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Background ICU survivorship includes a diverse burden of disease. Current questionnaires used for collecting information about health-related problems and their relation to quality of life lack detailed questions in several areas relevant to ICU survivors. Our aim was to construct a provisional questionnaire on health-related issues based on interviews with ICU survivors and to test if this questionnaire was able to show differences between ICU survivors and a control group. Methods Thirty-two ICU survivors were identified at a post-ICU clinic and interviewed at least six months after ICU discharge. Using an established qualitative methodology from oncology, all dysfunctions and disabilities were extracted, rephrased as questions and compiled into a provisional questionnaire. In a second part, this questionnaire was tested on ICU survivors and controls. Inclusion criteria for the ICU survivors were ICU stay at least 72 h with ICU discharge six months to three years prior to the study. A non-ICU-treated control group was obtained from the Swedish Population Register, matched for age and sex. Eligible participants received an invitation letter and were contacted by phone. If willing to participate, they were sent the questionnaire. Descriptive statistics were applied. Results Analysis of the interviews yielded 238 questions in 13 domains: cognition, fatigue, physical health, pain, psychological health, activities of daily living, sleep, appetite and alcohol, sexual health, sensory functions, gastrointestinal functions, urinary functions and work life. In the second part, 395 of 518 ICU survivors and 197 of 231 controls returned a completed questionnaire, the response rates being 76.2% and 85.3%, respectively. The two groups differed significantly in 13 of 22 comorbidities. ICU survivors differed in a majority of questions (p ≤ 0.05) distributed over all 13 domains compared with controls. Conclusions This study describes the development of a provisional questionnaire to identify health-related quality of life issues and long-term burden of disease after intensive care. The questionnaire was answered by 395 ICU survivors. The questionnaire could identify that they experience severe difficulties in a wide range of domains compared with a control group. Trial registry ClinicalTrials.gov Ref# NCT 02767180

Additional file 4. Figure S1: Examples of interview questions and verbal prompts and probes used in both original interviews and during cognitive interviews.

Additional file 1. Table S1: List of scales and questionnaires discussed during interviews with ICU survivors.

Additional file 5. Figure S2: Examples on construction of questions.

BackgroundICU survivorship includes a diverse burden of disease. To understand the extent of the problems, the right issues must be identified, and the right questions need to be asked to the patients. Current follow-up instruments lack detailed questions in several areas relevant to survivors. Our aim was to identify health-related problems relevant and unique to ICU survivors, and to construct a comprehensive questionnaire able to address these issues.Methods Thirty-three ICU survivors were interviewed at least six months after ICU discharge. All types of everyday dysfunctions and disabilities were extracted and compiled into a questionnaire. The questionnaire was tested on ICU survivors and non-ICU treated subjects. Inclusion criteria for the ICU survivors were an ICU stay of at least 72 hours with the ICU discharge six months to three years prior to the study. The non-ICU treated subjects were obtained from the Swedish Population Register, matched for age and sex. Eligible participants received an invitation letter and were contacted by phone. If willing to participate, they were sent the questionnaire. ResultsAnalysis of the interviews yielded 238 questions in 13 domains: cognition, fatigue, physical health, pain, psychological health, activities of daily life, sleep, appetite and alcohol, sexual health, sensory functions, gastrointestinal, urinary tract and work life.In total, 395 of 518 ICU survivors and 197 of 231 non-ICU treated subjects returned a completed questionnaire, the response rate being 76.2% and 85.3% respectively. The two groups differed significantly in 16 of 25 comorbidities. ICU survivors differed in a majority of questions (p ≤ 0.05) compared to non-ICU treated subjects, distributed over all 13 domains. ConclusionsThis study describes the first step in developing a designated questionnaire for identification of health-related quality of life issues and long-term burden of disease after intensive care. A first version of the questionnaire was answered by 395 ICU survivors. The questionnaire could identify that they experience severe difficulties in a wide range of domains compared to non-ICU treated subjects.Trial registrationClinicalTrials.gov Ref# NCT 02767180

