Fehlende Werte bei Patienten-berichteten Endpunkten in einer Längsschnittstudie bei fortgeschrittenem und metastasiertem Krebs

Missing patient-reported outcomes (PROs) are common in follow-up visits for longitudi-nal studies. However, the rates of missing values are relatively high in relation to health deterioration and premature death in patients with advanced stages of cancer. This study aims to investigate the rates and patterns of missing PROs data as well as to ex-plore the association between patient characteristics and time-to-dropout or time-to-death for a better understanding of how the missing data mechanism could be applied to missing PROs data in severely affected patients. This is an exploratory study using data from the Oncological Social Care Project. Missing rates and missing data patterns were reported using cumulative numbers and rates. The competing-risk analysis, using Fine and Gray’s proportional sub-distribution hazards model, was performed to explore factors associated with time-to-dropout when considering death as a competing event. Additionally, a Cox regression model was used to explore factors associated with time-to-death. A total of 362 patients were observed. The cumulative missing rate for assessing PROs was around 28% and 19%, caused by premature death and dropout, respectively. Being divorced or widowed (SHR=2.71; 95%CI: 1.12–6.56) and having poor social support (SHR=2.10; 95%CI: 1.01–4.35) were associated with early dropout. The presence of malignant neoplasm of pancreas cancer (HR = 2.48; 95%CI: 1.27–4.85) and a medium level of education (HR = 1.58; 95%CI: 1.02–2.45) were associated with premature death. Dropping out early from the study was associated with low baseline global health status/quality of life (GH/QoL) (SHR=1.14; 95%CI: 1.01–1.27) and low baseline role functioning, such as limited ability to do work or daily activities (SHR=1.10; 95%CI: 1.01–1.19). Furthermore, worsening scores of GH/QoL, functioning, and symptoms at baseline and at the last visit were associated with premature death. In the advanced stages of cancer research, high rates of missing PROs data should be expected. The worsening of health-related quality of life (e.g., GH/QoL, physical functioning, fatigue scores) was associated with missing PROs data, suggesting that the missing data is not completely random. The investigation of patient characteristics as-sociated with missing data is also informative and a prerequisite for further proper analysis of the data.Fehlende von den Patienten berichteten Ergebnisse (patient-reported outcomes: PROs) sind bei Nachuntersuchungen im Rahmen von Langzeitstudien üblich. Die Raten fehlender Werte sind jedoch relativ hoch, wenn es um die Verschlechterung des Gesundheitszustands und den vorzeitigen Tod von Patienten in fortgeschrittenen Krebsstadien geht. Ziel dieser Studie ist es, die Raten und Muster fehlender PRO-Daten zu untersuchen sowie den Zusammenhang zwischen Patientenmerkmalen und der Zeit bis zum Abbruch bzw. bis zum Tod zu erforschen, um besser zu verstehen, wie der Mechanismus fehlender Daten auf fehlende PRO-Daten bei schwer betroffenen Patienten angewendet werden könnte. Es handelt sich um eine explorative Studie, die Daten aus dem Oncological Social Care Project verwendet. Fehlende Raten und Muster fehlender Daten wurden anhand kumulativer Zahlen und Raten angegeben. Eine Analyse des konkurrierenden Risikos unter Verwendung des proportionalen Unterverteilungs-Hazards-Modells von Fine und Gray wurde durchgeführt, um Faktoren zu untersuchen, die mit der Zeit bis zum Abbruch in Verbindung stehen, wenn der Tod als konkurrierendes Risiko betrachtet wird. Zusätzlich wurde ein Cox-Regressionsmodell verwendet, um Faktoren zu untersuchen, die mit der Zeit bis zum Tod in Verbindung stehen. Insgesamt wurden 362 Patienten beobachtet. Die kumulative Missingrate für die Bewertung der PROs lag bei 28% bzw. 19%, verursacht durch vorzeitigen Tod bzw. Drop-out. Geschieden oder verwitwet zu sein (SHR=2,71; 95%KI: 1,12 – 6,56) und geringe soziale Unterstützung (SHR=2,10; 95%KI: 1,01 – 4,35) waren mit einem frühen Abbruch verbunden. Das Vorhandensein einer bösartigen Neubildung der Pankreas (HR=2,48; 95%KI: 1,27 - 4,85) und ein mittleres Bildungsniveau (HR=1,58; 95%KI: 1,02 - 2,45) waren mit einem vorzeitigen Tod assoziiert. Ein vorzeitiger Abbruch aus der Studie war mit einem niedrigen Ausgangswert für den globalen Gesundheitszustand/die Lebensqualität (GH/QoL) (SHR=1,14; 95%KI: 1,01 - 1,27) und einem niedrigen Ausgangswert für die Rollenfunktion, wie z. B. einer eingeschränkten Fähigkeit zur Ausübung von Arbeit oder täglichen Aktivitäten (SHR=1.10; 95%KI: 1,01 - 1,19) assoziiert. Darüber hinaus war eine Verschlechterung der Werte für GH/QoL, Funktionsfähigkeit und Symptome zu Studienbeginn und bei der letzten Visite mit einem vorzeitigen Versterben assoziiert. In den fortgeschrittenen Stadien der Krebsforschung sind hohe Raten an fehlenden PRO-Daten zu erwarten. Die Verschlechterung der gesundheitsbezogenen Lebensqualität (z. B. GH/QoL, körperlichen Funktionsfähigkeit, Müdigkeit) stand in Verbindung mit fehlenden PROs-Daten. Das bedeutet, dass der Mechanismus der fehlenden Daten nicht völlig zufällig ist. Die Untersuchung von Patientenmerkmalen, die mit fehlenden Daten in Verbindung stehen, ist aufschlussreich und eine Voraussetzung für die weitere korrekte Auswertung der Daten

