Reasons for not reaching or using web-based self-management applications, and the use and evaluation of Oncokompas among cancer survivors, in the context of a randomised controlled trial.

INTRODUCTION: The web-based self-management application Oncokompas was developed to support cancer survivors to monitor health-related quality of life and symptoms (Measure) and to provide tailored information (Learn) and supportive care options (Act). In a previously reported randomised controlled trial (RCT), 68% of 655 recruited survivors were eligible, and of those 45% participated in the RCT. Among participants of the RCT that were randomised to the intervention group, 52% used Oncokompas as intended. The aim of this study was to explore reasons for not participating in the RCT, and reasons for not using Oncokompas among non-users, and the use and evaluation of Oncokompas among users. METHODS: Reasons for not participating were assessed with a study-specific questionnaire among 243 survivors who declined participation. Usage was investigated among 320 participants randomised to the intervention group of the RCT via system data and a study-specific questionnaire that was assessed during the 1 week follow-up (T1) assessment. RESULTS: Main reasons for not participating were not interested in participation in scientific research (40%) and not interested in scientific research and Oncokompas (28%). Main reasons for not being interested in Oncokompas were wanting to leave the period of being ill behind (29%), no symptom burden (23%), or lacking internet skills (18%). Out of the 320 participants in the intervention group 167 (52%) used Oncokompas as intended. Among 72 non-users, main reasons for not using Oncokompas were no symptom burden (32%) or lack of time (26%). Among 248 survivors that activated their account, satisfaction and user-friendliness were rated with a 7 (scale 0-10). Within 3 (IQR 1-4) sessions, users selected 32 (IQR 6-37) topics. Main reasons for not using healthcare options in Act were that the information in Learn was already sufficient (44%) or no supportive care needs (32%). DISCUSSION: Main reasons for not reaching or using Oncokompas were no symptom burden, no supportive care needs, or lack of time. Users selected many cancer-generic and tumour-specific topics to address, indicating added value of the wide range of available topics.

The eHealth self-management application 'Oncokompas' that supports cancer survivors to improve health-related quality of life and reduce symptoms: which groups benefit most?

BACKGROUND: Oncokompas is a web-based self-management application that supports cancer survivors to monitor their health-related quality of life (HRQOL) and symptoms, and to obtain personalised feedback and tailored options for supportive care. In a large randomised controlled trial among survivors of head and neck cancer, colorectal cancer, and breast cancer and (non-)Hodgkin lymphoma, Oncokompas proved to improve HRQOL, and to reduce several tumour-specific symptoms. Effect sizes were however small, and no effect was observed on the primary outcome patient activation. Therefore, this study aims to explore which subgroups of cancer survivors may especially benefit from Oncokompas. MATERIALS AND METHODS: Cancer survivors (n = 625) were randomly assigned to the intervention group (access to Oncokompas, n = 320) or control group (6 months waiting list, n = 305). Outcome measures were HRQOL, tumour-specific symptoms, and patient activation. Potential moderators included socio-demographic (sex, age, marital status, education, employment), clinical (tumour type, stage, time since diagnosis, treatment modality, comorbidities), and personal factors (self-efficacy, personal control, health literacy, Internet use), and patient activation, mental adjustment to cancer, HRQOL, symptoms, and need for supportive care, measured at baseline. Linear mixed models were performed to investigate potential moderators. RESULTS: The intervention effect on HRQOL was the largest among cancer survivors with low to moderate self-efficacy, and among those with high personal control and those with high health literacy scores. Cancer survivors with higher baseline symptom scores benefitted more on head and neck (pain in the mouth, social eating, swallowing, coughing, trismus), and colorectal cancer (weight) specific symptoms. DISCUSSION: Oncokompas seems most effective in reducing symptoms in head and neck cancer and colorectal cancer survivors who report a higher burden of tumour-specific symptoms. Oncokompas seems most effective in improving HRQOL in cancer survivors with lower self-efficacy, and in cancer survivors with higher personal control, and higher health literacy.

Cost-utility of an eHealth application 'Oncokompas' that supports cancer survivors in self-management: results of a randomised controlled trial.

