A Drug Safety Briefing (II) in Transplantation from Real-World Individual Pharmacotherapy Management to Prevent Patient and Graft from Polypharmacy Risks at the Very Earliest Stage.

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.

Establishing an Integrative Oncology Service: Essential Aspects of Program Development.

PURPOSE OF REVIEW: Over the last 2 decades, integrative oncology (IO) has seen exponential growth within cancer care. It aims to combine evidence-based complementary therapies with conventional treatments to improve the well-being and quality of life for individuals dealing with cancer. The proliferation of integrative medicine programs in major cancer centers globally reflects varying approaches shaped by cultural, demographic, and resource-based factors. RECENT FINDINGS: Drawing upon the expertise of leaders in IO from the Society for Integrative Oncology (SIO) Clinical Practice Committee, this manuscript serves as a practical guide for establishing an IO practice. Collating insights from diverse professionals, including oncologists, integrative oncologists, supportive care physicians, researchers, and clinicians, the paper aims to provide a comprehensive roadmap for initiating and advancing IO services. The primary objective is to bridge the gap between conventional cancer care and complementary therapies, fostering a patient-centric approach to address the multifaceted challenges encountered by individuals with cancer. This paper delineates several key sections elucidating different aspects of IO practice. It delves into the core components necessary for an IO service's foundation, outlines the initial medical consultation process, and presents crucial tools essential for successful consultations. By consolidating insights and expertise, this manuscript seeks to facilitate the integration of IO into mainstream cancer care, ultimately enhancing patient outcomes and experiences.

Cerebral, systemic physiological and behavioral responses to colored light exposure during a cognitive task: A SPA-fNIRS study.

Colored light has important implications for human health and well-being, as well as for the aesthetics and function of various environments. In addition to its effects on visual function, colored light has significant effects on cognitive performance, behavior and systemic physiology. The aim of the current study was to comprehensively investigate how colored light exposure (CLE) combined with a cognitive task (2-back) affects performance, cerebral hemodynamics, oxygenation, and systemic physiology as assessed by systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). 36 healthy subjects (22 female, 14 male, age 26.3 ± 5.7 years) were measured twice on two different days. They were exposed to the sequence of blue and red light or vice versa in a randomized crossover design. During the CLE, the subjects were asked to perform a 2-back task. The 2-back task performance was correlated with changes in the concentration of oxygenated hemoglobin in the prefrontal cortex (red: r = -0.37, p = 0.001; blue: r = -0.33, p = 0.004) and the high-frequency component of the heart rate variability (red: r = 0.35, p = 0.003; blue: r = 0.25, p = 0.04). These changes were independent of the CLE. Sequence-dependent effects were observed for fNIRS signals at the visual cortex (VC) and for electrodermal activity (EDA). While both colors caused relatively similar changes in the VC and EDA at the position of the first exposure, blue and red light caused greater changes in the VC and EDA, respectively, in the second exposure. There was no significant difference in the subjects' 2-back task performance between the CLE (p = 0.46). The results of this study provide new insights into how human physiology and behavior respond to colored light exposure. Our findings are important for understanding the impact of colored light in our daily lives and its potential applications in a variety of settings, including education, the workplace and healthcare.

Infradian Rhythms in Cerebrovascular Oxygenation and Blood Volume in Humans at Rest: A 5-Year Study.

BACKGROUND: All parameters of human physiology show chronobiological variability. While circadian (cycle length ~ 24 h) rhythms of the neuronal, hemodynamic and metabolic aspects of human brain activity are increasingly being explored, infradian (cycle length > 24 h) rhythms are largely unexplored. AIM: We investigated if cerebrovascular oxygen saturation (StO2) and blood volume ([tHb]) values measured over many years in many subjects during resting show infradian rhythmicity. SUBJECTS AND METHODS:  Absolute StO2 and [tHb] values (median over a 5 min resting-phase while sitting) were measured in 220 healthy subjects (age: 24.7 ± 3.6 years, 87 males, 133 females) 2-4 times on different days over the right and left frontal lobe (FL) and occipital lobe (OL) by employing frequency-domain NIRS as part of different systemic physiology augmented functional near-infrared spectroscopy, SPA-fNIRS, studies. The data set consisted of 708 single measurements performed over a timespan of 5 years (2017-2021). General additive models (GAM) and cosinor modelling were used to analyze the data. RESULTS:  The GAM analysis revealed (i) a non-linear trend in the StO2 and [tHb] values over the 5-year span, (ii) a circannual (cycle length ~ 12 months) rhythm in StO2 at the FL (amplitude (A): 3.4%, acrophase (φ): June) and OL (A: 1.5%, φ: May) as well as in [tHb] at the OL (A: 1.2 µM, bathyphase (θ): June), and (iii) a circasemiannual (cycle length ~ 6 months) rhythm in [tHb] at the FL (A: 2.7 µM, φ: March and September, respectively). Furthermore, the circannual oscillations of StO2 (at the FL) and [tHb] (at the OL) were statistically significantly correlated with the day length, outdoor temperature, humidity and air pressure. DISCUSSION AND CONCLUSION:  We conclude that absolute values of StO2 and [tHb] show chronobiological variability on the group-level with a long-term nonlinear trend as well as circannual/circasemiannual rhythmicity. These rhythms need to be taken into account when defining reference values for StO2 and [tHb] and may correlate with the variability of cerebrovascular disease incidents over the year.

