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.

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.

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.

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.

[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.

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.

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.

Preoperative serum vascular endothelial growth factor can predict stage in colorectal cancer.

Neovascularization has been shown to be essential for the growth of solid tumors. Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis. This study was conducted to determine the significance of this cytokine as a tumor marker for staging colorectal cancer. Preoperative serum VEGF was measured in 108 colorectal cancer patients and in 136 normal healthy controls. The results of this study showed a significant difference between the four T classes, Union International Contre Cancer (UICC) stages, and Dukes' stages. In comparison to serum levels in controls (median, 173.8 pg/ml), VEGF levels were significantly elevated in T2 (P = 0.003), T3, and T4 (P < 0.0005); UICC I (P = 0.001), UICC II, UICC III, and UICC IV (P < 0.0005); and Dukes' A (P = 0.001), Dukes' B, and Dukes' C (P < 0.0005). Serum VEGF showed a significant elevation over control in node-negative (P < 0.0005) and in node-positive colorectal cancer (P < 0.0005) patients. Node-positive cancer had a significant elevation of serum VEGF compared to node-negative cancer (P = 0.008). This study reveals that preoperative serum VEGF can detect all but very early colorectal cancer i.e., T1 (P = 0.06).

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.

Antihypertensive efficacy and well-being during monotherapy and combination therapy with ketanserin.

The effects of ketanserin on blood pressure and well-being were investigated in 188 patients, aged 41-82 years, with mild to moderate essential hypertension. At entry, 107 were untreated, 42 were taking the diuretic combination hydrochlorothiazide (50 mg/day) plus amiloride (5 mg/day) and another 39 were taking the beta-blocker atenolol (100 mg/day). A single-blind, 4-week placebo run-in period was followed by 12 weeks' oral ketanserin treatment at 20 or 40 mg twice a day. This regimen significantly reduced systolic and diastolic blood pressures in each group. Response rates were greater in patients aged over 60 years. Compared with placebo, sleep disturbances, daytime fatigue and overall weakness decreased during ketanserin treatment (P less than 0.05 for all), but the incidence of dry mouth and stuffy nose increased. In patients older than 60 years there was a greater reduction of complaints than in younger patients. Ketanserin proved effective and well tolerated, improving peripheral circulatory symptomatology, particularly in older patients and those with a good blood pressure response.

The effect of hydralazine on arrhythmias in congestive cardiomyopathy.

We studied 12 patients with congestive cardiomyopathy who were given 75 mg hydralazine daily for 2 wk and 150 mg hydralazine daily for another 2 wk. Two 24-h ambulatory ECG recordings in a control period and two in each hydralazine period were performed and analysed. It was found that hydralazine therapy in congestive cardiomyopathy does not significantly increase or decrease the occurrence of ventricular or supraventricular arrhythmias.

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.

[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.

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.