PURPOSE: The eHealth self-management application 'Oncokompas' was developed to support cancer survivors in monitoring health-related quality of life (HRQOL) and symptoms, and obtaining personalized feedback and options for supportive care. The aim of this study was to assess the cost-utility of Oncokompas compared with care as usual (CAU) among cancer survivors. METHODS: Survivors were randomly allocated to the intervention or control group. Direct (non-)medical, indirect non-medical costs, and HRQOL were measured at 3- and 6-month follow-up, using iMTA Medical Consumption and Productivity Costs and the EuroQol-5D questionnaires. Mean cumulative costs and quality-adjusted life-years (QALYs) were compared between both groups. RESULTS: In total, 625 survivors were randomized into intervention (n = 320) or control group (n = 305). Base case analysis showed that incremental costs from a societal perspective were - €163 (95% CI, - 665 to 326), and incremental QALYs were 0.0017 (95% CI, - 0.0121 to 0.0155) in the intervention group compared with those in the control group. The probability that, compared with CAU, Oncokompas is more effective was 60%, less costly 73%, and both more effective and less costly 47%. Sensitivity analyses showed that incremental costs vary between - €40 and €69, and incremental QALYs vary between - 0.0023 and - 0.0057. CONCLUSION: Oncokompas is likely to be equally effective on utilities, and not more expensive than CAU, and will therefore contribute to sustainable cancer survivorship care in a (cost-)effective manner. IMPLICATIONS FOR CANCER SURVIVORS: Oncokompas seems to improve HRQOL and reduces the burden of several tumour-specific symptoms, while costs from a societal perspective are similar to CAU.

Linking dendroecology and association genetics in natural populations: Stress responses archived in tree rings associate with SNP genotypes in silver fir (Abies alba Mill.).

Genetic association studies in forest trees would greatly benefit from information on the response of trees to environmental stressors over time, which can be provided by dendroecological analysis. Here, we jointly analysed dendroecological and genetic data of surviving silver fir trees to explore the genetic basis of their response to the iconic stress episode of the 1970s and 1980s that led to large-scale forest dieback in Central Europe and has been attributed to air pollution. Specifically, we derived dendrophenotypic measures from 190 trees in the Bavarian Forest that characterize the resistance, resilience and recovery during this growth depression, and in the drought year in 1976. By focusing on relative growth changes of trees and by standardizing the dendrophenotypes within stands, we accounted for variation introduced by micro- and macroscale environmental differences. We associated the dendrophenotypes with single nucleotide polymorphisms (SNPs) in candidate genes using general linear models (GLMs) and the machine learning algorithm random forest with subsequent feature selection. Most trees at our study sites experienced a severe growth decline from 1974 until the mid-1980s with minimum values during the drought year. Fifteen genes were associated with the dendrophenotypes, including genes linked to photosynthesis and drought stress. With our study, we show that dendrophenotypes can be a powerful resource for genetic association studies that permit to account for micro- and macroenvironmental variation when data are derived from natural populations. We call for a wider collaboration of dendroecologists and forest geneticists to integrate individual tree-level dendrophenotypes in genetic association studies.

Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry.

Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro. Each Aspergillus isolate produced a distinct VOC profile. These profiles could not be confirmed in exhaled breath in vivo.

eNose technology can detect and classify human pathogenic molds in vitro: a proof-of-concept study of Aspergillus fumigatus and Rhizopus oryzae.

Invasive pulmonary mold disease (IPMD) is often fatal in neutropenic patients. This is because IPMD is difficult to diagnose timely, especially when non-Aspergillus molds are the causative agent, as they are usually not associated with a positive galactomannan assay. In 2013 we showed that exhaled breath analysis might be used to diagnose invasive aspergillosis through profiling of patterns in exhaled volatile organic compounds (VOCs) by electronic nose (eNose) technology. The current study aimed to determine (1) whether molds can be discriminated from other microorganisms (using two mold species: Aspergillus fumigatus and a pathogenic mold not associated with a positive galactomannan assay, i.c. Rhizopus oryzae) and (2) whether both molds can be discriminated from each other. First, we cultured strains of Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, A. fumigatus and R. oryzae in separate airtight bottles. We examined whether an eNose (Cyranose 320) could discriminate the headspaces of bottles with molds from those with bacteria/yeasts. Second, we examined whether an eNose could discriminate A. fumigatus and R. oryzae. Diagnostic algorithms were created using canonical discriminant analysis after principle component analysis. Primary outcome parameter was the validated accuracy. The eNose discriminated A. fumigatus from bacteria/yeasts with a cross-validated accuracy of 92.9% (sensitivity 95.2%, specificity 91.9%). The eNose had an accuracy (validated using split-half analysis) of 100% in discriminating A. fumigatus from R. oryzae. Our study suggests that an eNose can identify and classify molds in vitro. This warrants prospective in vivo studies aimed at detecting and classifying IPMD using exhaled breath.

Detection of Airway Colonization by Aspergillus fumigatus by Use of Electronic Nose Technology in Patients with Cystic Fibrosis.

