Direct improvement of quality of life in colorectal cancer patients using a tailored pathway with quality of life diagnosis and therapy (DIQOL): study protocol for a randomised controlled trial.

BACKGROUND: Medical treatment in patient-centred care in oncology is broadly managed and regulated in terms of guideline development, cancer centres, and quality assurance by cancer registries. In contrast to this quality management cycle (PDCA), there are no equal standards for patient-reported outcomes like quality of life (QoL). Therefore, the Tumour Centre Regensburg e.V., a population-based regional cancer registry covering a population of more than 2.2 million people in the Upper Palatinate and Lower Bavaria, Germany, designed and implemented a QoL pathway. In a complex intervention with QoL diagnosis and therapy (multidimensional therapeutic network), effectiveness for patients with breast cancer has been demonstrated. To provide local tailored QoL diagnosis and therapy to other cancer patients as well, external validity needs to be extended by adapting the QoL pathway to another tumour entity. METHODS/DESIGN: The QoL pathway will be tested for colorectal cancer patients in a pragmatic randomised controlled trial. Two hundred twenty primary colorectal cancer patients, surgically treated in one of four hospitals, will be included. QoL is measured in all patients 0, 3, 6, 12, and 18 months after surgery (European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-CR29). In the intervention group, QoL scores are transformed into a QoL profile. This is sent to the coordinating practitioner (general practitioner, internist, or oncologist) with an expert report including treatment recommendations for QoL deficits. The control group receives routine follow-up care attending the guideline recommendations for colorectal cancer without profile or expert report. At the primary endpoint (12 months), the rates of patients with diseased QoL in both groups are compared. DISCUSSION: This randomised trial is the first complex intervention investigating the effectiveness of an intervention with QoL diagnosis and tailored QoL therapy in colorectal cancer patients. The results will show if this QoL pathway improves the patients' QoL during follow-up care of their disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02321813 (registered December 2014).

Breast cancer survivors' recollection of their illness and therapy seven years after enrolment into a randomised controlled clinical trial.

BACKGROUND: Little is known about the subjective experience of breast cancer survivors after primary treatment. However, these experiences are important because they shape their communication about their illness in everyday life, usage and acceptance of healthcare, and expectations of new generations of patients. The present study investigated this topic by combining qualitative and quantitative methods. METHODS: Breast cancer survivors in Bavaria, Germany were mailed a questionnaire up to seven years after enrolment into a randomised controlled clinical trial and start of their therapy. This enquired about their worst experiences during the breast cancer episode, positive aspects of the illness and any advice they would give to newly diagnosed patients. A category system for themes was systematically created and answers were categorised by two independent raters. Frequencies of key categories were then quantitatively analysed using descriptive statistics. In addition, local treating physicians gave their opinion on the response categories chosen by their patients. RESULTS: 133 (80%) of 166 eligible patients who survived up to seven years returned the questionnaire. The most prominent worst experience reported by survivors was psychological distress (i.e. anxiety, uncertainty; prevalence 38%) followed by chemotherapy (25%), and cancer diagnosis (18%). Positive aspects of the illness were reported by 48% with the most frequent including change in life priorities (50%) and social support (22%). The most frequent advice survivors gave was fighting spirit (i.e. think positive, never give up; prevalence 42%). Overall, physicians' estimates of the frequency of these responses corresponded well with survivors' answers. CONCLUSIONS: Although physicians' understanding of breast cancer patients was good, psychological distress and chemotherapy-related side effects were remembered as particularly burdensome by a substantial part of survivors. On the one hand, patients' quality of life needs to be assessed repeatedly during medical follow-up to identify such specific complaints also including specific recommendations to the physician for targeted psychosocial and medical support. On the other hand the advices and positive aspects of the disease, reported by the survivors, can be used to promote positive ways of coping with the illness.

Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats.

BACKGROUND: In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF. METHODS: In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 mug/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-alpha and liver cytokine mRNA expression levels were determined. RESULTS: Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-alpha levels and a reduced expression of TNF-alpha and IL-1 in the liver. CONCLUSION: There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response.

