Evaluation of the noradrenergic system in Parkinson's disease: an 11C-MeNER PET and neuromelanin MRI study.

Pathological involvement of the noradrenergic locus coeruleus occurs early in Parkinson's disease, and widespread noradrenaline reductions are found at post-mortem. Rapid eye movement sleep behaviour disorder (RBD) accompanies Parkinson's disease and its presence predicts an unfavourable disease course with a higher propensity to cognitive impairment and orthostatic hypotension. MRI can detect neuromelanin in the locus coeruleus while 11C-MeNER PET is a marker of noradrenaline transporter availability. Here, we use both imaging modalities to study the association of RBD, cognition and autonomic dysfunction in Parkinson's disease with loss of noradrenergic function. Thirty non-demented Parkinson's disease patients [16 patients with RBD and 14 without RBD, comparable across age (66.6 ± 6.7 years), sex (22 males), and disease stage (Hoehn and Yahr, 2.3 ± 0.5)], had imaging of the locus coeruleus with neuromelanin sensitive MRI and brain noradrenaline transporter availability with 11C-MeNER PET. RBD was confirmed with polysomnography; cognitive function was assessed with a neuropsychological test battery, and blood pressure changes on tilting were documented; results were compared to 12 matched control subjects. We found that Parkinson's disease patients with RBD showed decreased locus coeruleus neuromelanin signal on MRI (P < 0.001) and widespread reduced binding of 11C-MeNER (P < 0.001), which correlated with amount of REM sleep without atonia. Parkinson's disease with RBD was also associated with a higher incidence of cognitive impairment, slowed EEG activity, and orthostatic hypotension. Reduced 11C-MeNER binding correlated with EEG slowing, cognitive performance, and orthostatic hypotension. In conclusion, reduced noradrenergic function in Parkinson's disease was linked to the presence of RBD and associated with cognitive deterioration and orthostatic hypotension. Noradrenergic impairment may contribute to the high prevalence of these non-motor symptoms in Parkinson's disease, and may be of relevance when treating these conditions in Parkinson's disease.

Decreased noradrenaline transporter density in the motor cortex of Parkinson's disease patients.

Reduced noradrenaline levels have been reported to occur in the motor cortices of PD patients postmortem. Imaging techniques have recently become available to specifically study noradrenergic terminal function in vivo using PET. The objective of this study was to evaluate cortical 11 C-MeNER binding in PD patients. Thirty PD patients and 12 healthy control subjects comparable in age, sex, and cognitive performance underwent PET imaging with 11 C-MeNER, a specific ligand of the noradrenaline transporter. Cortical noradrenaline transporter binding was compared at a voxel level using Statistical Parametric Mapping, whereas cortical thickness was assessed using FreeSurfer software with MRI. PD patients showed reduced 11 C-MeNER binding in the primary motor cortex unrelated to cortical thickness; other cortical regions did not differ between groups. In a subgroup analysis, patients with higher Hoehn & Yahr stage exhibited more pronounced 11 C-MeNER binding reductions. Loss of cortical noradrenergic projections to the primary motor cortex occurs in PD associated with disease stage. © 2018 International Parkinson and Movement Disorder Society.

The effect of expressive writing intervention for infertile couples: a randomized controlled trial.

