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

BACKGROUND: Non-adherence to medication is a challenging problem in daily clinical practice. OBJECTIVE: 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. METHODS: 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. RESULTS: The DACH cohort had significantly different levels of adherence depending on the IMID (P < 0.05) and the type of therapy (P < 0.05). Based on the significant influence of concerns on treatment adherence (P < 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. CONCLUSIONS: 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.

An expert consensus definition of failure of a treatment to provide adequate relief (F-PAR) for chronic constipation - an international Delphi survey.

BACKGROUND: As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. AIM: To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic constipation. METHODS: We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. RESULTS: The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). CONCLUSIONS: We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.

[Endoscopic and surgical procedures for enteral nutrition]. / Endoskopische und chirurgische Techniken zur enteralen Ernährung.

Standardized management of oncology patients necessarily includes screening for nutritional risk. Weight loss of > 5 kg within 3 months and diminished food intake are warning signals even in overweight patients. In case oral nutrition is neither adequate nor feasible even by fortification or oral nutritional supplements, the implantation of a percutaneous endoscopic gastrostomy (PEG) or fine needle catheter jejunostomy (FNCJ) offers enteral access for long-term nutritional support. Although the indications derive from fulfilling caloric needs, endoscopic or operative measures are not considered to be an urgent or even emergency measure. The endoscopist or surgeon should be fully aware and informed of the indications and make a personal assessment of the situation. The implantation of a feeding tube requires informed consent of the patient or legal surrogates. The review summarizes recent indications, technical problems and complications.

[Diverticulitis and indication for surgery--are there new data?]. / Operationsindikation bei Divertikulitis--Gibt es neue Daten?

The treatment in acute diverticulitis has undergone a considerable shift from an offensive to a more restrictive and individual indication for surgery. This review of the very recent literature with special regard to long-term observation of conservatively treated patients clearly shows that surgery is not required in any case of a first episode of severe diverticulitis, but should be recommended in high-risk patients under immunosuppression or chronic renal failure. In all other groups of patients the indication for surgery should be weighed on an individual basis after each episode, again aiming for the laparoscopic procedure. A therapeutic algorithm is proposed according to the Hansen-Stock classification.

Quantification of HBsAg and HBV-DNA during therapy with peginterferon alpha-2b plus lamivudine and peginterferon alpha-2b alone in a German chronic hepatitis B cohort.

BACKGROUND: Peginterferon alpha-2b (PEG-IFNa2b) and lamivudine are efficient treatment options for chronic hepatitis B virus (HBV) infection. We assumed that a combination therapy of PEG-IFNα-2b plus lamivudine will be more effective than PEG-IFNα-2b alone concerning loss of HBV-DNA, HBeAg seroconversion, and HBsAg reduction. PATIENTS AND METHODS: Patients with chronic hepatitis B were randomised to nine months treatment with PEG-IFNα-2b 1.5 µg/kg o. i. w. or PEG- IFNα-2b plus lamivudine 100 mg/d. The study was designed with 60 patients per treatment arm. The primary endpoint was defined as loss of HBV-DNA (< 400 copies/mL) 24 weeks after the end of therapy. HBV-DNA (PCR), HBsAg (Architect, Abbott), and HBeAg (Axsym, Abbott) were determined prior to and at the end of treatment as well as at follow-up. HBV-genotypes were determined by Innolipa (Innogenetics). RESULTS: Only 32 patients were randomised to combination therapy and 27 individuals to monotherapy due to low recruitment rates. On treatment reduction of HBV-DNA was significantly higher during combination therapy compared to PEG-IFNa-2b monotherapy (- 4.60 ± 2.71 vs. - 2.41 ± 2.17 log; p = 0.003). However, there was no difference in the number of cases achieving HBV-DNA < 400 copies/mL, ALT normalisation, or HBeAg seroconversion at follow-up. None of the parameters was significantly related to HBV-genotypes. In a post-hoc analysis serum HBsAg levels were analysed as an additional prognostic parameter for treatment response (n = 29). Combination therapy showed a stronger, but not significant HBsAg decline during (- 0.7 ± 1.17 log IU/mL vs. - 0.26 ± 0.61 log IU/mL; p = 0.35) and after therapy (- 0.68 ± 1.29 log IU/mL vs. - 0.24 ± 0.56 log IU/mL; p = 0.82). Two of three cases with a 2-log HBsAg decline to HBsAg levels < 100 IU/mL eliminated HBsAg during long-term follow-up. CONCLUSION: The study was underpowered with respect to the primary endpoint due to low recruitment rates. However, in the post-hoc analysis HBsAg decline was over two-fold stronger at the end of treatment and follow-up after combination therapy and did not rebound after lamivudine withdrawal. These results may indicate the usefulness of future combination therapies without discontinuation of nucleos(t)ide analogues.

Risk factors for bleeding complications after endoscopic variceal ligation therapy.

