Nurturing Hope: Reproductive Outcomes with Sinosomatics Following Unsuccessful IVF Attempts.

INTRODUCTION: For women who have experienced failed attempts at in vitro fertilization (IVF) and face medical issues leading to infertility, the renewed effort to seek fertility treatment, coupled with decreasing likelihood of success, can exert substantial emotional and physical strains. Consequently, many couples opt to discontinue treatment before attaining pregnancy. The objective of this study was to evaluate the reproductive outcomes in patients with unsuccessful prior IVF attempts who received a complementary treatment designed to alleviate emotional distress and burden. PATIENTS AND METHODS: A retrospective analysis of data from infertile patients who initiated the complementary intervention at a private clinic between January 2014 and December 2016 was conducted. Information on diagnosis, history of infertility, prior assisted reproductive technologies treatments, mode of conception, and pregnancy outcomes were retrieved. RESULTS: The data of 133 patients with a history of one or more unsuccessful IVF treatments were analyzed. Patients had an average age of 36.7 years (± 4.4 SD) and had been experiencing infertility for an average of 4.6 years (± 2.7 SD). The two main causes of their infertility were endometriosis (36.1%, 48 patients) and diminished egg quality (31.6%, 42 patients). By May 2020, a significant proportion of the patients, 81.2% (108 patients), had achieved pregnancy, leading to 94 live births, which represents a 70.7% success rate. These pregnancies mostly resulted from natural-cycle IVF (35.1%), donor cycles (23.4%), and conventional IVF (21.3%). The dropout rate was comparatively low at 23.3%. The median time from the start of complementary treatment to delivery was 18 months, with a range of 12 to 28 months. CONCLUSIONS: This study highlights the potential value of complementary treatment approaches in conjunction with standard medical care for women who have experienced unsuccessful IVF treatments in the past and thus face a reduced chance of motherhood. The reported 71% live birth rate is notably high, indicating that the inclusion of complementary treatments may provide women with past IVF failures a tangible opportunity for achieving successful pregnancy and childbirth. However, these findings need to be confirmed through randomized controlled studies.

Mapping expectancy-based appetitive placebo effects onto the brain in women.

Suggestions about hunger can generate placebo effects on hunger experiences. But, the underlying neurocognitive mechanisms are unknown. Here, we show in 255 women that hunger expectancies, induced by suggestion-based placebo interventions, determine hunger sensations and economic food choices. Functional magnetic resonance imaging in a subgroup (n = 57/255) provides evidence that the strength of expecting the placebo to decrease hunger moderates medial prefrontal cortex activation at the time of food choice and attenuates ventromedial prefrontal cortex (vmPFC) responses to food value. Dorsolateral prefrontal cortex activation linked to interference resolution formally mediates the suggestion-based placebo effects on hunger. A drift-diffusion model characterizes this effect by showing that the hunger suggestions bias participants' food choices and how much they weigh tastiness against the healthiness of food, which further moderates vmPFC-dlPFC psychophysiological interactions when participants expect decreased hunger. Thus, suggestion-induced beliefs about hunger shape hunger addressing economic choices through cognitive regulation of value computation within the prefrontal cortex.

Placebo effects on nausea and motion sickness are resistant to experimentally-induced stress.

Nausea often occurs in stressful situations, such as chemotherapy or surgery. Clinically relevant placebo effects in nausea have been demonstrated, but it remains unclear whether stress has an impact on these effects. The aim of this experimental study was to investigate the interplay between acute stress and placebo effects in nausea. 80 healthy female volunteers susceptible to motion sickness were randomly assigned to either the Maastricht Acute Stress Test or a non-stress control condition, and to either placebo treatment or no treatment. Nausea was induced by a virtual vection drum and behavioral, psychophysiological as well as humoral parameters were repeatedly assessed. Manipulation checks confirmed increased cortisol levels and negative emotions in the stressed groups. In the non-stressed groups, the placebo intervention improved nausea, symptoms of motion sickness, and gastric myoelectrical activity (normo-to-tachy (NTT) ratio). In the stressed groups, the beneficial effects of the placebo intervention on nausea and motion sickness remained unchanged, whereas no improvement of the gastric NTT ratio was observed. Results suggest that placebo effects on symptoms of nausea and motion sickness are resistant to experimentally-induced stress. Stress most likely interfered with the validity of the gastric NTT ratio to measure nausea and thus the gastric placebo effect.