Differences Between Good, Moderate and Poor Performers of a Verbal Fluency Task under Blue Light Exposure: An SPA-fNIRS Study.

Individuals have different performance levels for cognitive tasks. Are these performance levels reflected in physiological parameters? The aim of this study was to address this question by systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). We aimed to investigate whether different verbal fluency task (VFT) performances under blue light exposure were associated with different changes in cerebrovascular oxygenation and systemic physiological activity. The VFT performance of 32 healthy subjects (17 female, 15 male, age: 25.5 ± 4.3 years) was investigated under blue light exposure (120 lux). The VFT, which contained letter and category fluency tasks, lasted 9 min. There were rest periods without light exposure before and after the VFT for 8 min and 15 min, respectively. Based on their number of correct responses, subjects were classified into three groups, i.e., good, moderate, and poor performers. During the entire experiment, we simultaneously measured changes in cerebral and systemic physiological parameters using the SPA-fNIRS approach. We found that the better the subject's performance was, the smaller the task-evoked changes in cerebrovascular hemodynamics and oxygenation in the prefrontal cortex. Performance-dependent changes were also evident for skin conductance, arterial oxygen saturation and mean arterial pressure. This is the first VFT study that applies the comprehensive SPA-fNIRS approach to determine the relationship between task performance and changes in cerebral oxygenation and systemic physiology. Our study shows that these parameters are indeed related and the performance is reflected in the task-evoked cerebrovascular and systemic physiological changes.

Accuracy of Tissue Oxygen Saturation Measurements of a Textile-Based NIRS Sensor.

Pressure injuries (PI) are dangerous tissue lesions that heal very slowly and pose a high risk of serious infections. They are caused by pressure applied to the tissue, which stops blood circulation and therefore induces hypoxia, i.e., low tissue oxygen saturation (StO2). PI cause severe suffering and are expensive to treat. Hence it is essential to prevent them with a device that detects a dangerous situation, e.g., by measuring StO2 using near-infrared spectroscopy (NIRS). For such a device to be wearable without causing PI, it must not introduce pressure points itself. This can be achieved by integrating optical fibers into a textile to transport light to and from the tissue.The aim of this paper is to investigate the accuracy of StO2 measurements using a NIRS device based only on textile-integrated optical fibers.Bundles of fibers were stitched into a textile in such a way that loops of <1 mm diameters were formed at the stitching locations. Detection points (DPs) on the fabric consisted of 8 fibers with 3 loops each. Emission points (EPs) were made from 4 fibers with 3 loops each. All fiber ends of a DP were connected to an avalanche photodiode. One end of each fiber belonging to an EP was connected to an LED (740 nm, 810 nm, or 880 nm; 290, 560, or 610 mW).To verify the accuracy of this textile-based sensor, we placed it on a subject's forearm and compared the derived StO2 during arterial occlusion to the values of a gold-standard NIRS device (ISS Imagent), which was placed on the forearm too.We found that our textile-based sensor repeatedly measured StO2 values over a range of 40% with a deviation of <10% from the reference device.By showing the ability to measure StO2 using textile-integrated optical fibers accurately, we have reached a significant milestone on our way to building a wearable device to monitor tissue health and prevent PI.

A Prospective Observational Pilot Study on the Effects of the Activity-Based Stress Release Program on the Mental State and Autonomic Nervous System in Psychiatric Patients.

