Evaluation of digital construction, production and intraoral position accuracy of novel 3D CAD/CAM titanium retainers.

OBJECTIVES: New opportunities have arisen to manufacture three-dimensional computer-aided design/computer-aided manufacturing (3D CAD/CAM) retainers from titanium blocks by digital cutting technology. These novel technologies need to fulfill requirements regarding digital planning and position accuracy. The aim of the present study was to investigate the digital construction, the CAD/CAM production and the intraoral positioning accuracy of custom-manufactured novel 3D CAD/CAM titanium retainers. MATERIALS AND METHODS: A total of 37 prime4me® RETAIN3R (Dentaurum, Ispringen, Germany) retainers were inserted to stabilize the upper anterior front teeth. Following insertion, an intraoral scan was used to record the position. The intraoral position was compared to the virtual setup using 3D superimposition software. Measurement points were evaluated in all three dimensions (horizontal, sagittal and vertical planes). Data were analyzed using Kruskal-Wallis test followed by Dunn's multiple comparison test. RESULTS: A total of 185 measurements were performed. The horizontal plane and the sagittal plane demonstrated a high level of positioning accuracy between the planned and the intraoral position. Statistically significant deviations between the preceding virtual setup and the intraoral situation were observed in the vertical dimension. Within the retainer, the intraoral positioning accuracy decreased for the measurement points in the direction of the distal retainer segment. CONCLUSION: Based on the results, the present study shows a high level of congruence between the 3D virtually planning and the final intraoral position of the fabricated novel 3D CAD/CAM titanium retainers.

Real-world use, effectiveness and safety of anti-viral treatment in chronic hepatitis C genotype 3 infection.

BACKGROUND: Treatment of chronic hepatitis C genotype 3 (GT3) is more challenging compared with other genotypes. Since 2014, several new treatment regimens have been approved but sometimes based on limited data. AIM: To validate the use, effectiveness and safety of anti-viral treatment in chronic hepatitis C genotype 3 infection under real-word conditions. METHODS: The German Hepatitis C-Registry is a large national non-interventional real-world study for patients with chronic hepatitis C. A total of 1322 GT3 patients were enrolled (211 untreated and 1111 treated patients). RESULTS: Between February 2014 and September 2015, five different treatment strategies have been used (PegIFN+RBV, PegIFN+RBV+SOF, SOF+RBV, DCV+SOF±RBV, LDV/SOF±RBV). Treatment uptake and use of treatment concepts changed markedly and rapidly during the study influenced by new approvals, guideline recommendations, and label updates. PegIFN-based therapies constantly declined while DCV-based therapies increased with one interruption after the approval of LDV/SOF, which was frequently used until new guidelines recommended not using this combination for GT3. Per-protocol SVR ranged from 80.9% in the PegIFN+RBV group to 96.1% in PegIFN+RBV+SOF treated patients. Treatment-experienced patients with cirrhosis showed a suboptimal SVR of 68% for SOF+RBV but a high SVR of 90-95% for DCV+SOF±RBV. The safety analysis showed more adverse events and a stronger decline of haemoglobin for RBV containing regimens. CONCLUSIONS: Real-world data can validate the effectiveness and safety for treatment regimens that had previously been approved with limited data, in particular for specific subgroups of patients. The present study demonstrates how rapid new scientific data, new treatment guidelines, new drug approvals and label changes are implemented into routine clinical practice today.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

Treatment results of chronic hepatitis C genotype 5 and 6 infections in Germany.

Chronic hepatitis C due to HCV genotype 5 and 6 infection is infrequently reported and patients are usually not included in trials. As boceprevir and telaprevir are not approved for these genotypes, pegylated interferon plus ribavirin will remain the treatment of choice for the coming years. Patients infected with HCV genotype 5 or 6 were identified by data base search from an ongoing observational cohort study in Germany. Of the total 23 893 patients, 39 patients (0.2 %) carried a HCV genotype 5 and 39 patients a HCV genotype 6 (0.2 %). Compared to other genotypes patients with genotype 5 were older and more often had a history of blood transfusion. Patients with genotype 6 were more often Asian and showed higher baseline alanine transaminase. Therapy with pegylated interferon alfa-2a and ribavirin was initiated in 24 patients with HCV genotype 5 and 27 patients with HCV genotype 6. After completion of 48 weeks of therapy an end of treatment response was achieved in 79 % and 81 % of treated patients, respectively. Sustained virological response was achieved in 58 % of patients with genotype 5 and in 59 % genotype 6 patients. HCV genotype 5 and 6 infections are rare in Germany. Our findings suggest that most HCV genotype 6 infections are seen in migrants from Asia, whereas HCV genotype 5 infections seem more due to spontaneous local infections. Sustained virological response seems to be better than for patients with genotype 1 or 4 with similar treatment duration.

