Pediatric oncologists' perspectives on the use of complementary medicine in pediatric cancer patients in Switzerland: A national survey-based cross-sectional study.

BACKGROUND: There is a widespread use of complementary therapies among pediatric cancer patients. Previous studies provided evidence that communication between pediatric oncologists (POs) and patients/families about the use of these therapies is often incomplete. Furthermore, nationwide studies on this topic are rare. AIMS: We assessed POs' perspectives on the use of complementary medicine (CM) in Switzerland, on the basis of an edited survey previously used in a nationwide study. METHODS AND RESULTS: A link to an online survey was sent by e-mail to each of the fifty-two eligible pediatric oncologists in all nine Swiss Pediatric Oncology Group (SPOG) centers. Eligible respondents were board-certified (Switzerland or abroad) POs currently working at a SPOG center. The survey was available for a total period of 2 months. We received 29 filled questionnaires (overall response rate: 56%). Most POs (59%) indicated that they ask more than 50% of their patients about CM use. Frequent reasons for not asking about the use of CM were i) forgetting to ask (55%), ii) lack of knowledge on the subject (31%), and iii) lack of time (24%). More than every second PO (55%) reported having a lack of knowledge on the subject. A majority of POs (66% to 76%) indicated interest in learning more about specific CM topics (cannabinoids, hypnosis and relaxation, music therapy, herbal medicine, acupuncture, meditation, and yoga). More information and specific training opportunities on the use of CM was deemed important by 76% to 97% of POs. CONCLUSION: POs working in Switzerland identify complementary therapies as an important subject. Swiss POs are willing to acquire more knowledge on CM. More training seems to be necessary in order to increase awareness about the topic, to enhance communication about complementary therapies and thus to improve patient care.

A national survey of Swiss paediatric oncology care providers' cross-cultural competences.

BACKGROUND AND PURPOSE: Culturally diverse countries such as Switzerland face the challenge of providing cross-cultural competent care. Cross-cultural competent care needs an understanding of a patient's cultural context in order to provide safe and effective care. Therefore, we sought to examine cross-cultural competence of Swiss paediatric oncology care providers, and to explore their perceptions of barriers to and facilitators of cross-culturally competent care. DESIGN AND SAMPLE: We conducted a cross-sectional study. The data collection period was three weeks. Providers were recruited through collaborators at the participating paediatric oncology centres. All occupational groups who are in direct contact with patients and involved in their care were eligible (e.g., physicians, nurses, social workers, occupational therapists and physiotherapists). Surveying providers online, we captured five subscales of their cross-cultural competence and their perceptions as to how to facilitate cross-culturally competent paediatric oncology care. We employed the Cross-Cultural Competence of Healthcare Professionals (CCCHP) questionnaire. Besides descriptive and inferential statistics, we performed content analysis. FINDINGS: The response rate was 73.2% (n = 183/250). Analyses revealed differences in cross-cultural competence between occupational groups of paediatric oncology providers. Overall, social workers' cross-cultural competence was higher than nurses' or occupational therapists' and physiotherapists' cross-cultural competence. Physicians' cross-cultural competence was higher than nurses (with no statistically significant difference identified between physicians, occupational therapists and physiotherapists). Furthermore, our results suggest noteworthy differences among the four main occupational groups on the five CCCHP subscales. Physicians and social workers declared more positive attitudes than nurses; occupational therapists and physiotherapists reported lower skills than the other three groups; social workers scored higher on the emotions and empathy subscale than the other three groups; physicians were more knowledgeable and aware than nurses. Most frequently mentioned barriers were: language barriers (68.5%), different culture and values (19.2%), different illness understanding (9.2%). Most frequently mentioned facilitators were: professional translators (47.2%), continuous training (20.8%), professional cultural mediators (8.8%). CONCLUSIONS/IMPLICATIONS: Trainings and interventions are widely considered a principal strategy to advance providers' cross-cultural competence. Our findings of differences in cross-cultural competence among occupational groups further underpin the need to adapt training programmes and interventions to the respective occupational group and the respective dimension(s) of cross-cultural competence. In addition, professional translators and cultural mediators should be used. Lastly, reciprocal supervision and the promotion of multidisciplinary teams is crucial to enable oncology care providers to learn from each other and this exchange could also help to reduce some of the differences between the various occupational groups.

Complementary individual homeopathy in paediatric cancer care: A case series from a University Hospital, Switzerland.

