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Abstract Creative music therapy (CMT) has been shown to promote the development of brain function and structure in preterm infants. We aimed to investigate the effect of CMT on cerebral oxygenation and perfusion to examine how the brain reacts to CMT. Absolute levels of cerebrovascular oxygen saturation (StO2) were measured in clinically stable preterm-born neonates (n = 20, gestational age: ≥30 weeks and

Background and objectiveMindfulness has emerged as key construct in mental health over past decades. While current mindfulness-based interventions (MBIs) are usually rooted in Asian contemplative traditions, mindfulness practices can equally be found in other knowledge systems, including integrative medicine systems such as anthroposophic medicine (AM). The Activity-Based Stress Release (ABSR) program incorporates the latter as part of an 8-week-long online intervention combining mindfulness exercises, behavioral self-observation, and mindful movement practices derived from this integrative medicine frame. The program could offer additional means for cultivating mindfulness, thereby addressing the necessity for diverse approaches in conjunction with individual differences, diverse clinical demands, or restricted capacities to perform certain mindfulness practices. Using an observational repeated-measures design, the current study aimed to assess a large-scale online implementation of this program in terms of its feasibility, assessing perceived stress and mindfulness.MethodIndividuals who enrolled in any of the 37 ABSR program iterations carried out during 2023 and agreed to participate in the study completed online surveys including validated stress and mindfulness scales at the beginning, middle, end, and follow up of the intervention. Linear-mixed models were used for data analysis.ResultsA total of 830 individuals took part in the study, of which 53.5% filled in at least 2 surveys. In line with our expectation, mindfulness scores increased significantly over the course of the intervention, while stress scores decreased significantly in this timeframe. We further found differential effects of self-practice frequency and duration on the outcomes.ConclusionThis study provides a first indication of stress reduction in conjunction with the online implementation of this novel MBI. The work further suggests that this AM-based intervention indeed targets mindfulness, as do other MBIs, and that it is adaptable to an online format. However, given the observational single-arm design, controlled studies will be necessary to confirm these results. Nonetheless, the study adds a novel contribution to existent MBIs, which is significant in view of the need for diverse approaches to meet the heterogeneity of individual predispositions and clinical requirements. It remains to established by forthcoming research for which groups of individuals or clinical features this approach could be especially beneficial or less suitable.

IntroductionCancer is a debilitating disease with an often chronic course. One of the most taxing and prevalent sequelae in this context is cancer-related fatigue (CRF) resulting from the disease and/or associated treatments. Over the last years mindfulness-based interventions such as eurythmy therapy (ERYT), a mindful-movement therapy from anthroposophic medicine, have emerged as promising adjunct therapies in oncology. This prospective study investigated an online implementation of ERYT for CRF using a single arm repeated-measures design based on two consecutive studies.MethodStudy 1 consisted of an initial assessment before, during, after, and at follow up of a 6-week online ERYT-based program in a mixed sample of N = 165 adults with or without cancer diagnosis. Study 2 involved a similar design with an adapted 8-week online ERYT-based program in a sample of N = 125 adults who had been diagnosed with cancer. Outcomes were assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue, Perceived Stress Scale, Mindful Attention Awareness Scale, and Insomnia Severity Index (for Study 1 all, for Study 2 only the former three). We additionally performed an exploratory analysis regarding practice frequency and duration. Data were analyzed using Linear Mixed-Effect Models per outcome; ANOVA was used for practice times.ResultsFor Study 1, mixed-effects model estimates showed no significant effect on fatigue, but pointed to significantly improved emotional and physical well-being, reduced stress, as well as increased mindfulness (mixed subjects). Functional and social well-being or sleep quality did not change significantly. Study 2 model estimates on the other hand showed significantly improved CRF in conjunction with the ERYT-based online intervention, as well as improved stress and mindfulness scores (cancer-diagnosed subjects).ConclusionTaken together, while our results should be interpreted with caution given the single-arm design and relatively high dropout, they suggest online ERYT may be associated with a reduction in fatigue for individuals diagnosed with cancer, an increase in mindfulness, and benefits for stress and certain well-being indicators. The online group format is advantageous in view of affordability and accessibility, the latter being particularly relevant for individuals who due to high symptom severity cannot leave their homes. Randomized-controlled studies will be needed to confirm these findings.

Despite reliable evidence of adverse drug effects, the substantially increased prescription rates of proton pump inhibitors (PPIs) remain at a high level. This study analyzed the appropriateness of PPI prescriptions among residents of nursing homes in three regions of Germany. Baseline data of a cluster-randomized controlled trial were used to determine the prevalence of PPI prescriptions, the validity of indications, and the adequacy of the prescribed dosages according to 1. their drug approvals and 2. valid recommendation guidelines. Regression analyses were conducted to assess associated factors. A total of 437 residents in 37 nursing homes were included (mean age 83 ± 9.2 years, 72% women). The PPI prescription prevalence was 44% (n = 193). In 52/193 (27%) there was no adequate indication, and in 54 (39%) of 138 indicated PPI prescriptions it was overdosed. Yet, in only less than one-third (28%) of “adequate” prescriptions, the indication was according to the PPI approvals, whereas the majority (72%) were off-label indications in line with valid guideline recommendations. Non-indicated PPI prescription was associated with the total number of prescribed drugs (OR 1.32; 95% CI 1.18–1.62; p = 0.013). There were no associations with age, level of care dependency, cognitive impairment, prescription of psychotropic drugs, number of chronic diseases, number of physicians’ consultations, or study region. To conclude, in 55%, the high prescription prevalence among residents was either not indicated or overdosed. In total, only 20% (39/193) of cases of PPI use complied with the approved indications. There is a need for quality control of 1. PPI administration in German nursing homes, and 2. of guideline recommendations expanding the off-label PPI use by 72% within the indication scale, predominantly from wide prescription for low-dose ASA.

