[Health services research and guidelines--from the Association of the Scientific Medical Societies' (AWMF) perspective]. / Versorgungsforschung und Leitlinien--die Perspektive der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesell- schaften (AWMF).

The Association of the Scientific Medical Societies (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften) is an umbrella organization. It currently represents 151 scientific societies and thus the majority of medical researchers in Germany. Through the coordination and support of the scientific medical societies, the AWMF significantly contributes to health services research by establishing guidelines that ensure a high quality of healthcare. To this purpose, AWMF founded a guideline committee in 1995, whose objective is to assist AWMF member societies in the establishment of guidelines, the organization of training sessions for AWMF guideline representatives, the hosting of regular guideline conferences and the close cooperation with the German Medical Association (Bundesärztekammer, BAK) and the National Association of Statutory Health Insurance Physicians (Kassenärztliche Bundesvereinigung, KBV) in the development of national disease management guidelines (Nationale Versorgungs Leitlinien, NVL). Together with the Agency for Quality in Medicine [AQuMed; Arztliches Zentrum für Qualität in der Medizin (AZQ)], AWMF published a 'German Instrument for Methodological Guideline Appraisal' ('Deutsches Instrument zur methodischen Leitlinien-Bewertung', DELBI) in order to assure the quality of the guideline development process. A close cooperation has also developed between AWMF and the German Medical Association within the scope of their program for promoting health services research and with the Board of the German Network for Health Services Research (Deutsches Netzwerk for Versorgungsforschung, DNVF). Furthermore, AMWF has acknowledged a special need for improving the financial and conceptual promotion of a systematic evaluation of guideline development and the implementation and application of guidelines in everyday clinical practice.

[The German program for disease management guidelines. Background, methods, and development process]. / Nationale Versorgungsleitlinien von BAK, AWMF und KBV : Hintergrund, Methodik und Instrumente.

The Program for National Disease Management Guidelines (German DM-CPG Program) was established in 2002 by the German Medical Association (umbrella organization of the German Chambers of Physicians) and joined by the Association of the Scientific Medical Societies (AWMF; umbrella organization of more than 150 professional societies) and by the National Association of Statutory Health Insurance Physicians (NASHIP) in 2003. The program provides a conceptual basis for disease management, focusing on high-priority health-care topics and aiming at the implementation of best practice recommendations for prevention, acute care, rehabilitation and chronic care. It is organized by the German Agency for Quality in Medicine, a founding member of the Guidelines International Network (G-I-N). The main objective of the German DM-CPG Program is to establish consensus of the medical professions on evidence-based key recommendations covering all sectors of health-care provision and facilitating the coordination of care for the individual patient through time and across interfaces. Within the last year, DM-CPGs have been published for asthma, chronic obstructive pulmonary disease, type 2 diabetes, and coronary heart disease. In addition, experts from national patient self-help groups have been developing patient guidance based upon the recommendations for health-care providers. The article describes background, methods, and tools of the DM-CPG Program, and is the first of a publication series dealing with innovative recommendations and aspects of the program.

[German S3 practice guidelines on prevention of venous thromboembolism--New and established evidence]. / S3-Leitlinie zur Prophylaxe der venösen Thromboembolie--Neues und Bewährtes.

Any recommendations of the previous practice guidelines on prevention of venous thromboembolism have been put to the test and have been revised in the latest edition in case new evidence had become available. Recommendations which have proven themselves in clinical practice have remained unchanged such as algorithms for risk assessment, however there are now updates on the recommendations of novel oral anticoagulants for prevention of venous thromboembolism, on the use of mechanical prophylaxis, on heparin-induced thrombocytopenia and on prophylaxis in outpatients after surgical procedures.

The Prophylaxis of Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the third most common cardiovascular condition, after myocardial infarction and stroke. Prophylactic measures in accordance with current guidelines can significantly reduce the risk of VTE and the associated morbidity and mortality. Until now, the German interdisciplinary, evidence- and consensus-based (S3) clinical practice guideline on VTE prophylaxis was based on a complete review of all pertinent literature available in MEDLINE up to January 2008. More recent publications and drug approvals have made a thorough revision necessary. METHODS: A systematic search was carried out in the MEDLINE and Embase databases for publications that appeared from 1 January 2008 to 7 August 2013. Updates of 5 national and international reference guidelines and 2 new Health Technology Assessment (HTA) reports were considered as well. A structured consensus-finding process was carried out with delegates from 27 scientific medical societies and from the Union of Medical Specialist Associations. RESULTS: 46 randomized controlled trials (RCTs) were included for critical appraisal. New findings led to re-evaluation of the value of compression stockings in combination with pharmacological prophylaxis (open recommendation), and suggest equal value of non-vitamin K antagonist oral anticoagulants (NOACs) and low molecular weight heparins (LMWH) or fondaparinux in elective hip and knee replacement (strong recommendation). For patients undergoing hip fracture surgery, we recommend LMWH or fondaparinux. CONCLUSION: Further research is needed to assess the value of NOACs for pharmacological prophylaxis in orthopedic/trauma patients undergoing surgical procedures other than the ones mentioned above, and into the benefit and harm of new devices available for mechanical prophylaxis. The stringent implementation of basic measures such as early mobilization, movement exercises, and patient instruction is a key point to prevent venous thrombo - embolism.