[Endoscopic therapy for leaks in the gastrointestinal tract, the bile ducts and the pancreas]. / Endoskopische Therapie von Leckagen im Gastrointestinaltrakt, an den Gallenwegen und im Pankreas.

Surgery has been the mainstay of therapy in patients with gastrointestinal perforations, leakage or fistulas. New techniques for endoscopic closure of gastrointestinal perforations provide tools for an effective treatment by less invasive procedures. Temporary placement of covered self-expanding stents is an established therapy for oesophageal perforations and anastomotic leaks. Using conventional endoclips small perforations and leaks in the oesophagus and gastrointestinal tract may be closed. With the new over-the-scope-clips a more effective endoscopic full wall closure is possible in the upper gastrointestinal tract and the rectum. Endoscopically guided endoluminal vacuum therapy using polyurethane sponges is an established method for treating rectal leaks and is now increasingly used also in oesophageal leaks. Biliary leakage following endoscopic or surgical interventions is effectively treated with temporary bile stenting in most cases, but closure using metal stents or coiling may be necessary. Pancreatic leaks are a major therapeutic problem and may require multimodal therapies.

[Waiting time for and length of physicianc's consultation define the patient-physician interaction: results of a prospective study in 478 patients with chronic viral hepatitis]. / Wartezeiten und Länge des Arztgesprächs bestimmen aus Patientensicht die Qualität der Arzt-Patienten-Beziehung bei chronischer Hepatitis B und C: Ergebnisse einer prospektiven Studie bei 478 Patienten mit chronischer Virushepatitis.

BACKGROUND: Little is known about the physician-patient interaction in hepatitis B and C. METHODS: This study by the federal competence network hepatitis analysed the physician-patient interaction using the validated FAPI questionnaire. The questionnaire also contained questions concerning demography and disease characteristics. Of the total 1500 questionnaires sent out, 478 were returned (32 %) (20 % HBV vs. 80 % HCV). RESULTS: The FAPI index of patients with HBV/HCV infection (3.10 +/- 0,99) was lower than that in patients with other internal medicine diseases (3.61 +/- 0.92; n = 148). Women had lower values than men (2.98 vs. 3.25; p = 0.005). Patients with active HBV infection showed higher values than those with HCV infection (3.27 vs. 2.97; p < 0.05). Patients with successfully treated hepatitis B/C had higher values than those with active disease (3.36 vs. 3.02; p = 0.004). The index was lower in patients who waited > 2 weeks for the consultation when compared to those with a shorter wait (2.92 vs. 3.31; p < 0.001) and was also lower in patients who waited > 30 min at the consultation day when compared to those with a shorter wait (2.81 vs. 3.39; p < 0.001). The index gradually increased with the consultation length (2.47 < 10 min vs. 2.79 10 - 15 min vs. 3.21 15 - 30 min vs. 3.82 > 30 min; p < 0.001). The index was higher in patients seen by gastroenterologists (3.43) when compared with general practioners (3.10), internists (3.02) and clinical settings (3.13) (p < 0.05). A good information status was associated with higher FAPI values when compared with a bad information status (3.43 vs. 2.76; p < 0.001). Fibrosis, health insurance and age were not associated with FAPI index (p > 0.2). By multivariate analysis a long consultation, a good information status, patients' patience, short waiting times, and providing contact to a patient support group were independently associated with a high index. CONCLUSIONS: The physician-patient interaction in chronic viral hepatitis is worse than in other internal medicine diseases with problems being more pronounced in HCV infection and women when compared to men and HBV infection. Short waiting times and patients' patience ameliorated the interaction as well as the consultation length, the information status of the patient and providing contact to a patient support group. Type of health insurance did not affect either waiting times or physician-patient interaction; thus there is no hint for a two-class medicine in this part of hepatology.

