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.

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.

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.

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.

[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.

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.

Detection of colorectal carcinomas by intraoperative RIS in addition to preoperative RIS: surgical and immunohistochemical findings.

The immunoscintigraphic detection of tumour foci less than 1 cm in diameter fails even with single photon emission tomography (SPET) owing to low contrast against background activity. In an attempt to improve detection of macroscopically invisible tumour spread, intraoperative scintimetry (IOSM) with a hand-held gamma-probe was performed in addition to SPET 24-30 and 41-48 h after injection of the technetium-99m carcinoembryonic antigen (CEA MoA) on 12 patients with colorectal carcinoma and 3 patients with different neoplastic and inflammatory diseases. Tumour specimens were measured in vitro in a gamma well counter. For comparison, the presence and amount of CEA in the tumour cells were evaluated immunohistochemically. After modification, the gamma-probe originally designed for iodine-131 was 20 times more sensitive; activities of 99mTc located close to the collimator hole were measured with absolute sensitivity of 100 cps = 2.5 kBq 99mTc. The unfavourably high background activity affected both the in vitro and in vivo analysis: SPET results had been considered positive in 8 of 15 cases. In vitro tumour/non-tumour (t/nt) ratios greater than 2.0 were found in 4 cases. In vivo IOSM resulted in t/nt ratios greater than 2.0 in only 3 patients. In most cases, there was no coincidence of elevated t/nt ratios from the different methods. A correlation was derived between positive immunoscintimetric in vitro findings and immunohistochemically proven interstitial localization of CEA in tumor cells. In conclusion, the measurement technique of IOSM seems adequate, but clinical success will depend on a more specific enrichment of MoA in tumour tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

[Perforation of gastroduodenal ulcer. Risk factors and choice of procedure]. / Perforation des gastroduodenalen Ulkus. Risikofaktoren und Verfahrenswahl.

The well known surgical risk factors, such as age, time of perforation as well as size and localisation of necrosis, were confirmed in retrospective and prospective analyses of perforation of gastroduodenal ulcers (n = 504). Incidence was unchanged in the two different time-related groups, with 3.2 or 3.7 cases in one month. There was a clear-cut need for excision of the ulcer or necrotic margin. Perforation was attributable to malignant tumours in 2.1 per cent of the cases. The authors have definitely adopted the concept of earlier primary surgery (23 per cent of all cases, as compared to 10.4 per cent before). The risk associated to it was found to be lower than linked to palliative operations. The lethality rate was as low as 7.6 per cent, once due consideration was given to the above risk factors for adequate choice of surgical methods. Particular attention was given to ulcer localisation and clinical course. Hence, lethality has clearly dropped below earlier data.

[Identification of the recurrent laryngeal nerve in thyroid gland surgery--a status determination]. / Darstellung des Nervus recurrens bei Schilddrüsenoperationen--Standortbestimmung.

The recurrent laryngeal nerve palsy is the most important complication in thyroid surgery. It seems to be possible to reduce the rate of palsies by consequently identifying the recurrent laryngeal nerve. A comparison of statistics out of the literature with and without identification of the recurrent laryngeal nerve shows this. A follow-up of our patients of the years 1980-1982 (1312 operations) confirms this finding.

Increased thyrotropin binding in hyperfunctioning thyroid nodules.

The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

[Metastases of the thyroid gland--morphology and clinical aspects of 25 secondary thyroid neoplasms]. / Metastasen in der Schilddrüse--Morphologie und Klinik von 25 sekundären Schilddrüsengeschwülsten.

Morphological and clinical findings in 25 secondary tumours of the thyroid are described. The most common sources of such lesions were the kidneys (32%), lung (28%) and breast (20%). In the majority of cases, thyroidectomy was performed prior to identification and treatment of the primary cancer. Conversely, among renal cell carcinomas, the metastatic lesion frequently appeared many years after resection of the primary tumour. This suggests that secondary thyroid tumours occasionally may be the only important malignant disease remaining. Hence, adequate surgical treatment may prove to be life-prolonging or life-saving.