[Utilities: a solution of a decision problem?]. / Utilities--eine Lösung für ein Bewertungsproblem?

Utility is a concept that originates from utilitarianism, a highly influential philosophical school in the Anglo-American world. The cornerstone of utilitarianism is the principle of maximum happiness or utility. In the medical sciences, this utility approach has been adopted and developed within the field of medical decision making. On an operational level, utility is the evaluation of a health state or an outcome on a one-dimensional scale ranging from 0 (death) to 1 (perfect health). By adding the concept of expectancy, the graphic representation of both concepts in a decision tree results in the specification of expected utilities and helps to resolve complex medical decision problems. Criticism of the utility approach relates to the rational perspective on humans (which is rejected by a considerable fraction of research in psychology) and to the artificial methods used in the evaluation of utility, such as Standard Gamble or Time Trade Off. These may well be the reason why the utility approach has never been accepted in Germany. Nevertheless, innovative concepts for defining goals in health care are urgently required, as the current debate in Germany on "Nutzen" (interestingly translated as 'benefit' instead of as 'utility') and integrated outcome models indicates. It remains to be seen whether this discussion will lead to a re-evaluation of the utility approach.

Quality of life diagnosis and therapy as complex intervention for improvement of health in breast cancer patients: delineating the conceptual, methodological, and logistic requirements (modeling).

BACKGROUND AND AIMS: A system for quality of life (QoL) diagnosis and therapy in breast cancer patients was developed according to the Medical Research Council (MRC) framework of complex interventions. Along MRC's five phases in the continuum of evidence, the present paper deals with phase I: modeling (i.e., delineating the conceptual, methodological, and logistic requirements). BASIC ELEMENTS: Theoretical background is a new conceptualization of QoL that provides a rational basis to diagnose "diseased" QoL. A care pathway as the central part of modeling is composed of the following interrelated structural elements: patients (n = 170), clinicians (n = 10), experts in a quality of life unit (n = 5), coordinating practitioners (n = 38), local opinion leaders (n = 12), and professional therapists for QoL enhancing therapies (n = 75). Networking of these structural elements was achieved by clinical algorithm. In the clinical center, the patient and doctor delivered a questionnaire (EORTC) and health status report. The QoL unit transformed it into a profile and experts' report. The coordinating practitioner transformed the latter into a decision on QoL therapy and the care pathway ended with the professional therapists. Implementation of this system used a multifaceted strategy including educational outreach visits, local opinion leaders, and quality circles. CONCLUSION: The suffering cancer patient is the main focus of this QoL diagnosis and therapy system. It will have to pass the rigorous test of a definitive randomized trial.

Perioperative prophylaxis with granulocyte colony-stimulating factor (G-CSF) in high-risk colorectal cancer patients for an improved recovery: A randomized, controlled trial.

BACKGROUND: We aimed to improve the postoperative outcome of high-risk patients (American Society of Anesthesiologists class 3 and 4) recovering from colorectal cancer surgery by using recombinant human G-CSF (filgrastim) as perioperative prophylaxis. METHODS: In a double-blinded, placebo-controlled trial, 80 patients undergoing left-sided colorectal resection were randomized to filgrastim or placebo. Filgrastim (5 mug/kg) or placebo was administered in the afternoon on day -1, 0, and +1 relative to the operation. Primary endpoints were in a hierarchic order: quality of life (QoL) over time (determined at discharge, 2 and 6 months after operation with the European Organization for Research and Treatment of Cancer questionnaire) and the McPeek recovery score, which measures death and duration of stays in the intensive care unit and hospital. Predefined secondary endpoints were global QoL, subdomains of QoL, postoperative recovery, duration of stay, 6-month overall survival, complication rates, and cellular and immunologic parameters. RESULTS: There were no significant differences in both primary endpoints between the treatment groups. A significant improvement (P < .05) was obtained by filgrastim prophylaxis in the QoL subdomain family life /- social functioning,; thus, more patients recovered to their preoperative state (14 vs 4 with placebo) as determined by structured interviews. Duration of hospital stay (14 vs 12 days) and noninfectious complications were decreased from 8% to 3%. CONCLUSIONS: High-risk patients undergoing major operation for colorectal cancer profited from filgrastim prophylaxis with regard to duration of hospital stay, noninfectious complications, social QoL, and subjective recovery from operation. These endpoints, however, were secondary, and the primary endpoints (overall QoL and the McPeek index) did not show comparable benefits. A new confirmatory trial with the successful endpoints of this trial, as well as a cost analysis, will be needed to confirm the results before a general recommendation for the prophylactic use of G-CSF in high-risk cancer patients can be given.