Background and purpose: In uterine cervical cancer tumour spread reaching the para-aortic lymph nodes is the most significant independent pre-treatment predictor of progression-free survival. When introducing [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) in our clinic for patients with advanced cervical cancer planned for definitive radiochemotherapy, the purpose of this study was to quantify to what extent the added information lead to changes in radiotherapy planning. Material and methods: We included 25 consecutive patients with cervical cancer stages IB2 – IIIB planned for definitive radiochemotherapy between November 2010 and May 2012. The patients were examined both with magnetic resonance imaging (MRI) and FDG-PET/CT before treatment and after four weeks of treatment. Results: In 11/24 (46%) of the patients the FDG-PET/CT before treatment provided additional diagnostic information leading to changes in treatment planning compared to information from MRI. Seven of these eleven patients (64%) were alive and without evidence of disease at four-year follow-up. The MRI detected pelvic tumour spread not seen on the FDG-PET/CT in 2/24 patients. The disease-free four-year survival was 59%. Conclusions: Additional diagnostic information from FDG-PET/CT changed treatment strategy in almost half of the patients and may have increased chances of survival in this limited group of patients with locally advanced uterine cervical cancer. We recommend both modalities for nodal detection. Keywords: Cervical cancer, Nodal spread, Radiochemotherapy, FDG-PET/CT, MRI

To analyze the relationship between mean radiation dose to the bowels and the anal-sphincter and occurrence of 'defecation into clothing without forewarning', a specific and serious fecal incontinence symptom after gynecological radiotherapy. Additional potential risk factors associated with the symptom are explored.Data were collected for 519 eligible gynecological cancer survivors, treated with pelvic radiotherapy, with a median follow-up of 5.8 years, using a study-specific questionnaire and medical records. Correlations between defecation into clothing without forewarning and mean dose to organs at risk; the anal-sphincter region, the rectum, the sigmoid and the small intestines were investigated, also taking other risk factors into account.Twelve percent reported having had the symptom at least once in the preceding six months. Mean doses 50 Gy to the anal-sphincter region, the rectum, the sigmoid and the small intestines were related to the occurrence of the symptom. Significantly associated risk factors were deliveries with high birth weight, heart failure and lactose and/or gluten intolerance. After adjusting for these factors, mean doses 50 Gy to the anal-sphincter region, the sigmoid and the small intestines remained related to the occurrence of the symptom.Mean doses to the bowels and anal-sphincter region are related to the risk of defecation into clothing without forewarning in long-term gynecological cancer survivors treated with pelvic radiotherapy. Further radiobiological modeling may distinguish which organ(s) contribute most to development of the symptom.

The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future.Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model.The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs.In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.

Every year medical researchers make contact with a large number of cancer survivors with the aim of evaluating cancer treatment. For this reason we decided to investigate how Swedish cancer survivors perceived their participation in research studies focusing on the long-term consequences of being a survivor of gynaecological or urinary bladder cancer. Data were collected by means of two study-specific postal questionnaires, both consisting of questions covering physical symptoms, well-being and the experience of being a cancer survivor. Both questionnaires also included questions evaluating the participants' experience of being research subjects. The questionnaires were developed in close co-operation with cancer survivors. The study population consisted of 1068 cancer survivors. Of these, 95% (n=1003) reported that they thought the study was valuable and 54% (n=559) that they had been positively affected by participating. Four per cent (n=39) expressed that they had been negatively affected by their participation in the study. The vast majority of the cancer survivors thought that participating in their particular study was valuable.

