Primary outcome measures
Primary outcome measures were quality of life, fatigue and physical restriction (see Table
1).
Table 1
Time schedule of outcome assessment
Primary outcomes
| |
0
|
2
|
4
|
6
|
8
|
Quality of Life | EORTC QLQ-C30* | X | | X | | X |
Quality of Life | RSCL, overall question ** | X | X | X | X | X |
Fatigue | SFQ*** | X | X | X | X | X |
Physical restriction | GARS-4**** | X | X | X | X | X |
Secundary outcomes
| | | | | | |
Appetite | Appetite Questionnaire | X | | X | | X |
Nutritional intake | 3-Day food diary | X | | X | | X |
Medication | Medication list | X | X | X | X | X |
Body weight | Electronic weighing scale | X | X | X | X | X |
Triceps skinfold | | X | X | X | X | X |
Arm circumference | | X | X | X | X | X |
Muscle strength | Biceps and quadriceps strength | X | | X | | X |
Muscle strength | Handgrip strength | X | X | X | X | X |
Use of professional care services | Diary and health care registration | X | X | X | X | X |
Quality of life was assessed using the EORTC Quality of Life Questionnaire (QLQ-C30, version 3.0) [
11,
12]. The QLQ-C30 is a 30-item cancer-specific core questionnaire that addresses various domains of QoL. It contains five functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning), three symptom scales (fatigue, pain and nausea/vomiting), two items assessing global health and quality of life, and a number of single items addressing various symptoms (constipation, diarrhoea, dyspnea, anorexia and insomnia) and perceived financial impact. All items are scored on a 4-point Likert-type scale. The content areas covered by this questionnaire reflect the multi-dimensionality of the quality of life construct. The EORTC QLQ has been extensively used for assessing health-related quality of life in patients with a wide range of cancers. Studies in patients with advanced cancer with a short life expectancy showed that the questionnaire was well accepted, with a high completion rate and useful in detecting the effectiveness of palliative treatment over time. Results confirmed that the QLQ-C-30 is a reliable and valid measure of the quality of life in patients with advanced cancer [
13,
14].
In addition to the QLQ-C30, we used the overall question from the Rotterdam Symptom Checklist ("overall, how did you feel over the past week") as a general indicator of perceived QoL. The Rotterdam Symptom Checklist was originally validated in a Dutch study [
15] and has since then been used in numerous studies in cancer patients.
Fatigue was measured by the Short Fatigue Questionnaire (SFQ). The SFQ is a reliable and simple instrument to assess bodily fatigue [
16]. The questionnaire comprises 4 items. Each item is scored on a 7-point Likert scale.
Physical restriction was assessed by the Groningen Activity Restraint Scale (GARS-4) [
17]. The GARS-4 was developed to assess disability in the domains of personal care (11 items) and domestic activities (7 items). Studies in persons receiving home care, healthy seniors, patients with recent diagnosed cancer, multiple sclerosis, or rheumatoid arthritis showed that the GARS is an easy to administer, reliable, and valid measure for assessing disability in the domains of ADL (Activities of Daily Living) and IADL (Instrumental Activities of Daily Living) [
18,
19].
Secondary outcome measures
Secondary outcome measures were:
Appetite, assessed by four 100 mm visual analogue scales (VAS) related to hunger and satiety with words anchored at each end expressing the most positive or negative sensation. Some studies have investigated the correlation between hunger ratings and energy intake, i.e. the validity of the appetite ratings. Many of these have failed to demonstrate such a relationship, while others have found that there was an association [
20,
21]. Results obtained from VAS yield the most valuable information when combined with other aspects of energy balance [
22].
Nutritional intake was assessed by a 3-day food diary. Patients were taught to keep records, in portion sizes, of all the foods they had eaten on several days of the study. The portion sizes were described in household measures using the utensils commonly found in their homes. These household measures were quantified by volume by the investigator. In general, a 3-day record, randomized to cover seasonal and weekday variations is recommended to assess mean food consumption of a group of individuals [
23]. A review about the validity of self-reported energy intake showed that energy intake derived from all methods of food recording can be an imprecise measure that is substantially under-reporting in groups including adults, children and adolescents, obese persons, athletes, military personnel and trekking explorers [
24]. No data about patients with cancer are available.
Medication; changes were registered during each home visit.
Body height, measured to the nearest 0.1 centimeter.
Body weight was measured without shoes, using an electronic weighing scale (Soehnle 7407 Translucia, Germany) to the nearest 0.05 kg.
Triceps skin fold thickness was measured in duplicate with a Holtain
® skinfold caliper (CMS weighing equipment LTD, London UK) to calculate total body fat mass (FM) using the age- and gender-specific tables from Durnin and Womersley [
25]. Fat-free mass (FFM) was calculated by subtracting fat mass from body weight.
Mid-upper arm circumference of the dominant arm was measured with a flexible measuring tape, and
arm muscle area derived using the equation: (arm circumference - π × triceps skinfold)
2/4 π [
26]. Arm muscle area gives an indication of the body's muscle mass as its main protein reserve [
26].
Muscle strength of two major muscle groups (i.e. elbow flexor and knee extensor muscles) were assessed at the dominant arm and leg using a hand/held Microfet2
® dynamometer (Biometrics Europe BV, Almere, The Netherlands). This technique has been validated in several patient groups, mostly in patients whit limited muscle strength [
27‐
29]. The patient while sitting exerts a maximal force with the 90° flexed elbow, while the examiner pushes with the dynamometer against the patients' thumb pad until muscle strength is overcome (break test). Similarly, the patient exerts a maximal force with the 90° flexed knee, while the examiner pushes with the dynamometer against the patients' ankle until muscle strength is overcome. The strength of both muscle groups is measured twice at an interval of approximately one minute. Muscle strength is expressed in Newtonmeter (Nm) units and calculated by dividing the measured mean strength (dynamometer reading) by the distance from dynamometer position point to the medial humeral epicondylus medialis (elbow) and the medial femoral epicondylus medialis (knee).
Handgrip strength of the dominant hand was measured using a JAMAR hydraulic hand dynamometer (Saehan Corp. Masan, Korea). Handgrip strength is a simple, quick, easily performed, and readily available bedside test. Studies in several population groups showed strong positive correlations between handgrip strength and lean body mass [
30]. Furthermore, handgrip strength is correlated with total body muscle strength [
31].
In order to exclude inter-observer variability, longitudinal anthropometric and muscle strength measurements in each patient were performed by the same observer.
Caregiver burden
The second study objective was to evaluate whether ATP infusions could relieve family caregiver burden and reduce the use of professional health care services. Caregiver burden was measured at two levels: 1. informal care; 2. professional care. To measure caregiver burden we used the GARS-4. For each item it must be marked whether the patient, the family caregivers or health care professionals carried out the activities (not at all, partly, completely). Use of medical care services (hospital admissions, outpatient clinic visits, general practitioner contacts), and home care (both domestic and nursing care) was recorded every visit.
Process evaluation
The evaluation of feasibility of the ATP infusions was performed by open interviews with the staff of the day care center and the nurses of the infusion home teams after finishing patient recruitment. Aspects such as procedures concerning the transfer of ATP infusions from hospital to home, the responsibility of the general practitioner for the administration of home infusions and the technical and logistical bottlenecks were particularly evaluated. Furthermore, information about patient satisfaction regarding the safety and the burden of the ATP infusions was collected during each follow-up visit by one standard questionnaire for the patient and a second for his/her partner.