Introduction The role of religion and spirituality as social determinants of health has been widely discussed. Studies among people living with HIV describe positive and negative influences of religion and spirituality on health outcomes. With a HIV prevalence of 14.8% for females and 8.6% for males, and 22 000 AIDS-related deaths in 2020, HIV infection remains a life-threatening condition in Zimbabwe, especially in young people. The aim of this research was to measure the influence of religion and spirituality on the health outcomes of young people living with HIV in Zimbabwe.Methods A quantitative questionnaire with three different validated measures of religion and spirituality (Belief into Action Scale, Brief Religious Coping Index, Religious and Spiritual Struggles Scale), demographic, cultural, behavioural and health questions was administered to 804 young Zvandiri programme clients in rural, urban and peri-urban Zimbabwe between July and October 2021. Regression analysis established significant relations between the result of the three different measures and mental health and viral load results.Results Religious coping significantly reduced the probability of common mental disorder, while high religious activity increased the risk. The Religious and Spiritual Struggles Scale proved to be a reliable indicator of higher viral loads, risk for treatment failure and the probability of common mental disorder.Conclusions All three measures of religion and spirituality related to health outcomes. More research is needed to generalise and further explore these findings. Because the Religious and Spiritual Struggles Scale was a strong indicator for both, higher viral loads and common mental disorder, we suggest that it should be used and validated in other sub-Saharan contexts. It could serve as a new diagnostic tool for the early detection and prevention of treatment failure as well as of common mental disorder.

For early and long-term patient and graft survival, drug therapy in solid organ and hematopoietic stem cell transplantation inevitably involves polypharmacy in patients with widely varying and even abruptly changing conditions. In this second part, relevant medication briefing is provided, in addition to the scores defined in the previously published first part on the design of the Individual Pharmacotherapy Management (IPM). The focus is on the growing spectrum of contemporary polypharmacy in transplant patients, including early and long-term follow-up medications. 1. Unlike the available drug–drug interaction (DDI) tables, for the first time, this methodological all-in-one device refers to the entire risks, including contraindications, special warnings, adverse drug reactions (ADRs), and DDIs. The selection of 65 common critical drugs results from 10 years of daily IPM with real-world evidence from more than 60,800 IPM inpatient and outpatient medication analyses. It includes immunosuppressants and typical critical antimicrobials, analgesics, antihypertensives, oral anticoagulants, antiarrhythmics, antilipids, antidepressants, antipsychotics, antipropulsives, antiemetics, propulsives, proton pump inhibitors (PPIs), sedatives, antineoplastics, and protein kinase inhibitors. As a guide for the attending physician, the drug-related risks are presented in an alphabetical overview based on the Summaries of Product Characteristics (SmPCs) and the literature. 2. Further briefing refers to own proven clinical measures to manage unavoidable drug-related high-risk situations. Drug-induced injuries to the vulnerable graft and the immunosuppressed comorbid patient require such standardized, intensive IPM and the comprehensive preventive briefing toolset to optimize the outcomes in the polypharmacy setting.

IntroductionReligious/spiritual convictions and practices can influence health- and treatment-seeking behavior, but only few measures of religiousness or spirituality have been validated and used outside of the US. The Religious and Spiritual Struggles scale (RSS) measures internal and external conflict with religion and spirituality and has been validated mainly in different high-income contexts. The aim of this study was the validation of the RSS in the Zimbabwean context and among young people living with human immunodeficiency virus (YPLHIV) aged 14–24.MethodsData collection with an Open Data Kit (ODK) questionnaire with 804 respondents took place in 2021. The validation was performed by confirmatory factor analysis (CFA), using statistical equation modeling (SEM), and Mokken scale analysis (MSA). After the low confirmability of the original scale sub-dimensions exploratory factor analysis (EFA) was applied.ResultsThe EFA resulted in four new sub-domains that were different from the original six domains in the RSS but culturally more relevant. The new sub-domains are significantly related to health.DiscussionThe findings support the validity and relevance of the RSS and the new sub-domains in this context. As our study was limited to YPLHIV, further validation of the RSS among different population groups and contexts in the sub-Saharan region is encouraged.

For several, also vital medications, such as immunosuppressants in solid organ and hematopoietic stem cell transplantation, therapeutic drug monitoring (TDM) remains the only strategy for fine-tuning the dosage to the individual patient. Especially in severe clinical complications, the intraindividual condition of the patient changes abruptly, and in addition, drug-drug interactions (DDIs) can significantly impact exposure, due to concomitant medication alterations. Therefore, a single TDM value can hardly be the sole basis for optimal timely dose adjustment. Moreover, every intraindividually varying situation that affects the drug exposure needs synoptic consideration for the earliest adjustment. To place the TDM value in the context of the patient’s most detailed current condition and concomitant medications, the Individual Pharmacotherapy Management (IPM) was implemented in the posttransplant TDM of calcineurin inhibitors assessed by the in-house laboratory. The first strategic pillar are the defined patient scores from the electronic patient record. In this synopsis, the Summaries of Product Characteristics (SmPCs) of each drug from the updated medication list are reconciled for contraindication, dosing, adverse drug reactions (ADRs), and DDIs, accounting for defined medication scores as a second pillar. In parallel, IPM documents the resulting review of each TDM value chronologically in a separate electronic Excel file throughout each patient’s transplant course. This longitudinal overview provides a further source of information at a glance. Thus, the applied two-arm concept of TDM and IPM ensures an individually tailored immunosuppression in the severely susceptible early phase of transplantation through digital interdisciplinary networking, with instructive and educative recommendations to the attending physicians in real-time. This concept of contextualizing a TDM value to the precise patient’s condition and comedication was established at Halle University Hospital to ensure patient, graft, and drug safety.