Introduction: Fecal incontinence is a symptom reported by cancer survivors after pelvic radiotherapy and is recognized to be one of the most troubling symptom-induced sources of distress to patients. Objective: To investigate how fecal incontinence, patient-reported as emptying of all stools into clothing without forewarning, impact self-assessed quality of life from a social, psychological, sexual, and functional aspect among gynecological cancer survivors treated with pelvic radiotherapy. Methods: We identified a cohort of 789 eligible women in the Stockholm and Gothenburg areas treated with pelvic radiotherapy alone or as combined treatment of gynecological cancer. From the Swedish Population Registry, we identified 478 control women. Data were collected using a study-specific, validated, postal questionnaire including questions covering symptoms from the pelvic region, demographics, social functioning, psychological, and quality-of-life issues. Results: Participation was 78% for cancer survivors and 72% for control women. The fecal incontinence symptom emptying of all stools into clothing without forewarning was reported by 70 cancer survivors (12%), with lowered quality of life in 74% of the 70 cancer survivors. This symptom kept the survivors from going to parties (relative risk [RR], 11.8; 95% confidence interval [CI], 6.6-21.1), kept the survivors from traveling (RR, 9.3; 95% CI, 5.3-16.5), affected their work ability (RR, 7.9; 95% CI, 3.8-16.4), hindered their sexual life (RR, 9.2; 95% CI, 4.8-17.6), and changed them as persons (RR, 4.9; 95% CI, 2.9-8.1). The prevalence of the symptom emptying of all stools into clothing without forewarning among control women was 3 (1%) of 344. Conclusions: Among gynecological cancer survivors having undergone pelvic radiotherapy alone or as part of a combined treatment, fecal incontinence is associated with social, psychological, sexual, and functional consequences.

Background and purpose To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom ‘absence of vaginal elasticity’ and how time to follow-up influences this relation. Materials and methods The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patient’s age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. Results The dose-response parameters for ‘absence of vaginal elasticity’ according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL=−39.8, D50 = 49.7 (47.2–52.4) Gy, γ 50 = 1.40 (1.12–1.70) and LL = −37.4, D50 = 46.9 (43.5–50.9) Gy, γ 50 = 1.81(1.17–2.51) respectively. Conclusions The proposed model, which describes the influence of time to follow-up on the dose-response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom ‘absence of vaginal elasticity’ increases with time to follow-up, while D50decreases. • Alevronta E, Avall-Lundqvist E, Al-Abany M, et al. Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy. Radiother Oncol 2016. http://dx.doi.org/10.1016/j.radonc.2016.02.013 .

Purpose. The purpose of this study was to examine whether or not vaginal elasticity or lack of lubrication is associated with deep or superficial dyspareunia. We investigated gynecological cancer survivors treated with radiation therapy. Methods. In a population-based study with 616 women answering a questionnaire (participation rate 78%) and who were treated with radiotherapy for gynecological cancer, we analyzed information from 243 women (39%) who reported that they had had intercourse during the previous six months. Analyses included log-binomial regression (relative risks) and multiple imputations by chained equations in combination with Bayesian Model Averaging, yielding a posterior probability value. Age range of this cancer recurrent-free group of women was 29-80. Results. Dyspareunia affected 164 of 243 of the women (67%). One hundred thirty-four women (55%) reported superficial pain, 97 women (40%) reported deep pain, and 87 women (36%) reported both types of dyspareunia. The relative risk (RR) of deep dyspareunia was 1.87 (CI 1.41-2.49) with impaired vaginal elasticity compared to normal vaginal elasticity. Age and lower abdominal swelling were separate risk factors for deep dyspareunia. However, effects remain after adjusting for these factors. Conclusion. The relative risk of deep dyspareunia was almost twice as high with impaired vaginal elasticity compared to normal vaginal elasticity. If we wish to treat or even prevent deep dyspareunia in women with gynecological cancer, we may use our knowledge of the pathophysiology of deep dyspareunia and increasingly provide dilators together with instructions on how to use them for stretching exercises in order to retain vaginal elasticity. Results highlight the need for studies with more precise questions distinguishing superficial from deep dyspareunia so that in the future we may be able to primarily try to avoid reduced vaginal elasticity and secondarily reduce the symptoms. Funding Agencies|Swedish Cancer Society; Cancer Research Funds of Radiumhemmet; King Gustav V Jubilee Clinic Cancer Foundation, Gothenburg; Swedish State under ALF, Stockholm; Swedish State under ALF, Gothenburg

A questionnaire was developed, according to the European Organization for Research and Treatment of Cancer (EORTC) published guidelines, to supplement the EORTC quality of life questionnaire-core 30 (QLQ-C30) to assess the quality of life (QL) of women with ovarian cancer treated in clinical trials. The provisional 28-item module, OV28, assesses abdominal symptoms; peripheral neuropathy; other chemotherapy side-effects; hormonal symptoms; body image; attitude to disease and treatment; and sexual functioning. The first 24 items of the module (excluding sexual functioning) were included in a UK multicentre trial (SCOTROC). The trial data were used for preliminary scaling analysis. Two problematic items were identified. When these were treated as single items along with the 'other chemotherapy side-effects' the instrument showed excellent scale properties. Mean scale scores discriminated between trial patients pre- and on chemotherapy. This is a promising tool for assessing the QL of women with ovarian cancer. The EORTC international field study (Protocol 15982) to assess more fully the psychometric properties of the OV28 is well underway.