STUDY QUESTION: Is expressive writing intervention (EWI) efficacious in reducing distress and improving pregnancy rates for couples going through ART treatment? SUMMARY ANSWER: Compared to controls, EWI statistically significantly reduced depressive symptoms but not anxiety and infertility-related distress. WHAT IS KNOWN ALREADY: ART treatment is considered stressful. So far, various psychological interventions have been tested for their potential in reducing infertility-related distress and the results are generally positive. It remains unclear whether EWI, a brief and potentially cost-effective intervention, could be advantageous. STUDY DESIGN SIZE, DURATION: Between November 2010 and July 2012, a total of 295 participants (163 women, 132 men) were randomly allocated to EWI or a neutral writing control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were couples undergoing IVF/ICSI treatment. Single women and couples with Preimplantation Genetic Diagnosis or acute change of procedure from insemination to IVF, were excluded. EWI participants participated in three 20-min home-based writing exercises focusing on emotional disclosure in relation to infertility/fertility treatment (two sessions) and benefit finding (one session). Controls wrote non-emotionally in three 20-min sessions about their daily activities. The participants completed questionnaires at the beginning of treatment (t1), prior to the pregnancy test (t2), and 3 months later (t3). In total, 26.8% (79/295) were lost to follow-up. Mixed linear models were chosen to compare the two groups over time for psychological outcomes (depression, anxiety and infertility-related distress), and a Chi2 test was employed in order to examine group differences in pregnancy rates MAIN RESULTS AND THE ROLE OF CHANCE: One hundred and fifty-three participants received EWI (women = 83; men = 70) and 142 participants were allocated to the neutral writing control group (women = 83; men = 62). Both women and partners in the EWI group exhibited greater reductions in depressive symptoms compared with controls (P = 0.049; [CI 95%: -0.04; -0.01] Cohen's d = 0.27). The effect of EWI on anxiety did not reach statistical significance. Overall infertility-related distress increased marginally for the partners in the EWI group compared to the partners in the control group (P = 0.06; Cohen's d = 0.17). However, in relation to the personal subdomain, the increase was statistically significant (P = 0.01; Cohen's d = 0.24). EWI had no statistically significant effect on pregnancy rates with 42/83 (50.6%) achieving pregnancy in the EWI group compared with 40/80 (49.4%) in the control group (RR = 0.99 [CI 95% = 0.725, 1.341]; P = 0.94). LIMITATIONS, REASONS FOR CAUTION: The results for depressive symptoms corresponded to a small effect size and the remaining results failed to reach statistical significance. This could be due to sample characteristics leading to a possible floor-effect, as we did not exclude participants with low levels of emotional distress at baseline. Furthermore, men showed increased infertility-related distress over time. WIDER IMPLICATIONS OF THE FINDINGS: EWI is a potentially cost-effective and easy to implement home-based intervention, and even small effects may be relevant. When faced with infertility, EWI could thus be a relevant tool for alleviating depressive symptoms by allowing the expression of feelings about infertility that may be perceived as socially unacceptable. However, the implications do not seem to be applicable for men, who presented with increased infertility-related distress over time. STUDY FUNDING/COMPETING INTERESTS: The present study was supported by research grants from Merck Sharpe and Dohme and The Danish Agency for Science Technology and Innovation as part of a publicly funded PhD. The funding bodies had no influence on the data collection, analysis or conclusions of the study. None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, trial no. NCT01187095. TRIAL REGISTRATION DATE: 7th September 2010 DATE OF FIRST PATIENT'S ENROLMENT: 23rd November 2010.

Optimising psychological treatment for pain after breast cancer: a factorial design study protocol in Denmark.

INTRODUCTION: One in five breast cancer (BC) survivors are affected by persistent pain years after completing primary treatment. While the efficacy of psychological interventions for BC-related pain has been documented in several meta-analyses, reported effect sizes are generally modest, pointing to a need for optimisation. Guided by the Multiphase Optimization Strategy, the present study aims to optimise psychological treatment for BC-related pain by identifying active treatment components in a full factorial design. METHODS AND ANALYSIS: The study uses a 2×3 factorial design, randomising 192 women with BC-related pain (18-75 years) to eight experimental conditions. The eight conditions consist of three contemporary cognitive-behavioural therapy components, namely: (1) mindful attention, (2) decentring, and (3) values and committed action. Each component is delivered in two sessions, and each participant will receive either zero, two, four or six sessions. Participants receiving two or three treatment components will be randomised to receive them in varying order. Assessments will be conducted at baseline (T1), session by session, every day for 6 days following the first session in each treatment component, at post-intervention (T2) and at 12-week follow-up (T3). Primary outcomes are pain intensity (Numerical Rating Scale) and pain interference (Brief Pain Inventory interference subscale) from T1 to T2. Secondary outcomes are pain burden, pain quality, pain frequency, pain catastrophising, psychological distress, well-being and fear of cancer recurrence. Possible mediators include mindful attention, decentring, and pain acceptance and activity engagement. Possible moderators are treatment expectancy, treatment adherence, satisfaction with treatment and therapeutic alliance. ETHICS AND DISSEMINATION: Ethical approval for the present study was received from the Central Denmark Region Committee on Health Research Ethics (no: 1-10-72-309-40). Findings will be made available to the study funders, care providers, patient organisations and other researchers at international conferences, and published in international, peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05444101).