Abstract Background Delirium is one of the most frequent complications in hospitalized elderly patients with additional costs such as prolongation of hospital stays and institutionalization, with risk of reduced functional recovery, long-term cognitive impairment, and increased morbidity and mortality. We analyzed the effect of individual pharmacotherapy management (IPM) in the University Hospital Halle in geriatric trauma patients on complicating delirium and aimed to identify associated factors. Methods In a retrospective controlled clinical study of 404 hospitalized trauma patients ≥70 years we compared the IPM intervention group (IG) with a control group (CG) before IPM implementation. Delirium was recorded from the hospital discharge letter. The medication review and data records included baseline data, all medications, diagnoses, electrocardiogram (ECG), laboratory and vital parameters during hospitalization. The IPM internist and the senior trauma physician guaranteed personnel and structural continuity in the implementation of the interdisciplinary patient rounds. Results There was a highly matched congruence between CG and IG in terms of age, gender, residency, BMI, most diagnoses, and injury patterns to compare the two groups. The total number of medications per patient was 11.1 ± 4.9 (CG) versus 10.4 ± 3.6 (IG). Our targeted IPM focus on 6 frontline aspects with reduction of antipsychotics, anticholinergic burden, benzodiazepines, serotonergic opioids, elimination of pharmacokinetic and pharmacodynamic drug interactions and overdosage reduced complicating delirium from 5% to almost zero at 0.5%. The association of IPM with a significant 10-fold reduction, OR = 0.09 [95% CI 0.01–0.7], in univariable regression, maintained of clinical relevance in multivariable regression OR = 0.1 [95% CI 0.01–1.1]. Factors most strongly associated with complicating delirium in univariable regression were cognitive dysfunction, nursing home residency, muscle relaxants, antiparkinsonian agents, xanthines, transient disorientation documented in the fall risk scale, antibiotic-requiring infections, antifungals, antipsychotics, and intensive care stay, the two latter maintaining significance in multivariable regression. Conclusions IPM is associated with a highly effective prevention of complicating delirium in the elderly trauma patients. For patient safety it should be integrated as an essential preventative contribution. The associated factors help identify patients at risk.

Abstract Risk factors for oropharyngeal dysphagia (OD) in elderly patients are mainly central nervous system (CNS) and structural organic diseases or presbyphagia. We analysed the OD prevalence and association of OD with multimorbidity and polypharmacy using real-life data to complete this spectrum, with a focus on further and iatrogenic risk. This was a cross-sectional retrospective study based on a random sample of 200 patients admitted to a geriatric hospital. Data analysis included diagnoses, the detailed list of drugs, and an intense clinical investigation of swallowing according to Stanschus to screen for OD in each patient. The mean patient age was 84 ± 6.5 years. The prevalence of OD was 29.0%, without an effect of age, but a higher rate was found in men and in nursing home residents and an elevated risk of pneumonia. OD risk was slight in diabetes mellitus and COPD, and pronounced in CNS diseases. A relevant OD association was found, even after adjusting for CNS diseases, with antipsychotics, benzodiazepines, anti-Parkinson drugs, antidepressants, and antiepileptics. Further risk of OD was found with beta-blockers, alpha-blockers, opioids, antiemetics, antivertiginosa or antihistamines, metoclopramide, domperidone, anticholinergics, loop diuretics, urologics, and ophthalmics. From real-life data in patients with and without CNS diseases, we identified drug groups associated with a risk of aggravating/inducing OD. Restrictive indications for these drugs may be a preventative contribution, requiring implementation in dysphagia guidelines and an integrative dysphagia risk scale that considers all associated and cumulative medication risks in addition to diseases.

Abstract Light evokes robust visual and nonvisual physiological and psychological effects in humans, such as emotional and behavioral responses, as well as changes in cognitive brain activity and performance. The aim of this study was to investigate how colored light exposure (CLE) and a verbal fluency task (VFT) interact and affect cerebral hemodynamics, oxygenation, and systemic physiology as determined by systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). 32 healthy adults (17 female, 15 male, age: 25.5 ± 4.3 years) were exposed to blue and red light for 9 min while performing a VFT. Before and after the CLE, subjects were in darkness. We found that this long-term CLE-VFT paradigm elicited distinct changes in the prefrontal cortex and in most systemic physiological parameters. The subjects’ performance depended significantly on the type of VFT and the sex of the subject. Compared to red light, blue evoked stronger responses in cerebral hemodynamics and oxygenation in the visual cortex. Color-dependent changes were evident in the recovery phase of several systemic physiological parameters. This study showed that the CLE has effects that endure at least 15 min after cessation of the CLE. This underlines the importance of considering the persistent influence of colored light on brain function, cognition, and systemic physiology in everyday life.