Diabetic patients with acute myocardial infarction have a poor prognosis, which has been attributed to a higher incidence of congestive heart failure and fatal reinfarction. This study reports on the one-year morbidity and mortality in a randomized study with the aim of testing whether insulin-glucose infusion initiated as soon as possible after onset of myocardial infarction and followed by long-term subcutaneous insulin treatment may have a beneficial effect on outcome in diabetic patients. In all, 306 patients were recruited to the insulin-treated group, while 314 patients served as controls. The overall mortality after one year was 19% in the insulin group compared to 26% among controls (P < 0.05). The treatment effect was most pronounced in patients without prior insulin medication and at low cardiovascular risk. In this stratum the in-hospital mortality was reduced by 58% (P < 0.05) and the one-year mortality by 52% (P < 0.02). The most frequent cause of death in all patients was congestive heart failure (66%), but cardiovascular mortality (congestive heart failure, fatal reinfarction, sudden death and stroke) tended to be decreased in insulin-treated patients. However, this difference did not reach the level of statistical significance. The number of reinfarctions was 53 (28% fatal) in the insulin group compared to 55 (45% fatal) in the control group. The two groups did not differ as regards need for hospital care or coronary revascularization during the year of follow-up. In summary, left ventricular failure and fatal reinfarctions contribute to increased mortality in diabetic patients following acute myocardial infarction. Intensive insulin treatment lowered this mortality during one year of follow-up.

Lower limb lymphedema (LLL) is a common condition after pelvic cancer treatment but few studies have evaluated its effect on the quality of life and its consequences on daily life activities among gynecological cancer survivors.We identified a cohort of 789 eligible women, treated with pelvic radiotherapy alone or as part of combined treatment of gynecological cancer, from 1991 to 2003 at two departments of gynecological oncology in Sweden. As a preparatory study, we conducted in-depth interviews with gynecological cancer survivors and constructed a study-specific questionnaire which we validated face-to-face. The questionnaire covered physical symptoms originating in the pelvis, demographic, psychological, and quality of life factors. In relation to the lymph system, 19 questions were asked.Six hundred sixteen (78 %) gynecological cancer survivors answered the questionnaire and participated in the study. Thirty-six percent (218/606) of the cancer survivors reported LLL. Overall quality of life was significantly lower among cancer survivors with LLL. They were also less satisfied with their sleep, more worried about recurrence of cancer, and more likely to interpret symptoms from the body as recurrence. Cancer survivors reported that LLL kept them from physical activity (45 %) and house work (29 %) and affected their ability to partake in social activities (27 %) or to meet friends (20 %).Lower limb lymphedema has a negative impact on quality of life among gynecological cancer survivors, affecting sleep and daily life activities, yet only a few seek professional help.

Aim Annually about 500,000 women worldwide are diagnosed with cervical cancer. For many patients, young age at the time of diagnosis and a good prognosis regarding the disease imply a long life with the side-effects and sequels of various treatment options. The present study investigated the extent to which different quality of life (QoL) domains in patients during and after treatment for cervical cancer are affected according to menopausal status, treatment status and treatment modality. Methods QoL data from 346 cervical cancer patients from 14 countries who were included in a cervical cancer module validation study of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Group were analysed according to menopausal status, treatment status and treatment modality. QOL was assessed using the EORTC Quality of life Questionnaire (QLQ)-C30 and the QLQ-CX24 module. Statistical analyses were performed using descriptive statistics and analysis of covariance. Results Active treatment had the strongest negative impact on 13 different QoL domains: physical, role, emotional, cognitive, social functioning, global health/QoL, fatigue, nausea and emesis, pain, appetite loss, constipation, symptom experience and sexual enjoyment. Irradiation alone ± other therapy was associated with most symptoms of diarrhoea. Age had the most negative impact on sexual activity and the strongest positive effect on sexual worry. Conclusion Our results revealed that patients with cervical carcinoma had different side-effects with different impacts on QOL depending on the menopausal status and therapy modalities. Patients should be informed about the possibility that therapy may have a negative impact on QoL.