Improving quality of life in cancer patients through higher participation and health literacy: study protocol for evaluating the oncological social care project (OSCAR)

BACKGROUND: Cancer patients experience psychological and social distress due to their medical treatment and social issues. However, continuous and specialized social support is still lacking. In Germany, a group of company health insurance funds has developed an approach to support cancer patients with monthly structured interviews conducted by specially trained Social Care Nurses. The nurses will identify patient needs in order to provide help with medical, personal, and social matters. One aim of the scientific evaluation is to analyze the effect of the consultations on various patient-reported outcomes, especially quality of life. The evaluation concept will be described in this study protocol. METHODS/DESIGN: The evaluation is a non-randomized, controlled, multi-center intervention study with a mixed-method design. It consists of three research modules which include primary data from questionnaires, and claims data from the health insurance funds. In Module 1, cancer patients will be recruited to form an intervention group (OSCAR, n = 150) and a control group (n = 200) in four study centers for a period of 1 year. One baseline and three follow-up questionnaires will be conducted to survey the patient-reported outcomes. Relevant secondary outcomes are health literacy, participation, and physician-patient communication. In Module 2, claims data will be used to analyze cost effects and thereby assess effectivity and hospitalization. Module 3 will involve a qualitative analysis of project diaries kept by the Social Care Nurses. The diaries will record the nurses' practical experiences and the benefits of deploying OSCAR across the German healthcare system. DISCUSSION: OSCAR is an innovative way of providing cancer patients with continuous support to improve their quality of life. The evaluation concept aims to assess the effects of the monthly consultations by the Social Care Nurses on the patients, and will use a mixed-method design. The results are important for assessing the transferability of OSCAR to the healthcare system as a whole. TRIAL REGISTRATION: German Clinical Trials Register (DRKS-ID: DRKS00013640 ). Registered 29 December 2017