[New data and recommendations of antiviral therapy of chronic hepatitis B and C]. / Aktuelle Therapie der chronischen Hepatitis B und C.

According to the new German guidelines therapy of chronic hepatitis B is recommended when HBV-DNA is >10.000 copies/ml and when GPT is >twice the ULN or biopsy shows inflammation/fibrosis. When patients are not suitable for interferon therapy, mono-therapy with adefovir, entecavir, telbivudine of lamivudine may be initiated provided that HBV-DNA is <1 Mio. copies/ml and cirrhosis is absent. When viral load is high, entecavir should be preferred. HBV-DNA need to be checked for early detection of non-response or resistance. When resistance is present, combination therapy is recommended.New studies warrant individualization of previous recommendation for therapy of hepatitis C because one can now early evaluate how successful and long the therapy shall be. When viral load is low and HCV-RNA becomes negative after 4 weeks, therapy may be shortened to 24 weeks. Without such rapid response HCV-RNA needs to be checked after 12 and 24 weeks: when HCV-RNA becomes negative only after 24 weeks, a prolongation of therapy might be advisable.

[Changes in socio-economics, quality of life and knowledge of patients with chronic hepatitis C during the Hepatitis Competence Net Project]. / Entwicklung von sozioökonomischen Charakteristika, Lebensqualität und Wissensstand bei Patienten mit Hepatitis C während des Projektes Kompetenznetz Hepatitis.

AIMS AND METHODS: The study of the Patient Support Group Deutsche Leberhilfe e.V. and the Federal Hepatitis Competence Net prospectively analysed questionnaires about quality of life (SF12) and socio-economical data of patients with chronic hepatitis C (CHC). A 1st questionnaire 3 1/2 years ago gathered information in 714 CHC patients all of whom now received a 2nd questionnaire which was sent back by 503 subjects (71%). RESULTS: Both mental and physical SF 12 scores remained markedly decreased compared with scores for the general population which approximate 50 points (p<0.001). When compared to values obtained 3S years ago, mental scores increased from 41.2 to 42.5 and physical scores from 41.9 to 42.9 (changes not significant by analysis of variance; p>0.05). However, in patients with negative HCV-RNA, physical and mental scores significantly increased by 6.9 and 4.0 points (p<0.01). In contrast, mental and physical scores decreased by 2.4 and 2.5 points during follow-up in patients with fibrosis (Metavir F2-4) (p<0.05). SF 12-scores closely correlated with degrees of inflammation and fibrosis (p<0.001, respectively). Quality of life was associated with socio-economical data and gradually increased with higher school graduation. A high percentage of patients with CHC were unemployed (18%); of patients aged 65 years, 25% were already retired; 60% of the retired subjects received a disability pension, 37% because of CHC. Unemployed patients had lower SF 12 scores than patients with a job. Subjects with public employers had significantly lower SF 12 scores than privately or self-employed subjects. Complications of CHC markedly reduced SF 12 scores. Just 37% of subjects had a life insurance and only 9% had an insurance of occupational invalidity (values 2-3-times lower than those in the general German population). Insurance applications for life and occupational invalidity had been denied in 17 and 53%, respectively; the denial values were even higher than in the 1st questionnaire. CONCLUSIONS: The prospective follow-up shows that quality of life continuously improves after elimination of HCV, whereas mental and physical health get increasingly worse with ongoing fibrosis. The analysis demonstrates that many CHC subjects have severe socio-economical problems leading to unemployment, early retirement and lack of appropriate insurances. These problems further reduce the quality of life in CHC.

[Epidemiology of chronic hepatitis C in Germany--an analysis of 10,326 patients in hepatitis centres and outpatient units]. / Epidemiologie der chronischen Hepatitis C in Deutschland--Eine Analyse von 10,326 Hepatitis-C-Virus-Infizierten aus Schwerpunktpraxen und -ambulanzen.