Purpose To investigate the relative importance of patient-reported hip and sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its relationship to the absorbed doses in these organs. Methods and Materials We used data from a population-based study that included 650 long-term gynecological cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in Sweden with a median follow-up of 6 years (range, 2–15) and 344 population controls. Symptoms were assessed through a study-specific postal questionnaire. We also analyzed the hip and sacral dose-volume histogram data for 358 of the survivors. Results Of the survivors, one in three reported having or having had hip pain after completing RT. Daily pain when walking was four times as common among the survivors compared to controls. Symptoms increased in frequency with a mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the sacrum. Sacral pain also affected their walking ability and tended to increase with a mean absorbed dose >42.5 Gy. Conclusions Long-term survivors of gynecological cancer treated with pelvic RT experience hip and sacral pain when walking. The mean absorbed dose was significantly related to hip pain and was borderline significantly related to sacral pain. Keeping the total mean absorbed hip dose below 37.5 Gy during treatment might lower the occurrence of long-lasting pain. In relation to the controls, the survivors had a lower occurrence of pain and pain-related symptoms from the hips and sacrum compared with what has previously been reported for the pubic bone.

In preparation for studies of dose volume of ionizing radiation and long-term side effects, we assessed both variation in position and volume of organs at risk in the small pelvis. Material and methods. On 10 men and seven women we delineated the sigmoid, rectum, anal sphincter, bladder, penile bulb, and cavernous bodies in two CT scans taken between five to 69 days apart. Results. The measured overlap of the two delineated volumes divided by the maximum possible overlap, was below 50% for the sigmoid in six of 17 patients, for the distal 4 cm of the sigmoid in five of 17 patients, for the rectum in none of 17 patients, for the anal sphincter in three of 17 patients and for the urinary bladder in none of 17 patients. The smaller volume divided by the larger volume was below 50% in three of 17 patients for the sigmoid, in six of 17 patients for the 4 distal cm of the sigmoid, in two of 17 patients for the rectum, in two of 17 patients for the anal sphincter and in seven of 17 patients for the urinary bladder. For the urinary bladder the largest deviation was found cranially, 4.0 cm (SD 2.0 cm), the caudal part being relatively fixed. For the rectum the largest deviation was found in the anterior wall, 1.8 cm (SD 0.7 cm), with maximum documented variation in cranial direction of 3.2 cm (SD 1.8 cm). Conclusions. The sigmoid varies considerably in documented position with the largest deviation anteriorly, the urinary bladder change in volume with the extension mainly located cranially and for the rectum the anterior wall is the most mobile with the distension becoming more pronounced cranially. In modeling dose-volume effects one may consider our results.

PURPOSE: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors.METHODS AND MATERIALS: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire.RESULTS: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses

Aim of the study To make a comprehensive, detailed inventory of gastrointestinal symptoms reported by gynaecological cancer survivors and control women from the general population. Method We identified a cohort of 789 eligible women in the Stockholm and Gothenburg areas, treated with pelvic radiotherapy during the period 1991–2003, alone or as combined treatment, for gynaecological cancer. As controls, we randomly recruited 478 women, frequency matched by age and residence from the Swedish Population Registry. We collected data in 2006 by means of a study-specific, validated, postal questionnaire including 351 questions covering symptoms from the pelvic region. We asked about demographics, psychological and quality-of-life issues as well as social functioning. Results Participation was 78% for cancer survivors and 72% for controls. Mean follow-up was 7.2 years. In this large, population-based study, the greatest age-adjusted absolute risk difference between cancer survivors and control women was observed for the symptom defaecation urgency with faecal leakage and the highest age-adjusted relative risk for emptying of all stools into clothing without forewarning. Conclusions Cancer survivors having undergone pelvic radiotherapy alone or as part of combined treatment between the period 1991–2003 for a gynaecological malignancy had a higher occurrence of long-lasting gastrointestinal symptoms as compared to population controls.

