Axion Paradigm with Color-Mediated Neutrino Masses.

We propose a generalized Kim-Shifman-Vainshtein-Zakharov-type axion framework in which colored fermions and scalars act as two-loop Majorana neutrino-mass mediators. The global Peccei-Quinn symmetry under which exotic fermions are charged solves the strong CP problem. Within our general proposal, various setups can be distinguished by probing the axion-to-photon coupling at helioscopes and haloscopes. We also comment on axion dark-matter production in the early Universe.

E-Health intervention for subthreshold depression: Reach and two-year effects of a randomized controlled trial.

BACKGROUND: There is evidence for e-Health interventions for full-blown depression. Little is known regarding commonly untreated subthreshold depression in primary care. This randomized controlled multi-centre trial assessed reach and two-year-effects of a proactive e-Health intervention (ActiLife) for patients with subthreshold depression. METHODS: Primary care and hospital patients were screened for subthreshold depression. Over 6 months, ActiLife participants received three individualized feedback letters and weekly messages promoting self-help strategies against depression, e.g., dealing with unhelpful thoughts or behavioural activation. The primary outcome depressive symptom severity (Patient Health Questionnaire;PHQ-8) and secondary outcomes were assessed 6, 12 and 24 months. RESULTS: Of those invited, n = 618(49.2 %) agreed to participate. Of them, 456 completed the baseline interview and were randomized to ActiLife (n = 227) or assessment only (n = 226). Generalised estimation equation analyses adjusting for site, setting and baseline depression revealed that depressive symptom severity declined over time, with no significant group differences at 6 (mean difference = 0.47 points; d = 0.12) and 24 months (mean difference = -0.05 points; d = -0.01). Potential adverse effects were observed at 12 months, with higher depressive symptom severity for ActiLife than control participants (mean difference = 1.33 points; d = 0.35). No significant differences in rates of reliable deterioration or reliable improvement of depressive symptoms were observed. ActiLife increased applied self-help strategies at 6 (mean difference = 0.32; d = 0.27) and 24 months (mean difference = 0.22; d = 0.19), but not at 12 months (mean difference = 0.18; d = 0.15). LIMITATIONS: Self-report measures and lack of information on patients' mental health treatment. DISCUSSION: ActiLife yielded satisfactory reach and increased the use of self-help strategies. Data were inconclusive in terms of depressive symptom changes.

Multimodal Assessment of Smoking cue Reactivity During a Smoking Cue Exposure Task.

Background. Cue-reactivity as a characteristic symptom of substance use disorders (SUD) is highly context dependent. Paradigms with high context validity need to be established for the investigation of underlying neurobiological mechanisms. While craving can be assessed by self-report as one aspect of cue-reactivity (CR), the assessment of biological measures such as the autonomous response and EEG promises a holistic perspective including CR at an automatized level. In a multimodal approach, smoking cue exposure (CE) effects on heart rate variability (HRV), EEG frequency power, and craving as well as their interrelation were assessed. This pilot study focused on the validity of CR measurements in a naturalistic CE paradigm. Methods. EEG frequency power, HRV, and craving were assessed during resting state (RS) and smoking CE in smokers (n = 14) and nonsmoking controls (n = 10) to investigate the psychophysiological and subjective reactions to CE. Results. Increased beta power was found only in smokers during CE compared to the control condition. There was an inverse correlation of beta power and maximum craving. Likewise, HRV correlated negatively with maximum smoking urges in smokers immediately after the measurements, without differentiation between CE and control condition. Conclusion. The increased beta power in smokers during CE is discussed as increased inhibitory control related to reduced craving in smokers. Furthermore, increased craving during CE seems to be associated to decreased vagal activity. The multimodal measurements during the CE showed ecological validity to be fundamental for CE assessment in clinical populations to evaluate its predictive value.

Use of office based transnasal oesophagoscopy in management of Head & Neck conditions during the COVID-19 pandemic at the Royal Albert Edward Infirmary, Wigan, United Kingdom.