Slow breathing at 0.1 Hz (i.e., 6 cycles per minute, cpm) leads to strong cardiovascular oscillations. However, the impact of breathing below 6 cpm is rarely addressed. We investigated the influence of OM chanting, an ancient Indian mantra, with approx. 3 respiratory cpm (0.05 Hz) on the synchronisation of heart period (RR), respiration (RESP) and systolic blood pressure (SBP). Nine healthy, trained speech practitioners chanted three sequences of five subsequent OM with 2 min pauses in between. Each single OM chanting consisted of taking a deep breath and a long “OM” during expiration and lasted approx. 20 s. ECG, respiration and blood pressure were recorded continuously, of which the RR tachogram, RESP and SBP were derived. Synchronisation between the signals was computed using the phase difference between two signals. During OM chanting synchronisation among the oscillations of RR, SBP and RESP was significantly increased compared to rest. Furthermore, OM chanting at breathing frequencies between 0.046 and 0.057 Hz resulted in 0.1 Hz oscillations in RR and SBP. In conclusion, OM chanting strongly synchronized cardiorespiratory and blood pressure oscillations. Unexpected oscillations at 0.1 Hz in SBP and RR appear at breathing frequencies of approx. 0.05 Hz. Such frequency doubling may originate from an interaction of breathing frequency with endogenous Mayer waves.

Abstract Background Cancer-related fatigue (CRF) is the most taxing symptom for many breast cancer patients during and after therapy. In patients with metastatic disease, the prevalence of CRF exceeds 75%. Currently, there is no gold standard for the treatment of CRF. Physical activity can reduce CRF and is recommended during and after cancer treatment, but may be too burdensome for patients with metastatic breast cancer. The aim of this study is to assess the effect on fatigue of eurythmy therapy (ERYT) compared to slow movement fitness (CoordiFit) in metastatic breast cancer patients. Methods The ERYT/CoordiFit study is a randomized controlled, open-label, two-arm, multi-center Swiss clinical trial. A sample of 196 patients presenting with CRF will be recruited by oncologists from the departments of clinical oncology at each local study site. All participants will be randomly allocated to the intervention or control group in a 1:1 ratio. The control group is an active control intervention (CoordiFit) in order to control for potential non-intended effects such as therapist-patient interaction and participation in a program. Both ERYT and CoordiFit exercises are easy to learn, and the training sessions will follow the same frequency and duration schedule, i.e., 13 standardized therapy sessions of 45 min (once a week for 6 weeks and then once every second week) during the total intervention period of 20 weeks. The primary endpoint of the study is the change from baseline over the whole intervention period (i.e., including measurements at baseline, weeks 8, 14, and 20) in the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) subscale score. Discussion This study is the first-known randomized clinical trial assessing eurythmy therapy in the treatment of fatigue in metastatic breast cancer patients. Given the distress that fatigue causes patients, it is important to validate treatment options. If eurythmy therapy proves beneficial in CRF as part of this randomized controlled clinical trial, the study may be very impactful with implications not only for metastatic breast cancer patients but also for other cancer patients, health care personnel, scientists, and funding and regulatory bodies. Trial registration The ERYT/CoordiFit trial was registered at the US National Institutes of Health (ClinicalTrials.gov) on July 18, 2019, #NCT04024267 , and in the portal for human research in Switzerland on December 3, 2019, #SNCTP000003525 .

ObjectivesTo determine the prevalence of use of complementary medicine (CM) in Switzerland in 2017, its development since the 2012 Swiss Health Survey, and to examine specific and non-specific sociodemographic, lifestyle and health-related determinants of CM use as compared to determinants of conventional health care use.Materials and methodsWe used data of 18,832 participants from the cross-sectional Swiss Health Survey conducted by the Swiss Federal Statistical Office in 2017 and compared these data with those from 2012. We defined four CM categories: (1) traditional Chinese medicine, including acupuncture; (2) homeopathy; (3) herbal medicine; (4) other CM therapies (shiatsu, reflexology, osteopathy, Ayurveda, naturopathy, kinesiology, Feldenkrais, autogenic training, neural therapy, bioresonance therapy, anthroposophic medicine). Independent determinants of CM use and of conventional health care use were assessed using multivariate weighted logistic regression models.ResultsPrevalence of CM use significantly increased between 2012 and 2017 from 24.7% (95% CI: 23.9-25.4%) to 28.9% (95% CI: 28.1-29.7%), respectively, pConclusionPrevalence of CM use significantly increased in Switzerland from 2012 to 2017. Gender, nationality, age, lifestyle and BMI were independent specific determinants of CM use as compared to conventional health care use. Healthier lifestyle was associated with CM use, which may have potentially significant implications for public health and preventive medicine initiatives. The nationality of CM users underlines the role of culture in driving the choice to use CM but also raises the question of whether all populations have equal access to CM within a same country.

Harmful usage of tobacco is a global public health problem associated with adverse health effects and addiction. Yet, in the Peruvian Amazon, the native region of Nicotiana rustica L., this plant is used in remarkably different manners: it is considered a potent medicinal plant, applied in liquid form for oral ingestion to treat mental health problems, a common and ancient healing practice in this region. Using a transdisciplinary field research approach with mixed ethnopsychological methods, this work aimed to report for the first time a case study in this context. The intervention took place in the Peruvian Amazon (Loreto) and involved ritual tobacco ingestion in a weeklong retreat-like frame, administered by a specialized traditional Amazonian healer. The patient was a 37-year-old woman with diagnosed mood, anxiety, and attention deficit disorders, as well as a chronic somatic condition. We applied qualitative experience-sampling during and quantitative symptom assessments pre- and post-treatment. Our findings offer a detailed description of the experiential therapeutic process during the treatment week and suggest clinically relevant improvements in patient well-being. This work is significant in view of the globally prevalent harmful uses of tobacco and the current scientific trend of revisiting herbal psychoactives (e.g., cannabis, psilocybin) for their therapeutic potentials.

