of patients with chronic inflammatory bowel disease in the Rhine-Main Region: results of the first integrated health-care project IBD in Germany]. / Integrierte Versorgung von Patienten mit chronisch-entzündlichen Darmerkrankungen im Rhein-Main-Gebiet: Ergebnisse der ersten integrierten Versorgung CED in Deutschland.

INTRODUCTION: In our previous studies investigating the drug therapy in patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region, Germany, we detected serious discrepancies between treatment reality and treatment guidelines. Consecutively, patient outcome in this cohort was compromised. Following this pilot project a network between primary deliverers of care for IBD patients and one large health-care insurance company [BKK Taunus (Gesundheit), the second largest insurance company in Hessen, Germany] was established. PATIENTS AND METHODS: An analysis of treatment and socioeconomic data from 220 IBD patients (Crohn's disease - CD = 96, ulcerative colitis - UC = 124) entering the integrative health-care programme between 1.1.-30.9.2009 was performed. RESULTS: Remission rates for CD and UC in the integrated health-care programme could be improved from 60 - 73 % (CD) and from 61 - 79 % (UC). Guideline-conform treatment was observed in 81 % of patients with CD and 85 % with UC, respectively. Although medication costs increased, total costs could be cut by 162 304.- €, as secondary costs for hospitalisation and days off work could be reduced. CONCLUSION: The study shows that networking of deliverers of care for IBD patients with health insurances provides an excellent possibility to optimise medical treatment and can cut down costs significantly.

Female patients suffering from inflammatory bowel diseases are treated less frequently with immunosuppressive medication and have a higher disease activity: a subgroup analysis of a large multi-centre, prospective, internet-based study.

BACKGROUND: The introduction of immunosuppressants and biologic agents has led to active debate and research about optimal therapeutic strategies considering risk factors and predictors of clinical outcome in inflammatory bowel disease (IBD). Data about gender-specific treatment differences and risk factors is lacking for IBD. The aim of the present study was to evaluate gender-related differences in the treatment of a distinct IBD patient population treated in the Rhein-Main region, Germany. METHODS: Data about past medical history, disease status and medical treatment of 986 outpatients treated in ten gastroenterological practices and three hospitals were collected from November 1st 2005-July 31st 2007 and analyzed with regard to gender-related differences in therapy and disease management. RESULTS: With the exception of an extended disease duration in women, no significant gender-related differences in demographic and clinical characteristics were observed. Men showed a significantly higher remission rate than women (p=0.025), while women received significantly less immunosuppressive medication compared to men (p=0.011). In addition, treatment with immunosuppressants was not different in women with child-bearing potential compared to menopausal women. CONCLUSION: Our investigation demonstrates for the first time gender-specific differences in the therapeutic management in a large cohort of IBD patients.

[Are there gender-related differences in the therapeutic management of patients suffering from inflammatory bowel disease? Subgroup analysis of a prospective multicentre online-based trial]. / Gibt es geschlechtsspezifische Behandlungsunterschiede bei Patienten mit chronisch entzündlichen Darmerkrankungen? Eine Subgruppenanalyse einer prospektiven, multizentrischen, online-basierten Studie.

INTRODUCTION: The most frequently prescribed medications for patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region of Germany are aminosalicylates and corticosteroids irrespective of the disease activity. In contrast, immunomodulators only play a marginal role. As anti-TNF therapy is very costly, it is prescribed in outpatient services of hospitals rather than in gastroenterological practices. AIM: The aim of this study was to evaluate possible gender-related differences in the therapeutic management of IBD patients treated in the Rhein-Main region of Germany. METHODS: Data records about past medical history, disease status, laboratory values and medical treatment of outpatients of 10 gastroenterological practices and 3 hospitals were collected from November 1st 2005 to July 31st 2007 and analysed with regard to gender-related differences in therapy and disease management. RESULTS: Overall, no statistically significant difference in gender-specific medical treatment could be observed in the study cohort. However, detailed analyses revealed, that 1. women suffering from IBD, who are treated in outpatient services of hospitals, are more often under immunosuppressants, irrespective of disease activity, 2. in gastroenterological practices less than 3 % of patients are prescribed any immunosuppressive therapy (vs. 17 % [men] und 42 % [women] in hospital outpatient services), and 3. anti-TNF therapy is applied more frequently in men as compared to women in hospital outpatient services in both remission and active disease. CONCLUSION: This study discloses the gender-specific differences in the therapeutic management of IBD patients in a congested urban area in Germany. Further studies are required to confirm the tendencies detected.