OBJECTIVES: To assess the clinical and cost effectiveness of transnasal oesophagoscopy (TNO) in cases of suspected upper aerodigestive tract malignancy and define its role as a safe alternative to panendoscopy. We have also analysed if the implementation of TNO during the COVID-19 pandemic was beneficial in order to provide uninterrupted care to the patients with the limited resources available in these challenging times. METHODS: All patients who underwent TNO guided biopsies or dilatation attempted over a 7 month period during COVID- 19 pandemic were included by searching the hospital and department database at The Royal Albert Edward Infirmary. A comparative group of patients who underwent panendoscopy over 9 months were included for comparison. Demographic data, histological diagnosis, second procedure and cost involved were recorded. RESULTS: During this period, 20 TNO procedures (16 biopsies and 4 dilatations) were attempted which were compared with 20 panendoscopy procedures. The diagnostic accuracy of TNO biopsy for identifying benign and malignant pathology was 81.1%. The sensitivity and specificity for identifying malignancy was 76.9% and 100% respectively. The most common lesion location was laryngeal (43.8%) followed by oropharyngeal (37.5%), more specifically located at the tongue base. The median waiting period between the procedure being listed and TNO being performed was 5.5 days compared to 12 days for panendoscopy. There were 12/16 patients who did not require further interventions for histological diagnosis of the tumor. The TNO procedure was well tolerated with no complications and all were done under local anaesthesia as outpatient procedure without need for admission. TNO resulted in cost saving of £356 per case on a standard NHS tariff. CONCLUSION: TNO is a valuable diagnostic tool for patients with suspected UADT malignancy and dysphagia and has proven to be an asset during the COVID-19 pandemic when we have to make the best use of the limited theatre time and resources. Also, the cost analysis showed that outpatient based TNO can provide significant cost savings for the current standard of care. Furthermore, it has shown better patient tolerability, lesser complications and shortened the time for diagnosis and hence starting timely treatment for these patients.

Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. METHODS: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. RESULTS: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09). CONCLUSION: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

Role of real-world evidence in informing cancer care: lessons from colorectal cancer.

The term "real-world evidence" (rwe) describes the analysis of data that are collected beyond the context of clinical trials. The use and application of rwe have become increasingly common and relevant, especially in oncology, because there is growing recognition that randomized controlled trials (rcts) might not be sufficiently representative of the entire patient population that is affected by cancer, and that specific clinical research questions might be best addressed by real-world data. In this brief review, our main aim is to highlight the role of rwe in informing cancer care, particularly focusing on specific examples from colorectal cancer. Our hope is to illustrate the ways in which rwe can complement rcts in improving the understanding of cancer management and how rwe can facilitate cancer treatment decisions for real-world patients encountered in routine clinical care.

[On the legalization debate of non-medical cannabis consumption : Position paper of the German Association for Psychiatry, Psychotherapy and Psychosomatics]. / Zur Legalisierungsdebatte des nichtmedizinischen Cannabiskonsums : DGPPN-Positionspapier.

Calls are increasing for the legalization of cannabis. Some legal experts, various politicians, political parties and associations are demanding a change in drug policy. The legalization debate is lively and receiving wide coverage in the media. The German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) comments on the most important questions from a medical scientific perspective: can cannabis consumption trigger mental illnesses, what consequences would legalization have for the healthcare system and where is more research needed?

[Barriers to Addressing Pregnant Patients' Cigarette and Alcohol Use: A Focus Group Study with Gynecologists]. / Barrieren in der Thematisierung des Tabak- und Alkoholkonsums Schwangerer in der gynäkologischen Praxis. Eine Fokusgruppenstudie mit Frauenärzten.

Objectives/Purpose: Alcohol drinking and tobacco smoking pose high health risks for the unborn child. Even though routine testing during the course of pregnancy facilitates early intervention, addressing substance use in pregnancy seems to be more difficult. The aim of the study was to identify barriers to addressing pregnant patients' cigarette and alcohol use. Methods: 2 focus groups (in total N=10 participants) were conducted with gynaecologists. The transcripts of the discussions were analysed using Mayring's approach of qualitative text analysis. Results: Avoidance of addressing substance abuse directly, the social and educational background of patients influencing the communication in this matter and the physicians' ambivalence about their limits of responsibility were barriers often mentioned by the participants. Conclusion: In view of the several structural and individual barriers among gynaecologists identified in this study, gynaecologists obviously cannot be the only health professionals taking responsibility for coping with substance abuse among pregnant women. Strategies should be designed, e. g., to standardise the identification, counselling and referral process. Physicians should receive more support in improving their competences, and effective low-threshold treatment programmes for the women affected are required.