Objective: To analyze the thermogenic effects of footbaths with medicinal powders in oncological patients (ON) and healthy controls (HC). Intervention and Outcomes: Thirty-six participants (23 ON, 13 HC; 24 females; 49.9 ± 13.3 years) received 3 footbaths in a random order with cross-over design: warm water only (WA), warm water plus mustard (MU, Sinapis nigra), and warm water plus ginger (GI, Zingiber officinale). Warmth perception of the feet (Herdecke Warmth Perception Questionnaire, HeWEF) at the follow-up (10 minutes after completion of footbaths, t2) was assessed as the primary outcome measure. Secondary outcome measures included overall warmth as well as self-reported warmth (HeWEF) and measured skin temperature (high resolution thermography) of the face, hands and feet at baseline (t0), post immersion (t1), and follow-up (t2). Results: With respect to the warmth perception of the feet, GI and MU differed significantly from WA ( P ’s

There is large intersubject variability in cerebrovascular hemodynamic and systemic physiological responses induced by a verbal fluency task (VFT) under colored light exposure (CLE). We hypothesized that machine learning would enable us to classify the response patterns and provide new insights into the common response patterns between subjects. In total, 32 healthy subjects (15 men and 17 women, age: 25.5 ± 4.3 years) were exposed to two different light colors (red vs. blue) in a randomized cross-over study design for 9 min while performing a VFT. We used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach to measure cerebrovascular hemodynamics and oxygenation at the prefrontal cortex (PFC) and visual cortex (VC) concurrently with systemic physiological parameters. We found that subjects were suitably classified by unsupervised machine learning into different groups according to the changes in the following parameters: end-tidal carbon dioxide, arterial oxygen saturation, skin conductance, oxygenated hemoglobin in the VC, and deoxygenated hemoglobin in the PFC. With hard clustering methods, three and five different groups of subjects were found for the blue and red light exposure, respectively. Our results highlight the fact that humans show specific reactivity types to the CLE-VFT experimental paradigm.

Antimicrobial therapy is often a life-saving medical intervention for inpatients and outpatients. Almost all medical disciplines are involved in this therapeutic procedure. Knowledge of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) is important to avoid drug-related harm. Within the broad spectrum of antibiotic and antifungal therapy, most typical ADRs are known to physicians. The aim of this study was to evaluate relevant pharmacological aspects with which we are not so familiar and to provide further practical guidance. Individual pharmacotherapy management (IPM) as a synopsis of internal medicine and clinical pharmacology based on the entirety of the digital patient information with reference to drug information, guidelines, and literature research has been continuously performed for over 8 years in interdisciplinary intensive care and trauma and transplant patients. Findings from over 52,000 detailed medication analyses highlight critical ADRs and DDIs, especially in these vulnerable patients with polypharmacy. We present the most relevant ADRs and DDIs in antibiotic and antifungal pharmacology, which are less frequently considered in relation to neurologic, hemostaseologic, hematologic, endocrinologic, and cardiac complexities. Constant awareness and preventive strategies help avoid life-threatening manifestations of these inherent risks and ensure patient and drug safety in antimicrobial therapy.

In our previous investigations using systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) neuroimaging, we found larger variability between subjects in changes of cerebral hemodynamics and oxygenation induced by an intricate experimental paradigm involving colored light exposure and a cognitive task. We aimed to investigate the role the activity of the systemic physiology has on individual variations in the fNIRS data. Thirty-two healthy subjects (17 female, 15 male and age: 25.5 ± 4.3 years) were exposed to blue and red light for 9 min (colored light exposure, CLE) while performing a verbal fluency task (VFT). We found that (i), at the group level, the visual cortex showed a stronger deoxyhemoglobin concentration response during blue light exposure than during red light exposure, and (ii) this relationship was influenced by individually different baseline blood pressure values. Furthermore, we found other correlations between changes in fNIRS signals and changes in systemic physiology. Our study demonstrates the usefulness and necessity of the SPA-fNIRS approach to gain insights into the individual variability of hemodynamic responses measured with fNIRS, especially in the case of an intricate experimental paradigm (i.e., CLE-VFT) as used in our study.

IntroductionHarmful usage of tobacco is a public health problem of global concern and, in many countries, the main risk factor for non-communicable diseases. Yet, in the Peruvian Amazon, the geographical region believed to be tobacco’s historical birthplace, this plant is associated with a strikingly different usage and repute: Tobacco (especially Nicotiana rustica L.) in this area is described as a potent medicinal plant, used topically or via ingestion to treat a variety of health conditions. The goal of this transdisciplinary field study was to investigate clinical applications of the tobacco plant as per Amazonian medicine exemplified in the practice of a reputed Maestro Tabaquero, an Amazonian traditional healer whose medical specialization focuses on tobacco-based treatments.MethodsUsing a transdisciplinary clinical approach, we conducted in-depth interviews with the tabaquero applying the systematizing expert interview method, in order to map modes of preparation and administration, indications, contraindications, effects, risks, adverse effects, and systemic aspects of tobacco-based remedies.ResultsThe informant’s descriptions revealed refined knowledge on this plant’s therapeutic properties and scope, safety profile, and application techniques. The main indications mentioned included “problems of the mind,” of the respiratory system, parasitic illnesses (intestinal/skin), gout, and Amazonian epistemic conditions described as spiritual-energetic in nature. A liquid remedy taken orally was his most commonly used preparation, with acute/sub-acute effects involving a pronounced psychoactive component (altered state of consciousness) and physiological response (emesis, nausea). A skilled tabaquero that knows how to dose, administer, and intervene in case of adverse effects was considered imperative for safe treatment delivery.ConclusionsTo our knowledge, this is the first study employing a transdisciplinary clinical approach to examine therapeutic applications of tobacco by an Amazonian tabaquero. Our findings significantly contribute to the growing research literature on Amazonian medicine and emergent psychedelic-assisted therapies and could, in the long-term, open new treatment avenues in several domains. Forthcoming studies should assess toxicity/safety and clinical outcomes of patients receiving Amazonian tobacco-based treatment.