Amino acids - Guidelines on Parenteral Nutrition, Chapter 4.

Protein catabolism should be reduced and protein synthesis promoted with parenteral nutrion (PN). Amino acid (AA) solutions should always be infused with PN. Standard AA solutions are generally used, whereas specially adapted AA solutions may be required in certain conditions such as severe disorders of AA utilisation or in inborn errors of AA metabolism. An AA intake of 0.8 g/kg/day is generally recommended for adult patients with a normal metabolism, which may be increased to 1.2-1.5 g/kg/day, or to 2.0 or 2.5 g/kg/day in exceptional cases. Sufficient non-nitrogen energy sources should be added in order to assure adequate utilisation of AA. A nitrogen calorie ratio of 1:130 to 1:170 (g N/kcal) or 1:21 to 1:27 (g AA/kcal) is recommended under normal metabolic conditions. In critically ill patients glutamine should be administered parenterally if indicated in the form of peptides, for example 0.3-0.4 g glutamine dipeptide/kg body weight/day (=0.2-0.26 g glutamine/kg body weight/day). No recommendation can be made for glutamine supplementation in PN for patients with acute pancreatitis or after bone marrow transplantation (BMT), and in newborns. The application of arginine is currently not warranted as a supplement in PN in adults. N-acetyl AA are only of limited use as alternative AA sources. There is currently no indication for use of AA solutions with an increased content of glycine, branched-chain AAs (BCAA) and ornithine-alpha-ketoglutarate (OKG) in all patients receiving PN. AA solutions with an increased proportion of BCAA are recommended in the treatment of hepatic encephalopathy (III-IV).

Health care and cost of medication for inflammatory bowel disease in the Rhein-Main region, Germany: a multicenter, prospective, internet-based study.

BACKGROUND: Studies examining the treatment reality of IBD patients in Germany have been limited, as networking among deliverers of care and reliable documentation of medical, demographic, and economic data are lacking. The aim of the present study was to establish an internet-based treatment registry in order to evaluate treatment of IBD patients in Germany. METHODS: Between November 1(st), 2005, and January 31, 2007, 1024 outpatients with prevalent IBD from 10 gastroenterological private practices and 3 hospitals (UC = 439, CD = 567, ID = 18) were enrolled in the study. An internet-based registry was established that included data about medical history, disease status, diagnostic procedures, laboratory test results, and medical treatment. Data for private practices and hospitals were pooled in order to compare treatment habits between these types of medical facilities. The cost of medication was determined according to medications prescribed. RESULTS: There was no significant difference between the 2 patient groups in demographic and clinical characteristics. Marked differences were observed in medical treatment. The most frequently prescribed medications in the private practices for patients in remission and those with active disease were aminosalicylates and corticosteroids. Immunomodulators played a marginal role. In contrast, in the hospitals azathioprine/6-MP was predominantly used for the maintenance of remission. Patients with fistulizing CD were treated with infliximab. The mean annual cost of medications was 1826 +/- 1331euro/patient (median 1353euro) in the private practices and 1849euro +/- 2897euro/patient (median 960euro) at the University Hospital. CONCLUSIONS: The registry provides the first detailed data about the reality of treatment of IBD patients in Germany and reveals the necessity for networking among attending physicians in order to implement guidelines-conformed treatment.