IRIS - An Internet Based Intervention as a Suitable Path to Addictive Substance Use Prevention and Counselling in Pregnancy? Beneficiary Profiles and User Satisfaction.

Alcohol or tobacco consumption in pregnancy can harm the unborn child. Counselling on this subject is therefore of major importance. The aim of the presented study was not only to develop an internet based, professionally e-mail accompanied platform for alcohol or tobacco consuming pregnant women ("IRIS Platform") but also to analyse the beneficiary profiles and investigate the practicability and acceptance of the platform among women and referring gynaecologists. The offer comprised three 12-week counselling programmes (alcohol, tobacco, combined consumption). Altogether 32 women registered within the recruitment period of 20 weeks, only 9 of them at the suggestion of gynaecologists. Thirty were enrolled. The average age was 31 years. Ten women were pregnant for the first time, 14 unplanned. Most of them were smokers (n = 29). 75 % (n = 12 of 16) of them had smoked in the previous pregnancies, 5 of 16 women had suffered miscarriages. Six women completed the entire 12 week programme. The abstinence rate after 3 months was min. 18.5 % (ITT) in the tobacco group, while in the alcohol programme 3 women achieved abstinence. Satisfaction was reported especially for the eCoach initiative. The results demonstrate that an internet-based service like IRIS can be a useful form of support for tobacco or alcohol consuming pregnant women. A particular challenge is the accessibility of the persons concerned and the form in which alcohol consuming pregnant women are approached in daily medical practice. The individual contact to the eCoach can be a decisive form of support and aid to motivation.

Effects of transcranial direct current stimulation on craving, heart-rate variability and prefrontal hemodynamics during smoking cue exposure.

OBJECTIVE: Drug-related cue exposure elicits craving and risk for relapse during recovery. Transcranial direct current stimulation is a promising research tool and possible treatment for relapse prevention. Enhanced functional neuroconnectivity is discussed as a treatment target. The goal of this research was to examine whether transcranial direct current stimulation affected cortical hemodynamic indicators of functional connectivity, craving, and heart rate variability during smoking-related cue exposure in non-treatment-seeking smokers. METHOD: In vivo smoking cue exposure supported by a 2mA transcranial direct current stimulation (anode: dorsolateral prefrontal cortex, cathode: orbitofrontal cortex; placebo-controlled, randomized, double-blind) in 29 (age: M=25, SD=5) German university students (smoking at least once a week). Cue reactivity was assessed on an autonomous (heart rate variability) and a subjective level (craving ratings). Functional near-infrared spectroscopy measured changes in the concentration of deoxygenated hemoglobin, and seed-based correlation analysis was used to quantify prefrontal connectivity of brain regions involved in cue reactivity. RESULTS: Cue exposure elicited increased subjective craving and heart rate variability changes in smokers. Connectivity between the orbitofrontal and dorsolateral prefrontal cortex was increased in subjects receiving verum compared to placebo stimulation (d=0.66). Hemodynamics in the left dorsolateral prefrontal cortex, however, increased in the group receiving sham stimulation (η2=0.140). Transcranial direct current stimulation did not significantly alter craving or heart rate variability during cue exposure. CONCLUSION: Prefrontal connectivity - between regions involved in the processing of reinforcement value and cognitive control - was increased by anodal transcranial direct current stimulation during smoking cue exposure. Possible clinical implications should be considered in future studies.

Nutritional perspectives of children with Crohn's disease: a single-centre cohort observation of disease activity, energy expenditure and dietary intake.

BACKGROUND/OBJECTIVES: Children with Crohn's disease often demonstrate nutritional recovery during primary therapy at diagnosis, but long-term nutritional support is sometimes necessary. Evidence to inform best nutritional practice including energy and micronutrient requirements is limited. The principal objective of this study was to determine how energy expenditure and physical activity vary with disease activity over the first year following diagnosis. SUBJECTS/METHODS: Twenty children were studied at diagnosis with Crohn's disease and were followed up over 1 year while receiving treatment according to national guidelines. The majority of children (13) were treated with exclusive enteral nutrition. At study visits, height, weight, bioelectrical impedance, resting energy expenditure by indirect calorimetry, tri-axial accelerometer and blood investigations were performed alongside clinical assessment. RESULTS: There was no significant effect of disease activity on resting energy expenditure (REE). Physical activity was greater after primary therapy (Z=3.31, P<0.01). Median wPCDAI fell from 58 at diagnosis to 7.5 after primary therapy and was 7.5 at 1 year. Weight s.d.s increased from -1.67 to -0.86 and lean index s.d.s increased from -2.93 to -1.64, although the increase was mostly in the first 2 months. Median height s.d.s was unchanged throughout this study. There was a significant association between dietary intake and weight gain (r=0.8 P<0.01) but not height gain. Persistent micronutrient deficits beyond diagnosis were seen for both iron and vitamin D. CONCLUSIONS: This study has demonstrated that REE does not change significantly through different phases of disease activity, but physical activity is low at diagnosis. Children with Crohn's disease should be screened for deficiencies of iron and vitamin D.