[Ethinyl estradiol and hepatocarcinogenesis. An experimental study]. / Athinyloestradiol und Hepatocarcinogenese. Eine experimentelle Beobachtung.

The influence of ethinylostradiol on hepatocarcinogenesis was investigated in the female Dawley-rat. After 14 weekly gastric instillations of 50 mg diethylnitrosamine/kg and simultaneous administration of diet supplemented with ethinylostradiol 10 mg/l kg diet, 77.8% of the rats developed a hepatocellular carcinoma. In contrast, only 31.8% had carcinoma of the liver under similar experimental conditions. The relation of preneoplastic lesions correlated with that of carcinoma induction in both groups. If the results were to be valued on clinical relevance without difficulties a new orientation on surgical indication and transformation of the dignity of benign focal nodular hyperplasia would have to be considered.

[Differential indications in perforation of gastroduodenal ulcer]. / Differentialindikation bei der Perforation des gastroduodenalen Ulcus.

The differential indication of perforated peptic gastroduodenal ulcer is presented giving emergency surgical intervention preference. Simple closure after radical excision with a mortality rate of 12.1% as demonstrated in our clinical material is generally performed and in some selected cases the so-called primary definitive therapy excision, SPV or distal gastric resection. In cases of doubt simple closure is performed. An absolute acute indication for simple closure is also valid for the atypical perforation.

Histopathologic types and clinical behaviour of occult papillary carcinoma of the thyroid.

On studying 182 papillary neoplasms of the thyroid, 32 nonencapsulated lesions were found to be occult papillary carcinomas (maximum diameter 1.5 cm); out of these 32 patients 18 cases of cervical lymph node metastases were observed. Histologically, 4 circumscribed microcarcinomas, 3 partially encapsulated carcinomas, and 25 occult sclerosing carcinomas were distinguished. The mean diameter of the 4 circumscribed tumours as compared to that of the remaining 28 lesions proved to be statistically significantly smaller, but no significant differences could be observed regarding the rate of lymph node metastasis. One occult sclerosing carcinoma showed a morphologic pattern different from the remaining cases--namely that it had an exclusively solid appearance in the primary lesion and also in its lymph nodes metastases. The follicle cell origin of this lesion was established immunohistochemically by patchy thyroglobulin synthesis. The excellent prognosis of the occult category of papillary thyroid carcinoma was confirmed by a follow-up (mean 7.7 years, range 1.1 to 16.3 years), in which only 2 instances of eradicable recurrent lymph node metastases within the group of occult sclerosing carcinomas were recorded.

[Postoperative course and tactics of aftercare in hyperthyroidism]. / Postoperativer Verlauf und Taktik der Nachsorge der Hyperthyreose.

In a follow-up study of 112 patients who had subtotal thyroidectomy because of Graves' disease and nodular goitre with hyperthyroidism, 81% were euthyroid, 10,7% developed hypothyroidism and 8% had persistent or recurrent hyperthyroidism. 12,5% of the euthyroid patients had goitre; 10 of these patients had cold thyroid nodules. The assessment of the dignity of the cold nodules and guidelines for the therapeutic procedure are stressed. The importance of considering clinical findings on one hand and thyroid function tests on the other hand in the choice of effective treatment - prophylaxis against euthyroid goitre, substitution with hormones, iodine-131 therapy, antithyroid drugs or reoperation - is outlined.

[Stress tolerance of patients with hemorrhage from ulcus ventriculi sive duodeni]. / Belastbarkeit des Kranken mit Blutung aus einem Ulcus ventriculi sive duodeni.

448 patients with severe haemorrhage from gastroduodenal ulcera during the last 15 years are presented. Within this period indication, organisation and the choice of method have changed in 3 phases. Included are the endoscopic diagnosis and treatment with very good results. As a result of endoscopy there is a negative selection of patients for surgery causing a depression of the results after surgical treatment. The propagation for early indication even in high risk patients still has validity.