Agreement between routinely used immunoassays for thyroid function testing in non-pregnant and pregnant adults.

OBJECTIVE: Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non-pregnant and pregnant adults. DESIGN: Cross-sectional study. PARTICIPANTS: Serum samples were obtained from 192 blood donors (non-pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease. MEASUREMENTS: Each sample was used for measurement of thyroid-stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI). RESULTS: In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30-1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48-1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61-1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37-2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69-3.62 mIU/L)). CONCLUSION: Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non-pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease.

Stimulating thyrotropin receptor antibodies in early pregnancy.

OBJECTIVES: Thyrotropin-receptor antibodies (TRAb) are used to diagnose Graves' hyperthyroidism in pregnant women. Bioassays provide a measure of thyrotropin-receptor stimulatory antibodies (TSI) specifically. The objective was to measure TSI in pregnant women for establishment of a pregnancy-specific cut-off and comparison with immunoassay measurements of TRAb. METHODS: The retrospective Danish study was performed within the North Denmark Region Pregnancy Cohort (2011-2015) that includes stored biobank samples from early pregnancy (median week 10) with immunoassay measurements of thyroid function parameters and TRAb. TSI were measured in the same samples using the Turbo TSI bioassay (Quidel/Ortho-Clinical Diagnostics) with a recommended cut-off of 0.0241 IU/L in non-pregnant adults. A pregnancy-specific TSI cut-off (95-percentile) was established using Regression on Order Statistics. RESULTS: The established TSI cut-off was 0.0418 IU/L (95 % CI: 0.0417-0.0419). Among women with early pregnancy hyperthyroidism (n=438), 43 women (9.8 %) were TSI positive using the established cut-off, and these women had lower TSH (median 0.008 mIU/L) compared to women with TSI levels below 0.0241 (median TSH 0.040 mIU/L) or in the range from 0.0241 to 0.0418 (median TSH 0.033 mIU/L). Among the 438 women with early pregnancy hyperthyroidism, 22 women were positive for TSI and TRAb, 388 were negative for both, and 28 women were positive for either TSI or TRAb. CONCLUSIONS: This is the first study on TSI measurements in a large cohort of early pregnant women. A pregnancy-specific cut-off for TSI was established and agreement in the classification with immunoassay measurements of TRAb was seen in 94 % of cases.

Vitamin B12 reference intervals.

INTRODUCTION: P-Vitamin B12 is a commonly used biochemical test. Evaluation of test results and diagnosis of vitamin B12 deficiency are challenging, and the role of different biochemical methods remains unclear. METHODS: The aim of this study was to establish reference intervals for plasma vitamin B12 concentration using different immunoassays (method 1: Alinity, Abbott Laboratories; method 2: Cobas 6000, Roche Diagnostics; method 3: Atellica IM, Siemens Healthineers). Direct reference intervals were established among blood donors (n = 129) and indirect reference intervals among adult patient results of plasma vitamin B12 concentration requested by general practitioners in the North Denmark Region from 15 August to 15 October 2022 (n = 34,181). Finally, the frequency of low vitamin B12 concentration using different uniform cut-offs was evaluated. RESULTS: Direct reference intervals (2.5-97.5 percentiles) were as follows for method 1: 168-553 pmol/l; method 2: 202-641 pmol/l; and method 3: 211-551 pmol/l. Indirect reference intervals were as follows for method 1: 133-541 pmol/l; method 2: 172-619 pmol/l; and method 3: 182-162-206 pmol/l. When different cut-offs were applied to patient results, the frequency of having a vitamin B12 concentration below 250 pmol/l differed by biochemical method: 33% (method 1), 17% (method 2) and 14% (method 3). CONCLUSION: Measurement of plasma vitamin B12 concentration using different immunoassays revealed results and reference intervals that were not interchangeable. Clinical guidelines for the diagnosis of vitamin B12 deficiency should consider the biochemical methods used. FUNDING: None. TRIAL REGISTRATION: None.

A kind reminder-A qualitative process evaluation of women's perspectives on receiving a reminder of type 2 diabetes follow-up screening after gestational diabetes.