Little is known about the epidemiology of chronic hepatitis C (CHC) in Germany and especially about the importance of transmission, duration of infection, genotypes, symptoms and quality of life of the patients. The current study prospectively evaluates epidemiological and clinical data of patients infected with the hepatitis C virus (HCV). Using online data entry, various characteristics of 10,326 untreated patients with CHC were documented from March 2003 until May 2006 in 352 centres all over Germany. Mean age of patients was 43.4 years. Patients infected by i.v. drug abuse were considerably younger (36.5 years) than the remaining patients (49.2 years). As indicated by their native language, 64.4% of the patients came from Germany and 19.2% from Russia. 61.7% were infected with genotype 1 and 34.9% with genotype 2 or 3. 45.5% of the patients had been infected by i.v. drug abuse. In at least 5.4% of the patients liver cirrhosis had been proved by biopsy. 63.5% of the patients felt an impairment of quality of life caused by CHC. In many patients infected with hepatitis C socio-economic issues are existent. This is reflected, i.e., in very high rates of unemployment in special subpopulations. Coinfections with hepatitis B and HIV occurred in 1.5% and 4.7%, respectively. Nearly 80% of patients were managed near their homes. The data of the 10 326 patients represent about 2% of all German patients with CHC. This database is up to now the largest of its kind and gives a representative insight into the epidemiological situation of CHC in Germany.

Safety, tolerability and efficacy of peginterferon alpha-2a and ribavirin in chronic hepatitis C in clinical practice: The German Open Safety Trial.

The combination treatment of peginterferon alpha-2a (PEG-IFN alpha-2a; Pegasys) plus ribavirin (RBV) is recommended as a standard care for HCV infections. Side effects and aspects of efficacy and safety have to be balanced. This study evaluates clinical practice data on safety and efficacy of HCV treatment with PEG-IFN in combination with RBV over 24 and 48 weeks. This study was a phase III, multi-centre, open-label study with two treatment groups: PEG-IFN in combination with RBV for 24 or 48 weeks. The allocation to the treatment groups was at the discretion of the investigator; 309 patients entered active treatment: 90 patients received PEG-IFN plus RBV for 24 weeks and 219 patients PEG-IFN plus RBV for 48 weeks. A sustained virological response (SVR) was achieved in 48.9% of all patients. Genotype 1 patients with a 48-week combination treatment achieved an SVR of 39.9%. In the 48-week group a low baseline viral load was associated with a higher SVR rate (47.0% vs. 32.4%). For genotype 2 or 3 patients, the SVR was 67.9%. For these patients there was no relevant difference between patients with low and high viral loads; 97.7% of the patients experienced at least one adverse event. The incidence of serious adverse events was distinctly lower in the 24-week group (4.4% vs. 10.5%). This investigation confirms the well-known risk-benefit ratio found in controlled studies in a clinical practice setting. The safety profile is similar and shows the highest incidence of adverse events in the first 12 weeks of treatment.

[Socio-economical aspects, quality of life and state of knowledge in hepatitis B patients. Socio-economical aspects in hepatitis B]. / Sozioökonomische Charakteristika, Lebensqualität und Wissensstand bei Patienten mit Hepatitis-B-Virusinfektion in Deutschland. Sozioökonomische Aspekte bei Hepatitis B.