Prevention of fatal pulmonary embolism and mortality in surgical patients: a randomized double-blind comparison of LMWH with unfractionated heparin.

The incidences of fatal pulmonary embolism and death in surgical patients receiving low-molecular-weight heparin thromboprophylaxis have not been previously determined in large, adequately designed clinical trials and information on the relative efficacy and safety of unfractionated and low-molecular-weight heparin in preventing these clinical endpoints is not available. In a double-blind study, 23078 surgical patients randomly received the low-molecular-weight heparin, certoparin (3000 anti Xa IU) subcutaneously once-daily, or unfractionated heparin (5000 IU) subcutaneously three-times daily, for a minimum of 5 days. The primary outcome measure, autopsy-proven fatal pulmonary embolism recorded up to 14 days after the end of prophylaxis, occurred in 0.152% (95% confidence interval (CI) 0.10, 0.20%; 35 of 23078 patients) of cases, with no significant difference between the certoparin-treated patients (0.147% (95% CI 0.077, 0.217%; 17 of 11542 patients) and patients treated with unfractionated heparin (0.156% (95% CI 0.084, 0.228%; 18 of 11,536 patients, P=0.868). The autopsy rate was 70.2%. Comparing mortality, there was no significant difference between the groups (1 .44% [166 of 11542 certoparin patients] versus 1.27% [146 of 11536 unfractionated heparin patients]; P=0.279). The safety profiles of both treatment groups were similar. Once-daily certoparin and three-times daily unfractionated heparin are equally effective and safe in reducing fatal pulmonary embolism and death to low levels in surgical patients and mirror the findings of comparative efficacy studies using surrogate endpoints.

Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients: the MC-4 cancer substudy.

Cancer patients undergoing surgery are at a high risk of venous thromboembolism, but few studies have described the rate of autopsy-confirmed fatal pulmonary embolism after heparin thromboprophylaxis. In a post hoc analysis of a randomized study (MC-4), which compared the efficacy and safety of certoparin (3000 anti-Xa IU, subcutaneously, once-daily) with unfractionated heparin (5000 IU, subcutaneously, three-times daily) in 23078 patients undergoing surgery lasting more than 30 min, the incidence of autopsy-confirmed fatal pulmonary embolism, death and bleeding in the cancer patients (n=6124) was compared with non-cancer patients (n=16954). Fatal pulmonary embolism was significantly more frequent in cancer patients (0.33% [20/6124]) than in non-cancer patients (0.09% [15/16954], relative risk (RR), 3.7 [95% confidence intervals (CI), 1.80, 7.77], p=0.0001) at 14 days post-prophylaxis. Perioperative mortality was also significantly higher in cancer patients than in noncancer patients (3.14% [192/6124] vs. 0.71% [120/16954], RR, 4.54 [95% CI, 3.59, 5.76], p=0.0001), as were blood loss (p<0.0001), and transfusion requirements (p<0.0001). Prevention of venous thromboembolism in cancer surgical patients remains a clinical challenge.

Impact of spleen preservation in patients with gastric cancer.

BACKGROUND: Resection of the spleen en bloc with the stomach for gastric cancer is still widely performed for a curative resection (R0), but the presence of the spleen may have a favorable effect on recurrence control and survival. The hypothesis that the spleen suppresses tumor growth from minimal residual disease in the critical early postsurgical period and reduces the risk of recurrent disease was tested. PATIENTS AND METHODS: Patients were included who underwent gastrectomy, with or without splenectomy, for gastric adenocarcinoma. Standardized, strongly-defined criteria were used to accurately stratify patients, who had an extended (D2) lymph node dissection, into the curative and non-curative resection groups. Limited, D1 resection confounds appropriate R-stratification and thus D1 patients were excluded. Prospectively-defined primary endpoints were early (within two years) and overall recurrence and death from any cause and secondary endpoints were postsurgical risks (morbidity, mortality) and metastases to the splenic hilum nodes. RESULTS: Overall survival for the total population studied (n = 202) was better for preservation-versus-resection of the spleen among R0 patients (p = 0.0001), but not for those with non-curative resection (p = 0.42). For the R0 D2 group of patients, preservation (n = 59) over resection (n = 67) of the spleen, there was no significant difference in in-hospital postoperative morbidity or mortality (3.4% vs. 0%). At a median follow-up of 112 months, significantly the preservation of the spleen, lowered the risks of early recurrence (HR, 0.33; 95% CI, 0.16 to 0.69; p = 0.003) and death from any cause (p = 0.009) after adjustment analysis. Since at baseline there was a significant imbalance of tumor stage in favor of the spleen-preservation group, we conducted a stage-stratified subgroup analysis. This treatment effect remained consistent in the subgroup analyses according to nodal and serosal status, while in multivariate analysis preservation of the spleen was an independent predictor of outcome. An overestimation of the risk for residual disease in the splenic hilum nodes in the case of spleen preservation was obtained in 94% of splenectomized patients. CONCLUSION: Our findings indicate that preservation of the spleen may be associated with a reduced risk of early and overall recurrence translated into a better survival in patients receiving curative surgery for gastric cancer. A large randomized trial is needed to confirm this finding. Indications for splenectomy are few, being limited to those patients with advanced proximal cancers.