Currently, there is no noninvasive test that can reliably diagnose early invasive pulmonary aspergillosis (IA). An electronic nose (eNose) can discriminate various lung diseases through an analysis of exhaled volatile organic compounds. We recently published a proof-of-principle study showing that patients with prolonged chemotherapy-induced neutropenia and IA have a distinct exhaled breath profile (or breathprint) that can be discriminated with an eNose. An eNose is cheap and noninvasive, and it yields results within minutes. We determined whether Aspergillus fumigatus colonization may also be detected with an eNose in cystic fibrosis (CF) patients. Exhaled breath samples of 27 CF patients were analyzed with a Cyranose 320. Culture of sputum samples defined the A. fumigatus colonization status. eNose data were classified using canonical discriminant analysis after principal component reduction. Our primary outcome was cross-validated accuracy, defined as the percentage of correctly classified subjects using the leave-one-out method. The P value was calculated by the generation of 100,000 random alternative classifications. Nine of the 27 subjects were colonized by A. fumigatus. In total, 3 subjects were misclassified, resulting in a cross-validated accuracy of the Cyranose detecting IA of 89% (P = 0.004; sensitivity, 78%; specificity, 94%). Receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.89. The results indicate that A. fumigatus colonization leads to a distinctive breathprint in CF patients. The present proof-of-concept data merit external validation and monitoring studies.

Spigelian hernia and cryptorchidism.

Spigelian hernias are rare anterior abdominal wall hernias. A recent association has been made between paediatric spigelian hernias and cryptorchidism. We report this phenomenon in a 60-year-old adult male.

[News in emergency medicine 2009]. / Notfall - News 2009.

The field of Emergency Care Medicine is a very dynamic part of the Medical Science. That is why there is a huge amount of publications on this topic every year. This article is my personal selection of recently published scientific work on pulmonary embolism, classification of circulatory shock, betablockers in acute decompensated heart failure, advanced cardiac life support, subarachnoid hemorrhage, inhalation therapy with ipratropium-bromide, community acquired pneumonia, diverticulosis, gout and pancreatitis. Last but not least there is a choice of prophylactic interventions, you might not yet be aware of. Some of the discussed publications may help you manage the next patient you'll encounter, when you're on call next time.

[News in emergency medicine 2007]. / Notfall--News 2007.

During the year 2007 one could read plenty of interesting publications in the field of Emergency Care Medicine. I made a personal choice out of this recent literature for a workshop at the 6th Zentralschweizer Internistenwoche to discuss new aspects of Emergency Care patients that you could encounter tomorrow in your unit.

[Systematic diagnosis of erythrocytosis]. / Systematische diagnostiek van erytrocytose.

Erythrocytosis is a phenomenon with life-threatening complications and a broad differential diagnosis. Erythrocytosis is usually secondary to a cardiopulmonary condition leading to a low arterial oxygen tension. A probable diagnosis can often be made on the basis of the history, physical examination, a measurement of the peripheral oxygen saturation, and simple laboratory tests. The differential diagnosis can be narrowed down by a determination of the erythropoietin concentration and the JAK2 mutation. If the erythrocytosis is found to be non-physiological, then reduction of the haematocrit via bloodletting and, depending on the diagnosis, treatment with acetylsalicylic acid are indicated.

Quality of life after brachytherapy in patients with glioblastoma multiforme.

As quality of life (QoL) is perhaps the most important outcome for patients treated for glioblastoma multiforme (GBM), we measured QoL in GBM patients after brachytherapy. QoL was assessed by questionnaires for both patients and partners before brachytherapy and at various times during follow-up in 21 GBM patients by an extension of the Rotterdam Symptom Checklist (e-RSCL), consisting of four subscales. The Karnofsky Performance Scale (KPS) was also measured. Analysis of variance was done to evaluate the direct effect of brachytherapy (visit 1-2, short-term) and during follow up (visit 1-4, longer-term). Significant short-term effects were found for two subscales of the e-RSCL. Longer-term effects were found for all four subscales and for the KPS. A high correlation between partner and patient's QoL assessment was found. QoL in GBM patients after brachytherapy can therefore be carefully monitored with a subjective instrument such as the e-RSCL. Patients and partners experience QoL equally.

Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status.