The Department of Haematology/Oncology at the University Children's Hospital Bern (HONK), has adopted an integrative approach in addition to state of the art oncological care and implemented a collaboration with the Institute of Complementary Medicine IKOM, University of Bern, over the past 10 years. Stakeholder satisfaction with this service was high. We present descriptive data and report on 4 exemplary patients treated with additional individualized homeopathy (iHOM). Data concerning frequency of consultations, pathologies, follow-ups and clinical results were reviewed and summarized using descriptive statistics. 94 paediatric oncologic patients consulted for iHOM. Indications for the complementary treatment was wide-ranging. No interactions with conventional treatment and no adverse side-effects of iHOM were detected. We present four characteristic patient histories, in which iHOM was used in addition to standard treatment for mucositis, permissive tissue infection, insomnia and affective dysfunctions. All four patients clinically improved in an immediate temporal relationship to the additional treatment. CONCLUSION: The collaboration between HONK and IKOM established iHOM in paediatric oncology in Bern. In this setting, iHOM was a safe and supportive additional treatment for various indications during the conventional cancer care. However, no generalizable results can be deducted from these data. We emphasize future research on this topic.

Assessment of residency program outcomes via alumni surveys.

BACKGROUND: One trend in medical education is outcomes-oriented training. Outcomes usually refer to individuals' acquisition of competencies, for example, during training in residency programs. However, little is known about outcomes of these programs. In order to fill this gap, human resource (HR) data were analyzed and alumni of a pediatric residency program were surveyed at the Department of Pediatrics, Bern University Hospital, Switzerland. METHODS: Residency program outcomes (demographics, career choices, part-time or full-time work status, competencies, feedback) were assessed through in-house HR databases, publicly available data on the Internet (physician directory and practice homepages), and 2 alumni surveys (S1, S2). RESULTS: In all, 109 alumni met the inclusion criteria. Retention rate at the hospital was low (14%). Forty-six alumni (42%) in private practice were eligible for alumni surveys. Response rates were 87% (S1) and 61% (S2). Time intervals between 2 career decisions (selecting specialty of pediatrics vs selecting setting of private practice) varied widely (late-training decision to enter private practice). Mean employment level in private practice was 60% (range 20%-100%). Most valued rotation was emergency medicine; most desired competencies in future colleagues were the ability to work in a team, proficiency in pediatrics, and working economically. CONCLUSION: A broadened view on outcomes - beyond individuals' competency acquisition - provides informative insights into a training program, can allow for informed program updates, and guide future program development.

Cancer's positive flip side: posttraumatic growth after childhood cancer.

BACKGROUND: Surviving childhood cancer may result in positive psychological changes called posttraumatic growth (PTG). Knowing about the possibility of positive changes may facilitate survivors' reintegration in daily life. We aimed to (1) describe PTG in Swiss childhood cancer survivors including the most and the least common PTG phenomena on the subscale and item levels and (2) determine factors associated with PTG. METHOD: Within the Swiss Childhood Cancer Survivor Study (SCCSS), we sent two questionnaires to childhood cancer survivors registered in the Swiss Childhood Cancer Registry (SCCR). Eligible survivors were diagnosed after 1990 at age ≤16 years, survived ≥5 years, and were aged ≥18 years at the time the second questionnaire was sent. We included the Posttraumatic Growth Inventory (PTGI) to assess five areas of PTG. We investigated the association of PTG with socio-demographic characteristics, self-reported late effects, and psychological distress, which were assessed in the SCCSS and clinical variables extracted from the SCCR. We used descriptive statistics to describe PTG and linear regressions to investigate factors associated with PTG. RESULTS: We assessed PTG in 309 childhood cancer survivors. Most individuals reported to have experienced some PTG. The most endorsed change occurred in "relation with others," the least in "spiritual change." PTG was significantly higher in survivors with older age at diagnosis (p = 0.001) and those with a longer duration of treatment (p = 0.042), while it was lower in male survivors (p = 0.003). CONCLUSIONS: Supporting experiences of PTG during follow-up may help survivors successfully return to daily life.

Use of Complementary and Alternative Medicine in Children with Cancer: A Study at a Swiss University Hospital.