Exploring Pain, Quality of Life, and Emotional Well-Being in Patients with Advanced Pancreatic Cancer Practicing Spiritual Meditation: A Pilot Study.

INTRODUCTION: Studies on mind-body approaches in patients with advanced pancreatic ductal adenocarcinoma (PDAC) are rare. We performed a pilot study with follow-up until 1 year to explore changes in pain, quality of life (QoL), stress, and negative emotions in patients with advanced PDAC, who regularly practiced a standardized form of spiritual meditation in addition to standard medical care. METHODS: At baseline and every 2 months for a maximum of 1 year, global pain, QoL (global, SEIQoL, FACT-G), spiritual well-being (FACIT-Sp), perceived stress (PSQ-20), anxiety and depression (HADS), and diurnal cortisol secretion (cortisol slope) were assessed. Changes from baseline were explored by pairwise comparisons of available cases. RESULTS: Twenty participants (11 women, 62 ± 9.9 SD years) participated in the study, of whom 9 patients survived the study year. Pairwise comparisons revealed transient improvements of pain after 4 and 6 months (both p values < 0.05), of global QoL after 4, 6, 8, 10 months (all p values < 0.05), of SeiQoL scores after 4 months (p < 0.05), of FACT-G scores after 6 months (p < 0.05), and of FACIT-Sp scores after 2 and 6 months (both p values < 0.05). Furthermore, overall stress levels (PSQ-20) decreased from baseline to 2, 6, and 8 months (all p values < 0.05), and anxiety declined from baseline to 6 months (p < 0.05). Depression scores and the cortisol slope did not change. CONCLUSION: This pilot study demonstrated the acceptability and feasibility of studies on spiritual meditation in patients with advanced PDAC. Randomized controlled trials are warranted to study the effects of spiritual meditation and other mind-body interventions on pain, QoL, and emotional well-being in this patient population.Bislang gibt es kaum Studien zu Mind-Body-Ansätzen bei Patienten mit fortgeschrittenem duktalem Adenokarzinom der Bauchspeicheldrüse (PDAC). Wir führten eine explorative Pilotstudie mit einer einjährigen Nachbe- obachtungszeit durch, um Veränderungen von Schmerzen, Lebensqualität, Stress und negativen Emotionen bei Patienten mit fortgeschrittenem PDAC zu untersuchen, die zusätzlich zur medizinischen Standardversorgung regelmäßig eine standardisierte Form der spirituellen Meditation praktizierten.Zu Beginn der Studie und alle zwei Monate wurden über einen Zeitraum von maximal einem Jahr die globalen Schmerzen, die Lebensqualität (global, SEIQoL, FACT-G), das psychologische Wohlbefinden (FACIT-Sp), Stress (PSQ-20), Angst und Depression (HADS) sowie die circadiane Cortisolausschüttung (Cortisolabfall) untersucht. Die Änderungen gegenüber dem Ausgangswert wurden mit paarweisen Vergleichen der jeweils verfügbaren Fälle auf Signifikanz getestet.20 Patienten (11 Frauen, 62 ± 9.9 SD Jahre) nahmen an der Studie teil, von denen 9 das Studienjahr überlebten. Paarweise Vergleiche zeigten vorübergehende Verbesserungen der Schmerzen nach 4 und 6 Monaten (beide p-Werte < 0.05), der globalen Lebensqualität nach 4, 6, 8 und 10 Monaten (alle p-Werte < 0.05), der SeiQoL-Werte nach 4 Monaten (p < 0.05), der FACT-G-Werte nach 6 Monaten (p < 0.05) und der FACIT-Sp-Werte nach 2 und 6 Monaten (beide p-Werte < 0.05). Außerdem war der Gesamtstress (PSQ-20) nach 2, 6 und 8 Monaten (alle p-Werte < 0.05) sowie die Ängstlichkeit nach 6 Monaten (p < 0.05) signifikant gesunken. Die Depressionswerte und der circadiane Cortisolabfall änderten sich nicht.Diese Pilotstudie weist auf die Akzeptanz und Durchführbarkeit von Studien zu spiritueller Meditation bei Patienten mit fortgeschrittenem PDAC hin. Randomisierte kontrollierte Studie sollten folgen, um die Effekte von spiritueller Meditation und anderen Mind-Body-Interventionen auf Schmerzen, Lebensqualität und emotionales Wohlbefinden in dieser Patientengruppe zu untersuchen.