Aim: To investigate whether the early administration of Euphrasia eye drops® in preterm neonates presenting with ocular discharge fosters the resolution of the ocular discharge and reduces the need for topical antibiotic therapy, as compared to placebo.Methods: We conducted a randomized double-blind placebo-controlled trial at the University Children's Hospital Bern, Switzerland. Preterm neonates with white, yellow, or green ocular discharge were included. Infants were randomly assigned (1:1) to the Euphrasia arm (Euphrasia eye drops®, Weleda AG, Arlesheim) or the placebo arm (NaCl 0.9%). Euphrasia or placebo was administrated at a dose of one drop in each eye four times a day over a period of 96 h. The primary outcome was the treatment success, defined as no ocular discharge at 96 h and no use of topical antibiotic therapy during the 96-h intervention.Results: A total of 114 neonates were screened and 84 were randomized. Among neonates in the Euphrasia arm, 22 (55.0%) achieved our primary outcome compared to 21 (51.2%) in the placebo arm (p = 0.85). In the Euphrasia arm, time to resolution of reddening tended to fall within the shorter bracket of 24 to 48 h (24 (92.3%) vs. 12 (80.0%) in the placebo arm, p = 0.34) and relapse or first signs of reddening during the 96-h intervention tended to be lower [3 (7.9%) eyes vs. 8 (18.2%) eyes in the placebo arm, p = 0.17]. Tearing at 96 h tended to be lower in the Euphrasia arm [5 (12.8%) eyes in the Euphrasia arm vs. 12 (27.3%) eyes in the placebo arm, p = 0.10].Discussion: Euphrasia did not significantly improve treatment success, defined as no ocular discharge at 96 h and no use of topical antibiotic therapy during the 96-h intervention. However, results suggest that Euphrasia may be of benefit for symptoms such as reddening and tearing, and thus improve the comfort of patients.Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04122300 and at the portal for human research in Switzerland SNCTP000003490.

Abstract Background Breathing retraining techniques have received increased attention in the management of asthma, because there is growing evidence of the usefulness of such methods in improving quality of life, reducing symptoms and reducing bronchodilator use. Our study investigated the effect of anthroposophic therapeutic speech (ATS), which uses sounds and syllabic rhythm to improve articulation, breathing and cardiorespiratory interaction, in patients with asthma in a real-life outpatient setting. Methods In a randomised controlled crossover trial, patients with asthma in three centres in Switzerland and Germany were randomised to either receive 11 ATS sessions or to wait. Subsequently, patients changed either to wait or to receive ATS. Primary outcomes were changes from the beginning to the end of each phase in the Asthma Quality of Life Questionnaire (AQLQ) and spirometry parameters. Secondary outcomes were changes in inhaled glucocorticoids, the Asthma Control Test (ACT), peak flow and asthma exacerbations. Results Altogether, 63 patients were randomised, of which 56 were enrolled and 49 completed the study. Statistically significant differences between the ATS groups and waiting control groups were found for the overall AQLQ score (d = 0.86, p = 0.001) and the domain scores for symptoms, activity limitation and emotional function as well as ACT score (d = 0.53, p = 0.048). No significant differences were observed in spirometry parameters, inhaled glucocorticoids, peak flow and days without asthma exacerbation per week. No serious adverse events occurred during ATS sessions. Conclusions ATS significantly improves asthma control and quality of life in patients with asthma. Whether ATS may improve lung function remains to be shown. Trial registration ClinicalTrials.gov NCT02501824. Retrospectively registered on 8 July 2015.

BACKGROUND In Switzerland, complementary medicine (CM) is officially recognised within the healthcare system and mainly practised in an integrative manner, in conjunction with conventional medicine. As in other countries, there is high demand for and use of CM with children. However, there has so far been no research into the attitude towards, training in and offer of CM among paediatricians in Switzerland. Our study addresses this gap by investigating these topics with an online survey of paediatricians in Switzerland. METHODS We conducted a national online survey using a 19-item, self-reporting questionnaire among all ordinary and junior members of the Swiss Society of Paediatrics (SSP). A comparison of the study sample with the population of all paediatricians registered with the Swiss Medical Association (FMH) allowed an assessment of the survey’s representativeness. The data analysis was performed on the overall group level as well as for predefined subgroups (e.g. sex, age, language, workplace and professional experience). RESULTS 1890 paediatricians were approached and 640, from all parts of Switzerland, responded to the survey (response rate 34%). Two thirds of respondents were female, were aged between 35 and 55 years, trained as paediatric generalist and worked in a practice. Apart from young paediatricians in training, the study sample was representative of all Swiss paediatricians. 23% had attended training in CM, most frequently in phytotherapy, homeopathy, acupuncture/traditional Chinese medicine (TCM) and anthroposophic medicine. 65% were interested in CM courses and training. 16% provide CM services to their patients and almost all paediatricians (97%) are asked by patients/parents about CM therapies. More than half of the responding paediatricians use CM for themselves or their families. 42% were willing to contribute to paediatric CM research. CONCLUSIONS In a representative sample of paediatricians in Switzerland, their personal attitude towards CM is positive, emphasised by great interest in CM training, a willingness to contribute to CM research and a high rate of paediatricians who use CM for themselves and their families. In contrast, the percentage of paediatricians offering CM is currently rather low despite strong demand for CM for children. This study provides key pointers for the future development of complementary and integrative medicine for children in Switzerland.