[Normative definition of staff requirement for a guideline-adherent inpatient qualified detoxification treatment in alcohol dependence]. / Personalbedarfsermittlung für eine leitliniengerechte stationäre Qualifizierte Entzugsbehandlung bei Alkoholabhängigkeit.

The central element of the "qualified withdrawal treatment" of alcohol dependence is - in addition to physical withdrawal treatment - psychotherapy. The treatment of the underlying addictive disorder that is displayed by intoxication, harmful behaviour and withdrawal symptoms is only possible with a combination of somatic and psychotherapeutic treatment elements. The successfully established multimodal therapy of the "qualified alcohol withdrawal treatment", postulated in the current S3-Treatment Guidelines, requires a multi-disciplinary treatment team with psychotherapeutic competence. The aim of the present work is to calculate the normative staff requirement of a guideline-based 21-day qualified withdrawal treatment and to compare the result with the staffing regulations of the German Institute for Hospital Reimbursement. The present data support the hypothesis that even in the case of a hundred per cent implementation of these data, adequate therapy of alcohol-related disorders, according to the guidelines, is not feasible. This has to be considered when further developing the finance compensation system based on the described superseded elements of the German Institute for Hospital Reimbursement.

Long-term visual outcomes in intraocular retinoblastoma with eye preservation.

PURPOSE: Inconsistent data exist on long-term visual outcomes in survivors of retinoblastoma. No studies have been reported on role of ocular coherence tomography (OCT) in predicting visual acuity. We assessed visual acuity in patients with retinoblastoma treated at our center in whom affected eyes were preserved. METHODS: Patients who had completed a 2-year follow-up and were more than 5 years of age at assessment were included. Clinical data were obtained from database and factors predicting visual acuity were analyzed. OCT was performed in these patients to assess central macular thickness (CMT). RESULTS: Visual outcomes were assessed in 45 eyes of 43 patients, of which 38 (88 %) had bilateral retinoblastoma. The median age at diagnosis was 12 months. Sixty percent (27/45) had International classification of retinoblastoma group C or D disease with 40 % eyes showing macular lesions. The far visual acuity was better than 6/12 in 53 % (24/45), 6/12 to 6/60 in 40 % (18/45) and 6/60 in 7 % (6/60). Macular location and International classification of retinoblastoma predicted poor vision (p = 0.06 and 0.07, respectively). CMT was less than 200 µm in 3 of 36 eyes (8 %) and 1 eye showed epiretinal membrane. Radiotherapy was associated with foveal thinning (p = 0.003). Two of 3 eyes with foveal thinning had a vision of 6/60. CONCLUSIONS: Good visual outcomes were observed in half of retinoblastoma patients treated with eye preservation. Macular location and International classification of retinoblastoma group C and D predicted poor visual acuity, while previous radiotherapy predicted foveal thinning, which was associated with poor visual acuity.

[Psychiatric comorbidities with tobacco-related disorders]. / Psychiatrische Komorbiditäten bei tabakbedingten Störungen.

The coincidence of tobacco smoking and psychiatric disorders is of great epidemiological and therapeutic importance. Tobacco smoking by people with mental disorders leads to disproportionately high somatic health risks, an adverse clinical course, poorer clinical outcomes and reduced quality of life (QoL). The etiological causes of the high comorbidity between smoking and mental disorders are still unclear: currently, tobacco smoking is discussed as being either the consequence or contributory cause of psychological disorders or both disorders share common antecedents and interactions. Psychiatric patients are motivated to quit and smoking cessation is not generally less effective with smokers with mental disorders than with mentally healthy individuals. Specific smoking cessation programs in the inpatient and outpatient settings are time-consuming and complex but effective. Within the framework of the current S3 guidelines the international evidence has been updated and transformed into treatment guidelines following an elaborate consensus process. Basically the same interventional measures should be used as with mentally healthy individuals; however, smokers with a psychological comorbidity often need more intensive adjuvant psychotherapeutic interventions and often need pharmaceutical support, (bupropion, varenicline and nicotine replacement therapy). Due to the overall unsatisfactory findings the treatment guidelines are partially based on clinical consensus decisions. In this field, a considerable need for research has been determined.

