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Introduction: Predictive analytics may be a useful adjunct to identify training needs for exploration class medical officers onboard deep space vehicles., Methods: This study used a preliminary version of NASA's newest medical predictive analytics tool, the Medical Extensible Database Probabilistic Risk Assessment Tool (MEDPRAT), to test the application of predictive analytics to exploration crew medical officer curriculum design for 5 distinct design reference mission (DRM) profiles. Partial and fully treated paradigms were explored. Curriculum elements were identified using a leave-one-out analysis and a threshold of 5% risk increase over the fully treated baseline., Results: For the partial treatment scenario, among the 5 DRM profiles 4-32 curriculum elements met the 5% RRI increase. For the absolute treatment scenario, among the 5 DRM profiles, 13-126 curriculum elements met the 5% RRI increase. For the partial treatment paradigm, 13 capabilities are present in at least 3 of the 5 DRM profiles, and these elements may constitute a common baseline curriculum. This covers 41% of the skillsets needed for an ISS-like profile, 100% of a late Artemis-like profile, 41% of a Mars mission-like profile, 100% of a Starship orbital-like profile, and 68% of a Starship lunar flyby-like profile., Conclusions: This proof-of-concept study demonstrated that predictive analytics can rapidly generate generic and mission profile-specific exploration CMO curricula using an evidence-based process driven by optimizing mission risk reduction. This technique may serve as part of a human-machine team approach to medical curriculum planning for future space missions. It has significant potential to improve astronaut health and save time and effort for planners, trainers, and trainees., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Anemia is a complex condition with diverse causes and poses diagnostic challenges amid the expanding landscape of laboratory testing. Implementation of an anemia diagnostic management team (DMT) can aid health care providers in navigating this complexity., Methods: This quasi-experimental study assessed the impact of an anemia DMT on laboratory test ordering by primary care providers for anemic patients. This study included adult patients (≥18 years) with anemia (hemoglobin <12.0 g/dL for nonpregnant women, hemoglobin <13.0 g/dL for men) presenting to a family medicine clinic. Cases reviewed by the DMT (n = 100) were compared with a control group (n = 95)., Results: The DMT recommended additional testing for 76 patients. Significantly more patients in the DMT group underwent follow-up tests compared with controls (59% vs 34%; P < .001). Moreover, the DMT group underwent a higher mean number of tests per patient (1.70 ± 2.2 vs 0.95 ± 1.9; P = .01)., Conclusion: Implementation of an anemia DMT influenced follow-up testing patterns in anemic patients, potentially enhancing diagnostic thoroughness and patient care., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate that different receptor-ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin α IIb β 3 mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying drug-disease interactions and inter-individual variability, our work reveals a need for personalized anti-thrombotic drug selection that accommodates each patient's pathological profile., (© 2024. The Author(s).)

Background: Specimens with incorrect patient information are both a critical safety error and difficult to identify. Estimates of sample mislabelling rely on subjective identification of mislabelling, with the possibility that not all mislabelled samples are being caught., Methods: We determined the blood type of two or more complete blood count specimens with the same patient label and assessed for discrepancies. We additionally determined the rate of identified sample mislabelling for the study period., Results: We found a rate of 3.17 per 1000 discrepancies over the study period. These discrepancies most likely represent occult, or unidentified, mislabelled samples. In contrast, the rate of identified sample mislabelling was 1.15 per 1000., Conclusions: This study suggests that specimens identified as, or known to be, mislabelled represent only a fraction of those mislabelled. These findings are currently being confirmed in our laboratory and are likely generalisable to other institutions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

INTRODUCTION: This paper describes the method for assigning medical diagnostic and treatment capabilities and resources to the database which assists with an updated probabilistic risk analysis (PRA) tool for exploration class medical system planning. The National Aeronautics and Space Administration has used PRA since 2011 to inform mission medical system design, but existing tools are designed only for low Earth orbit. An updated PRA tool was needed to assist with exploration class missions. METHODS: A team of medical experts with a wide range of expertise and experience, including Space Medicine, was assembled to build capability and resource tables for the new PRA tool. This team met over 8 mo and used practice guidelines, literature, and experience to build capability and resource tables (CRTs) for each condition in the new PRA tool database. RESULTS: This process led to CRTs for each condition and a total of 617 distinct capabilities and 839 discrete resources. CONCLUSION: The CRT method is an effective way to translate medical practice guidelines into capabilities and resources usable by PRA tools for exploration class medical system planning. This same method may be used in commercial space ventures and in other applications in which medical predictive analytics are informative. Levin DR, Nelson AM, Zahner C, Stratton ER, Anderson A, Steller J. A method to determine capabilities and resources for spacecraft medical systems . Aerosp Med Hum Perform. 2024; 95(7):403-408.