A study for the evaluation of safety and tolerability of intravenous high-dose iron sucrose in patients with iron deficiency anemia due to gastrointestinal bleeding.

INTRODUCTION: The provision of adequate iron to support erythropoiesis in iron deficient patients is a time-consuming process which may present compliance problems for patients in the outpatient setting. The aim of the present study was to evaluate the safety and tolerability of intravenous high-dose iron sucrose therapy specifically in patients with iron deficiency anemia (IDA) due to gastrointestinal blood loss. METHODS: A single dose of iron sucrose of 7 mg iron/kg body weight (not exceeding 500 mg) was infused over 3.5 hours in 31 consecutive patients with IDA due to gastrointestinal blood loss. Safety and tolerability of the therapy was assessed by the occurrence of adverse events under therapy and up to one week after completion of the study. Further examinations comprised vital parameters, ECG, and clinical chemistry including iron indices. RESULTS: A total of 14 adverse events were observed in 10 patients, of which two adverse events in two patients were considered as being definitely related to drug administration. None of the patients had to be withdrawn from therapy. Significant changes in vital parameters and ECG during therapy and follow-up were not observed and clinical chemistry remained unchanged. DISCUSSION: A single intravenous high-dose iron sucrose therapy in patients with IDA due to gastrointestinal blood loss appears to be safe and therefore is a therapeutic option which may save time and improve patient compliance.

Combining infliximab and methotrexate in fistulizing Crohn's disease resistant or intolerant to azathioprine.

BACKGROUND: Crohn's disease is complicated by fistulas in 20-40% of patients at some time during the course of their illness. Azathioprine has been reported to heal fistulas in 30-40% of cases. Long-lasting effects by the anti-tumour necrosis factor-alpha antibody infliximab most often require repeated infusions. Methotrexate has been shown to be an effective drug in maintaining remission in Crohn's disease. AIM: To evaluate the combination of infliximab and methotrexate as therapy for fistulas in patients with Crohn's disease. METHODS: Twelve consecutive patients (mean age, 29.5 years) with fistulizing Crohn's disease resistant or intolerant to azathioprine were followed prospectively. Patients received three infusions of infliximab (5 mg/kg) and long-term methotrexate (20 mg/week). Therapy success was defined as sustained closure of fistulas > or = 6 months after fistula closure. RESULTS: In four of the 12 patients, complete closure of fistulas that persisted for > or = 6 months (median follow-up, 13.25 months) was observed. In three further patients, a partial response was noted. In five patients, persistent therapy success could not be achieved or therapy had to be stopped due to side-effects. CONCLUSIONS: A combination of infliximab with long-term methotrexate may be a promising concept in fistulizing Crohn's disease. Our data indicate the need for larger controlled trials.

[Pathogenesis and treatment of pruritus in patients with cholestasis]. / Pathophysiologie und Therapie von Pruritus bei cholestatischen Leberkrankheiten.

The pathogenesis of initiating the pruritus in patients with cholestasis is still not completely understood. One hypothesis is, that the cause for initiating the pruritus in patients with cholestasis is the activation of nerves in the skin. The activating substances are unknown, probably they are substances who accumulate in patients with cholestasis. Therefore one of the conventional approaches to treat pruritus is to remove pruritogenic substances from the body. Examples of this approach include the administration of anion exchange resins as cholestyramine or the administration of hepatic enzyme-inducing drugs such as rifampicin or phenobarbital. None of these drugs has been conclusively shown to be efficacious. A new hypothesis is the association of pruritus with altered central neurotransmission. Altered opioid concentrations probably play a central role in the pathogenesis of pruritus. This hypothesis is corroborate by the possibility of treating pruritus in patients with cholestasis with opiate antagonists such as naloxone or nalmefene. The treatment with ondansetron may also have effects on the pruritus of patients with cholestasis. A completely new treatment strategy is the application of dronabinol (r-9-tetrahydrocannabinol).