[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.

[Diagnosis and therapy of illness-related quality of life in breast cancer patients. Protocol of a randomized clinical trial at the Regensburg Tumour Centre]. / Diagnostik und Therapie der krankheitsbezogenen Lebensqualität bei Patientinnen mit Mammakarzi- nom. Protokoll einer randomisierten klinischen Studie am Tumorzentrum Regensburg.

BACKGROUND: The project conducted at the Tumour Centre in Regensburg aims to integrate quality of life (QL) diagnostics with the therapy of breast cancer patients and to evaluate the efficacy of QL diagnostics in the context of a randomized clinical trial. METHODS: The Regensburg Tumour Centre provides the infrastructure of the present project (telemedicine, project groups, quality circle). The treatment of breast cancer patients is based on the recent national breast cancer therapy guideline, including assorted QL-enhancing therapy options such as pain therapy, physiotherapy and lymphatic drainage, psychotherapy, social counselling and rehabilitation, nutrition and sports. During an implementation phase a new method of QL diagnostics has been developed. Five experts with varying professional background use the individual patient's QL profile and clinical and socio-demographic information in order to generate a QL report including a treatment recommendation. The study is designed as a two- arm randomized clinical trial with one test group (communication of the QL findings to the co-ordinating physician) and a control group (no communication). Patients with newly diagnosed breast cancer who are treated in the study region by one of the co-ordinating doctors will be included in this randomized study. At designated points in time QL assessments (EORTC QLQ-C30 plus BR23) will be conducted over a 12-months period. EXPECTED RESULTS: We expect that patients in the test group will experience a lower amount of QL deficits at the end of the study period (M = 1, SD = 2) than patients in the control group (M = 2, SD = 2). The statistical confirmation of this expected effect requires a total sample size of N = 200 (n = 100 vs. n = 100, alpha = 5% [two-tailed], beta = 10%). CONCLUSIONS: This is the first study to evaluate a new form of QL diagnostics in the complexity of a real patient care environment, and it promises to make the inclusion of the quality of life concept into the current breast cancer treatment guideline more tangible.

Early self-reported impairments in arm functioning of primary breast cancer patients predict late side effects of axillary lymph node dissection: results from a population-based cohort study.

OBJECTIVES: Improvements in the life expectancy of women with breast cancer raise important questions how to improve quality of life (QoL) for women sustaining complications and side effects of cancer treatment. The presented study examined the prevalence of arm morbidity in a cohort of primary breast cancer patients over time as a result of the extent of axillary lymph node dissection. Of particular interest is the question of using a recognized QoL assessment instrument at defined assessment points as an endpoint criteria of oncological treatment. METHODS: A prospective, population-based, longitudinal cohort study of patients with primary breast cancer was performed (n = 389). QoL data (EORTC QLQ C30 + BR23) and clinical data were assessed at designated time points. Primary endpoint of this analysis was patient reported arm morbidity assessed with the three-idem scale in the BR 23 (swelling, moving, pain). RESULTS: 20% of the patients evidenced considerable impairments in arm functioning. Arm morbidity was significantly related to the number of lymph nodes dissected (P < 0.002 entire cohort, P < 0.001 lymph node negatives) and was independent of age, stage of the disease, kind of breast surgery and radiation treatment. Early impairments in arm functioning (below 50 score values) assessed within 6 months after axillary surgery was a good predictor for late arm morbidity at 12 months RR 11.5 (CI 95% 4.7-28.4), 24 months RR 6.0 (CI95% 2.8-13.3) and 36 months RR 3.8 (CI 95% 1.8-7.9). CONCLUSIONS: Arm morbidity after axillary surgery is a severe and chronic condition affecting many breast cancer patients. The recognized QoL assessment instrument depict patients with severe impairments in arm functioning after axillary lymph node dissection and predict late arm morbidity. To increase patients' quality of life it thus may serve as a valid assessment tool for screening, allowing early referral for treatment and monitoring.