Changes in Subjective Time and Self during Meditation.

This study examined the effects of meditative states in experienced meditators on present-moment awareness, subjective time, and self-awareness while assessing meditation-induced changes in heart-rate variability and breathing rate. A sample of 22 experienced meditators who practiced meditation techniques stressing awareness of the present moment (average 20 years of practice) filled out subjective scales pertaining to sense of time and the bodily self and accomplished a metronome task as an operationalization of present-moment awareness before and after a 20 min meditation session (experimental condition) and a 20 min reading session (control condition) according to a within-subject design. A mixed pattern of increased sympathetic and parasympathetic activity was found during meditation regarding heart-rate measures. Breathing intervals were prolonged during meditation. Participants perceived their body boundaries as less salient during meditation than while reading the story; they also felt time passed more quickly and they paid less attention to time during meditation. No significant differences between conditions became apparent for the metronome task. This is probably the first quantitative study to show how the experience of time during a meditation session is altered together with the sense of the bodily self.

Central correlates of placebo effects in nausea differ between men and women.

INTRODUCTION: Despite growing evidence validating placebo effects in nausea, little is known about the underlying cortical mechanisms in women and men. Therefore, the present study examined sex differences and electroencephalography (EEG) characteristics of the placebo effect on nausea. METHODS: On 2 consecutive days, 90 healthy subjects (45 females) were exposed to a nauseating visual stimulus. Nausea was continuously rated on an 11-point numeric rating scale, and 32 EEG channels were recorded. On day 2, subjects were randomly allocated to either placebo treatment or no treatment: the placebo group received sham acupuncture, whereas the control group did not receive any intervention. RESULTS: In contrast to the control group, both sexes in the placebo group showed reduced signs for anticipatory nausea in the EEG, indexed by increased frontal lobe and anterior cingulate activity. Among women, the improvement in perceived nausea in the placebo group was accompanied by decreased activation in the parietal, frontal, and temporal lobes. In contrast, the placebo-related improvement of perceived nausea in men was accompanied by increased activation in the limbic and sublobar (insular) lobes. CONCLUSION: Activation of the parietal lobe in women during the placebo intervention may reflect altered afferent activity from gastric mechanoreceptors during nausea-induced tachyarrhythmia, whereas in men, altered interoceptive signals in the insular cortex might play a role. Thus, the results suggest different cerebral mechanisms underlying the placebo effects in men and women, which could have implications for the treatment of nausea.

Open-Label Placebo Administration Decreases Pain in Elderly Patients With Symptomatic Knee Osteoarthritis - A Randomized Controlled Trial.

Background: Recent studies indicate that the administration of open-label placebos (OLP) can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of OLP treatments on pain, functional disability, and mobility in patients with arthritic knee pain. Methods: Sixty patients (55% females; mean age, 66.9 ± 9.7 SD years) were randomized to one of two OLP treatments (n = 41) or no treatment (NT; n = 19). OLP treatments were accompanied by the verbal suggestion "to decrease pain" (OLP-pain, n = 20) or "to improve mood" (OLP-mood, n = 21). Pain and mood levels were monitored on 11-point Numeric Rating Scales (NRSs) in a patient diary, and global clinical improvement (CGI-I) was assessed at the end of the study. At baseline and after 21 days, patients filled in validated questionnaires to assess symptoms and functional disability of the knee (WOMAC), mental and physical quality of life (SF-36), state anxiety (STAI-state), perceived stress (PSQ-20), and self-efficacy (GSE). In addition, knee mobility (neutral zero-method), heart rate variability (HRV), and diurnal cortisol levels were evaluated before and after treatment. Results: Evaluation of daily pain ratings indicated significant pain decrease in the OLP groups compared to NT (p = 0.013, d = 0.64), with no difference between the OLP-pain and the OLP-mood groups (p = 0.856, d = 0.05). OLP treatment also improved WOMAC pain (p = 0.036, d = 0.55), again with no difference between the two OLP groups (p = 0.65, d = 0.17). WOMAC function and stiffness, knee mobility, stress, state anxiety, quality of life, and self-efficacy did not change differently between groups. Conclusion: OLP treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. OLP administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee OA. Trial Registration: German Clinical Trials Register (https://www.drks.de/), DRKS00015191 (retrospectively registered).