BACKGROUND: In our pilot study, we investigated the psychological (well-being and personal coping strategies) and physiological (assessed by heart rate variability (HRV)) effects of the newly developed activity-based stress release (ABSR) program for people with depressive disorders, also in combination with burnout symptoms and/or anxiety disorders. METHODS: A single-arm prospective observational study was carried out. Twenty participants diagnosed with depression and burnout or anxiety disorders were invited to participate in the 8-week ABSR program. All participants filled in two questionnaires (the multidimensional mental state questionnaire and the Ehrenfeld inventory on coping style) before, directly after and 2 months after the 8-week ABSR program. In addition, all participants were offered a 24-hour Holter ECG measurement before, directly after and 2 months after the 8-week ABSR program to measure HRV. RESULTS: Calmness and serenity showed a statistically significant improvement after the 8-week ABSR program. However, complete questionnaire sets were not available from all of the participants. In the four individuals who had agreed to a 24-hour Holter ECG, the overall HRV and parasympathetic activity increased. CONCLUSIONS: The ABSR program is an encouraging novel therapeutic approach: A significant improvement in calmness and serenity was observed after ABSR. A larger and controlled trial of this treatment option in depression and burnout is recommended. It should be further investigated how ABSR affects task-evoked and resting brain activity, and what effects it has on the cardiovascular system in general (better blood flow and normalization of activity are to be expected).

A Drug Safety Concept (I) to Avoid Polypharmacy Risks in Transplantation by Individual Pharmacotherapy Management in Therapeutic Drug Monitoring of Immunosuppressants.

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.

Spiritual and religious aspects influence mental health and viral load: a quantitative study among young people living with HIV in Zimbabwe.

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.

Underdiagnosed CKD in Geriatric Trauma Patients and Potent Prevention of Renal Impairment from Polypharmacy Risks through Individual Pharmacotherapy Management (IPM-III).

The aging global patient population with multimorbidity and concomitant polypharmacy is at increased risk for acute and chronic kidney disease, particularly with severe additional disease states or invasive surgical procedures. Because from the expertise of more than 58,600 self-reviewed medications, adverse drug reactions, drug interactions, inadequate dosing, and contraindications all proved to cause or exacerbate the worsening of renal function, we analyzed the association of an electronic patient record- and Summaries of Product Characteristics (SmPCs)-based comprehensive individual pharmacotherapy management (IPM) in the setting of 14 daily interdisciplinary patient visits with the outcome: further renal impairment with reduction of eGFR ≥ 20 mL/min (redGFR) in hospitalized trauma patients ≥ 70 years of age. The retrospective clinical study of 404 trauma patients comparing the historical control group (CG) before IPM with the IPM intervention group (IG) revealed a group-match in terms of potential confounders such as age, sex, BMI, arterial hypertension, diabetes mellitus, and injury patterns. Preexisting chronic kidney disease (CKD) > stage 2 diagnosed as eGFR < 60 mL/min/1.73 m2 on hospital admission was 42% in the CG versus 50% in the IG, although in each group only less than 50% of this was coded as an ICD diagnosis in the patients' discharge letters (19% in CG and 21% in IG). IPM revealed an absolute risk reduction in redGFR of 5.5% (11 of 199 CG patients) to 0% in the IPM visit IG, a relative risk reduction of 100%, NNT 18, indicating high efficacy of IPM and benefit in improving outcomes. There even remained an additive superimposed significant association that included patients in the IPM group before/beyond the 14 daily IPM interventions, with a relative redGFR risk reduction of 0.55 (55%) to 2.5% (5 of 204 patients), OR 0.48 [95% CI 0.438-0.538] (p < 0.001). Bacteriuria, loop diuretics, allopurinol, eGFR ≥ 60 mL/min/1.73 m2, eGFR < 60 mL/min/1.73 m2, and CKD 3b were significantly associated with redGFR; of the latter, 10.5% developed redGFR. Further multivariable regression analysis adjusting for these and established risk factors revealed an additive, superimposed IPM effect on redGFR with an OR 0.238 [95% CI 0.06-0.91], relative risk reduction of 76.2%, regression coefficient -1.437 including patients not yet visited in the IPM period. As consequences of the IPM procedure, the IG differed from the CG by a significant reduction of NSAIDs (p < 0.001), HCT (p = 0.028) and Würzburger pain drip (p < 0.001), and significantly increased prescription rate of antibiotics (p = 0.004). In conclusion, (1) more than 50% of CKD in geriatric patients was not pre-recognized and underdiagnosed, and (2) the electronic patient records-based IPM interdisciplinary networking strategy was associated with effective prevention of further periinterventional renal impairment and requires obligatory implementation in all elderly patients to urgently improve patient and drug safety.