Context.—: Laboratories face the challenge of providing quality patient care while managing costs and turnaround times (TATs). To this end, we brought the heparin-induced thrombocytopenia (HIT) antibody test in-house with the goal of reducing costs and the time to diagnosis., Objectives.—: To determine the cost-effectiveness and return on investment of our in-house HIT antibody test by comparing it to send-out assays with TATs of 2, 3, or 4 days., Design.—: We performed a retrospective chart review of all patients with a HIT antibody assay and analysis of laboratory financial records. Analysis included the percentage of patients receiving alternative treatment, cost of treatment, startup costs of bringing the test in-house, and average TAT of the in-house test., Results.—: We found significant reductions in the cost of treatment for patients and the overall cost to the health care system. The in-house assay became cost-effective at between 8 and 20 tests, with a return on investment of up to 298%., Conclusions.—: Bringing the HIT antibody assay in-house becomes cost-effective at a very low test volume with excellent return on investment. This novel analysis can provide a framework for other laboratory medicine professionals to analyze the benefits of bringing this and other assays in-house., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Problem: Research activity in residency develops skills essential for the practice of medicine and has many benefits for residents, residency programs, the community of medicine, and patients. However, resident participation in research and innovation remains limited, with several barriers that are difficult to address without significant overhead or changes to curriculum., Approach: In September 2021, the Society for Innovation and Research (SIR), a resident-led organization dedicated to promoting and supporting resident achievement in research and innovation, was founded. Using only 1 hour of protected didactic time a month, SIR workshops provide critical mentoring and feedback to make resident research a success as well as education on various topics of interest to residents. In addition, SIR celebrates and publicizes resident research success and lays the groundwork for interested residents to participate in innovation., Outcomes: The authors analyze the success of SIR in increasing resident research productivity by analyzing PubMed-indexed publications for 11 semesters from fall 2018 to fall 2023. After the launch of SIR, the mean (SD) total number of publications increased from 5.3 (2.4) to 13.3 (1.6) (P = .01), the total mean (SD) number of residents publishing increased from 3.7 (1.3) to 10.0 (1.2) (P = .009), and the mean (SD) total number of coauthored articles increased from 0.1 (0.3) to 2.8 (1.3) (P = .007)., Next Steps: The skill set acquired from participation in research during residency is more critical than ever in the wake of the COVID-19 pandemic. SIR initiatives are generalizable to most residency programs in most specialties and require little overhead in terms of physical space, digital resources, and staffing. The authors are currently exploring expanding the SIR program to other residencies at U.S. institutions and have set up processes for the mantle of SIR leadership to be passed down among the pathology resident body., (Copyright © 2024 the Association of American Medical Colleges.)

