An adverse drug event manager facilitates spontaneous reporting of adverse drug reactions.

INTRODUCTION: Spontaneous reporting of adverse drug reactions (ADRs) is used for continuous risk-benefit evaluation of marketed pharmaceutical products and for signal detection. The Adverse Drug Event Manager (ADEM) is a service offered to clinicians employed at hospitals in the Capital Region of Denmark. The ADEM assists healthcare professionals in reporting suspected ADRs to the Danish Health Authority. The aim of this retrospective observational study was to quantify and describe ADRs reported via the ADEM in 2014. METHODS: All ADR reports handled by the ADEM in 2014 were recorded anonymously and analysed descriptively. RESULTS: A total of 484 ADRs were reported through the ADEM in 2014 (the median number of reports per month was 37; range: 17-78). The majority of the reports came from departments of internal medicine (61%), psychiatry (14%) and dermatology, ophthalmology or otorhinolaryngology (11%). The drugs most frequently reported were lisdexamphetamine (n = 40), rivaroxaban (n = 16) and warfarin (n = 15) (vaccines excluded). In 13 out of 484 reports, the ADR was associated with a fatal outcome. CONCLUSION: The findings of this study indicate that an ADEM promotes and facilitates spontaneous ADR reporting and helps raise awareness about ADRs, including how and why they should be reported. Hopefully, this will assist national and European spontaneous reporting systems in their work to increase patient safety nationally and abroad. FUNDING: none. TRIAL REGISTRATION: not relevant. .

Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

STUDY OBJECTIVES: To investigate whether administration of an oral dose of 6 mg melatonin before bedtime perioperatively in breast cancer surgery could change sleep outcomes measured by actigraphy. METHODS: This paper reports secondary outcomes from a double-blind, placebo-controlled, randomized clinical trial where patients received 6 mg melatonin (n = 27) or placebo (n = 21) approximately 60 minutes before bedtime 3 nights preoperatively until at least one week postoperatively. Participants were monitored in the entire period with actigraphy, and were instructed to complete visual analogue scale (VAS) for sleep, and the Karolinska Sleepiness Scale (KSS) each morning. RESULTS: Administration of 6 mg oral melatonin approximately 1 hour before bedtime resulted in significantly increased sleep efficiency and reduced wake after sleep onset for the entire 2-week postoperative period. No other significant differences for actigraphy determined sleep outcomes or subjective outcome parameters in the perioperative period were found between the groups. Overall, the patients sleep outcomes were within normal ranges and no participants had pathological sleep disturbances. CONCLUSIONS: Melatonin significantly changed sleep efficiency and wake after sleep onset after surgery, but had no effects on other objective sleep outcomes or on subjective sleep quality (VAS and KSS).

Safety and Tolerability of Lisdexamfetamine: A Retrospective Cohort Study.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder in children. Pharmacotherapy plays a main role in multimodal treatment, albeit adverse effects are a concern. Lisdexamfetamine is a newer pharmacological option and post-marketing studies on adverse events are limited. OBJECTIVE: The aim of this study was to investigate the treatment-emergent adverse events (TEAEs) in patients receiving lisdexamfetamine in a clinical setting. METHODS: We performed a retrospective cohort study at the Department of Child and Adolescent Psychiatry of Glostrup Hospital in Copenhagen, Denmark. We included all consecutive patients >6 years old, with an ICD-10 diagnosis of ADHD who were initiated on lisdexamfetamine between May 2013 and July 2014. TEAEs were assessed by a clinician and chart audit. RESULTS: Forty-three patients (91 % male) with a median age of 11 (range 8-15) years were included and received lisdexamfetamine for a median of 188 days (range 3-433). In total, 23.3 % of the patients discontinued treatment due to a TEAE. 88 % of the patients experienced at least one TEAE and the time to first TEAE ≤4 weeks in 83.8 % of the patients. A new TEAE was experienced by 39.5 % of the patients compared with the TEAEs that patients had experienced when taking previous ADHD medication. The most common TEAEs (≥ 5 %) were decreased appetite, difficulty falling asleep, tics, stomach ache and weight loss. A subjectively assessed good or good but time-limited (during the day only) effect was observed in 62.7 %. CONCLUSION: Lisdexamfetamine treatment in this small group of patients who had received previous stimulant medication for ADHD was well tolerated and the TEAEs were consistent with findings in previous trials, although more than one third of the patients experienced TEAEs not observed with previously taken ADHD medication. Both the number of patients experiencing TEAEs and the rates of discontinuation due to TEAEs were higher than previously reported.

Factors affecting post-operative sleep in patients undergoing colorectal surgery ­ a systematic review.

INTRODUCTION: Understanding factors affecting post-operative recovery is of great importance to efforts at reducing morbidity and mortality after general surgery. Post-operatively, most patients suffer from objectively and subjectively measurable reduced sleep quality. We aimed to review the available literature on post-operative sleep in patients undergoing colorectal surgery. METHODS: This systematic review was conducted according to the PRISMA guidelines, searching the electronic data-bases PubMed, Embase and the Cochrane Library. All articles were evaluated according to pre-defined inclusion criteria. RESULTS: Five studies were included in the review. Sleep quality was affected by type of surgery (open or laparoscopic), the administration/mode of application of analgesics (epidural analgesia or continuous wound infusion) and the level of pain. Patients who listened to new age music and a "relaxing text" had better quality of post-operative sleep than controls. Overall, pain interfered with subjective, post-operative sleep quality and adequate treatment of pain improved subjective sleep quality. CONCLUSION: Sleep quality is sensitive to various factors in the perioperative period, and impairment of sleep quality can be prevented by simple improvements in perioperative care.