BACKGROUND: Bleeding from esophageal varices is a severe complication of portal hypertension. Endoscopic band ligation (EBL) is the treatment of choice for acute variceal bleeding. It is also performed for primary and secondary prophylaxis of bleeding from esophageal varices. After EBL, patients are at risk of postinterventional bleeding; the risk factors for this complication are poorly evaluated. METHODS: We retrospectively analyzed data from patients who underwent EBL. We evaluated clinical data, laboratory and endoscopic findings. RESULTS: 255 patients with 387 ligation sessions were included in the analysis. Patients with bleeding complications had a significantly higher severity of liver disease as measured by a higher Child-Pugh score (10.5 vs. 8, p = 0.002), lower albumin (26.5 vs. 31.9 [g/L], p = 0.0001) and lower prothrombin activity (46.5 vs. 70 [%], p = 0.0001). The incidence of bacterial infection was significantly higher in patients with postinterventional bleeding. As well, the white blood cell count was significantly higher in the bleeding group (9.5 vs. 6.5 [× 10 (9) /L], p = 0.030). In patients with bleeding events we observed an elevated heart rate compared to those without this complication (80 vs. 72 [bpm], p = 0.017). Furthermore, we found a lower hemoglobin level (5.9 vs. 6.4 [mmol/L], p = 0.028) and a lower hematocrit (0.280 vs. 0.314, p = 0.031) in the bleeding group. Younger patients suffered more often from postinterventional bleeding (52.5 vs. 58 [years], p = 0.012). CONCLUSION: There are clinical data which can be ascertained easily in order to reflect the risk of bleeding complications after EBL.

Resistance management in chronic hepatitis B complicated by renal failure.

Therapy of chronic hepatitis B has improved by the invention of the potent nucleos(t)ide analogues entecavir, telbivudine and tenofovir disoproxil. Due to increasing prevalence of lamivudine resistance the appropriate first line therapy may prevent emergence of any new resistance and avoid combination therapy. The present case describes a complex history of chronic hepatitis B in the setting of renal failure after two renal transplants illustrating why lamivudine should not be used as first line treatment option any more. Instead, entecavir offers high antiviral potency, low risk for resistance and possible individual dose titration by an oral solution.

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease using multiple Plicator implants: 12-month multicenter study results.

BACKGROUND: The full-thickness Plicator (Ethicon Endosurgery, Sommerville, NJ, USA) was developed for endoscopic treatment of gastroesophageal reflux disease (GERD). The goal is to restructure the antireflux barrier by delivering transmural pledgeted sutures through the gastric cardia. To date, studies using this device have involved the placement of a single suture to create the plication. The purpose of this study was to evaluate the 12-month safety and efficacy of this procedure using multiple implants to restructure the gastroesophageal (GE) junction. METHODS: A multicenter, prospective, open-label trial was conducted at four tertiary centers. Eligibility criteria included symptomatic GERD [GERD Health-Related Quality-of-Life (GERD-HRQL) questionnaire, off of medication], and pathologic reflux (abnormal 24-h pH) requiring daily proton pump inhibitor therapy. Patients with Barrett's epithelium, esophageal dysmotility, hiatal hernia > 3 cm, and esophagitis (grade III or greater) were excluded. All patients underwent endoscopic full-thickness plication with linear placement of at least two transmural pledgeted sutures in the anterior gastric cardia. RESULTS: Forty-one patients were treated. Twelve months post treatment, 74% of patients demonstrated improvement in GERD-HRQL scores by > or = 50%, with mean decrease of 17.6 points compared with baseline (7.8 vs. 25.4, p < 0.001). Using an intention-to-treat model, 63% of patients had symptomatic improvements of > or = 50%, with mean GERD-HRQL decrease of 15.0 (11.0 vs. 26.0, p < 0.001). The need for daily proton pump inhibitor (PPI) therapy was eliminated in 69% of patients at 12 months on a per-protocol basis, and 59% on an intention-to-treat basis. Adverse events included postprocedure abdominal pain (44%), shoulder pain (24%), and chest pain (17%). No long-term adverse events occurred. CONCLUSIONS: Endoscopic full-thickness plication using multiple Plicator implants can be used safely and effectively to improve GERD symptoms and reduce medication use.

Do we need gastric acid?

Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression.

Treatment of massive cecal bleeding in a 28-Year-old patient with homozygous factor V deficiency with activated factor VII.

Factor V deficiency is usually accompanied with recurrent epistaxis, menorrhagia and haemorrhages after trauma. So far, gastrointestinal bleeding has not been reported. We describe here the first case of severe cecal bleeding in a 28-year-old woman with homozygous factor V deficiency. As a reasonable alternative to large amounts of fresh frozen plasma, we indicated recombinant activated factor VII (rFVIIa), as supra-physiological concentrations directly activate factor X and prothrombin on the surface of activated platelets. With this regimen, the bleeding immediately stopped and the patient was discharged three days later. Rotation thromboelastometry studies showed a marked improvement in clot generation after rFVIIa infusion. We conclude that massive cecal mucosal bleeding is a possible manifestation of homozygous factor V deficiency and rFVIIa could be a successful therapy.