A validation of the religious and spiritual struggles scale among young people living with HIV in Zimbabwe: Mokken scale analysis and exploratory factor analysis.

Introduction: Religious/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. Methods: Data 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. Results: The 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. Discussion: The 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.

Phytotherapy in paediatric skin disorders - A systematic literature review.

OBJECTIVES: Although skin disorders in children and adolescents are increasingly treated with phytotherapies in practice, there are very few studies investigating this topic, and no systematic review exists that summarizes the current state of research. This review examines which herbal medicines show to be effective to treat atopic dermatitis, diaper dermatitis, and skin lesions or wounds. METHODS: Clinical studies were searched according to PRISMA-guidelines in the medical databases of PubMed, EMBASE, and CINAHL and summarised in a systematic review. RESULTS: Among the 429 articles screened, 17 studies with a total of 2358 participants were identified that suited our inclusion criteria. Thereof seven studies each on the treatment of atopic dermatitis and skin lesions or wounds and three on diaper dermatitis. The phytotherapeutics investigated were based on the following herbs: Evening primrose, blackcurrant, polypodium leucotomos, calendula, aloe vera, chamomile, comfrey, hamamelis, olive, hypericum, neem, white oak, and myrrh. They have mainly been analysed in randomized controlled trials, but also in (long-term) observational studies, prospective trials and case series. CONCLUSIONS: Based on the application of the Jadad score, eight out of 17 of the studies examined were of low quality. Yet we found some indication that evening primrose oil may be effective for treating atopic dermatitis in children, while comfrey appears to have a positive effect on wound healing. Interestingly, none of the studies found positive effects for treating skin disorders with aloe vera or chamomile.

Indigenous-Amazonian Traditional Medicine's Usage of the Tobacco Plant: A Transdisciplinary Ethnopsychological Mixed-Methods Case Study.

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.

Changes in Cerebral Oxygenation and Systemic Physiology During a Verbal Fluency Task: Differences Between Men and Women.

BACKGROUND: Sex differences in behavioural performance of a cognitive task have been repeatedly reported in the literature. Whether such differences are also relevant for evoked cerebral haemodynamic and oxygenation responses as well as systemic physiological changes is a topic of ongoing investigations. AIM: We investigated whether changes in cerebral oxygenation and systemic physiological activity are sex-dependent during a verbal fluency task (VFT). SUBJECTS AND METHODS: VFT performance and changes in cerebral oxygenation and systemic physiology were investigated in 32 healthy right-handed adults (17 females, 15 males, age: 25.5 ± 4.3 years). The total duration of the VFT was 9 min. During this phase, subjects were also exposed to blue light (peak wavelength: 450 nm, illuminance: 120 lux). Before and after the VFT, subjects were in darkness. In this study, we used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. Absolute concentration changes of oxyhaemoglobin ([O2Hb]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), as well as tissue oxygen saturation (StO2) were measured bilaterally over the prefrontal cortex (PFC) and visual cortex (VC). Systemic physiological parameters were also recorded in parallel (e.g., end-tidal CO2, heart rate, respiration rate, skin conductance). RESULTS: We found that: (i) Females were better VFT performers in comparison to males. (ii) Changes in [O2Hb] and [HHb] in the VC were higher for males compared to females during the VFT under blue light exposure. (iii) Lower and higher StO2 changes were detected for males compared to females in the PFC and VC, respectively. (iv) Sex-dependent changes were also evident for end-tidal CO2, heart rate, respiration rate, and pulse-respiration quotient. CONCLUSIONS: Our study showed that sex differences are not only observed in task performance but also in the magnitudes of changes in cerebral and physiological parameters. The findings of the current study emphasise that sex differences in brain activation and systemic physiological activity need to be considered when interpreting functional neuroimaging data. These findings offer a broad range of implications for educational purposes and facilitate a better understanding of the effects of sex on behavioural performance as well as human physiology.

Frontal Cerebral Oxygenation in Humans at Rest: A Mirror Symmetry in the Correlation with Cardiorespiratory Activity.