School start times and academic achievement - A systematic review on grades and test scores.

Early school times clash with the late sleep of adolescents, leading to wide-spread sleep restriction in students. Evidence suggests that delaying school starts is beneficial for sleep and recent studies investigated whether this also translates into improved academic achievement. We thus conducted a systematic review of the literature on school start times, grades and test scores in middle and high-school students. We reviewed 21 studies following the PRISMA guidelines and assessed the evidence quality using a pre-defined risk of bias tool. Nine studies reported no association of later starts with achievement, while the remaining reported mixed (5), positive (5), negative (1) or unclear (1) results. Considering the heterogeneity in academic outcomes, study types, amount of delay and exposure, and the substantial risk of bias, a meta-analysis was not warranted - instead we provide grouped reviews and discussion. Overall, no generalisable improvements in achievement with later starts emerge beyond the level of single studies. This does not necessarily preclude improvements in students' learning but highlights shortcomings of the literature and the challenges of using grades and test scores to operationalise academic achievement. Given other previously reported positive outcomes, our results suggest that schools could start later while achievement is likely maintained.

New species of the genus Spio (Annelida, Spionidae) from the southern and western coasts of Korea.

A new spionid polychaete, Spiopigmentata sp. nov., is described from the southern and western coasts of Korea. This new species differs from its congeners by the combination of the following morphological characteristics: the presence of orange-brown pigmentation on the anterior part of the prostomium, black pigmentation on the peristomium and along the body, U-shaped nuchal organs, a comparatively long extension of metameric dorsal ciliated organs, three pairs of white dots per chaetiger, two to three posterior abranchiate chaetigers, and the presence of tridentate neuropodial hooded hooks. The partial 16S ribosomal DNA (rDNA) and nuclear 18S rDNA sequences of the new species and Spio sp. 2 reported by Abe and Sato-Okoshi (2021) from Japan showed high similarity, indicating that these two specimens belong to the same species. A detailed description and illustrations of the new species, together with molecular information, are provided.

Shared Decision Making - A Key Competence of All Health Care Professionals. Evaluation and Adaptation of a Digitally Enhanced Learning and Teaching Unit.

The Covid-19 pandemic induced a radical shift towards digitally enhanced learning and teaching (DELT). Success of this adaptation depended on how much DELT had been provided before. The Bavarian Virtual University (BVU) is a university network to fund, promote and support DELT. The Ludwig-Maximilians-University Munich as a part of this network implemented the DELT course "Shared decision making (SDM) - a part of evidence-based medicine" in 2015. Based on regular evaluations and due to the latest developments, a media-didactic and content-related adaptation will be conducted now. Clinical cases will be embedded in a framework structure of SDM. Videos, podcasts and literature of doctor-patient interaction will be provided. To enable different health care professions to have a positive learning experience, the course will be linguistically adapted. The interaction between students and teacher will be enhanced by a transparent distribution of tasks and an issue-specific chat forum. SDM is an interdisciplinary general concept. With regard to the academization of different health care professions, the demand for DELT will increase. However, medical competencies can`t be taught fully online, since face-to-face patient interaction is mandatory. Communication skills can be practiced theoretically but have to be applied in reality.

Reduced frequency of perforin-positive CD8+ T cells in menstrual effluent of endometriosis patients.