Thyroid fetal male microchimerisms in mothers with thyroid disorders: presence of Y-chromosomal immunofluorescence in thyroid-infiltrating lymphocytes is more prevalent in Hashimoto's thyroiditis and Graves' disease than in follicular adenomas.

The presence of fetal cells in a maternal compartment is defined as fetal-maternal microchimerism, which has been detected in thyroids of mothers suffering from autoimmunity. We analyzed the immunohistology of paraffin-embedded thyroid specimen taken at surgery from 49 women with Hashimoto's thyroiditis (n = 25), Graves' disease (n = 15), or nodular or diffuse follicular adenomas (n = 9), whose childbirth history was positive for sons. By fluorescence in situ hybridization we screened for X-chromosome- and Y-chromosome-specific staining and compared the finding with human leukocyte antigen (HLA) DQ types of the mothers and, where available, their offspring. In 23 thyroids we found Y-chromosome-specific staining, which was more frequent in thyroid autoimmune disease (60% Hashimoto's thyroiditis and 40% Graves' disease) than in follicular adenomas (22.2%). There was no significant difference for HLA DQ alleles among women whose thyroids showed Y-chromosome staining and those without. However, a subgroup of all investigated microchimerism-positive mother-child pairs and women with Hashimoto's thyroiditis and Graves' disease more often had the susceptibility alleles HLA DQA1*0501-DQB1*0201 or DQB1*0301. In conclusion, fetal microchimerism is observed in thyroids of mothers with sons, and this is found more frequently in thyroid autoimmune diseases.

Benefits and risks of preventing thromboembolism with enoxaparin in patients with general surgery in real world--the CLEVER study.

BACKGROUND: We aimed to document enoxaparin use in real world and identify the risk factors for bleeding complications. METHODS: Postauthorization study in 448 surgical patients receiving enoxaparin prophylaxis. Complete compression ultrasound (CCUS) was performed at day 10 ± 3. RESULTS: During treatment, 11 of 448 patients had suspected deep venous thrombosis (DVT) but none confirmed. One patient had symptoms of pulmonary embolism ([PE] 0.22%; 95% confidence interval [CI] -0.21-0.66). There were no asymptomatic cases detected upon CCUS. At the 90-day follow-up, 4 (0.9%) of the 440 patients had DVT symptoms (95% CI 0.02-1.80) and none had PE; 5.4% had major and 11.6% any type of bleeding complications. Major bleeding was more frequent in those with kidney disease (odds ratio [OR] 5.53), those who are bedridden (OR 5.49), those with peridural indwelling catheters (OR 4.01), and those on nonsteroidal anti-inflammatory drugs (OR 3.33). CONCLUSIONS: Enoxaparin is effective and safe in surgical patients to prevent venous thromboembolism.

Second liver resections are safe and effective treatment for recurrent hepatic metastases from colorectal cancer: a bi-institutional analysis.

OBJECTIVE: To determine the value of repeat liver resection for recurrent colorectal metastases to the liver. SUMMARY BACKGROUND DATA: Liver resection represents the best and a potentially curative treatment for metastatic colorectal cancer to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver. METHODS: This study reports the combined experience of repeat liver resection for recurrent liver metastases at an American and a European surgical oncology center. Patients were identified from prospective databases and records were retrospectively reviewed. A total of 126 patients (American n = 96, 1986-2001; European n = 30, 1985-1999) underwent repeat liver resection. Patient characteristics were similar in the two institutions. Median follow-up from first liver resection was 88 and 105 months, respectively. RESULTS: Operations performed included 90 minor resections and 36 resections of a lobe or more. The 1-, 3-, and 5-year survival rates were 86%, 51%, and 34%. There were 19 actual 5-year survivors to date. By multivariate regression analysis (proportional hazard model), more than one lesion and tumor size larger than 5 cm were independent prognostic indicators of reduced survival. The interval between the first and second liver resection was not predictive of outcome. CONCLUSIONS: Repeat liver resection for colorectal liver metastases is safe. Patients with a low tumor load are the best candidates for a repeat resection. In well-selected patients, further resection of the liver can provide prolonged survival after recurrence of colorectal liver metastases.