BACKGROUND: Although several studies published reference values for frontal cerebral tissue oxygen saturation (StO2) measured with near-infrared spectroscopy (NIRS) based cerebral oximetry, a detailed investigation, whether and which factors from systemic physiology are related to the individual StO2 values, is missing. AIM: We investigated how the state of the cardiorespiratory system is linked to StO2 values at rest. SUBJECTS AND METHODS: Absolute StO2 values (median over a 5 min resting-phase while sitting) were obtained from 126 healthy subjects (age: 24.0 ± 0.2 years, 45 males, 81 females) over the left and right prefrontal cortex (PFC) by employing frequency-domain NIRS as part of a systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) study. In addition, heart rate (HR) and respiration rate (RR) were measured, and the pulse respiration quotient (PRQ) was determined (PRQ = HR/RR). General additive models (GAM) were used to analyse the data. RESULTS: The GAM analysis revealed a specific relationship between the overall PFC StO2 values (mean over right and left PFC) and the variables HR and RR: HR was positively correlated with mean StO2, while RR showed no correlation. In the mirror case, RR was negatively linearly correlated with the frontal cerebral oxygenation asymmetry (FCOA), which was not correlated with HR. The right PFC StO2 was not linked to the RR, whereas the left PFC StO2 was. Positive correlations of the PRQ with the mean PFC StO2 as well as the FCOA were also found. GAM modelling revealed that the individual FCOA values are explained to a large extent (deviance explained: 88.8%) by the individual mean PFC StO2 and PRQ. We conclude that (i) the state of the cardiorespiratory system is significantly correlated with StO2 values and (ii) there is a mirror symmetry with regard to the impact of cardiorespiratory parameters on the mean PFC StO2 and FCOA.

In Vitro Validation of a New Tissue Oximeter Using Visible Light.

There is a clinical need to measure local tissue oxygen saturation (StO2), oxy-, deoxy- and total haemoglobin concentration ([O2Hb], [HHb], [tHb]) in human tissue. The aim was to validate an oximeter called OxyVLS applying visible light spectroscopy (VLS) to determine these parameters without needing to assume a reduced scattering coefficient (µ's). This problem is solved by appropriate calibrations. Compared to near-infrared spectroscopy (NIRS), OxyVLS determines the oxygenation in a much smaller more superficial volume of tissue, which is useful in many clinical cases. OxyVLS was validated in liquid phantoms with known StO2, [tHb], and µ's and compared to frequency domain NIRS as a reliable reference. OxyVLS showed a high accuracy for all the mentioned parameters and was even able to measure µ's. Thus, OxyVLS was successfully tested in vitro.

Intersubject Variability in Cerebrovascular Hemodynamics and Systemic Physiology during a Verbal Fluency Task under Colored Light Exposure: Clustering of Subjects by Unsupervised Machine Learning.

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.

Individual Pharmacotherapy Management (IPM)-IV: Optimized Usage of Approved Antimicrobials Addressing Under-Recognized Adverse Drug Reactions and Drug-Drug Interactions in Polypharmacy.

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.

Prevalence, specific and non-specific determinants of complementary medicine use in Switzerland: Data from the 2017 Swiss Health Survey.

OBJECTIVES: To 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 METHODS: We 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. RESULTS: Prevalence 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, p<0.001). We identified the following independent specific determinants of CM use: gender, nationality, age, lifestyle and BMI. Female gender and nationality were the most specific determinants of CM use. Current smoking, being overweight and obesity were determinants of non-use of CM, while regular consumption of fruits and/or vegetables and regular physical activity were determinants of CM use. CONCLUSION: Prevalence 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.

Systemic physiology augmented functional near-infrared spectroscopy: a powerful approach to study the embodied human brain.

In this Outlook paper, we explain why an accurate physiological interpretation of functional near-infrared spectroscopy (fNIRS) neuroimaging signals is facilitated when systemic physiological activity (e.g., cardiorespiratory and autonomic activity) is measured simultaneously by employing systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). The rationale for SPA-fNIRS is twofold: (i) SPA-fNIRS enables a more complete interpretation and understanding of the fNIRS signals measured at the head since they contain components originating from neurovascular coupling and from systemic physiological sources. The systemic physiology signals measured with SPA-fNIRS can be used for regressing out physiological confounding components in fNIRS signals. Misinterpretations can thus be minimized. (ii) SPA-fNIRS enables to study the embodied brain by linking the brain with the physiological state of the entire body, allowing novel insights into their complex interplay. We envisage the SPA-fNIRS approach will become increasingly important in the future.