BACKGROUND: Though complementary and alternative medicine (CAM) are frequently used by children and adolescents with cancer, there is little information on how and why they use it. This study examined prevalence and methods of CAM, the therapists who applied it, reasons for and against using CAM and its perceived effectiveness. Parent-perceived communication was also evaluated. Parents were asked if medical staff provided information on CAM to patients, if parents reported use of CAM to physicians, and what attitude they thought physicians had toward CAM. STUDY DESIGN: All childhood cancer patients treated at the University Children's Hospital Bern between 2002-2011 were retrospectively surveyed about their use of CAM. RESULTS: Data was collected from 133 patients (response rate: 52%). Of those, 53% had used CAM (mostly classical homeopathy) and 25% of patients received information about CAM from medical staff. Those diagnosed more recently were more likely to be informed about CAM options. The most frequent reason for choosing CAM was that parents thought it would improve the patient's general condition. The most frequent reason for not using CAM was lack of information. Of those who used CAM, 87% perceived positive effects. CONCLUSIONS: Since many pediatric oncology patients use CAM, patients' needs should be addressed by open communication between families, treating oncologists and CAM therapists, which will allow parents to make informed and safe choices about using CAM.

Synthetic versus natural curcumin: bioequivalence in an in vitro oral mucositis model.

BACKGROUND: Curcumin (CUR) is a dietary spice and food colorant (E100). Its potent anti-inflammatory activity by inhibiting the activation of Nuclear Factor-κB is well established. METHODS: The aim of this study was to compare natural purified CUR (nCUR) with synthetically manufactured CUR (sCUR) with respect to their capacity to inhibit detrimental effects in an in vitro model of oral mucositis. The hypothesis was to demonstrate bioequivalence of nCUR and sCUR. RESULTS: The purity of sCUR was HPLC-confirmed. Adherence and invasion assays for bacteria to human pharyngeal epithelial cells demonstrated equivalence of nCUR and sCUR. Standard assays also demonstrated an identical inhibitory effect on pro-inflammatory cytokine/chemokine secretion (e.g., interleukin-8, interleukin-6) by Detroit pharyngeal cells exposed to bacterial stimuli. There was bioequivalence of sCUR and nCUR with respect to their antibacterial effects against various pharyngeal species. CONCLUSION: nCUR and sCUR are equipotent in in vitro assays mimicking aspects of oral mucositis. The advantages of sCUR include that it is odorless and tasteless, more easily soluble in DMSO, and that it is a single, highly purified molecule, lacking the batch-to-batch variation of CUR content in nCUR. sCUR is a promising agent for the development of an oral anti-mucositis agent.

Antibacterial and antiinflammatory kinetics of curcumin as a potential antimucositis agent in cancer patients.

The antiinflammatory agent curcumin (diferuloylmethane) has a potential to mitigate cancer therapy-induced mucositis. We assessed the in vitro extent of its bactericidal activity and determined the kinetics of its antiinflammatory effect on pharyngeal cells. Bactericidal activity was assessed using the LIVE/DEAD® Kit after 4 h of exposure to curcumin (50-200 µM) in 18 oropharyngeal species commonly associated with bacteremia in febrile neutropenia. Moraxella catarrhalis or its outer membrane vesicles were used to determine the inhibitory effect of curcumin on bacteria-induced proinflammatory activity as determined by cytokine release into the supernatant of Detroit 562 pharyngeal cells using the Luminex® xMAP® technology. Curcumin exerted a concentration-dependent bactericidal effect on all 18 species tested. After 4 h at 200 µM, 12 species tested were completely killed. Preincubation of Detroit cells with 200 µM curcumin for 5 to 60 min resulted in complete suppression of the release of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, granulocyte macrophage-colony stimulating factor, and vascular endothelial growth factor. Fibroblast growth factor-2 and interferon-γ were not affected. Repetitive exposure to curcumin resulted in repetitive suppression of cytokine/chemokine expression lasting from 4 to 6 h. Through reduction of oral microbial density as well as suppression of inflammation cascades curcumin may prevent cancer therapy-induced oral mucositis, e.g., when applied as multiple daily mouth washes.

Clinicopathologic features and long-term outcomes of NUT midline carcinoma.

PURPOSE: NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations. EXPERIMENTAL DESIGN: A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses. RESULTS: The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% [1-year PFS 15% (5-24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%-31% (1-year OS: 30% (27-34%)]. Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome. CONCLUSIONS: NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.

Voriconazole-induced phototoxicity in children.