Granulocyte colony-stimulating factor prophylaxis improves survival and inflammation in a two-hit model of hemorrhage and sepsis.

OBJECTIVE: We evaluated the effects of a granulocyte-colony stimulating factor (G-CSF) prophylaxis in two clinically relevant situations, hemorrhage on the day before infection (e.g., trauma) and acute hemorrhage followed subsequently by infection (e.g., operative complication). A two-hit model of hemorrhage and polymicrobial peritoneal contamination and infection (PCI) was used to assess the influence of G-CSF on the outcome, bacterial clearance, and cytokine pattern. DESIGN: Clinic modeling randomized laboratory trial. SETTING: University laboratory. SUBJECTS: One hundred thirty-two male rats. INTERVENTIONS: In trial 1 we compared a) preoperative PCI only; b) preoperative hemorrhage plus PCI; and c) hemorrhage plus PCI plus G-CSF prophylaxis (n=18 rats/group). In trial 2, intraoperative hemorrhage was assessed with the same trial design. Primary end point was survival at 120 hrs. In trial 2 additionally, six rats per group and six naive control rats were used for secondary end point analysis. MEASUREMENTS AND MAIN RESULTS: Primary end point was mortality at 120 hrs. Secondary end points were granulocyte counts, bacterial clearance, and local cytokine levels. In trial 1 survival rate was 56% after PCI only, 17% after hemorrhage plus PCI, and 61% after hemorrhage plus PCI plus G-CSF (p<.01). In trial 2 survival rate was 33% after PCI only, 17% after hemorrhage plus PCI, and 50% after hemorrhage plus PCI plus G-CSF (p<.05). In trial 2, neutrophil counts were doubled to 66% 1 hr after hemorrhage (p<.05), colony-forming units of microbes in the lung and liver were halved to 166+/-56 and 134+/-28 colony-forming units (p<.05 for liver), and the macrophage inflammatory protein-2 expression in the lung was halved to 0.88+/-0.06 pg of complementary DNA (p<.05) by G-CSF prophylaxis compared with hemorrhage and PCI. CONCLUSIONS: Hemorrhage (first hit) sensitized the host for a second hit of polymicrobial PCI independent of the timing. G-CSF prophylaxis improved survival and clearance of microbes and reduced the proinflammatory chemokine macrophage inflammatory protein-2 in the lung.

Evaluation of the McPeek postoperative outcome score in three trials.

BACKGROUND: Postoperative outcome of patients is determined by recovery characteristics and self-reported quality of life. The first can be assessed with the McPeek score which values three aspects of recovery: mortality, postoperative critical care and duration of hospitalization. MATERIALS AND METHODS: We calculated the McPeek score of 669 patients in three trials: (1) colorectal cancer surgery, (2) antihistamine/volume loading in various operations, and (3) cholecystectomy. Beforehand, the average of intensive care unit treatment and duration of hospitalization were determined for the different operations to define McPeek score points. The score was tested on reliability, validity, and sensitivity. In addition, clinical applicability was assessed in a survey. RESULTS: The score was reliable with similarly distributed score points in the three trials at different institutions. Inter-rater reliability was high (97% overlap). Validity was proven by moderate high correlation to convergent criteria such as complications (trial I to III r=0.43, r=0.38, r=0.60), preoperative American Society of Anesthesiologists class (ASA) (r=0.24, r=0.28, r=0.57), and age (r=0.23, r=0.32, r=0.31). The score was different between patients with and without neoplasms (P<0.001, trial II) and between elective or emergency patients (P<0.001, trial III). In a survey, investigators reported that the score was easy to assess and more comprehensive than four other scores. CONCLUSIONS: The McPeek score values the postoperative outcome on a nonlinear scale. A priori, the average duration of hospitalization and critical care for a specific operation has to be defined. Our validation suggests that it is a reliable, valid, sensitive, and practical instrument for outcome analysis after anesthesia and surgery.