Endometriosis is a widespread disease and commonly reduces the life quality of those affected. Scientific literature indicates different underlying immunological changes. Frequently examined tissues are peripheral blood, endometrial tissue and peritoneal fluid. Yet, knowledge on immunological differences in menstrual effluent (ME) is scarce. In this study, between January 2018 and August 2019, 12 women with endometriosis (rASRM classification: stages I-IV) and 11 healthy controls were included. ME was collected using menstrual cups and venous blood samples (PB) were taken. Mononuclear cells were obtained from ME (MMC) and PB (PBMC) and analyzed using flow cytometry. Concentrations of cell adhesion molecules (ICAM-I and VCAM-I) and cytokines (IL-6, IL-8 and TNF-α) were measured using ELISA. CD8 + T cells obtained from ME were significantly less often perforin-positive in women with endometriosis compared to healthy controls. A comparison between MMC and PBMC revealed that MMC contained significantly less T cells and more B cells. The CD4/CD8 ratio was significantly higher in MMC, and Tregs were significantly less frequently in MMC. In ME, T cells and NK cells expressed significantly more CD69. NK cells obtained from ME were predominantly CD56bright/CD16dim and had a lower frequency of perforin + cells compared to PBMC NK cells. Moreover, ICAM-1 plasma levels were significantly reduced in women with endometriosis compared to healthy controls. In conclusion, CD8 + T cells obtained from the ME were significantly less perforin-positive in endometriosis patients indicating a reduced cytotoxic potential. MMC are distinctively different from PBMC and, thus, seem to be of endometrial origin.

Annelids of the eastern Australian abyss collected by the 2017 RV 'Investigator' voyage.

In Australia, the deep-water (bathyal and abyssal) benthic invertebrate fauna is poorly known in comparison with that of shallow (subtidal and shelf) habitats. Benthic fauna from the deep eastern Australian margin was sampled systematically for the first time during 2017 RV 'Investigator' voyage 'Sampling the Abyss'. Box core, Brenke sledge, and beam trawl samples were collected at one-degree intervals from Tasmania, 42°S, to southern Queensland, 24°S, from 900 to 4800 m depth. Annelids collected were identified by taxonomic experts on individual families around the world. A complete list of all identified species is presented, accompanied with brief morphological diagnoses, taxonomic remarks, and colour images. A total of more than 6000 annelid specimens consisting of 50 families (47 Polychaeta, one Echiura, two Sipuncula) and 214 species were recovered. Twenty-seven species were given valid names, 45 were assigned the qualifier cf., 87 the qualifier sp., and 55 species were considered new to science. Geographical ranges of 16 morphospecies extended along the eastern Australian margin to the Great Australian Bight, South Australia; however, these ranges need to be confirmed with genetic data. This work providing critical baseline biodiversity data on an important group of benthic invertebrates from a virtually unknown region of the world's ocean will act as a springboard for future taxonomic and biogeographic studies in the area.

Nonpharmacological Interventions for Pediatric Migraine: A Network Meta-analysis.

CONTEXT: Migraine is a common neurologic disorder in children and adolescents. However, a comparison of multiple nonpharmacological treatments is lacking. OBJECTIVE: To examine whether nonpharmacological treatments are more effective than waiting list and whether there are differences between interventions regarding efficacy. DATA SOURCES: Systematic review and network meta-analysis of studies in Medline, Cochrane, Embase, and PsycINFO published through August 5, 2019. STUDY SELECTION: Randomized controlled trials of nonpharmacological treatments in children and adolescents diagnosed with episodic migraine. DATA EXTRACTION: Effect sizes, calculated as standardized mean differences (SMDs) for the primary outcome efficacy, were assessed in a random-effects model. RESULTS: Twelve studies (N = 576) were included. When interventions were classified into groups on the basis of similarity of treatment components, self-administered treatments, biofeedback, relaxation, psychological treatments, and psychological placebos were significantly more effective than waiting list with effect sizes ranging between SMD = 1.14 (95% confidence interval, 0.09 to 2.19) for long-term psychological placebos to SMD = 1.44 (95% confidence interval, 0.26 to 2.62) for short-term self-administered treatments. However, when all interventions were examined individually (ie, 1 node per intervention), none were significantly more effective compared with waiting list, mainly because of lack of statistical power. LIMITATIONS: Because of our focus on pediatric migraine, only a small number of studies could be included. CONCLUSIONS: Our findings reveal that components of nonpharmacological interventions are effective in treating pediatric migraine. Some effects have to be interpreted carefully because they are based on small studies. Future researchers should identify factors associated with individual responses in large, multicentered studies.