Women bear a burden: gender differences in health of older migrants from Turkey

Studies show that older migrants have poorer health than native populations in Western Europe. To date, little systematic research has explored the differences between men and women within older populations with migration backgrounds. This article examines gender-specific aspects and mediating mechanisms of self-reported health among older migrants from Turkey. Using a mixed method approach, data and results from a quantitative survey and a qualitative study conducted in Berlin, Germany, are analysed and integrated at the interpretive level. Standardised face-to-face interviews were carried out with the help of a network approach with 194 older migrants from Turkey (93 women, 101 men, mean age: 68). Potential mediators showing significant gender differences are included in a parallel multiple mediation analysis. The documentary method is used to analyse 11 semi-structured narrative interviews with first-generation labour migrants from Turkey. Women reported significantly worse subjective health than men (c = 0.443, bCI [0.165-0.736]), conveyed through greater functional limitations (ab = 0.183, bCI [0.056-0.321]) and emotional loneliness (ab = 0.057, bCI [0.008-0.128]). Respondents to the qualitative study perceived that women age earlier and have poorer health due to the burden of performing a greater variety of social roles. Higher levels of emotional loneliness among women could be caused by their experiences of negatively assessed partnerships. Our results show that as a group, older female migrants have an elevated health vulnerability. A broader scientific foundation regarding gender differences in the health of older migrants and their causes is needed to promote gender-sensitive prevention and care for this group

Characteristics and patient-reported outcomes associated with dropout in severely affected oncological patients: an exploratory study

Background: Patient-reported outcome measures (PROMs) are commonly-used surrogates for clinical outcomes in cancer research. When researching severe diseases such as cancer, it is difficult to avoid the problem of incomplete questionnaires from drop-outs or missing data from patients who pass away during the observation period. The aim of this exploratory study was to explore patient characteristics and the patient-reported outcomes associated with the time-to-dropout. Methods: In an Oncological Social Care Project (OSCAR) study, the condition of the participants was assessed four times within 12 months (t0: baseline, t1: 3 months, t2: 6 months, and t3: 12 months) by validated PROMs. We performed competing-risk regressions based on Fine and Gray's proportional sub-distribution hazards model for exploring factors associated with time-to-dropout. Death was considered a competing risk. Results: Three hundred sixty-two participants were analyzed in the study. 193 (53.3%) completed a follow-up after 12 months, 67 (18.5%) patients dropped out, and 102 patients (28.2%) died during the study period. Poor subjective social support was related to a higher risk of drop-out (SHR = 2.10; 95%CI: 1.01-4.35). Lower values in health-related quality of life were related to drop-out and death. The sub-scales global health status/QoL, role functioning, physical functioning, and fatigue symptom in the EORTC QLQ-C30 were key characteristics of early drop-out. Conclusion: Severely affected cancer patients with poor social support and poor quality of life seem more likely to drop out of studies than patients with higher levels of social support and a better quality of life. This should be considered when planning studies to assess advanced cancer patients. Methods of close continued monitoring should be actively used when patient experiences a substantial deterioration in their health-related quality of life and symptoms during the study. Results for such studies have to be interpreted with caution in light of specific drop-out mechanisms

Identifying and handling unbalanced baseline characteristics in a non-randomized, controlled, multicenter social care nurse intervention study for patients in advanced stages of cancer

Purpose: Given the psychosocial burdens patients in advanced stages of cancer face, innovative care concepts are needed. At the same time, such vulnerable patient groups are difficult to reach for participation in intervention studies and randomized patient inclusion may not be feasible. This article aims to identify systematic biases respectively selection effects occurring during the recruitment phase and to discuss their potential causes based on a non-randomized, multicenter intervention study with patients in advanced stages of cancer. Methods: Patients diagnosed with at least one of 16 predefined cancers were recruited at four hospitals in three German cities. The effect of social care nurses' continuous involvement in acute oncology wards was measured by health-related quality of life (EORTC QLQ-C30), information and participation preferences, decisional conflicts, doctor-patient communication, health literacy and symptom perception. Absolute standardized mean difference was calculated as a standardized effect size to test baseline characteristics balance between the intervention and control groups. Results: The study enrolled 362 patients, 150 in the intervention and 212 in the control group. Except for gender, both groups differed in relevant socio-demographic characteristics, e.g. regarding age and educational background. With respect to the distribution of diagnoses, the intervention group showed a higher symptom burden than the control group. Moreover, the control group reported better quality of life at baseline compared to the intervention group (52.6 points (SD 21.7); 47.8 points (SD 22.0), ASMD = 0.218, p = 0.044). Conclusion: Overall, the intervention group showed more social and health vulnerability than the control group. Among other factors, the wide range of diagnoses included and structural variation between the recruiting clinics increased the risk for bias. We recommend a close, continuous monitoring of relevant social and health-related characteristics during the recruitment phase as well as the use of appropriate statistical analysis strategies for adjustment, such as propensity score methods