Sexual Health in COPD: A Systematic Review and Meta-Analysis.

COPD has a profound impact on the lives of patients and their partners, but the influence on physical, psychological and social aspects of sexual health has not been reviewed systematically. Searches for studies of the impact of COPD on sexual health were conducted independently by two authors in the databases of PubMed, PsycINFO, Embases, CINAHL, Web of Science, Scopus and The Cochrane Library. English-language quantitative and qualitative studies assessing one or more aspects of sexual health in patients diagnosed with COPD were narratively reviewed and, when possible, subjected to meta-analytic evaluation. A total of 31 studies, including 4 qualitative, were included. Twelve studies assessing erectile dysfunction with the International Index of Erectile Function were subjected to meta-analysis. The pooled prevalence of erectile dysfunction was 74% (95% CI: 68-80%) in a total of 1187 patients with COPD, compared with 56% (37-73%) in 224 age-matched, non-COPD controls. The sexual health outcomes assessed in the remaining studies varied considerably, compromising the comparability of the results. None of the qualitative studies had sexual health as their primary focus. Compared with non-COPD individuals, erectile dysfunction appears to be more prevalent among patients with COPD, but more studies including non-COPD controls are needed to confirm this finding. In addition, the impact of COPD on other physical, psychological and social aspects of sexual health remains unclear due to the lack of comparable assessment methods and study designs.

Sleep, psychological distress, and clinical pregnancy outcome in women and their partners undergoing in vitro or intracytoplasmic sperm injection fertility treatment.

OBJECTIVES: To explore the prevalence of poor sleep quality in couples undergoing fertility treatment and study possible associations. PARTICIPANTS: 163 women and 132 partners receiving in vitro (IVF) or intracytoplasmic sperm injection (ICSI) fertility treatment. SETTING: Three public Danish fertility clinics. DESIGN AND MEASUREMENTS: Participants completed the Pittsburgh Sleep Quality Index (PSQI) at three time-points as part of a larger RCT. Additional data from patient records and questionnaires were included to evaluate possible associations with treatment protocol type, psychological distress, and pregnancy outcome. RESULTS: Mean PSQI global scores before treatment were 8.1 (standard deviation = 2.3), with 91% of participants having PSQI scores > 5, indicating poor sleep quality. Scores did not differ between women and their partners and did not change during treatment. Statistically significant associations were found between sleep quality and depressive symptoms and state anxiety (p < .001). No difference in PSQI scores was found between protocol types. While there was a trend towards higher clinical pregnancy rates among women with good sleep quality (PSQI ≤ 5 = 72.7%, PSQI 6-10 = 52.6% and PSQI ≥ 11 = 42.3%), the differences did not reach statistical significance (p = .10-.21). CONCLUSIONS: Poor sleep quality is a prevalent problem among couples undergoing fertility treatment and is associated with psychological distress and possibly with pregnancy outcomes. Success rates after fertility treatment remain moderate, and poor sleep quality, a potentially modifiable factor, could be relevant to screen for and treat among couples undergoing fertility treatment. The high prevalence of poor sleep quality calls for further investigation.

The association between psychosocial interventions and fertility treatment outcome: A systematic review and meta-analysis.