A specific and unique aspect of cardiorespiratory activity can be captured by dividing the heart rate (HR) by the respiration rate (RR), giving the pulse-respiration quotient (PRQ = HR/RR). In this review article, we summarize the main findings of studies using and investigating the PRQ. We describe why the PRQ is a powerful parameter that captures complex regulatory states of the cardiorespiratory system, and we highlight the need to re-introduce the use of this parameter into modern studies about human physiology and pathophysiology. In particular, we show that the PRQ (i) changes during human development, (ii) is time-dependent (ultradian, circadian, and infradian rhythms), (iii) shows specific patterns during sleep, (iv) changes with physical activity and body posture, (v) is linked with psychophysical and cognitive activity, (vi) is sex-dependent, and (vii) is determined by the individual physiological constitution. Furthermore, we discuss the medical aspects of the PRQ in terms of applications for disease classification and monitoring. Finally, we explain why there should be a revival in the use of the PRQ for basic research about human physiology and for applications in medicine, and we give recommendations for the use of the PRQ in studies and medical applications.

When brain activity is measured by neuroimaging, the canonical hemodynamic response (increase in oxygenated hemoglobin ([O2Hb]) and decrease in deoxygenated hemoglobin ([HHb]) is not always seen in every subject. The reason for this intersubject-variability of the responses is still not completely understood. This study is performed with 32 healthy subjects, using the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. We investigate the intersubject variability of hemodynamic and systemic physiological responses, due to a verbal fluency task (VFT) under colored light exposure (CLE; blue and red). Five and seven different hemodynamic response patterns were detected in the subgroup analysis of the blue and red light exposure, respectively. We also found that arterial oxygen saturation and mean arterial pressure were positively correlated with [O2Hb] at the prefrontal cortex during the CLE-VFT independent of the color of light and classification of the subjects. Our study finds that there is substantial intersubject-variability of cerebral hemodynamic responses, which is partially explained by subject-specific systemic physiological changes induced by the CLE-VFT. This means that both subgroup analyses and the additional assessment of systemic physiology are of crucial importance to achieve a comprehensive understanding of the effects of a CLE-VFT on human subjects.

An increasing cancer incidence affecting any age and social class is putting serious strain on populations and health care systems around the world. This systematic literature search aims (i) to examine the correlation of heart rate variability (HRV) and cancer patients’ prognosis, (ii) to examine the relationship of HRV and clinicopathological features, and (iii) to compare HRV between different patient groups, and between patient and control groups. We conducted a systematic literature review following the PRISMA Statement. We searched the PubMed and EMBASE databases for publications released by December 2017. The search terms were: “cancer” AND “heart rate variability” AND “human” NOT “animal” NOT “review.” A total of 19 studies were finally included in this review. Most publications were high-quality observational studies. The studies showed that higher HRV correlated positively with patients’ progression of disease and outcome. Thus, we conclude that individuals with higher HRV and advanced coping mechanisms seem to have a better prognosis in cancer progression. HRV appears to be a useful aspect to access the general health status of cancer patients.

T1 maps have been shown to yield useful diagnostic information on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma, both for native T1 and ΔT1, the relative reduction while breathing pure oxygen. As parameter quantification is particularly interesting for longitudinal studies, the purpose of this work was both to examine the reproducibility of lung T1 mapping and to compare T1 found in COPD and asthma patients using IRSnapShotFLASH embedded in a full MRI protocol. 12 asthma and 12 COPD patients (site 1) and further 15 COPD patients (site 2) were examined on two consecutive days. In each patient, T1 maps were acquired in 8 single breath-hold slices, breathing first room air, then pure oxygen. Maps were partitioned into 12 regions each to calculate average values. In asthma patients, the average T1,RA = 1206ms (room air) was reduced to T1,O2 = 1141ms under oxygen conditions (ΔT1 = 5.3%, p < 5⋅10-4), while in COPD patients both native T1,RA = 1125ms was significantly shorter (p < 10-3) and the relative reduction to T1,O2 = 1081ms on average ΔT1 = 4.2%(p < 10-5). On the second day, with T1,RA = 1186ms in asthma and T1,RA = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. ΔT1 reduction was the least repeatable parameter and varied from day to day by up to 23% in individual asthma and 30% in COPD patients. While for both patient groups T1 was below the values reported for healthy subjects, the T1 and ΔT1 found in asthmatics lies between that of the COPD group and reported values for healthy subjects, suggesting a higher blood volume fraction and better ventilation. However, it could be demonstrated that lung T1 quantification is subject to notable inter-examination variability, which here can be attributed both to remaining contrast agent from the previous day and the increased dependency of lung T1 on perfusion and thus current lung state.