PURPOSE: Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. In breast cancer, tumor VEGF has been shown to have a good correlation with relapse-free survival. The aim of this study was to determine the relation of serum VEGF levels to the various indices of breast cancer and known tumor markers carcinoembryonic antigen and CA15.3. EXPERIMENTAL DESIGN: Preoperative serum VEGF levels were determined in 200 women with breast cancer and compared with serum VEGF levels in 88 healthy female controls. RESULTS: The serum VEGF levels of the cancer patients as a group were significantly elevated compared with those of the controls (P < 0.0005). VEGF levels were elevated in patients with invasive cancer of ductal/no specific type, ductal carcinoma in situ, and estrogen receptor (ER)-positive tumors. Patients with lobular carcinoma and ER-negative tumors had serum VEGF levels comparable with those in the controls. VEGF was more sensitive than CA15.3 and carcinoembryonic antigen in detecting breast cancer. CONCLUSIONS: Preoperative serum VEGF detects breast cancer with a sensitivity of 62.1%. The relationship to cancer type and ER status may have future therapeutic implications. Additional long-term studies are required to determine the prognostic significance of serum VEGF.

Iatrogenic thoracic migration of the stomach complicating laparoscopic nissen fundoplication.

BACKGROUND: Intrathoracic gastric herniation after laparoscopic Nissen fundoplication is an uncommon but potentially life-threatening complication that may present in the early or late postoperative period. METHODS: A retrospective analysis was performed on all patients undergoing antireflux surgery from December 1991 to June 1999. RESULTS: Nine cases of gastric herniation occurred after 511 operations (0.17%). Patients presented with the condition 4 days to 29 months after surgery. Eight of these nine patients (89%) had reported vomiting in the immediate postoperative period. Seven patients (78%) reported persistent odynophagia. A factor common to all patients was that posterior crural repair had not been performed. CONCLUSIONS: Measures should be undertaken to prevent postoperative vomiting after laparoscopic Nissen fundoplication. Posterior crural repair is essential after surgery in all cases.

Laparoscopic ultrasound for the detection of hepatic metastases during laparoscopic colorectal cancer surgery.

PURPOSE: The search for liver metastases before surgery forms an accepted part of colorectal cancer surgical practice. Intraoperative ultrasound and manual palpation of liver together form the criterion standard as far as screening for metastases is concerned. However, extracorporeal imaging, such as ultrasound and magnetic resonance imaging, are also widely used. The purpose of this study was to demonstrate the efficacy of laparoscopic ultrasound scan in detection of liver metastases during laparoscopic colorectal cancer surgery by comparison with conventional imaging modalities. METHODS: A prospective, controlled study was undertaken. A total of 76 consecutive patients undergoing laparoscopic colorectal resections for malignancy were recruited. Patients underwent preoperative liver ultrasound scan and intraoperative blinded laparoscopic ultrasound scan examination performed by a single surgeon. Contrast-enhanced magnetic resonance imaging was performed within 30 days of surgery. RESULTS: Conventional ultrasound scan was negative in all cases. Metastases were identified during simple laparoscopic inspection of the liver in one case. Two cases shown by laparoscopic ultrasound scan to have definite metastases were confirmed by magnetic resonance imaging. In seven further instances laparoscopic ultrasound scan identified suspicious liver masses. In three cases these were confirmed to be metastases at magnetic resonance imaging; one was confirmed as a cyst, and the remaining three suspicious lesions were confirmed at serial magnetic resonance imaging scans to be benign and of no significance. CONCLUSION: Laparoscopic ultrasound scan with a flexible-tipped probe permits satisfactory hepatic examination. It is superior to conventional ultrasound scan and seems to be as effective as magnetic resonance imaging, although the latter modality is still required to delineate identified lesions.

[Heparin and insulin in the treatment of acute hypertriglyceridemia-induced pancreatitis]. / Heparin und Insulin in der Therapie der akuten Hypertriglyzeridämie-induzierten Pankreatitis.