BACKGROUND The authors report on the development and validation of a cervical cancer module for the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QoL) questionnaire (QLQ), which was designed to assess disease-specific and treatment-specific aspects of QoL in patients with cervical cancer. METHODS The cervical cancer module (EORTC QLQ-CX24) was developed in a multicultural, multidisciplinary setting to supplement the EORTC QLQ-C30 core questionnaire. The QLQ-C30 and the cervical cancer module were administered to 346 patients with cervical cancer who underwent radical hysterectomy and received radiotherapy and chemotherapy. Psychometric analyses were performed by using data from 2 independent samples. RESULTS The QLQ-CX24 consists of 3 multiitem scales and 5 single-item scales. Multitrait scaling analyses revealed high internal consistencies for the subscales with Cronbach α coefficients ranging from .72 to .87 (Symptom Experience, .72; Body Image, .86; Sexual/Vaginal Functioning, .87). Convergent and discriminant validity were fulfilled with scaling errors below 3%. The QLQ-CX24 was capable of discriminating between clinical subgroups. All items exhibited good compliance with

Department of Obstetrics and Gynecology, University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria EORTC Quality of Life Unit, EORTC Data Centre, Brussels, Belgium Imperial Cancer Research Fund Psychology Research Group, Western General Hospital, Edinburgh, UK Sahlgrenska University Hospital, Gotenborg, Sweden Hospital of Navarre, Pamplona, Spain Hotel Dieu, Paris, France Department of Biological Psychiatry, University Innsbruck, Austria Department of Obstetrics and Gynecology, University of Rijeka, Croatia

The effect of metoprolol on mortality was compared with that of placebo in a double-blind randomised trial in patients with definite or suspected acute myocardial infarction. Treatment with metoprolol or placebo started as soon as possible after the patient's arrival in hospital and was continued for 90 days. Metoprolol was given as a 15 mg intravenous dose followed by oral administration of 100 mg twice daily. 1395 patients (697 on placebo and 698 on metoprolol) were included in the trial. Definite acute myocardial infarction developed in 809 and probable infarction in 162. Patients were allocated to various risk groups and within each group patients were randomly assigned to treatment with metoprolol or placebo. There were 62 deaths in the placebo group (8·9%) and 40 deaths in the metoprolol group (5·7%), a reduction of 36% (p

18 patients with valvular aortic stenosis were given an i.v. glucose tolerance test and an i.v. insulin tolerance test before and 4-36 months after valve replacement. Insulin and C-peptide response to the glucose challenge was smaller preoperatively whereas the glucose response was the same pre- and postoperatively. The effect on blood glucose of the i.v. insulin challenge was more pronounced preoperatively. It is concluded that insulin sensitivity was increased preoperatively and it is suggested that this was a metabolic adaptation to the haemodynamic situation in aortic stenosis, which may have implications for preoperative glucose-insulin-potassium treatment.

The mortality and morbidity were assessed during a 2-year follow-up in an acute intervention trial in suspected acute myocardial infarction with metoprolol (a selective beta 1-blocker). On admission to the trial, the 1395 participating patients were randomly allocated to metoprolol or placebo for 3 months. Thereafter, if there was no contraindication, patients with infarction and/or angina pectoris were continued on metoprolol for 2 years. A lower mortality was observed after 3 months in patients randomised to metoprolol. The difference remained after 2 years. The difference in 2-year mortality rate was restricted to patients randomised early after onset of pain. Late infarction was observed more often in the placebo group during the first 3 months. When the two groups thereafter were treated similarly, the difference successively declined and did not remain after 2 years. A similar incidence of angina pectoris was observed in the two groups at each check up. During the early recovery period, more patients in the metoprolol group returned to work. No such difference was observed later on.