[Prevention of gastrointestinal malignancies]. / Prävention von Malignomen des Verdauungstrakts.

Malignancies of the gastrointestinal tract are the most common causes of cancer-related deaths in Germany. They also induce significant morbidity. Despite both surgical and medical therapeutic improvements, advanced stages of these cancers can rarely be cured. Preventive and screening measures are suitable to decrease gastrointestinal cancer-related mortality. Weight reduction and cessation of smoking are effective in preventing esophageal, pancreatic and colorectal cancer. Treatment of infections like chronic viral hepatitis and helicobacter pylori gastritis is able to protect from hepatocellular and gastric cancer, respectively. Colonoscopy is one of the best established screening methods. It allows early detection of colorectal neoplasia. Preneoplastic adenomas can be endoscopically removed during the same session. We here review simple prevention strategies and effective screening methods in gastrointestinal cancers of relevance in daily practice.

Antireflux stents for palliation of malignant esophagocardial stenosis.

Placement of self-expanding metal stents (SEMS) for palliation of malignant stenoses at the gastroesophageal junction is often associated with stent migration and reflux symptoms. SEMS with an antireflux mechanism have been developed to overcome the latter problem. The aim of this study was to evaluate the safety and efficacy of antireflux Z-stents. Patients with advanced squamous cell or adenocarcinoma of the distal esophagus or cardia suffering from dysphagia received an antireflux Z-stent. Technical success, complications of the procedure, clinical symptoms before and after stent placement, reinterventions and survival were recorded. Follow-up was accomplished by patient interviews and a standardized questionnaire for primary care physicians. Eighteen consecutive patients received an antireflux Z-stent. Seventeen of 18 stents were placed technically successful in a single endoscopic procedure. Mean dysphagia score improved from 2.2 to 0.6. Four patients (22%) had permanent reflux symptoms, an additional nine (50%) were taking proton pump inhibitors on a regular basis. In 10 patients, a re-intervention was necessary mainly due to dislocation of the stent. To ensure adequate nutrition three and two patients received a percutaneous gastrostomy and a jejunostomy, respectively. Median survival from stent insertion was 54 days (range, 3-201). Although placement of an antireflux Z-stent is technically feasible, its application is hampered by frequent stent migration and insufficient prevention of gastroesophageal reflux. Further technical improvements of stents or alternative methods like brachytherapy are required for satisfactory palliation of malignant gastroesophageal stenosis.

Coexistence of autoimmune pancreatitis and primary biliary cirrhosis in a Caucasian patient - a rare cause of cholestasis.

In contrast to Asia, autoimmune pancreatitis is rare in the Western population. The present case report describes the coexistence of primary biliary cirrhosis and autoimmune pancreatitis accompanied by sclerosing cholangitis of the intrahepatic bile ducts and the hilar region. It is important to differentiate sclerosing cholangitis due to autoimmune pancreatitis from primary sclerosing cholangitis and primary biliary cirrhosis, because the former responds to steroids, while the latter do not. The article highlights important diagnostic difficulties and suggests racial differences between Caucasian and Asian patients.

[Tropical and subtropical helminthoses]. / Tropische und subtropische Helminthosen.

Human helminthic infestations are extraordinarily common in tropical regions and represent a significant burden for those countries and their populations. The risk of intestinal helminthoses is further increased by poverty. Particularly in children helminthoses lead to malnutrition (ascariasis etc) or iron and protein deficiency (ancylostomiasis). Tropical helminthoses like schistosomiasis and filariasis can cause severe organ damage, starvation, and early death. In contrast, returning travellers very rarely acquire tropical helminthoses, if they follow simple hygienic rules. Furthermore, the worm burden in returning travelers hardly ever is high enough to cause severe illness. Therefore, tropical helminthosis is more common in immigrants from endemic areas compared to returning travelers.

[Indigenous helminthiasis]. / Einheimische Helminthosen.

Worldwide an estimated 1.5-2 billion people are infested with helminths. Over the last decades, in industrialized countries prevalence rates of human helminthic infections were decreased by means of wastewater and food control. In this article, we review the geographic distributions as well as the impact on the public health system of the most prevalent helminthiases. Special emphasis is given to Echinococcus, Enterobiasis, and Toxocariasis. Intestinal larvae or eggs of helminths can be detected in faeces. Pinworms are collected with a strip of cellophane tape with the sticky side towards the anus. Tissue helminthosis, like Toxocariasis or Trichinosis are associated with eosinophilia and can be diagnosed with sensitive immunological methods or by biopsy. Infection with Echinococcus multilocularis is the most serious parasitic disease in central Europe. Although current therapeutic options are limited, 5 year survival rates were markedly improved by the combination of medical and surgical treatment.