This study investigated the response of arsenic-stressed yeast (Saccharomyces cerevisiae) towards homeopathically potentized Arsenicum album, a duckweed nosode, and gibberellic acid. The three test substances were applied in five potency levels (17x, 18x, 24x, 28x, 30x) and compared to controls (unsuccussed and succussed water) with respect to influencing specific growth parameters. Five independent experiments were evaluated for each test substance. Additionally, five water control experiments were analyzed to investigate the stability of the experimental setup (systematic negative control experiments). All experiments were randomized and blinded. Yeast grew in microplates over a period of 38 h in either potentized substances or water controls with 250 mg/l arsenic(V) added over the entire cultivation period. Yeast's growth kinetics (slope, Et50, and yield) were measured photometrically. The test system exhibited a low coefficient of variation (slope 1.2%, Et50 0.3%, yield 2.7%). Succussed water did not induce any significant differences compared to unsuccussed water. Data from the control and treatment groups were both pooled to increase statistical power. In this study with yeast, no significant effects were found for any outcome parameter or any homeopathic treatment. Since in parallel experiments arsenic-stressed duckweed showed highly significant effects after application of potentized Arsenicum album and duckweed nosode preparations from the same batch as used in the present study, some specific properties of this experimental setup with yeast must be responsible for the lacking response.

Clinical trials have reported statistically significant and clinically relevant effects of homeopathic preparations. We applied ultraviolet (UV) spectroscopy to investigate the physical properties of homeopathic preparations and to contribute to an understanding of the not-yet-identified mode of action. In previous investigations, homeopathic preparations had significantly lower UV light transmissions than controls. The aim of this study was to explore the possible effects of external factors (UV light and temperature) on the homeopathic preparations. Homeopathic centesimal (c) dilutions, 1c to 30c, of copper sulfate (CuSO4), decimal dilutions of sulfur (S8), 1x to 30x, and controls (succussed potentization medium) were prepared, randomized, and blinded. UV transmission was measured at six different time points after preparation (from 4 to 256 days). In addition, one series of samples was exposed to UV light of a sterilization lamp for 12 h, one was incubated at 37°C for 24 h, and one was heated to 90°C for 15 min. UV light transmission values from 190 or 220 nm to 340 nm were measured several times and averaged. After each exposure, UV transmission of the homeopathic preparations of CuSO4 was significantly reduced compared to the controls, particularly after heating to 37°C. Overall, the nonexposed CuSO4 preparations did not show significantly lower UV transmission compared to controls; however, the pooled subgroup of measurements at days 26, 33, and 110 yielded significant differences. UV light transmission for S8 preparations did not show any differences compared to controls. Our conclusion is that exposure to external factors, incubation at 37°C in particular, increases the difference in light transmission of homeopathic CuSO4 preparations compared to controls.

The article has three parts. The first part exposes Schopenhauer’s critique of Kant who tries to derive morality from pure reason. The second part exhibits Schopenhauer’s ethics of compassion which is based on the insight that the will can only be moved by the “weal and woe” of a being and that moral action thus can only be possible where the other’s well-being or misery is the immediate motive. Schopenhauer claims that we encounter this phenomenon in our experience, namely in the everyday phenomenon of compassion. The advantages of this ethics of compassion over utilitarianism are demonstrated. The third part discusses some difficulties, e.g. whether this approach can cope with the area of justice.

BackgroundComplementary medicine (CM) is popular in Switzerland. Several CM methods (traditional Chinese medicine/acupuncture, homeopathy, anthroposophic medicine, neural therapy, and herbal medicine) are currently covered by the mandatory basic health insurance when performed by a certified physician. Treatments by non-medical therapists are partially covered by a supplemental and optional health insurance. In this study, we investigated the frequency of CM use including the evolvement over time, the most popular methods, and the user profile.MethodsData of the Swiss Health Surveys 2007 and 2012 were used. In 2007 and 2012, a population of 14,432 and 18,357, respectively, aged 15 years or older answered the written questionnaire. A set of questions queried about the frequency of use of various CM methods within the last 12 months before the survey. Proportions of usage and 95% confidence intervals were calculated for these methods and CM in general. Users and non-users of CM were compared using logistic regression models.ResultsThe most popular methods in 2012 were homeopathy, naturopathy, osteopathy, herbal medicine, and acupuncture. The average number of treatments within the 12 months preceding the survey ranged from 3 for homeopathy to 6 for acupuncture. 25.0% of the population at the age of 15 and older had used at least one CM method in the previous 12 months. People with a chronic illness or a poor self-perceived health status were more likely to use CM. Similar to other countries, women, people of middle age, and those with higher education were more likely to use CM. 59.9% of the adult population had a supplemental health insurance that partly covered CM treatments.ConclusionsUsage of CM in Switzerland remained unchanged between 2007 and 2012. The user profile in Switzerland was similar to other countries, such as Germany, United Kingdom, United States or Australia.

[This corrects the article DOI: 10.1371/journal.pone.0141985.].

QUESTIONS UNDER STUDY: This study investigated the use among the Swiss adult population and regional dissemination of various methods of complementary medicine (CM) provided by physicians or therapists in Switzerland. METHODS: Data of the Swiss Health Survey 2007 were used, which comprised a telephone interview followed by a written questionnaire (18,760 and 14,432 respondents, respectively) and included questions about people's state of health, health insurance and usage of health services. Users and non-users of CM were compared using logistic regression models. RESULTS: The most popular CM methods were homeopathy, osteopathy, acupuncture and shiatsu/foot reflexology. 30.5% of women and 15.2% of men used at least one CM method in the 12 months preceding the survey. Lake Geneva region and central Switzerland had more CM users than the other regions. Women, people between 25 and 64 years of age and people with higher levels of education were more likely to use CM. 53.5% of the adult population had a supplemental health insurance for CM treatments. 32.9% of people with such an insurance used CM during the 12 months preceding the survey, and so did 12.0% of people without additional insurance. CONCLUSIONS: Almost one fourth of the Swiss adult population had used CM within the past 12 months. User profiles were comparable to those in other countries. Despite a generally lower self-perceived health status, elderly people were less likely to use CM.