Economic Evaluation of Complementary and Alternative Medicine in Oncology: Is There a Difference Compared to Conventional Medicine?

OBJECTIVE: To analyze the financial burden of complementary and alternative medicine (CAM) in cancer treatment. MATERIALS AND METHODS: Based on a systematic search of the literature (Medline and the Cochrane Library, combining the MeSH terms 'complementary therapies', 'neoplasms', 'costs', 'cost analysis', and 'cost-benefit analysis'), an expert panel discussed different types of analyses and their significance for CAM in oncology. RESULTS: Of 755 publications, 43 met our criteria. The types of economic analyses and their parameters discussed for CAM in oncology were cost, cost-benefit, cost-effectiveness, and cost-utility analyses. Only a few articles included arguments in favor of or against these different methods, and only a few arguments were specific for CAM because most CAM methods address a broad range of treatment aim parameters to assess effectiveness and are hard to define. Additionally, the choice of comparative treatments is difficult. To evaluate utility, healthy subjects may not be adequate as patients with a life-threatening disease and may be judged differently, especially with respect to a holistic treatment approach. We did not find any arguments in the literature that were directed at the economic analysis of CAM in oncology. Therefore, a comprehensive approach assessment based on criteria from evidence-based medicine evaluating direct and indirect costs is recommended. CONCLUSION: The usual approaches to conventional medicine to assess costs, benefits, and effectiveness seem adequate in the field of CAM in oncology. Additionally, a thorough deliberation on the comparator, endpoints, and instruments is mandatory for designing studies.

Spirituality in Oncology: Relations between Spirituality, Its Facets, and Psychological and Demographic Factors in Cancer Patients in Germany.

INTRODUCTION: Cancer diagnoses are constantly increasing in clinical practice. Therefore, more and more patients are interested in how they can actively participate in the process of treatment. Spirituality represents a hidden issue of the population, which counts as a branch of complementary and alternative treatment. Therefore, the aim of our study was to investigate whether there are associations between spirituality and demographic and psychosocial factors, as well as religious beliefs, in cancer patients. METHODS: We conducted a survey with 451 participants in 10 oncology centers between March and July 2021. A composition of the following 9 different questionnaires was used to collect data on spirituality, demographics, resilience, self-efficiency, life satisfaction, and sense of coherence: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp12), General Life Satisfaction Short Scale (L-1), Resilienzskala Kurzform (RS-13), Sense of Coherence Scale - Leipziger Kurzform (SOC-L9), Allgemeine Selbstwirksamkeit Kurzskala (AKSU), Adolescent Food Habits Checklist, Likert-Scale of daily activities, questionnaire of the Working group Prävention und Integrative Onkologie (PRiO), and personal opinion on the cause of the disease. Calculated data and analyzed group differences using ANOVA Bonferroni were used to test associations between spirituality and the variables studied. For more detailed examination of spirituality, we took a closer look at the different components of spirituality - peace, meaning, and faith - and their relation to each other (three-factor spirituality analyses). RESULTS: Higher spirituality scores in total as well as meaning, peace, and faith were each associated with higher levels of resilience and life satisfaction. Higher religious belief was found to be associated with higher spiritual attitudes. High personal self-efficiency was found in people with higher spiritual beliefs in general as well as higher meaning and peace. Meaning and peace emerge as essential components of spiritual well-being and show a stronger association with expressions of general spirituality than faith. CONCLUSION: Spirituality takes a crucial role among the resources of life-threatening diseases. As such, further research is needed to expand and integrate patient options into a modernized concept of care. Our data indicate that higher spiritual well-being is associated with a more tolerant approach to illness. Thus, addressing spiritual needs in therapy is associated with better psychological adjustment to the individual situation and reduces negative distress. To promote spiritual needs in the future, cognitive as well as affective components of spirituality should be emphasized.

Online information on complementary and alternative medicine for cancer patients: evidence-based recommendations.

BACKGROUND: Many cancer patients use complementary and alternative medicine (CAM). Most websites offering online information on CAM are not helpful for them. METHODS: We extracted decisive elements for online information on CAM by analyzing the literature on the information needs of cancer patients and on counseling cancer patients on CAM. RESULTS: Key issues for online information on CAM are the qualification of the authors, transparency and accountability of the information, description of the aims, a scientific approach, description of treatment alternatives, support for the patient-physician relationship, individualized information, a summary of the information, disclosure of funding, and the privacy policy. CONCLUSIONS: The communicative challenge will be to convey information without destroying hope and motivation. We suggest that CAM topics should be integrated into broader information provided on cancer (etiology, conventional treatment). By also providing information for physicians, such a website could promote shared decision-making. Online information will gain the status of independent expert knowledge if provided by a well-known scientific organization as, e.g., a national cancer society.