Outcome and quality of life in medicine: a conceptual framework to put quality of life research into practice.

It is rather counterproductive to get caught up in never ending discussions on what quality of life (QOL) is and whether it can be assessed. This article is based on the idea that it is much more important to improve the conceptual frameworks that allow the use of the QOL concept in clinical practice. Survival of the QOL concept within the medical community will depend on its contributions to a better understanding of patients and to improving patient care. It is important to accept that QOL should not be viewed in isolation but in synopsis, with other psychologic concepts and clinical data. We propose a profile format that presents QOL data in a way that is easily accessible for clinicians, allowing action to be taken immediately. QOL profiles are never a substitute but a starting point for a patient-doctor interaction. A profile driven interaction has the potential to be structured, efficient, and leading to action.

Integrated outcome assessment after anterior cervical discectomy and fusion: myelocompression but not adjacent instability affect patient-reported quality of life and cervical spine symptoms.

STUDY DESIGN: The authors conducted a cross-sectional study. OBJECTIVE: Integrated assessment of adjacent instability (AI), myelocompression (MC), magnetic resonance imaging (MRI) signs of myelopathy (MRISM), physician-assessed clinical signs and symptoms, including clinical signs of myelopathy (CSM), patients' self-reported symptoms and quality of life after anterior cervical discectomy and fusion (ACDF). MATERIALS AND METHODS: Fifty-four patients who had ACDF between 1986 and 1995 received MRI scans, conventional and flexion/extension radiographs to assess myelocompression, MRISM, fusion, and AI. Clinical outcome was assessed using signs and symptoms based on selected items of Odom's criteria, Oswestry low back pain disability questionnaire, and the neck disability index. Patients reported their quality of life (QL) on a standardized instrument (Profiles of QL of Chronically Ill [PLC]) and by a specific validated Cervical Spine Symptom Scale (CSSS). RESULTS: Myelocompression was found more frequently than expected (24%). MRISM were seen in 2 patients (4%). One of the 2 patients developed CSM. Fusion was achieved in 94% (with kyphosis in 17%). AI was found in 30%. However, only myelocompression but not AI was associated with statistically significant decreases in most QL scores (i.e., everyday capabilities, positive mood) and high cervical spine symptom burden (all P's < 0.05). CONCLUSIONS: The study results underline the need for a better understanding of the biomechanical changes in the adjacent unfused segments. Consensus is needed on postoperative follow-up guidelines, including pain management strategies. Future studies on the outcome of ACDF will profit from an integrated outcome approach, including assessments based on imaging, physicians, and patients.

[A concept for the implementation and evaluation of the guideline "Early Detection of Breast Cancer in Germany"]. / Implementierung und Evaluation von Leitlinien auf nationaler Ebene: Entwicklung eines Konzeptes für die Stufe-3-Leitlinie "Brustkrebs-Früherkennung in Deutschland".

Systematically developed, evidence- and consensus-based guidelines are important tools for improving health care services. The effectiveness of a guideline does not only relate to its methodological quality but also to the implementation strategy used. The following paper describes the systematic development of a strategy for implementing and evaluating the guideline "Early Detection of Breast Cancer in Germany" as part of a national project. A multi-faceted systematic implementation strategy has been developed addressing existing barriers and building on projects that have recently been introduced in Germany to improve the early detection and management of breast cancer. The aim is to induce behavioural changes in women as healthcare recipients and physicians as healthcare providers, both involved in the medical decision-making process within the scope of the guideline. Furthermore, it supports organisational changes to assure compliance with the guideline by means of quality assurance and quality management. To ensure evaluation of the implementation process a set of quality indicators have been identified for the baseline assessment of structures, provider performance and outcomes. Both the effectiveness of the implementation process and the effectiveness of the guideline itself will be measured by using the same set of indicators for reevaluation within a pre-defined time interval of 18 months. The quasi-experimental design of this uncontrolled before and after implementation study outlined in the present paper allows the assessment of clinically relevant changes using quality indicators that measure the effectiveness of the guideline on a national level.