Tablets as an Option for Telemedicine—Evaluation of Diagnostic Performance and Efficiency in Intracranial Arterial Aneurysm Detection

Purpose: To evaluate a commercially available mobile device for the highly specialized task of detection of intracranial arterial aneurysm in telemedicine. Methods: Six radiologists with three different levels of experience retrospectively interpreted 60 computed tomography (CT) angiographies for the presence of intracranial arterial aneurysm, among them 30 cases with confirmed positive findings. Each radiologist reviewed the angiography datasets twice: once on a dedicated medical-grade workstation and on a commercially available mobile consumer-grade tablet with an interval of 3 months. Diagnostic performance, reading efficiency and subjective scorings including diagnostic confidence were analyzed and compared. Results: Diagnostic performance was comparable on both devices regardless of readers' experience, and no significant differences in sensitivity (66-87.5%) and specificity (79.4-87%) were found. Results obtained with tablets and medical workstations were also comparable in terms of subjective assessment across all reader groups. Conclusions: There was no significant difference between tablet and workstation readings of angiography datasets for the presence of intracranial arterial aneurysm. Sensitivity, specificity, efficiency and subjective scorings were similar with the two devices for all three reader groups. While medical workstations are 10 times more expensive, tablets allow higher mobility especially for radiologists on call

External application of liver compresses to reduce fatigue in patients with metastatic cancer undergoing radiation therapy, a randomized clinical trial

Background: Liver compresses are frequently used in integrative medicine as supportive therapy during cancer treatment in order to reduce fatigue. We performed a pilot study to test whether the external application of yarrow liver compresses impacts fatigue in patients with metastatic cancer undergoing radiation therapy. Methods: A randomized prospective pilot trial was performed including patients with brain metastasis or bone metastasis of solid tumors. Patients underwent either palliative radiation therapy (RT) of the metastatic lesions (control group) over two weeks or the same RT with additional external application of yarrow liver compresses once daily during RT. The primary objective was improvement on the general fatigue subscale of the multidimensional fatigue inventory (MFI-20) at the end of treatment, where a mean difference of two points is considered clinically relevant. Secondary objectives included psychological distress, quality of life and qualitative analysis with self-established visual analogue scales (VAS). Mean differences in general fatigue at the end of treatment compared to baseline were analyzed using the ANCOVA test. Results: From 09/2017 to 08/2019 a total of 39 patients were randomized. Due to drop outs 24 patients (12 per group) were available for analysis. Patients in the intervention group received a mean number of 10.5 (range, 7-14) applications of yarrow liver compresses. The mean improvement at the end of therapy on the general fatigue subscale of the MFI-20 was 2 points in favor of the intervention group (p = 0.13), and all other MFI-20 subscales showed at least a trend towards improvement in favor of the intervention group. Likewise, psychological distress and VAS data was improved, the latter reaching statistical significance for the symptoms fatigue, tension and lack of drive. Major toxicities were not observed. Conclusions: External application of liver compresses appears to reduce fatigue within a clinical relevant range in patients with metastatic cancer undergoing radiation therapy. Trial registration: ISRCTN, ICTRP DRKS0001299

PRO B: evaluating the effect of an alarm-based patient-reported outcome monitoring compared with usual care in metastatic breast cancer patients—study protocol for a randomised controlled trial