Objectives: Analysis of laboratory value often lacks assessment of the laboratory's impact on quality of care. In this study, we aimed to determine the impact of bringing a heparin-induced thrombocytopenia (HIT) antibody assay in-house on a quality metric-patient hospital length of stay (LOS)-and assess any associated cost savings., Methods: A retrospective review of patient visits with a HIT antibody assay over a 7-year period determined the mean LOS in send-out vs in-house HIT antibody assay cohorts as well as cohorts of positive and negative results. Our systemwide mean LOS and metrics of acuity were analyzed. We performed a financial analysis of estimated cost savings., Results: We found a mean LOS reduction of 3.97 days in the in-house cohort, with no evidence of a systemwide LOS decrease or a decline in patient acuity. This reduction was largely driven by a reduction in LOS among patients with a negative assay result. We found an estimated total cost savings of $3.9 million and an estimated mean savings per patient of $7,305, despite escalating health care costs over time., Conclusions: We demonstrated a reduction in LOS following the introduction of an in-house HIT antibody assay that cannot be attributed to either systemwide initiatives or reduced patient acuity and was driven largely by patients with negative assays. This reduction was associated with significant estimated cost savings., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Head and neck positioning is a key element of craniofacial reconstructive surgery and can become challenging when intervention necessitates broad exposure of the calvarium. We present a case of craniosynostosis secondary to Apert's syndrome requiring anterior and posterior cranial vault access during surgical correction. A modified sphinx position was used that required significant neck extension. The patient had concurrent Chiari I malformation with brain stem compression so intraoperative neuromonitoring (IONM) was used to ensure that there were no negative effects on the neural elements with positioning. This highlights benefits of IONM in a setting not typically associated with its use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Diagnostic management teams (DMT) are groups of experts with specialized knowledge to guide test selection and interpretation of results. They have been active in institutions over the past 20 years. To date, there are limited data on whether the presence of experts to advise healthcare providers on appropriate laboratory test selection and interpretation of complex test results positively impacts patient care., Methods: A retrospective study at a regional healthcare system with 257,000 patient encounters between 2011 and 2022 reviewing test interpretations provided by clinical laboratory experts on a diagnostic management team., Results: Cases reviewed by the coagulation DMT were 6 times more likely to have an established, scientifically based diagnosis compared to those without a DMT. Patients who have a coagulation DMT review were twice as likely to receive a diagnosis vs. having no diagnosis., Conclusions: This study demonstrates that for several objective clinical outcomes, specifically diagnostic conclusions and length of stay, a DMT of coagulation experts assessing patients' test results has had a major impact on outcomes and delivery of care., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

The use of Rho(D) immune globulin in Rh-negative pregnant women has become standard of care, but many practicing clinicians do not know the dosing recommendations for this essential medication. In this article, we describe a case of a 15-year-old girl who presented with intrauterine fetal demise and was found to have massive fetomaternal hemorrhage. Kleihauer-Betke testing results indicated nearly 460 mL of fetal blood in the maternal circulation. The patient ultimately received 4800 µg of Rho(D) immune globulin, a dose that required close coordination with the obstetrical service and pharmacy. Although this is an unusual case of large-volume, potentially chronic, fetomaternal hemorrhage, it is also an excellent illustration of the principles for diagnosing this condition, as well as providing dosing guidelines for Rho(D) immunoglobulin to prevent alloimmunization., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The primary objective of this noninterventional, observational study was to assess the effectiveness of the Petasites hybridus leaf extract (Ze 339) on early allergic and late inflammatory symptoms of allergic rhinitis in Swiss outpatients. This study was conducted by general practitioners and allergologists. Data from 226 patients were collected during three documented visits. The intermediate visit was ideally made 2-4 weeks after the baseline visit, followed by the final visit approximately 2-4 months later. The mean study duration was 63 days, with 75% of patients being treated for at least 4 weeks. Of the patients, 58.5% started with Ze 339 monotherapy, and 41.5% received other antiallergic and/or sympathomimetic drugs. In both groups, the allergic total symptom score and the inflammatory total symptom scores were significantly ( p < 0.001) reduced, and the scores for quality of life were improved. Both physicians and patients were very satisfied with the treatment and the concept of therapy, not only for short-term (seasonal) therapy but also for long-term therapy. The tolerability was good: only three mild gastrointestinal adverse events occurred. In summary, the effectiveness of P. hybridus leaf extract Ze 339 for the treatment of early allergic and late inflammatory symptoms of allergic rhinitis could be confirmed.