RATIONALE, AIMS AND OBJECTIVES: Women with previous gestational diabetes mellitus (GDM) are more than eight times more likely to develop type 2 diabetes (T2DM) compared to women without GDM. Annual follow-up T2DM-screening is recommended, but participation rates decrease rapidly after the first year. In the North Denmark Region, an electronic reminder has been tested with the aim of improving follow-up care for women with prior GDM. The aim of this study was to explore women's perspectives on receiving an electronic reminder, and the role of reminders in both women's decision-making and informed choice regarding participation in follow-up screening. METHODS: A qualitative process evaluation informed by a critical realistic perspective. Data consisted of 20 semi-structured interviews with women previously diagnosed with GDM who had received the reminder. Interviews were analyzed using reflexive thematic analysis. RESULTS: The reminder affected women's decision-making and informed choices through a range of mechanisms. Its personalized design prompted feelings of co-responsibility and care from the healthcare system, supported continuity in women's care pathways, and helped women bridge the gap between healthcare sectors. Women's perception of diabetes risk and the importance of follow-up influenced their decision-making. Participation in follow-up screening was influenced by several contextual factors, as women's everyday life impeded their prioritizing follow-up screening. Women who experienced being met by their general practitioner (GP) with acknowledgement rather than stigmatization and received supportive information tailored to their life situation were more motivated to participate in future follow-up screenings. CONCLUSION: The reminder indicated both concern and co-responsibility for women's follow-up care after GDM and was well received by the women. It supported participation in follow-up screening through an emphasis on shared decision-making and informed choice. Women's interaction with their GP played a significant role.

The role of social technologies in community care - A realist evaluation of a Danish web-based citizen-to-citizen platform adopted in community care to promote belonging and mental health.

As social technologies increase in popularity, there is a growing interest in incorporating them into mental health interventions. Research shows that the use of social technologies may support belonging and mental health. Findings, however, are contradictory and highlight the need to clarify the processes and mechanisms by which this technology may have positive effects. This study conducted a realist evaluation of a web-based citizen-to-citizen platform adopted within community care in a Danish Municipality. It focused on how, for whom and under what circumstances the web-based platform worked to promote belonging and mental health. The evaluation was structured in subsequent phases of development, testing, and refinement of programme theories. A purposeful sampling frame was developed based on the programme theories, and 27 interviews were conducted. With variations, the platform was found to support its users in meeting their social needs by (a) expanding their access to social networks; (b) allowing them to overcome barriers related to reaching out to new people in real life and (c) providing them with an improved starting point for identification of a relational match. Whether this resulted in improved belongingness and mental health was strongly affected by individual and relational circumstances. Findings suggest that web-based platforms that aim to enable citizens to locate friends and activity partners can serve as helpful tools in interventions striving to promote mental health in the community, as they may support people to fulfil a need for belongingness. However, the impact of such tools is highly dependent on the individual's abilities to use the initiatives to form relationships of sufficient quality to accommodate these needs. People with previous relational difficulties, and who have struggled to achieve feelings of belonging and citizens with limited digital literacy, may need support to realise the social opportunities provided by these technologies.

Kisspeptin-52 partially rescues the activity of the hypothalamus-pituitary-gonadal axis in underweight male rats dosed with an anti-obesity compound.

Energy metabolism and reproduction are closely linked and reciprocally regulated. The detrimental effect of underweight on reproduction complicates the safety evaluation of anti-obesity drugs, making it challenging to distinguish pathological changes mediated through the intended drug-induced weight loss from direct drug effects on reproductive organs. Four-weeks dosing of normal weight Sprague Dawley rats with a glucagon-like peptide 1 (GLP-1)/glucagon receptor co-agonist induced a robust weight loss, accompanied by histological findings in prostate, seminal vesicles, mammary glands, uterus/cervix and vagina. Characterization of the hypothalamus-pituitary-gonadal (HPG) axis in male rats revealed reduced hypothalamic Kiss1 mRNA levels and decreased serum luteinizing hormone (LH) and testosterone concentrations following co-agonist dosing. These alterations resemble hypogonadotropic hypogonadism typically seen in adverse energy deprived conditions, like chronic food restriction. Concomitant daily administration of kisspeptin-52 from day 21 to the end of the four-week co-agonist dosing period evoked LH and testosterone responses without normalizing histological findings. This incomplete rescue by kisspeptin-52 may be due to the rather short kisspeptin-52 treatment period combined with a desensitization observed on testosterone responses. Concomitant leptin treatment from day 21 did not reverse co-agonist induced changes in HPG axis activity. Furthermore, a single co-agonist injection in male rats slightly elevated LH levels but left testosterone unperturbed, thereby excluding a direct acute inhibitory effect on the HPG axis. Our data suggest that the reproductive phenotype after repeated co-agonist administration was driven by the intended weight loss, however, we cannot exclude a direct organ related effect in chronically treated rats.

[Genital herpes simplex virus infection in pregnancy].

In this review, we discuss genital herpes - a common sexually transmitted infection, which can be transmitted to the baby during birth. Neonatal herpes is a rare but serious infection. In 2019, the Danish Society of Obstetrics and Gynecology revised the guideline for management of genital herpes in pregnancy. Recommendations include antiviral therapy from gestational week 36 in case of primary- or recurrent infection in current pregnancy. Delivery by cesarean section is recommended in case of primary infection in the third trimester. Women with recurrent herpes can deliver vaginally, as risk of neonatal infection is low.