Hypertriglyceridaemia is thought to be the aetiology in 3% of patients with acute pancreatitis, often associated with poorly controlled diabetes mellitus or chronic alcohol abuse. However, in patients with non-biliary pancreatitis, chylomicronaemia is an underrated cause of acute pancreatitis. The activity of lipoprotein lipase (LPL) is crucial in removing triglycerides from the plasma; LPL gene mutations combined with secondary alterations in plasma lipoproteins, such as occur in pregnancy, diabetes mellitus, and alcohol abuse can cause severe hypertriglyceridaemia and pancreatitis. Heparin and insulin stimulate LPL activity. During a 12 months' period we consecutively screened all patients with the diagnosis of acute non-biliary pancreatitis for hypertriglyceridaemia, to evaluate the prevalence of hypertriglyceridaemia-induced pancreatitis and to assess the outcome under standardised treatment with intravenous heparin and insulin. Hypertriglyceridaemia-induced pancreatitis was diagnosed in 5 out of 46 patients (11%) with acute pancreatitis. In 2 patients hypertriglyceridaemia was associated with diabetes mellitus, in one patient with pregnancy and in another with chronic alcohol abuse. Four patients had to be referred to the intensive care unit. Plasma concentrations of triglycerides were (median +/- range) 43 mmol/l (14.7 to 80.4); pancreas amylase was 574 U/l (155 to 1606), and lipase was 1003 U/l (330 to 3010). All patients had oedematous pancreatitis demonstrated by CT scan. Treatment with i.v. heparin and i.v. insulin decreased trigylceride levels to less than 10 mmol/l within 2.8 days (1 to 6), the amylase and lipase levels returned to normal after 3 and 4 days respectively, and the abdominal pain was resolved. Hypertriglyceridaemia is a common and under-diagnosed etiology of acute non-biliary pancreatitis. Intravenous heparin and insulin is safe and effective in the treatment of hypertriglyceridaemia-induced pancreatitis. Low fat diet, supplements of (n-3) fatty acids ("fish oil") and fibrates are recommended for long-term maintenance therapy.

Revival of tetracyclines--in the treatment of visceral leishmaniasis?

A 37-year-old immigrant from Kosovo who had been in Switzerland for 2 years developed fever, cough, weight loss and malaise. Serology (complement binding reaction) was positive for leptospirosis. The symptoms resolved very rapidly under vibramycin 2 x 100 mg/day for 3 weeks. However, a flare-up occurred after cessation of medication. Reexposure to tetracyclines improved the symptoms though they did not subside completely. Bone marrow analysis demonstrated intracellular leishmania (amastigotes). Analysis of frozen serum preserved since the first hospitalisation and samples from the second admission were positive for leishmania (indirect fluorescence antibody test) and confirmed the diagnosis of visceral leishmaniasis. Reevaluation of the serology for leptospirosis was negative using the specific microagglutination method. Treatment with antimony for 28 days resolved all symptoms. The parasites of visceral leishmaniasis grow intracellularly and eradication may be impossible in patients with an impaired cellular immune response. Flare-ups thus recur in 60-100% of patients with organ transplants or AIDS, despite regular treatment. Our finding raises the question whether relapses are suppressed in immunocompromised patients by tetracyclines, drugs known to be well tolerated even under long-term exposure. Randomised studies are required in this setting.

Inflammatory bowel disease and the genes for the natural resistance-associated macrophage protein-1 and the interferon-gamma receptor 1.

The genes for the interferon-gamma receptor 1 and the natural resistance-associated macrophage protein 1 (NRAMP1) control the immune response to intracellular microbial pathogens. Such pathogens, in particular Mycobacterium paratuberculosis, have been implicated in the pathogenesis of Crohn's disease. We studied markers in the genes for NRAMP1 and two mutations in the interferon-gamma receptor in relation to inflammatory bowel disease (IBD) in the following groups: 270 healthy individuals, 74 patients with Crohn's disease, 72 patients with ulcerative colitis, and 40 patients with primary sclerosing cholangitis. We studied the allele frequencies of two restriction fragment length polymorphisms in the gene for NRAMP1 and the prevalence of two mutations in the interferon-gamma receptor 1 gene. The markers in the NRAMP1 gene were not associated with inflammatory bowel disease. Also, the mutations in the interferon-gamma receptor 1 were not found in the 186 IBD patients. Genetic markers in NRAMP1 are thus not associated with IBD. Therefore this gene is not likely to play a role in the pathogenesis of IBD. The mutation in the interferon-gamma receptor was not found in our IBD patients group.

Optimal education techniques for basic surgical trainees: lessons from education theory.

"Calmanisation" of surgical training and the introduction of the "New Deal" on doctor's hours has led to a reduction in "in service" training and a proliferation of training courses. Little research has been done into the optimum design of these courses. Education theory has shown that individuals have optimal learning styles and that these styles tend to be generalised across professional groups. It was decided, therefore, to investigate the optimal learning styles of basic surgical trainees. A learning style inventory was used to assess the preferred learning style of 52 basic surgical trainees. The predominant learning styles (86.5%) were convergent (n = 31) or accommodative (n = 14) whilst only 5 (9.6%) assimilative and 2 (3.9%) divergent styles were detected. Convergent and accommodative learners rely principally on hands on experience and problem solving as their optimal learning technique. Given the shorter hours and duration of Basic Surgical Training, in service practical training and surgical courses should be structured accordingly.