Short stature in retinoblastoma survivors: a cross-sectional study of 138 patients.

PURPOSE: Short stature has been reported in pediatric cancer survivors. Data on retinoblastoma survivors are limited. We conducted a cross-sectional study to assess the height in retinoblastoma survivors. METHOD: The recorded height was compared with median height for age and sex as per the Indian Academy of Pediatrics. Z-score less than -2 was considered short statured. RESULT: Thirty percent of the survivors were short statured. The mean height was shorter than the mean 50th percentile height (119.7 ± 14.8 vs 128.7 ± 15 cm, p < 0.001). Previous chemotherapy showed a trend toward association (p = 0.09). CONCLUSION: Short stature affects a significant number of retinoblastoma survivors.

[Psychotherapy and pharmacotherapy for harmful tobacco use and tobacco dependency]. / Psycho- und Pharmakotherapie bei schädlichem Tabakgebrauch und -abhängigkeit.

Tobacco consumption is one of the major preventable health risk factors. In Germany approximately 110,000 people prematurely die from tobacco-related diseases and approximately 50% of regular smokers are considered to be tobacco dependent. Nevertheless, motivation to quit smoking is low and the long-term abstinence rates after attempts to stop smoking without professional support are far below 10%. As part of the S3 treatment guidelines 78 recommendations for motivation and early interventions for smokers unwilling to quit as well as psychotherapeutic and pharmacological support for smokers willing to quit were formulated after an systematic search of the current literature. More than 50 professional associations adopted the recommendations and background information in a complex certification process. In this article the scientific evidence base regarding the psychotherapeutic and pharmacological treatment options as well as recommendations and further information about indications and treatment implementation are presented. By following these guidelines for treatment of heavy smokers who are willing to quit combined with individual and group therapies on the basis of behavioral treatment strategies and pharmacological support, long-term success rates of almost 30% can be achieved.

[Methodology of the S3 guidelines on alcohol and tobacco-related disorders]. / Methodik der S3-Leitlinien für alkohol- und tabakbezogene Störungen.

BACKGROUND: From 2010 until 2015 two interdisciplinary evidence-based guidelines were developed to summarize the current knowledge regarding screening, diagnostics and treatment of alcohol and tobacco-related disorders. METHODS: Both guidelines were prepared under the auspices of the German Society for Psychiatry, Psychotherapy and Psychosomatics (Deutsche Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde, DGPPN) and the German Society for Addiction Research and Therapy (Deutsche Gesellschaft für Suchtforschung und -therapie, DG-Sucht). To meet the methodological criteria for the highest quality guidelines (S3 criteria) as defined by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) the following criteria were realized: (1) a systematic search, selection and appraisal of the international literature, (2) a structured process to reach consensus and (3) inclusion of all relevant representatives of future guideline users. RESULTS: More than 60 clinical experts and researchers analyzed the scientific literature. In total 41 international and national guidelines (23 for alcohol and 18 for tobacco) were used. Moreover, 83 systematic Cochrane reviews (alcohol 28, tobacco 55) and 5863 articles (alcohol 2213, tobacco 3650) were analyzed. A total of 7 expert groups formulated 174 recommendations for the screening, diagnosis and treatment of alcohol-related disorders. Six expert groups created 81 recommendations for the screening, diagnosis and treatment of tobacco-related disorders. Approximately 50 scientific associations, professional organizations, patient and family initiatives, as well as representatives of the healthcare system formed a consensus group. In seven 1 and 2-day conferences, all clinical recommendations were discussed and approved by this group. Both guidelines will be revised on a regular basis to guarantee that the clinical recommendations are kept up to date. CONCLUSIONS: Both systematically developed, evidence-based treatment guidelines are comprehensive instruments to provide orientation and assist the decision-making process for physicians, psychologists and other therapists as well as patients and their families in the diagnosis and treatment of alcohol and tobacco use related disorders.