Stress is an increasing problem that can result in various psychiatric and somatoform symptoms. Among others, benzodiazepines and valerian preparations are used to treat stress symptoms. The aim of this study was to investigate whether the prescription of a fixed herbal extract combination of valerian, lemon balm, passionflower, and butterbur (Ze 185) changes the prescription pattern of benzodiazepines in hospitalized psychiatric patients. In a retrospective case-control study, anonymized medical record data from 3,252 psychiatric in-house patients were analysed over a 3.5-year period. Cases (n = 1,548) with a prescription of Ze 185 and controls (n = 1,704) were matched by age, gender, hospitalization interval, and main International Classification of Diseases, Version 10 F-diagnoses. The primary objective was to investigate the effect of Ze 185 on the prescription pattern of benzodiazepines. Secondary objectives investigated the prescriptions of concomitant drugs and effectiveness of the hospital stay. Distribution of drug classes was analysed using the WHO's anatomic-therapeutic-chemical code. Data showed that both treatment modalities had a comparable clinical effectiveness but with significantly less prescriptions of benzodiazepines in the Ze 185 group (p = .006). This is of clinical importance because suitable alternatives to benzodiazepines are desirable. To obtain more support for this hypothesis, a dedicated randomized, controlled clinical trial monitoring drug safety is required., (© 2020 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Introduction: Acute bronchitis is defined as a sudden inflammation of the bronchial tubes in the lung mainly caused by viral infection. It is characterized by a persistent cough which can be productive or dry. It is the most common disease in industrialized countries, and thus herbal expectorants enjoy a high popularity in many European countries due to their favorable risk-benefit ratio., Objective: The present noninterventional study was intended to gain further data on the application of a cough syrup containing ivy leaf extract EA 575® by evaluating its efficacy and safety in children and adults with symptoms of acute bronchitis. Acetylcysteine (ACC) was chosen as comparator drug (common mono preparations). Material and Methods . The study was conducted at 25 medical practices throughout Switzerland as prospective, open, noninterventional study., Results: At entry visit, all clinical assessments including coughing fits, sputum, dyspnoea, rales, severity of the diseases, and coughing quality were rated with moderate intensity in both groups. At the final visit after seven days of treatment, there was a comparable improvement in both groups for all assessments except dyspnoea and number of cough attacks which showed a higher improvement in the EA 575® group compared with ACC. Further, cough-associated sleeping disorders improved more in the EA 575® group. Both, physicians and patients described the efficacy of EA 575® comparable with acetylcysteine. Observations of the tolerability were comparable for both products. The study results indicate that ivy leaf extract might be an effective alternative to acetylcysteine with respect to the improvement of respiratory function in children and adults at a slightly better evaluation of efficacy., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Esther Kruttschnitt et al.)

Purpose: To compare the influence of Cimicifuga racemosa extract (CR, Ze 450) and menopausal hormone therapy (MHT) on metabolic parameters and body weight in symptomatic menopausal women., Methods: In this monocentric retrospective cohort study, women over 40 years old with a first consultation between 2009 and 2016 were screened. Included in the final analysis were women treated with either MHT or CR and having at least one follow-up consultation. Metabolic serum parameters (lipids, glucose, insulin, and HOMA-IR), body weight, and menopausal symptoms [Menopause Rating Scale (MRS)-II] were the main outcome measures. Statistical analysis by uni- and multi-variable linear mixed-effects regression models assuming a linear effect of time., Results: 174 women were included in the final analysis (CR n = 32, MHT n = 142). There was no difference between the groups regarding baseline characteristics (age, BMI, serum metabolic parameters, hormones, and blood pressure) and total MRS-II score, while reproductive stage differed significantly with more postmenopausal women treated with CR (83%) than MHT (55%) (p = 0.038). Median follow-up time was 12 months. In both groups, metabolic serum parameters and body weight did not change over the follow-up period, while total and MRS-II subscores improved., Conclusion: Menopausal symptoms improved significantly in both groups (MHT and CR), while serum metabolic parameters and body weight did not change in MHT- or CR-treated women.