Na+/HCO3- cotransport in normal and cystic fibrosis intestine.

In a search for the HCO(3)(-) supply mechanisms to the enterocyte we cloned and sequenced an intestinal subtype of the Na(+)HCO(3)(-) cotransporter isoform I (dNBC1), which turned out to be identical to the pancreatic NBC1 subtype (pNBC1). Within the intestine, we found particularly high NBC1 expression levels in the duodenum and proximal colon. Experiments with stripped rabbit duodenum in Ussing-chambers revealed that Na(+)HCO(3)(-) cotransport (NBC) and CO(2) hydration/Na(+)/H(+) exchange were equally important duodenal HCO(3)(-) supply pathways and were both upregulated during cAMP-mediated secretion. In the proximal colon, however, HCO(3)(-) secretion was low but NBC1 expression even higher than in the duodenum. Ussing-chamber experiments with an NBC-specific inhibitor revealed that NBC, coupled to basolateral Cl(-)/HCO(3)(-) exchange, was an important alternative Cl(-) supply pathway to Na(+)K(+)2Cl(-) cotransport (NKCC) during cAMP-stimulated colonic Cl(-) secretion. To investigate the functional integrity of anion uptake pathways in the absence of cystic fibrosis transmembrane conductance regulator (CFTR), we fluorometrically assessed NBC and NKCC transport rates and cell volume before and during forskolin-stimulation in isolated colonic crypts from normal and CFTR (-/-) mice. Although forskolin stimulation decreased cell volume only in normal, not in CFTR (-/-) crypts, it activated NBC and NKCC to a similar degree in both normal and CFTR (-/-) crypts. We conclude that, depending on the intestinal segment, NBC1 plays an important role in basolateral HCO(3)(-) or Cl(-) uptake. Expression and activation by cAMP is preserved in CFTR (-/-) intestine.

A functional CFTR protein is required for mouse intestinal cAMP-, cGMP- and Ca(2+)-dependent HCO3- secretion.

1. Most segments of the gastrointestinal tract secrete HCO3-, but the molecular nature of the secretory mechanisms has not been identified. We had previously speculated that the regulator for intestinal electrogenic HCO3- secretion is the cystic fibrosis transmembrane regulator (CFTR) channel. To prove this hypothesis, we have now measured HCO3- secretion by pH-stat titration, and recorded the electrical parameters of in vitro duodenum, jejunum and ileum of mice deficient in the gene for the CFTR protein ('CF-mice') and their normal littermates. 2. Basal HCO3- secretory rates were reduced in all small intestinal segments of CF mice. Forskolin, PGE2, 8-bromo-cAMP and VIP (cAMP-dependent agonists), heat-stable enterotoxin of Escherichia coli (STa), guanylin and 8-bromo-cGMP (cGMP-dependent agonists) and carbachol (Ca2+ dependent) stimulated both the short-circuit current (Isc) and the HCO3- secretory rate (JHCO3-) in all intestinal segments in normal mice, whereas none of these agonists had any effect on JHCO3- in the intestine of CF mice. 3. To investigate whether Cl(-)-HCO3- exchangers, which have been implicated in mediating the response to some of these agonists in the intestine, were similarly active in the small intestine of normal and CF mice, we studied Cl- gradient-driven 36Cl- uptake into brush-border membrane (BBM) vesicles isolated from normal and CF mouse small intestine. Both the time course and the peak value for 4,4'-diisothiocyanostilbene-2',2-disulphonic acid (DIDS)-inhibited 36Cl- uptake was similar in normal and CF mice BBM vesicles. 4. In summary, the results demonstrate that the presence of the CFTR channel is necessary for agonist-induced stimulation of electrogenic HCO3- secretion in all segments of the small intestine, and all three intracellular signal transduction pathways stimulate HCO3- secretion exclusively via activation of the CFTR channel.