[Short version of the guideline "Early Detection of Breast Cancer in Germany"]. / Kurzfassung der Stufe-3-Leitlinie "Brustkrebs-Früherkennung in Deutschland".

The aim of this evidence-, consensus- and outcome-based good clinical practice guideline is to help physicians, and women in making appropriate healthcare decisions about the early detection of breast cancer. The principle of early detection of breast cancer comprises the detection and diagnosis of pre-malignant breast tumours (UICC stage 0, carcinoma in situ) with a possible cancer risk reduction and the detection and diagnosis of breast cancer at an early stage (UICC stage 1) with a scientifically proven 90% chance of cure. By establishing a nation-wide comprehensive quality assurance program for the early detection of breast cancer this guideline lays the foundation for a timely reduction of breast cancer mortality and achievement of cure with less impairment of patient's quality of life. It would appear that this guideline makes major improvements in women's healthcare feasible.

Dependence of positive effects of granulocyte colony-stimulating factor on the antibiotic regimen: evaluation in rats with polymicrobial peritonitis.

We tested the hypothesis that the ability of granulocyte colony-stimulating factor (G-CSF) to prevent death from fecal peritonitis is influenced by the composition of the antibiotic regimen with which it is administered. We used a rodent model of polymicrobial peritoneal contamination and infection and the concept of clinical modeling randomized trials (CMRTs), which includes the conditions of randomized, clinical trials and complex clinical interventions (e.g., anesthesia, volume substitution, antibiotics, surgery, postoperative analgesia). With the peritonitis model we obtained a mortality dose-response curve that was sensitive to antibiotic prophylaxis. G-CSF was most efficacious when it was administered both prophylactically and after the onset of peritonitis. Cefuroxime/metronidazole, ofloxacin/metronidazole, and amoxicillin/clavulanate improved survival in combination with G-CSF best, whereas cefotaxime or ceftriaxone with and without metronidazole did not. G-CSF administration was associated with improved polymorphonuclear neutrophil phagocytosis and enhanced bacterial clearance. Pro-inflammatory cytokine release (tumor necrosis factor-a, interleukin-6, macrophage inflammatory protein-2) was decreased in plasma and in the peritoneal fluid. Their expression was lowered in various organs on the protein and mRNA level. The results were used to design a clinical trial to test the ability of G-CSF to prevent serious infections in patients with colorectal cancer surgery. In this trial G-CSF application and antibiotic prophylaxis were performed with the most effective scheduling and combinations (cefuroxime/metronidazole and ofloxacin/metronidazole) as defined here.

Mild preseptic hypothermia is detrimental in rats.

OBJECTIVE: We evaluated the effects of mild hypothermia (32 degrees C), established before experimental intra-abdominal sepsis, on outcome, cytokine pattern, and muscle tissue oxygenation. DESIGN: Clinic modeling randomized laboratory trial. SETTING: University laboratory. SUBJECTS: Ninety-six male rats. INTERVENTIONS: In a group-sequential design, using 42 rats per group, we compared mild hypothermia with normothermia before peritonitis. Peritoneal inoculation with human stool bacteria was performed to simulate clinical trial conditions. Additionally, 12 rats underwent preoperative mild hypothermia without infection. MEASUREMENTS AND MAIN RESULTS: Primary end point was mortality at 120 hrs. Secondary end points were systemic cytokine concentrations, granulocyte counts, and muscle oxygen partial pressure. Survival rate was 40% (16 of 42) after preseptic hypothermia and 62% (26 of 42) after preseptic normothermia (p =.048). All hypothermic rats without infection survived. Interleukin-10 concentrations were 1843 +/- 96 pg/mL after preseptic hypothermia, 945 +/- 225 pg/mL with preseptic normothermia, and 520 +/- 121 pg/mL after hypothermia without infection (p<.001). Macrophage inflammatory protein-2 was comparable in the treatment groups. Interleukin-6 concentrations were 106 +/- 24 pg/mL after preseptic hypothermia and 276 +/- 76 pg/mL with preseptic normothermia (p<.05). Postinfection granulocyte count was 1.7 x 10(9)/L after hypothermia and 2.4 x 10(9)/L after normothermia (p =.2). After infection, muscle oxygen partial pressure was 47 +/- 10 mm Hg with preseptic hypothermia, 85 +/- 12 mm Hg in preseptic normothermia, and 49 +/- 9 mm Hg after hypothermia without infection (p =.7). CONCLUSIONS: In this rat model of intra-abdominal sepsis, mild preseptic hypothermia (32 degrees C) reduced survival, impaired granulocyte recruitment, and changed cytokine balance, suggesting immunosuppression.