Chronobiology, cognitive function and depressive symptoms in surgical patients.

Biological rhythms are essential for the regulation of many life processes. Disturbances of the circadian rhythm are known to affect human health, performance and well-being and the negative consequences are numerous and widespread. Cognitive dysfunction, fatigue, pain, sleep disturbances and mood disorders, such as anxiety and depression, are common problems arising around the time of surgery or in the course of a cancer diagnosis and subsequent treatment period. The importance of investigating prevention or treatment possibilities in these populations is significant due to the extent of the problems and the derived consequences on morbidity and mortality. Genetic predisposition to these problems is also an issue in focus. In this thesis we initially investigated whether the specific clock gene genotype PER(5/5) was associated with the development of postoperative cognitive dysfunction one week after non-cardiac surgery. We did not find any association, although this could have been due to the size of the study. Yet, if PER3(5/5) is associated with a higher incidence of postoperative cognitive dysfunction, the risk seems to be only modestly increased and by less than 10%. Melatonin is a hormone with well-known chronobiotic and hypnotic effects. In addition, exogenous melatonin is also known to have anxiolytic, analgesic, antidepressant and positive cognitive effects. Based on the lack of studies investigating these effects of melatonin, we conducted the MELODY trial in which we investigated the effect of 6 mg oral melatonin on depressive symptoms, anxiety, sleep, cognitive function and fatigue in patients with breast cancer in a three month time period after surgery. Melatonin had an effect on reducing the risk of developing depressive symptoms and also increased sleep efficiency perioperatively and total sleep time postoperatively. No effect was found on anxiety, sleep quality, sleepiness, general well-being or pain, however melatonin seemed to positively influence the ability to complete trial participation compared to placebo. Postoperative cognitive dysfunction was not a problem in this limited population. With regard to safety in our study, melatonin treatment for three months did not cause any serious adverse effects. Finally, we systematically reviewed the literature on the prophylactic or therapeutic effect of melatonin for depression or depressive symptoms in adult patients and assessed the safety of melatonin in these studies. The quantity, size and quality of trials investigating this question were not high and there was no clear evidence of an effect, although some studies were positive. In conclusion, further research is warranted with regard to the prophylactic effect and treatment effect of melatonin in depression, depressive symptoms, cognitive disturbances and symptom clusters of cancer patients in general. In addition, more hypothesis-generating studies with regard to the genetic heritability of POCD are needed.

Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background. Sleep disturbances and cognitive dysfunction are common in patients with breast cancer. Disturbed sleep leads to poor cognitive performance and exogenous melatonin may improve sleep and attenuate cognitive dysfunction. We hypothesized that melatonin would improve sleep and cognitive function after surgery. Methods. This study reports secondary endpoints from a randomized, double-blind, placebo-controlled trial. Women, 30-75 years, were randomized to 6mg oral melatonin/placebo for 3 months. We assessed postoperative cognitive dysfunction (POCD) with a neuropsychological test battery, sleep with a diary, and sleep quality with VAS. Results. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26); 11 withdrew (10 placebo, 1 melatonin, P = 0.002). The incidence of POCD was 0% (0/20) [95% CI 0.0%; 16.8%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 2 weeks postoperatively (P = 1.00) and 6.3% (1/16) [95% CI 0.0%; 30.2%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 12 weeks postoperatively (P = 0.38). Sleep efficiency was significantly greater in the melatonin group; mean difference was 4.28% [95% CI 0.57; 7.82] (P = 0.02). The total sleep period was significantly longer in the melatonin group; mean difference was 37.0 min [95% CI 3.6; 69.7] (P = 0.03). Conclusion. Melatonin increased sleep efficiency and total sleep time but did not affect cognitive function. The dropout rate was significantly lower in the melatonin group. This trial is registered with Clinicaltrials.gov NCT01355523.

The effect of MELatOnin on Depression, anxietY, cognitive function and sleep disturbances in patients with breast cancer. The MELODY trial: protocol for a randomised, placebo-controlled, double-blinded trial.

Introduction Breast cancer represents about one-third of all cancer diagnoses and accounts for about 15% of cancer deaths in women. Many of these patients experience depression, anxiety, sleep disturbances and cognitive dysfunction. This may adversely affect quality of life and also contribute to morbidity and mortality. Melatonin is a regulatory circadian hormone having, among others, a hypnotic and an antidepressive effect. It has very low toxicity and very few adverse effects compared with the more commonly used antidepressants and hypnotics. Methods and analysis The objective of this double-blind, randomised, placebo-controlled trial is to investigate whether treatment with oral melatonin has a prophylactic or ameliorating effect on depressive symptoms, anxiety, sleep disturbances and cognitive dysfunction in women with breast cancer. Furthermore, the authors will examine whether a specific clock-gene, PER3, is correlated with an increased risk of depressive symptoms, sleep disturbances or cognitive dysfunction. The MELODY trial is a prospective double-blinded, randomised, placebo-controlled trial in which the authors intend to include 260 patients. The primary outcome is depressive symptoms measured by the Major Depression Inventory. The secondary outcomes are anxiety measured by a Visual Analogue Scale, total sleep time, sleep efficiency, sleep latency and periods awake measured by actigraphy and changes in cognitive function measured by a neuropsychological test battery. Tertiary outcomes are fatigue, pain, well-being and sleep quality/quantity measured by Visual Analogue Scale and sleep diary and sleepiness measured by the Karolinska Sleepiness Scale. The PER3 genotype is also to be determined in blood samples.