OBJECTIVE: Does psychosocial intervention affect pregnancy outcomes in women and couples undergoing assisted reproductive technology (ART) treatment?. DESIGN: A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) evaluating the efficacy of psychosocial intervention on pregnancy outcomes in women and couples undergoing ART treatment. The primary outcome was Pregnancy Rates. Secondary outcomes were Live Birth Rate (LBR) and Abortion Rate (AR). MATERIALS AND METHODS: Databases searched were Pubmed, PsycINFO, Embase, CINAHL and The Cochrane Library. 1439 records were screened, 15 were eligible and included in the meta-analyses (N = 2434). Data was extracted using the Covidence software. Effect sizes were reported as relative risks with 95% confidence-intervals and p-values. RESULTS: A positive association was found between psychosocial intervention and pregnancy rates (RR = 1.12 CI=(1.01;1.24), p = 0.033). Long-duration interventions and mind-body intervention types were found to be associated with increased pregnancy rates (RR 1.21, CI= (1.04;1.43), p = 0.017) and (RR = 1.25, CI= (1.00;1.55), p = 0.046) respectively. Q and I2tests suggested no to low heterogeneity. Funnel plots, Trim and Fill analyses and Fail-safe numbers were applied to adjust for possible publication bias. CONCLUSIONS: Our findings suggest a positive association between psychosocial interventions, particularly long-duration interventions, and pregnancy rate in infertile women and couples in ART treatment. The findings are in line with findings from other reviews and meta-analyses exploring the same topic. More good quality RCTs need to be performed to increase the quality of guidance for infertile women and couples. The effect of psychosocial interventions on LBR and AR remain to be examined.

Associations of bedtime, sleep duration, and sleep quality with semen quality in males seeking fertility treatment: a preliminary study.

BACKGROUND: Poor sleep has been linked to a number of adverse health outcomes. Recent studies suggest that late bedtimes, short or long sleep durations, and poor sleep quality may impair semen quality. No study has previously explored all three factors in relation to semen quality. RESULTS: One hundred and four men and their partners treated at three fertility clinics in Denmark between 2010 and 2012 completed an online-version of the Pittsburgh Sleep Quality Index (PSQI). The results of the semen analyses conducted at the fertility clinics were self-reported and categorised as normal or reduced.Early bedtime (< 10:30 PM) was more often associated with normal semen quality compared with both regular (10:30 PM-11:29 PM) and late (≥11:30 PM) bedtime (OR: 2.75, 95%CI: 1.1-7.1, p = 0.04 and OR: 3.97, 95%CI: 1.2-13.5, p = 0.03). Conventional sleep duration (7.5-7.99 h) was more often associated with normal semen quality than both short (7.0-7.49 h) and very short (< 7.0 h) sleep duration (OR: 1.36, 95% CI: 1.2-12.9, p = 0.03 and OR: 6.18, 95%CI: 1.6-24.2, p = 0.01). Although poor sleep quality was associated with reduced semen quality in the descriptive statistics (p = 0.04), no differences were found between optimal (PSQI ≤6) and either borderline (PSQI 7-8) or poor (PSQI ≥9) sleep quality (OR: 1.19, 95%CI: 0.4-3.4, p = 0.75 and OR: 2.43, 95%CI: 0.8-7.1, p = 0.11) in multivariate regression models. CONCLUSION: Early bedtimes (< 10:30 PM) and conventional sleep duration (7.5-7.99 h) were associated with self-reported normal semen quality. The role of subjective sleep quality remains uncertain.