Quality of life of patients with maxillofacial defects after treatment for malignancy.

PURPOSE: The purpose of the study was to investigate how cancer patients with maxillofacial defects evaluate their quality of life after prosthodontic therapy, complemented by a retrospective interview for judging the various therapy steps. The results were compared with a nontumor control group (multiple tooth extractions) and with population-based norm data. MATERIALS AND METHODS: A total of 34 patients were included in the study, 17 in each group. Patients first filled in a questionnaire and then answered additional questions in a standardized interview. RESULTS: At the time of investigation, tumor patients did not significantly differ from nontumor patients regarding global quality of life. However, tumor patients had significantly less favorable values regarding role functioning, speech, mouth opening, and dry mouth, as well as pain and swallowing. In comparison with the reference data of the German population, tumor patients had considerable deficits (> 20 points) regarding role functioning, dyspnea, and financial difficulties. Other deficits (> 10 points) became apparent in global quality of life, fatigue, insomnia, and appetite. When reflecting the course of disease and recovery, tumor patients rated the diagnosis as the most stressful event and reported that the family was most instrumental in the recovery process. CONCLUSION: Patients with maxillofacial defects after treatment for malignancy suffer from numerous clearly definable quality of life-related symptoms and problems, even after prosthodontic treatment. These patients need psychologic care at the time of diagnosis to alleviate the burden of the cancer diagnosis and prepare for the demanding treatment. After completion of the prosthodontic treatment, therapy options for pain or speech problems should be offered.

Deleterious effects of mild hypothermia in septic rats are ameliorated by granulocyte colony-stimulating factor.

BACKGROUND: The authors studied the effects of mild hypothermia on the outcome in a rat model of intraabdominal sepsis and tested whether granulocyte colony-stimulating factor (G-CSF) augments the host response and improves outcome during mild hypothermia. METHODS: A rat model of peritoneal contamination and infection with human stool bacteria was used to simulate clinical trials that included increasing complexity. In trial 1, postoperative hypothermia (32 degrees C) was compared with normothermia (38 degrees C), without supportive treatment (10 rats per group). In trial 2, with a more severe infection, rats were given antibiotic prophylaxis. Using 20 rats per group, the authors compared postoperative hypothermia (32 degrees C), normothermia, and postoperative hypothermia (32 degrees C) with 20 mug/kg G-CSF prophylaxis given 12 h before surgery and 12 h and 36 h after surgery. The primary endpoint was death at 120 h. Secondary endpoints were systemic cytokine concentrations, leukocyte counts, and the phagocytic activity of granulocytes and monocytes. RESULTS: In trial 1, 50% of the normothermia group and 10% of the postoperative hypothermia group survived. In trial 2, 50% of the normothermia group, 20% of the hypothermia group, and 60% of the hypothermia plus G-CSF group survived. Postoperative hypothermia plus G-CSF reduced plasma concentrations of interleukin-6 (hypothermia group, 511 +/- 104 pg/ml; hypothermia plus G-CSF group, 247 +/- 51 pg/ml) and macrophage inflammatory protein-2 (hypothermia group, 239 +/- 43 pg/ml; hypothermia plus G-CSF group, 178 +/- 21 pg/ml). CONCLUSIONS: In this rat model of intraabdominal sepsis, postoperative hypothermia was deleterious. However, G-CSF treatment, initiated before contamination, reduced the mortality rate, increased the neutrophil count, and downgraded the systemic cytokine response.