BACKGROUND: Little is known about socio-economical consequences and information status of patients with chronic hepatitis B virus (HBV) infection. AIMS AND METHODS: The present study prospectively analyzed questionnaires about socio-economical consequences and information status including the SF12 quality-of-life analysis in HBV-infected subjects. Overall 1500 questionnaires were distributed by clinics, practioners, patient support groups and internet; 255 questionnaires were sent back. Results were compared with a recent study in 714 HCV infected patients (Z Gastroenterol 2006; 44: 305-317). RESULTS: HBV-infected patients were younger (mean 46 vs. 52 years), more likely to be male (62 vs. 44%) and to come from abroad (30 vs. 9%) when compared with HCV-infected subjects. Only 1 and 4% of HBV- and HCV-infected subjects, respectively, considered the public information about hepatitis as good or very good, 73 and 77%, however, as bad or very bad. Mental and physical quality-of-life (SF12) was better in HBV- than in HCV-infected subjects, but reduced when compared with a sex- and age-matched general population (p < 0.001). Quality-of-life decreased with increases in HBV-DNA, fibrosis and inflammation. In both HBV- and HCV-infected subjects there were information deficits concerning the risks for infection; some of these were more pronounced in HBV-infected subjects when compared to HCV-infected ones. German subjects with HBV and HCV infection are in general well informed about their infection (73-87% knew ALT and histology results); however, HBV-infected subjects are less well informed in particular about viral load and HBeAg (59 and 30%) when compared with HCV infected subjects who knew HCV-RNA and genotype in 80-85%. CONCLUSIONS: The information deficits about viral load are of concern for HBV-infected subjects because these data are more important in HBV than in HCV infection. This lack of information likely reflects a lack of attentiveness towards HBV-DNA levels by the patients' physician. Both HBV- and HCV-infected subjects have problems at work and with various insurances; both have a reduced quality-of-life which correlates with viral load and degree of inflammation and fibrosis. Both populations consider the public information status about viral hepatitis to be bad.

[Socioeconomic characteristics, quality of life, and state of knowledge of patients with hepatitis C viral infection in Germany--socioeconomic aspects in hepatitis C]. / Sozio-ökonomische Charakteristika, Lebensqualität und Wissensstand bei Patienten mit Hepatitis-C-Virusinfektion in Deutschland--Sozio-ökonomische Aspekte bei Hepatitis C.

BACKGROUND: Little is known as yet about the socio-economic consequences for patients with hepatitis C in Germany. AIMS AND METHODS: The study of the Deutsche Leberhilfe e. V., supported by the federal hepatitis competence net, prospectively analyzed questionnaires about quality-of-life, education and work situation, insurance, and various other socio-economical aspects of patients with chronic hepatitis C. The questionnaire included questions about the information status of patients concerning hepatitis C in general and their individual disease. Overall, 1500 questionnaires were distributed by clinics, general practitioners, patient-support groups and via the internet; 714 were sent back and analyzed. RESULTS: Most of the 714 patients were born in Germany; 56 % were women and 44 % men, with a mean age of 52 years and a hepatitis duration of 18 years. More than 60 % of subjects younger than 65 years of age did not have a regular job, and 27 % were already retired. Only 47 % had a sufficient retirement insurance, whereas almost all had a health insurance. Only 12 % had an insurance covering work invalidity, and of those who had applied for the latter insurance, it was denied in 29 %. About 80 % of subjects reported that the hepatitis disturbed various aspects of their life. Only 4 % considered the public knowledge about hepatitis C as good or very good, but 80 % as bad or very bad. Of the subjects 40 % did not know how they had been infected; 37 % considered blood products as their infection mode, but only 10 % drug abuse. Almost all subjects knew that HCV cannot be transmitted via shaking hands, use of bathrooms, kisses or food (< 1 %, respectively). Surgery (17 %) and the dentist (15 %), however, were mentioned relatively often as a major risk for infection. About 80 % of subjects knew recent quantitative data on ALT and HCV-RNA, their genotype and the results of liver biopsy. Both mental and physical scores in the SF12 questionnaire were markedly reduced by about one standard deviation in subjects with HCV infection when compared with the general German population. Mental and physical scores deteriorated with increases in inflammatory and fibrosis scores. Subjects with negative HCV-RNA and normal ALT had the best quality of life, whereas subjects with high levels of HCV-RNA and ALT had the worst. CONCLUSIONS: The data show that the public opinion is wrong when pretending that hepatitis C today is just a disease of drug addicts. Our analysis demonstrates for the first time that many HCV-infected subjects in Germany have problems with their insurance and jobs. German subjects are well informed about their infection including genotype, liver histology, ALT and HCV-RNA; on the other hand, there are information deficits and fears concerning the mode of infection. The recent analysis clearly shows that HCV-infected subjects consider the public information about the HCV infection as catastrophically bad. The recent data in addition show that elimination of HCV decisively ameliorates quality of life, whereas mental and physical health get increasingly worse with progressive liver disease and unsuccessful antiviral therapies.