CONTEXTE: Un mauvais sommeil a été associé à plusieurs issues néfastes pour la santé. De récentes études suggèrent que les heures de coucher tardives, des durées de sommeil courtes ou longues, et une mauvaise qualité de sommeil altèrent la qualité du sperme. Aucune étude n'a à ce jour exploré les trois facteurs en relation avec la qualité du sperme. RÉSULTATS: Cent quatre hommes et leurs partenaires traités dans trois cliniques de fertilité au Danemark entre 2010 et 2012 ont rempli un questionnaire correspondant à une version en ligne de l'Indice de Qualité du Sommeil de Pittsburg (IQSP). Les résultats des analyses de sperme réalisées dans les cliniques de fertilité ont été autodéclarés et classés comme normaux ou réduits.Une heure de coucher précoce (< 22 h30) était plus souvent associée à une qualité normale du sperme comparativement à la fois à une heure régulière (22 h30-23 h29) et à une heure tardive (≥23 h30) de coucher (OR: 2.75, 95% CI: 1.1­7.1, p = 0.04 et OR: 3.97, 95% CI: 1.2­13.5, p = 0.03). Une durée conventionnelle de sommeil (7.5­7.99 heures) était plus souvent associée à une qualité normale du sperme qu'une courte (7.0­7.49 heures) et qu'une très courte (< 7.0 heures) durée de sommeil (OR: 1.36, 95% CI: 1.2­12.9, p = 0.03 et OR: 6.18, 95% CI: 1.6­24.2, p = 0.01). Bien qu'une mauvaise qualité du sommeil ait été associée à une qualité réduite du sperme dans les statistiques descriptives (p = 0.04), aucune différence n'a été retrouvée entre une qualité du sommeil optimale (IQSP ≤6) et une qualité soit limite (IQSP 7­8) ou soit pauvre (IQSP ≥9) du sommeil (OR: 1.19, 95% CI: 0.4­3.4, p = 0.75 et OR: 2.43, 95% CI: 0.8­7.1, p = 0.11) dans les modèles de régression multivariée. CONCLUSIONS: Des heures de coucher précoces (< 22 h30) et une durée conventionnelle de sommeil (7.5­7.99 heures) ont été associées à une qualité normale autodéclarée du sperme. Un éventuel rôle de la qualité suggestive du sommeil reste incertain.

Comparison of three infertility-specific measures in men and women going through assisted reproductive technology treatment.

We compared the psychometric properties of COMPI Fertility Problem Stress Scales, Fertility Problem Inventory, and Fertility Quality of Life Tool in 293 patients enrolled for assisted reproductive technology. COMPI Fertility Problem Stress Scales and Fertility Problem Inventory subscales presented higher internal consistency. COMPI Fertility Problem Stress Scales differentiated best between its domains. Fertility Problem Inventory revealed better concurrent validity. Fertility Quality of Life Tool presented better fit. While discrimination for depression was similar between measures, Fertility Quality of Life Tool was better at discriminating anxiety. Results suggest that while all compared measures are reliable and valid in assessing the psychosocial adjustment to infertility, the choice of measure should be based according to the assessment goals.

Observations on muscle activity in REM sleep behavior disorder assessed with a semi-automated scoring algorithm.

OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent. METHODS: An EMG computer algorithm for scoring 'tonic', 'phasic' and 'any' submental muscle activity during REM sleep was evaluated compared with human visual ratings. Subsequently, 52 subjects were analyzed with the algorithm. Duration and maximal amplitude of muscle activity, and self-awareness of RBD symptoms were assessed. RESULTS: The computer algorithm showed high congruency with human ratings and all subjects with RBD were correctly identified by excess of submental muscle activity, when artifacts were removed before analysis. Subjects with RBD exhibited prolonged bouts of 'phasic' muscle activity with high amplitude. Self-awareness of RBD symptoms correlated with amount of REM sleep without atonia. CONCLUSIONS: Our proposed algorithm was able to detect and rate REM sleep without atonia allowing identification of RBD. Increased duration and amplitude of muscle activity bouts were characteristics of RBD. Quantification of REM sleep without atonia represents a marker of RBD severity. SIGNIFICANCE: Our EMG computer algorithm can support a diagnosis of RBD while the quantification of altered muscle activity provides a measure of its severity.

Predictors of pain during oocyte retrieval.

INTRODUCTION: Pain during oocyte retrieval remains prevalent despite detailed and specific pain management protocols. Exploring the role of psychosocial risk factors of pain during the oocyte retrieval could identify possible targets for prevention. The present study assessed pain prevalence and possible risk factors for experiencing extreme pain levels in a large cohort of women receiving assisted reproductive technologies (ART) treatment. METHODS: Participants were 810 first attendees about to begin treatment with ART. The participants completed questionnaires at three time points: at their 21st day of the cycle, during the waiting time before the oocyte retrieval surgery and after the oocyte retrieval. RESULTS: Fifty-one (6.9%) of the women reported the oocyte retrieval to be very or extremely painful. The results of a multiple logistic regression indicated that the significant predictors of high pain intensity, measured before the oocyte retrieval, were negative gynecological experiences and side effects of hormonal treatment. Variables measured after the oocyte retrieval associated with pain intensity were higher levels of anxiety during the oocyte retrieval, lower levels of perceived control and longer duration of the procedure. DISCUSSION: The findings of the present study may help to identify those women who are at increased risk of experiencing unacceptable pain levels during oocyte retrieval procedures and the medical staff is advised to take psychological factors into account.

Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the evidence on the efficacy of psychosocial interventions for improving pregnancy rates and reducing distress for couples in treatment with assisted reproductive technology (ART). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PsycINFO, PubMed, EMBASE, CINAHL, Web of Science and The Cochrane Library between 1978 and April 2014. STUDY SELECTION: Studies were considered eligible if they evaluated the effect of any psychosocial intervention on clinical pregnancy and/or distress in infertile participants, used a quantitative approach and were published in English. DATA EXTRACTION: Study characteristics and results were extracted and the methodological quality was assessed. Effect sizes (ES; Hedges g) were pooled using a random effects model. Heterogeneity was assessed using the Q statistic and I(2), and publication bias was evaluated using Egger's method. Possible moderators and mediators were explored with meta-analyses of variances (ANOVAs) and meta-regression. RESULTS: We identified 39 eligible studies (total N=2746 men and women) assessing the effects of psychological treatment on pregnancy rates and/or adverse psychological outcomes, including depressive symptoms, anxiety, infertility stress and marital function. Statistically significant and robust overall effects of psychosocial intervention were found for both clinical pregnancy (risk ratio=2.01; CI 1.48 to 2.73; p<0.001) and combined psychological outcomes (Hedges g=0.59; CI 0.38 to 0.80; p=0.001). The pooled ES for psychological outcomes were generally larger for women (g: 0.51 to 0.73) than men (0.13 to 0.34), but the difference only reached statistical significance for depressive symptoms (p=0.004). Meta-regression indicated that larger reductions in anxiety were associated with greater improvement in pregnancy rates (Slope 0.19; p=0.004). No clear-cut differences were found between effects of cognitive-behavioural therapy (CBT; g=0.84), mind-body interventions (0.61) and other intervention types (0.50). CONCLUSIONS: The present meta-analysis suggests that psychosocial interventions for couples in treatment for infertility, in particular CBT, could be efficacious, both in reducing psychological distress and in improving clinical pregnancy rates.

The effect of an expressive writing intervention (EWI) on stress in infertile couples undergoing assisted reproductive technology (ART) treatment: a randomized controlled pilot study.

OBJECTIVES: Infertile couples undergoing fertility treatments may experience stress and could benefit from psychological intervention. Expressive Writing Intervention (EWI) has shown promising results on various psychological outcomes, yet only one study has applied the method to infertility-related stress. Our aim was to assess feasibility and effectiveness of EWI for patients in treatment with Assisted Reproductive Technology (ART). DESIGN AND PARTICIPANTS: Patients enrolling in their first ART treatment at the fertility clinic, Aarhus University Hospital, Denmark were offered to participate. A total of 82 participants (45 women, 37 men), mean age: 33.17, were randomized to home-based EWI or neutral writing control group and completed an infertility-related stress questionnaire at treatment enrollment, 3 weeks later (at the time of down regulation), and 6 weeks after the intervention. The intervention took place 2 weeks after treatment start. RESULTS: Mixed between-within ANOVA showed a main effect of time (Wilks Lambda = 0.68, F(2,28) = 6.48) as well as a significant interaction effect between group (control/ EWI) and time (Wilks Lambda = 0.83, F(2,28) = 2.92). Infertility-related stress decreases were observed after the intervention in the EWI group compared to controls. Six weeks after the intervention, stress tended to increase in both groups, with the control group, follow-up stress levels exceeding baseline stress scores, whereas the follow-up scores of EWI-participants' did not exceed baseline levels. CONCLUSIONS: Our preliminary results suggest EWI to be a feasible, cost-effective, and efficient method for alleviating infertility-related stress, although results should be considered preliminary and further testing with a larger sample is warranted.