Usage of Complementary and Alternative Methods, Lifestyle, and Psychological Variables in Cancer Care.

BACKGROUND/AIM: People who are undergoing cancer treatment often ask themselves what they can do in addition to conventional medical therapy with regard to nutrition, activity, and complementary methods. However, we know little about the motivation why people opt for one or the other measure. The aim of this study was therefore to examine the extent of physical activity (PA), healthy nutrition, and the use of complementary methods in relation to both demographic and psychological data. MATERIALS AND METHODS: A questionnaire was used to collect data on demographic data, resilience, coherence, self-efficacy, spirituality, satisfaction, and complementary and alternative medicine (CAM) behavior, PA, and diet. Between March and July 2021, data from 446 patients were collected. Regression models and correlation analyzes were used to examine the associations between CAM use, diet and PA with the other variables surveyed. RESULTS: CAM usage could only be predicted based on the patient's spirituality. Women used CAM more often and ate more healthily. Healthy eating was also related to younger age, shorter medical history, resilience, satisfaction, and coherence. In addition, the results showed that daily PA was related to the level of resilience, spirituality, and self-efficacy. CONCLUSION: Which people or why patients use CAM remains a question to be further investigated. Our data suggest that CAM seeks to address similar needs that others find in spirituality. In order to promote a healthy diet and PA in cancer patients in the future, various psychological variables seem conceivable. Resilience stands out, which is related to an overall healthier lifestyle.

Membrane hydraulic permeability changes during cooling of mammalian cells.

In order to predict optimal cooling rates for cryopreservation of cells, the cell-specific membrane hydraulic permeability and corresponding activation energy for water transport need to be experimentally determined. These parameters should preferably be determined at subzero temperatures in the presence of ice. There is, however, a lack of methods to study membrane properties of cells in the presence of ice. We have used Fourier transform infrared spectroscopy to study freezing-induced membrane dehydration of mouse embryonic fibroblast (3T3) cells and derived the subzero membrane hydraulic permeability and the activation energy for water transport from these data. Coulter counter measurements were used to determine the suprazero membrane hydraulic permeability parameters from cellular volume changes of cells exposed to osmotic stress. The activation energy for water transport in the ice phase is about three fold greater compared to that at suprazero temperatures. The membrane hydraulic permeability at 0 °C that was extrapolated from suprazero measurements is about five fold greater compared to that extrapolated from subzero measurements. This difference is likely due to a freezing-induced dehydration of the bound water around the phospholipid head groups. Using Fourier transform infrared spectroscopy, two distinct water transport processes, that of free and membrane bound water, can be identified during freezing with distinct activation energies. Dimethylsulfoxide, a widely used cryoprotective agent, did not prevent freezing-induced membrane dehydration but decreased the activation energy for water transport.

Liposomes alter thermal phase behavior and composition of red blood cell membranes.

Unilamellar liposomes composed of natural phospholipids provide a new promising class of protective agents for hypothermic storage, cryopreservation, or freeze-drying of red blood cells (RBCs). In this study, FTIR spectroscopy, MALDI-TOF MS, and colorimetric assays were used to investigate the effects of liposomes composed of a homologous series of linear saturated phosphatidylcholine phospholipids (18:0; 16:0; 14:0; 12:0) on RBC membranes. RBCs were incubated with liposomes at 37°C and both the liposomal and the RBC fraction were analyzed after incubation. FTIR studies showed that liposomes composed of short acyl chain length lipids cause an increase in RBC membrane conformational disorder at suprazero temperatures, whereas long acyl chain length lipids were found to have little effects. The increased lipid conformational disorder in the RBC membranes coincided with a decrease in the cholesterol-to-phospholipid ratio. The opposite effects were found in the liposomes after incubation with RBCs. MALDI-TOF MS analysis showed the presence of short acyl chain length lipids (14:0 and 12:0) in RBC membranes after incubation, which was not observed after incubation with liposomes containing long acyl chain length lipids (18:0 and 16:0). Liposomes alter RBC membrane properties by cholesterol depletion and lipid addition.

Liposomes composed of unsaturated lipids for membrane modification of human erythrocytes.