In 80 patients who underwent heart surgery the incidence of electrocardiographic (ECG) changes after the operation was analysed. A precordial grid containing 24 leads and leads II, III and aVF was used. Electrocardiographic measurements were taken the day before the operation and again 5 days after the operation. New Q-waves were observed in 2 patients (2.5%) in the 24 precordial leads, in 2 patients in leads II, III and aVF, and in one patient in both precordial leads and leads II, III and aVF. New T-wave inversions were observed in 20 patients (25%) in the 24 precordial leads, in 5 patients (6%) in leads II, III and aVF, and in 3 patients in both precordial leads and leads II, III and aVF. A similar serum enzyme activity was observed both in patients developing Q-waves as well as T-wave inversions compared with cases in whom ECG changes did not appear.

In this study, increased glycogen content in the myocardium, accompfished by preoperative glucose-insulin-potassium infusions, in patients operated for cardiac valvular diseases results in decreased myocardial damage, as judged from CK B leakage.

Myocardial protection during open heart surgery is achieved by general cooling and cold cardioplegia. However sympathetic activation during the operation causes raised circulating catecholamine levels that might negatively influence the myocardial metabolism. Moreover, local liberation of catecholamines, in "poorly perfused' regions of the myocardium in patients with ischemic heart disease, might occur. In respect of these problems, we studied the influence of noradrenaline at different temperatures on the isolated perfused rat heart. The temperatures chosen were: 10, 20, 32, 37 and 39 degrees C. The results show clearcut adverse effect of noradrenaline at 32 degrees and higher, on metabolism and hemodynamic performance. At lower temperatures there still seem to be an adverse effect of noradrenaline although not statistically significant. The results of this study indicates the importance of presurgical myocardial protection especially of badly perfused myocardial areas. Such protection could be accomplished by beta-blockade and/or loading of the myocardium with glycogen by glucose-insulin-potassium infusion.

Twenty-nine patients were randomly allocated to two groups before undergoing aorto-coronary bypass surgery. In one group the beta-blocking medication was withdrawn three days preoperatively, and in the other group it was maintained. The patients in the latter group were additionally given 100 mg metoprolol per os two hours before surgery. The degree of myocardial injury, as judged from cumulated activity of S-CK B, was less when the beta-blockade was maintained.

In a double blind study of metoprolol in the treatment of suspected acute myocardial infarction 698 patients (study group) received metoprolol and 697 a placebo (control group). Metoprolol was given in an intravenous dose of 15 mg as soon as possible after admission to hospital followed by 50 g by mouth four times a day for two days and thereafter 100 mg twice a day for three months. A placebo was similarly given. Congestive heart failure occurred in a similar percentage of patients in both the study (27%) and the control groups (30%). Its severity was estimated by calculating the total dose of frusemide given during the first four days in hospital. Less frusemide was given to patients treated with metoprolol compared with those given a placebo in the total series. An appreciably lower total dose of frusemide was given to patients included in the trial less than or equal to 12 hours after the onset of pain and treated with metoprolol compared with a placebo, while no difference was seen among patients treated later. The initial heart rate, systolic blood pressure, and infarct site affected the results.

The variability of chest pain is described in 389 patients with acute myocardial infarction. Whereas 17% were free from severe pain after arrival in hospital, 11% required more than 10 analgesic injections. In 27% of the series analgesics were given more than 24 h after arrival in hospital. Predictors for the severity of chest pain were the rate-pressure product and degree of chest pain soon after arrival in hospital as well as electrocardiographic signs of myocardial infarction at entry. Patients with more severe chest pain had a higher 2-year mortality rate and a higher incidence of ventricular fibrillation and congestive heart failure during hospitalization.

A four-hour insulin "clamp" technique was used to study the dose-response relationship between a wide range of plasma concentrations of insulin (5.0-7000 mU/l), free fatty acids, adrenaline and noradrenaline in 28 patients directly after open heart surgery. The influence of beta-blockers is discussed. All patients had elevated levels of free fatty acids at the beginning of the study (1020 +/- 77 mumol/l). After 4 hours the decline in free fatty acids was significant in all insulin-treated patients and most pronounced in the groups with insulin concentrations of more than approximately 350 mU/l, i.e. when insulin was infused with 0.3 units/kg bw/hour or more. No significant decrease in free fatty acids was observed in the control group. Adrenaline and noradrenaline in plasma were markedly increased throughout the study and were unaffected by the insulin infusions in all groups.