Hypericum perforatum L. (St. John's wort) is used to treat mild-to-moderate depression. Its potential safety risks are pharmacokinetic drug interactions via cytochrome P450 (CYP) enzymes and P-glycoprotein, presumably caused by hyperforin. In a phase I, open-label, nonrandomized, single-sequence study, the low-hyperforin Hypericum extract Ze 117 was investigated using a drug cocktail in 20 healthy volunteers. No pharmacokinetic interactions of Ze 117 were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein. Area under the curve (AUC) and peak plasma concentration (C max ) of the used probe drugs showed 90% confidence intervals (CIs) of the geometric mean ratios of the drugs taken together with Ze 117 vs. probe drug alone, well within the predefined bioequivalence range of 80-125%. Though Ze 117 did not induce dextromethorphan metabolism by CYP2D6, it weakly increased dextromethorphan AUC ratio (mean 147.99, 95% CI 126.32-173.39) but not the corresponding metabolic ratio. Ze 117 does not show clinically relevant pharmacokinetic interactions with important CYPs and P-glycoprotein., (© 2019 Max Zeller & Söhne AG. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: Considering the negative effects of stress on health, there is a growing interest in stress-reducing interventions. The present study examines the effects of a fixed combination of valerian, passion flower, lemon balm, and butterbur extracts (Ze 185) on biological and affective responses to a standardized psychosocial stress paradigm., Purpose: The aim of the present study was to investigate the efficacy of Ze 185 on cortisol and anxiety stress responses to acute psychosocial stress in healthy subjects., Study Design: This study was a randomized, placebo-controlled, double blind study with 3 parallel groups., Methods: 72 healthy male participants were randomized to 3 groups (Ze 185, placebo or no treatment) during 4 days prior to a standardized psychosocial stress paradigm. Principle outcomes were salivary cortisol and self-reported anxiety responses to stress assessed at the fourth day., Results: The stress paradigm induced significant and large cortisol and self-reported anxiety responses. Groups did not differ significantly in their salivary cortisol response to stress, but participants in the Ze 185 condition showed significantly attenuated responses in self-reported anxiety in comparison to placebo (F(3, 41) = 3.33, p = 0.03) and no treatment (F(3, 43) = 2.77, p = 0.05)., Conclusion: The results show that Ze 185 significantly attenuated the subjective emotional stress response during an acute stress situation, without affecting biological stress responses. Given that a circumscribed biological stress response is to be considered as an adaptive mechanism, Ze 185 reduces self-reported anxiety response to stress without affecting assumingly adaptive biological stress responses., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Ze339, an herbal extract from Petasites hybridus leaves is effective in treatment of allergic rhinitis by inhibition of a local production of IL-8 and eicosanoid LTB 4 in allergen-challenged patients. However, the mechanism of action and anti-inflammatory potential in virally induced exacerbation of the upper airways is unknown. This study investigates the anti-inflammatory mechanisms of Ze339 on primary human nasal epithelial cells (HNECs) upon viral, bacterial and pro-inflammatory triggers. To investigate the influence of viral and bacterial infections on the airways, HNECs were stimulated with viral mimics, bacterial toll-like-receptor (TLR)-ligands or cytokines, in presence or absence of Ze339. The study uncovers Ze339 modulated changes in pro-inflammatory mediators and decreased neutrophil chemotaxis as well as a reduction of the nuclear translocation and phosphorylation of STAT molecules. Taken together, this study suggests that phyto drug Ze339 specifically targets STAT-signalling pathways in HNECs and has high potential as a broad anti-inflammatory drug that exceeds current indication. © 2016 BioFactors, 43(3):388-399, 2017., (© 2017 International Union of Biochemistry and Molecular Biology.)

The cardinal climacteric symptoms of hot flushes and night sweats affect 24-93% of all women during the physiological transition from reproductive to post-reproductive life. Though efficacious, hormonal therapy and partial oestrogenic compounds are linked to a significant increase in breast cancer. Non-hormonal treatments are thus greatly appreciated. This systematic review of published hormonal and non-hormonal treatments for climacteric, and breast and prostate cancer-associated hot flushes, examines clinical efficacy and therapy-related cancer risk modulation. A PubMed search included literature up to June 19, 2014 without limits for initial dates or language, with the search terms, (hot flush* OR hot flash*) AND (clinical trial* OR clinical stud*) AND (randomi* OR observational) NOT review). Retrieved references identified further papers. The focus was on hot flushes; other symptoms (night sweats, irritability, etc.) were not specifically screened. Included were some 610 clinical studies where a measured effect of the intervention, intensity and severity were documented, and where patients received treatment of pharmaceutical quality. Only 147 of these references described studies with alternative non-hormonal treatments in post-menopausal women and in breast and prostate cancer survivors; these results are presented in Additional file 1. The most effective hot flush treatment is oestrogenic hormones, or a combination of oestrogen and progestins, though benefits are partially outweighed by a significantly increased risk for breast cancer development. This review illustrates that certain non-hormonal treatments, including selective serotonin reuptake inhibitors, gabapentin/pregabalin, and Cimicifuga racemosa extracts, show a positive risk-benefit ratio. Key pointsSeveral non-hormonal alternatives to hormonal therapy have been established and registered for the treatment of vasomotor climacteric symptoms in peri- and post-menopausal women.There are indications that non-hormonal treatments are useful alternatives in patients with a history of breast and prostate cancer. However, confirmation by larger clinical trials is required.

Introduction: Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index., Methods: The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography., Results: A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008)., Conclusion: The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy.