Previous studies have shown that certain saturated lipids protect red blood cells (RBCs) during hypothermic storage but provide little protection during freezing or freeze-drying, whereas various unsaturated lipids destabilize RBCs during hypothermic storage but protect during freezing and freeze-drying. The protective effect of liposomes has been attributed to membrane modifications. We have previously shown that cholesterol exchange and lipid transfer between liposomes composed of saturated lipids and RBCs critically depends on the length of the lipid acyl chains. In this study the effect of unsaturated lipids with differences in their number of unsaturated bonds (18:0/18:1, 18:1/18:1, 18:2/18:2) on RBC membrane properties has been studied. RBCs were incubated in the presence of liposomes and both the liposomal and RBC fraction were analyzed by Fourier transform infrared spectroscopy (FTIR) after incubation. The liposomes caused an increase in RBC membrane conformational disorder at suprazero temperatures. The fluidizing effect of the liposomes on the RBC membranes, however, was found to be similar for the different lipids irrespective of their unsaturation level. The gel to liquid crystalline phase transition temperature of the liposomes increased after incubation with RBCs. RBC membrane fluidity increased linearly during the first 8 hours of incubation in the presence of liposomes. The increase in RBC membrane fluidity was found to be temperature dependent and displayed Arrhenius behaviour between 20 and 40°C, with an activation energy of 88 kJ mol⁻¹. Taken together, liposomes composed of unsaturated lipids increase RBC membrane conformational disorder, which could explain their cryoprotective action.

Cancer patients and the Internet: a survey of the 'Quality of Life' Working Groups of the Arbeitsgemeinschaft für Internistische Onkologie and the Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie.

BACKGROUND: Patient-reported outcomes, such as quality of life (QoL) assessment, are becoming more important as endpoint in clinical trials and for decision making regarding new anticancer product approvals. Nevertheless, numerous obstacles exist regarding the implementation of QoL assessment in the daily practice of medical oncologists. Regular, computerized or internet home-based QoL assessments could be a step forward. METHODS: Using a 15-item paper questionnaire, we conducted a survey among 1580 cancer patients regarding their willingness to use internet QoL assessment, and collected personal data and information about current disease and performance status. RESULTS: Younger patients (i.e. ≤65 years) significantly more often had internet access (78% versus 36%; χ(2) test, p < 0.001). Moreover, the availability of internet access correlated with higher education levels. 55% of all polled patients are willing to use an internet-based QoL assessment tool, regardless of the type of internet access, whereas almost two-thirds (n = 600; 65%) of patients with their own internet access would be willing to use it for providing statements about QoL. Of these, especially younger patients in good health status with higher education degrees indicated their willingness to use such tools. CONCLUSION: These data may serve as a basis for identifying patient groups willing to participate in pilot projects to evaluate the implementation of internet-based regular assessment of QoL in cancer.

Membrane Stability during Biopreservation of Blood Cells.

SUMMARY: Storage methods, which can be taken into consideration for red blood cells and platelets, include liquid storage, cryopreservation and freeze-drying. Red blood cells can be hypothermically stored at refrigerated temperatures, whereas platelets are chilling sensitive and therefore cannot be stored at temperatures below 20 °C. Here we give an overview of available cryopreservation and freeze-drying procedures for blood cells and discuss the effects of these procedures on cells, particularly on cellular membranes. Cryopreservation and freeze-drying may result in chemical and structural modifications of cellular membranes. Membranes undergo phase and permeability changes during freezing and drying. Cryo- and lyoprotective agents prevent membrane damage by different mechanisms. Cryoprotective agents are preferentially excluded from membrane surfaces. They decrease the activation energy for water transport during freezing and control the rate of cellular dehydration. Lyoprotectants are thought to stabilize membranes during drying by forming direct hydrogen bonding interactions with phospholipid head groups. In addition, lyoprotectants can form a glassy state at room temperature. Recently liposomes have been investigated to stabilize blood cells during freezing and freeze-drying. Liposomes modify the composition of cellular membranes by lipid and cholesterol transfer, which can stabilize or destabilize the low temperature response of cells.

Functional characterization of muscarinic autoreceptors in rat and human neocortex.