Background: Despite the progress of research and treatment for breast cancer, still up to 30% of the patients afflicted will develop distant disease. Elongation of survival and maintaining the quality of life (QoL) become pivotal issues guiding the treatment decisions. One possible approach to optimise survival and QoL is the use of patient-reported outcomes (PROs) to timely identify acute disease-related burden. We present the protocol of a trial that investigates the effect of real-time PRO data captured with electronic mobile devices on QoL in female breast cancer patients with metastatic disease. Methods: This study is a randomised, controlled trial with 1:1 randomisation between two arms. A total of 1000 patients will be recruited in 40 selected breast cancer centres. Patients in the intervention arm receive a weekly request via an app to complete the PRO survey. Symptoms will be assessed by study-specific optimised short forms based on the EORTC QLQ-C30 domains using items from the EORTC CAT item banks. In case of deteriorating PRO scores, an alarm is sent to the treating study centre as well as to the PRO B study office. Following the alarm, the treating breast cancer centre is required to contact the patient to inquire about the reported symptoms and to intervene, if necessary. The intervention is not specified and depends on the clinical need determined by the treating physician. Patients in the control arm are prompted by the app every 3 months to participate in the PRO survey, but their response will not trigger an alarm. The primary outcome is the fatigue level 6 months after enrolment. Secondary endpoints include among others hospitalisations, use of rescue services and overall QoL. Discussion: Within the PRO B intervention group, we expect lower fatigue levels 6 months after intervention start, higher levels of QoL, less unplanned hospitalisations and less emergency room visits compared to controls. In case of positive results, our approach would allow a fast and easy transfer into clinical practice due to the use of the already nationwide existing IT infrastructure of the German Cancer Society and the independent certification institute OnkoZert

Development of Cortical Lesion Volumes on Double Inversion Recovery MRI in Patients With Relapse-Onset Multiple Sclerosis

Background and Objective: In multiple sclerosis (MS) patients, Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to detect cortical lesions (CL). While the quantity and distribution of CLs seems to be associated with patients' disease course, literature lacks frequent assessments of CL volumes (CL-V) in this context. We investigated the reliability of DIR for the longitudinal assessment of CL-V development with frequent follow-up MRIs and examined the course of CL-V progressions in relation to white-matter lesions (WML), contrast enhancing lesions (CEL) and clinical parameters in patients with Relapsing-Remitting Multiple Sclerosis (RRMS).Methods: In this post-hoc analysis, image- and clinical data of a subset of 24 subjects that were part of a phase IIa clinical trial on the “Safety, Tolerability and Mechanisms of Action of Boswellic Acids in Multiple Sclerosis (SABA)” (ClinicalTrials.gov, NCT01450124) were included. The study was divided in three phases (screening, treatment, study-end). All patients received 12 MRI follow-up-examinations (including DIR) during a 16-months period. CL-Vs were assessed for each patient on each follow-up MRI separately by two experienced neuroradiologists. Results of neurological screening tests, as well as other MRI parameters (WML number and volume and CELs) were included from the SABA investigation data.Results: Inter-rater agreement regarding CL-V assessment over time was good-to-excellent (κ = 0.89). Mean intraobserver variability was 1.1%. In all patients, a total number of 218 CLs was found. Total CL-Vs of all patients increased during the 4 months of baseline screening followed by a continuous and significant decrease from month 5 until study-end (p < 0.001, Kendall'W = 0.413). A positive association between WML volumes and CL-Vs was observed during baseline screening. Decreased CL-V were associated with lower EDSS and also with improvements of SDMT- and SCRIPPS scores.Conclusion: DIR MRI seems to be a reliable tool for the frequent assessment of CL-Vs. Overall CL-Vs decreased during the follow-up period and were associated with improvements of cognitive and disability status scores. Our results suggest the presence of short-term CL-V dynamics in RRMS patients and we presume that the laborious evaluation of lesion volumes may be worthwhile for future investigations.Clinical Trial Numbers:www.ClinicalTrials.gov, “The SABA trial”; number: NCT0145012