The Physical, Psychological, and Social Day-to-Day Experience of Women Living With Endometriosis Compared to Healthy Age-Matched Controls-A Mixed-Methods Study.

Background: Endometriosis is characterized by lesions of endometrial tissue outside the uterus. Chronic pain is considered as main symptom, but challenges can relate to various physical, mental, and social aspects of the women's lives. The aim of our study was to gain a holistic understanding of the everyday reality of women with endometriosis compared to healthy controls. Methods: The total sample comprised 12 hormone-free endometriosis patients (EP) and 11 age-matched healthy women (HC). A mixed-methods design was used comprising semi-structured interviews, standardized questionnaires and a comprehensive diary to assess pain ratings and various mental and physical symptoms over the course of a menstrual cycle. Interviews were recorded, transcribed, and evaluated according to phenomenological analysis using the MAXQDA software. Results: Interviews showed that living with endometriosis was associated with an impairment in everyday life. Physical strains, especially pain, high levels of psychological distress, and social limitations have been reported. Living with endometriosis affected the patients' personality and they "no longer felt like themselves." Physical and psychological symptoms were reported to interfere with social interaction and participation. Evaluation of the standardized questionnaires revealed significant impairments in EP compared to HC in regard to anxiety and depression scores (both p < 0.001; Hospital Anxiety and Depression Scale), mental and physical quality of life (both p < 0.001; Short-Form Health Survey-12), stress ratings (p < 0.001; Patient Health Questionnaire-15) and functional well-being (p < 0.001; Functional Well-being-7). The highest levels of mean pelvic pain and dyschezia were observed in EP during menstruation, but mean pain ratings and dyschezia were increased in EPs compared to HP during the whole cycle. EP reported mental symptoms (e.g., depressed mood or anxiety) mainly during menstruation, while HC did not show any mental symptoms during the cycle. In addition, physical symptoms were elevated during the entire cycle in EPs (all p < 0.01). Discussion: The mixed-methods approach enabled to interpret the interviews, the standardized questionnaires, and the symptom diary in a broader context of everyday life. The symptoms do not appear to act independently, but rather influence each other. This leads to a complex interplay of physical, mental, and social impairments, with pain often being the starting point.

What Should Clinicians Tell Patients about Placebo and Nocebo Effects? Practical Considerations Based on Expert Consensus.

INTRODUCTION: Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. OBJECTIVE: There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. METHODS: Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. RESULTS: There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. CONCLUSIONS: The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients' needs, and on developing standardized disclosure training modules for clinicians.

Molecular classification of the placebo effect in nausea.

In this proof-of-concept study, we tested whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 participants were exposed to a nauseating stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and (in females) gastric activity could be verified. Using label-free tandem mass spectrometry, 74 differentially regulated proteins were identified as correlates of the placebo effect. Gene ontology (GO) enrichment analyses identified acute-phase proteins and microinflammatory proteins to be involved, and the identified GO signatures predicted day-adjusted scores of nausea indices in the placebo group. We also performed GO enrichment analyses of specific plasma proteins predictable by the experimental factors or their interactions and identified 'grooming behavior' as a prominent hit. Finally, Receiver Operator Characteristics (ROC) allowed to identify plasma proteins differentiating placebo responders from non-responders, comprising immunoglobulins and proteins involved in oxidation reduction processes and complement activation. Plasma proteomics is a promising tool to identify molecular correlates and predictors of the placebo effect in humans.

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.

Importance: Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking. Objective: To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability. Data Sources: Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018. Study Selection: Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers. Data Extraction and Synthesis: Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model. Main Outcomes and Measures: Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason). Results: Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention. Conclusions and Relevance: Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.