Electrically evoked overflow of [(3)H]acetylcholine in slices of rat neocortex and of human neocortex (freshly obtained during neurosurgical treatment of epilepsy or deep-seated tumors) was used to functionally characterize the muscarinic receptor subtype, which mediates autoinhibition of acetylcholine release in these tissues. In the rat neocortex, the following pK(B) values [CI(95)] were calculated from the shifts to the right of the concentration-response curves of the full agonist oxotremorine in presence of subtype preferring muscarinic receptor antagonists: tripitramine: 9.1 [8.8, 9.4], tripinamide: 8.6 [8.5, 8.7], AQ-RA 741 (11-[[4-[4-(diethylamino)butyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido(2,3-b)[1,4]benzodiazepine-6-one): 8.2 [8.0, 8.4], himbacine: 8.0 [7.9, 8.1], 4-diphenylacetoxy-N-methylpiperidine methobromide: 8.0 [7.8, 8.1], methoctramine: 7.5 [7.4, 7.6], AF-DX 116 (11[[2-[(diethyl-amino)methyl]-1-piperidinyl] acetyl] 5,11-dihydro-6H-pyrido(2,3-b)[1,4]benzodiazepine-6-one): 7.1 [7.0, 7.3], hexahydro-sila-difenidol: 6.8 [6.7, 6.9], pirenzepine: 6.6 [6.4, 6.7], and 3,6a,11,14-tetrahydro-9-methoxy-2-methyl-12H-isoquino[1,2-b]pyrrolo[3,2-f] [1,3]benzoxazine-1-carboxylic acid ethyl ester (PD 102807): 6.0 [5.8, 6.2]. In the human neocortex the following values were found: tripitramine: 9.4 [9.3, 9.6], tripinamide: 9.0 [8.9, 9.2], AF-DX 116: 6.7 [6.4, 6.9], hexahydro-sila-difenidol: 6.6 [6.2, 6.9], and PD 102807: 6.5 [6.3, 6.6]. In correlation plots, these pK(B) values correspond best to published binding data on native or recombinant M(2) receptors but not to those on M(1), M(3), M(4), and M(5) receptors, suggesting that muscarinic autoreceptors of both the rat and human neocortex belong to the M(2) subtype. This observation lends further support to the development of M(2) receptor selective brain penetrating antagonists for application in Alzheimer's disease.

Interactions from complementary and alternative medicine in patients with melanoma.

Biological-based (BbCAM) methods from complementary and alternative medicine (CAM) may interact with cancer treatments, reduce efficacy, or enhance adverse effects. Although CAM usage has been evaluated well in other cancer entities, data on melanoma patients are still missing. The aim of this study was to determine CAM usage of melanoma patients using a standardized questionnaire to identify potential interactions with established and new systemic melanoma therapies. This multicenter study was carried out in seven German skin cancer centers. During routine care contact, CAM usage of former and current melanoma treatment was assessed in melanoma patients. The probability of interaction was classified into four categories ranging from 'interaction unlikely' (I), 'possible' (II), 'likely' (III), or 'no data' (IV). The questionnaire was filled out by 1157 patients, of whom 1089 were eligible for evaluation. CAM usage was reported by 41% of melanoma patients, of whom 63.1% took BbCAM such as vitamins, trace elements, supplements, or phytotherapeuticals. Of 335 patients with former or current therapy, 28.1% used BbCAM. The melanoma treatment included interferon, radiotherapy, chemotherapy, BRAF-inhibitor, or other tyrosine kinase inhibitors and ipilimumab. On the basis of our model of likelihood of interaction, we found that 23.9% of those on cancer therapy and 85.1% of those also using BbCAM were at some risk of interactions. The main limitation of our study is that no reliable and comprehensive database on clinical relevant interactions with CAM in oncology exists. Most patients receiving a melanoma-specific treatment and using BbCAM methods are at risk for interactions, which raises concerns on the safety and treatment efficacy of these patients. To protect melanoma patients from potential harm by the combination of their cancer treatment and CAM usage, patients should systematically be encouraged to report their CAM use, while oncologists should be trained on evidence of CAM, and patient guidance for saver CAM use.

Use of complementary and alternative medicine: A multicenter cross-sectional study in 1089 melanoma patients.

BACKGROUND: About half of patients with cancer use complementary and alternative medicine (CAM). So far, data on melanoma patients are missing. OBJECTIVE: The aim of our study was to evaluate the prevalence and predictors for the use of CAM in this patient group. METHODS: All patients with melanoma being attended at one of 7 skin cancer centres in Germany between March 2012 and March 2013 were invited to take part in a survey using a structured questionnaire on CAM. The physicians filled in a second part on the diagnosis, state and former and current therapy. RESULTS: Nearly half of the 1089 participants (41.0%) used CAM and half of those using CAM (56.8%) marked that this made them feel better. Biological-based CAMs which consists of substances taken were used by 25.9% of all patients (63.1% of those using CAM). Predictors of CAM use were education, psychological support, interest in CAM and previous CAM use. CAM users show higher physical activity, more often use psychosocial help and have contact with a self-help group. Family and friends (41.0%) as well as print media (41.7%) are the main sources of information. Most important reasons to use CAM are to strengthen one's own forces (57.7%) or the immune system (63.4%) and to be able to do something for oneself (53.7%). CONCLUSION: Communication on CAM should become a regular topic in counselling melanoma patients. To increase safety, patients and physicians must have access to evidence-based information on these methods and their interactions with modern cancer treatments.