Voriconazole is used in antifungal prophylaxis. We performed a retrospective review of immunocompromised children receiving prophylaxis with voriconazole during major hospital renovation, who developed phototoxic skin reactions. The overall incidence of phototoxic skin reactions was 33%. A voriconazole dose of ≥6 mg/kg of body weight per dose twice daily was associated with a significantly greater risk to develop phototoxic skin reactions compared with lower doses.

Topical curcumin can inhibit deleterious effects of upper respiratory tract bacteria on human oropharyngeal cells in vitro: potential role for patients with cancer therapy induced mucositis?

PURPOSE: Curcumin exerts its anti-inflammatory activity via inhibition of nuclear factor κB. Oropharyngeal epithelia and residing bacteria closely interact in inflammation and infection. This in vitro model investigated the effects of curcumin on bacterial survival, adherence to, and invasion of upper respiratory tract epithelia, and studied its anti-inflammatory effect. We aimed to establish a model, which could offer insights into the host-pathogen interaction in cancer therapy induced mucositis. METHODS: Moraxella catarrhalis (Mcat) and the oropharyngeal epithelial cell line Detroit 562 were used. Time-kill curves assessed the inhibition of bacterial growth and adherence assays and gentamicin protection assays determined the effect of curcumin-preincubated cells on bacterial adherence and invasion. Curcumin-mediated inhibition of pro-inflammatory activation by Mcat was determined via interleukin-8 concentrations in the supernatants. The synergistic role of secretory IgA (sIgA) on adherence was investigated. RESULTS: Curcumin was bactericidal at concentrations >50 µM. Preincubation of Detroit cells for 60 min demonstrated that concentrations >100 µM inhibited bacterial adherence. Together with sIgA, curcumin inhibited adherence at concentrations ≥50 µM. Both 100 and 200 µM curcumin significantly inhibited Mcat cell invasion. Finally, curcumin inhibited Mcat-induced pro-inflammatory activation by strongly suppressing IL-8 release. At a concentration of 200 µM, 10 min of curcumin exposure inhibited IL-8 release significantly, and complete suppression required a pre-exposure time of ≥45 min. CONCLUSION: Curcumin, in clinically relevant concentrations for topical use, displayed strong antibacterial effect against a facultative upper respiratory tract pathogen by inhibiting bacterial growth, adherence, invasion, and pro-inflammatory activation of upper respiratory tract epithelial cells in vitro.

Non-classical karyotypic features in relapsed childhood B-cell precursor acute lymphoblastic leukemia.

Karyotype analysis of acute lymphoblastic leukemia (ALL) at diagnosis has provided valuable prognostic markers for treatment stratification. However, reports of cytogenetic studies of relapsed ALL samples are limited. We compared the karyotypes from 436 nonselected B-cell precursor ALL patients at initial diagnosis and of 76 patients at first relapse. We noticed a relative increase of karyotypes that did not fall into the classic ALL cytogenetic subgroups (high hyperdiploidy, t(12;21), t(9;22), 11q23, t(1;19), <45 chromosomes) in a group of 29 patients at relapse (38%) compared to 130 patients at presentation (30%). Non-classical cytogenetic aberrations in these 29 patients were mostly found on chromosomes 1, 2, 7, 9, 13, 14, and 17. We also describe six rare reciprocal translocations, three of which involved 14q32. The most frequent abnormalities were found in 9p (12/29 cases) and were associated with a marked decrease in the duration of the second remission, but not of the probability of 10-year event-free survival after relapse treatment. From 29 patients with non-classical cytogenetic aberrations, only 8 (28%) had been stratified to a high risk-arm on the first treatment protocol, suggesting that this subgroup might benefit from the identification of new prognostic markers in future studies.

Treatment of intestinal and hepatic mucormycosis in an immunocompromized child.

During ALL chemotherapy, a 4-year-old patient presented with febrile neutropenia and abdominal pain. Ultrasound examinations were repeatedly normal. Computerized tomography on day 7 demonstrated appendicitis and multiple hepatic foci identified as mucormycosis (Absidia corymbifera). Successful outcome was achieved by aggressive re-surgery, long-term antifungal therapy with serum level-monitored posaconazole, and recovery of neutrophil counts. Considering the interference of posaconazole with CYP3A4, vincristine was administered during 72 hr posaconazole windows. Pediatric intestinal mucormycosis, still associated with a >70% case-fatality rate, calls for early imaging and surgery to establish the diagnosis, reduce the fungal mass, and provide a rationale for using posaconazole.