Background: Root extracts of Cimicifuga racemosa (L.) Nutt. have been successfully used in the treatment of climacteric complaints., Method: In this observational study, Cimicifuga racemosa (CR) extract Ze 450 was studied in 442 unselected ambulatory female outpatients with menopausal complaints under daily practice conditions. Physicians were suggested to treat patients for the first 3 months with 13 mg/d CR (high dose, HD) and to continue over additional 6 months either with this treatment or to switch to 6.5mg/d CR (low dose, LD). The choice of treatment and its dose, however, was fully at the discretion of the physician., Results: After 3-months treatment with HD, symptom severity (Kupperman Menopause Index, KMI) decreased significantly (p<0.001) from baseline values. Continuation of treatment with HD or LD decreased total KMI and its sub-item scores further (HD, LD: p<0.001). However, more patients (84.9%) responded to HD than to LD (78.4%) and showed an improvement of symptoms (p=0.011)., Conclusion: This observational study demonstrated that treatment with CR in unselected patients with climacteric complaints under the conditions of daily practice resulted in a significant improvement of menopausal symptoms assessed by the total KMI score and its sub-item scores with an effect size similar to that in a previous randomized, controlled clinical trial., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Background: Preparations of Vitex agnus castus L. (VAC) have been shown to be effective to treat irregular menstrual cycles, cyclical mastalgia and symptoms of the premenstrual syndrome (PMS). However, the dose-effect relationship for the treatment of PMS has not yet been established. This study aimed to investigate the clinical effects of three different doses of the VAC extract Ze 440 in comparison to placebo in patients suffering from PMS., Methods: In a multicenter, double-blind, placebo-controlled, parallel-group study, 162 female patients with PMS (18-45 years) were randomized to either placebo or different doses of Ze 440 (8, 20 and 30 mg) over three menstrual cycles. PMS symptoms' severity was assessed by patients using visual analog scales (VAS) for the symptoms irritability, mood alteration, anger, headache, bloating and breast fullness., Results: Each of the treatments was well tolerated. Improvement in the total symptom score (TSS) in the 20mg group was significantly higher than in the placebo and 8 mg treatment group. The higher dose of 30 mg, on the other hand, did not significantly decrease symptom severity compared to the 20mg treatment, providing a rational for the usage of 20mg. Corresponding results were observed with the single PMS symptom scores., Conclusion: This study demonstrated that the VAC extract Ze 440 was effective in relieving symptoms of PMS, when applied in a dose of 20mg. Therefore, for patients suffering from PMS, 20mg Ze 440 should be the preferred daily dose., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa) have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo). Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic), assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients' self-assessments of general quality of life (QoL), responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65-19.35) score points, P < 0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55-11.39) score points, P = 0.0003 for 6.5 mg). QoL and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and QoL were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women.

Background: Allergic rhinitis symptoms of itching, sneezing, rhinorrhea, and nasal obstruction significantly decrease patients' quality of life. Compared with histamine and leukotriene receptor antagonists, the petasol butenoate complex Ze 339 displays pharmacologically distinct properties. In vitro it inhibits the biosynthesis of leukotrienes and mediator release from activated eosinophils., Objective: This study aimed to assess the efficacy and mode of action of Ze 339, desloratadine, and placebo on allergic rhinitis symptoms, nasal airflow, and local mediator levels after unilateral nasal allergen provocation., Methods: In this double-blind, randomized, crossover study 18 subjects with allergic rhinitis to grass pollen received Ze 339, desloratadine, and placebo for 5 days before nasal allergen challenge with grass pollen extract. Rhinomanometry, symptom assessment, and local inflammatory mediator measurement were performed during the 24 hours after allergen challenge., Results: With Ze 339, the patient's time to recovery (5.4 ± 1.6 hours) from nasal obstruction after allergen challenge (time for return to 90% of baseline value ± SEM) was significantly shorter than with placebo (9.1 ± 2.3 hours, P = .035) and desloratadine (10.7 ± 2.5 hours, P = .022). Likewise, Ze 339's standardized symptom assessment for nasal obstruction (3.2 ± 1.3 hours) showed significantly faster relief (time for return to baseline value ± SEM compared with placebo, 8.3 ± 2.4 hours; P = .027) and desloratadine (4.5 ± 1.2 hours, P = .030). One interesting finding was that Ze 339 significantly reduced IL-8 and leukotriene B(4) levels in nasal secretions before challenge., Conclusion: When compared with desloratadine and placebo, Ze 339 shows better efficacy in relieving nasal obstruction symptoms and inhibiting critical components of the chemokine network and as such represents a novel symptomatic and possible prophylactic treatment for allergic rhinitis., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)