Patients' and health professionals' experience of the Danish fast track treatment pathway for head and neck cancer patients receiving oral rehabilitation.

Objective: This study aims to investigate the responsiveness of the Danish treatment pathway for head-and-neck-cancer (HNC) patients receiving oral rehabilitation.Material and Methods: Eighteen HNC-patients who had received oral rehabilitation as well as five medical and four oral health care professionals involved in the treatment of HNC-patients filled in a questionnaire on responsiveness. The responsiveness was further described in individual interviews in the HNC-patients and focus group interviews in the health care professionals. All interviews were semi-structured and analysed using the grounded theory.Results: Patients and health care professionals overall reported good responsiveness of the pathway. Prompt attention was in both groups considered the most important aspect, although the patients found it difficult to cope mentally with the fast-track and the health care professionals reported insufficiencies giving prompt attention. The patients in general described a good relationship with their health care professionals, but along with the health care professionals also reported some problems regarding communication. Further, the health care professionals reported a gap between medical treatment and oral rehabilitation.Conclusions: The Danish treatment pathway for HNC-patients was, in general, evaluated positively. Communication and relationship between patient and health care professional can affect the responsiveness of the pathway.

A role for both HLA-F and HLA-G in reproduction and during pregnancy?

The human major histocompatibility complex includes a group of non-classical HLA class I genes, HLA-E, -F and -G. While nearly all focus since the discovery of these class Ib molecules have been on basic biochemistry and molecular biology of HLA-G and HLA-E, as well as their expression patterns, functions in immune modulation and during pregnancy, and also possible implications in a range of diseases, in infertility and pregnancy complications, HLA-F has nearly been ignored. However, recent discoveries show that HLA-F can be expressed as both open conformers binding to a number of KIRs on primarily NK cells, as well as peptide-bound HLA-F binding to ILT2 and ILT4. Furthermore, a number of reports indicate a possible involvement of HLA-F in viral infections, in cancer immunology, and in fertility and reproduction, which may initiate more interest in this rather unknown HLA class I molecule. In this short review, we focus on recent discoveries that indicate a functional role for HLA-F in reproduction and during pregnancy, and the role of HLA-F in relation to HLA-G.

The Effect of Diet-induced Obesity on Toxicological Parameters in the Polygenic Sprague-Dawley Rat Model.

The obese rodent serves as an indispensable tool for proof-of-concept efficacy and mode-of-action pharmacology studies. Yet the utility of this disease model as an adjunct to the conventional healthy animal in the nonclinical safety evaluation of anti-obesity pharmacotherapies has not been elucidated. Regulatory authorities have recommended employing disease models in toxicology studies when necessary. Our study investigated standard and exploratory toxicology parameters in the high-fat diet (HFD)-induced obese, polygenic Sprague-Dawley rat model in comparison to chow diet (CD)-fed controls. We sought to establish feasibility of the model for safety testing and relevance to human obesity pathophysiology. We report that both sexes fed a 45% kcal HFD for 29 weeks developed obesity and metabolic derangements that mimics to a certain extent, common human obesity. Minor clinical pathologies were observed in both sexes and considered related to CD versus HFD differences. Histopathologically, both sexes exhibited mild obesity-associated findings in brown and subcutaneous white fat, bone, kidneys, liver, lung, pancreas, salivary parotid glands, and skeletal muscle. We conclude that chronic HFD feeding in both sexes led to the development of an obese but otherwise healthy rat. Therefore, the diet-induced obese Sprague-Dawley rat may serve as a suitable model for evaluating toxicity findings encountered with anti-obesity compounds.

[Harlequin ichthyosis with a diaphragmatic hernia and a new mutation].

Harlequin ichthyosis (HI) is a rare and severe form of the autosomal recessive congenital ichthyosis. This is a case report of a 30-year-old healthy woman with a pregnancy resulting in preterm birth of a child with severe HI, who did not survive. At the autopsy, the child was found with HI and a diaphragmatic hernia of the Bochdalek type. Genetic analysis showed, that the child was homozygous for the mutation c.5121_5124del in ABCA12. The parents were related and were found heterozygous of this mutation. This clinical presentation with this new mutation has not been described in the literature before.

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).

New and chronic use of hypnotics after diagnosis with early breast cancer. A retrospective cohort study.

BACKGROUND: To determine use and investigate factors associated with use of hypnotics the first year after a diagnosis with breast cancer. MATERIAL AND METHODS: A retrospective registry based cohort study linking clinical data from the Danish Breast Cancer Group with the National Prescription Drug Database and other health and administrative registries. We included 26 082 women diagnosed with early breast cancer as first time primary cancer during 1996-2006. Use of hypnotics was measured as redeemed prescriptions in the first year after diagnosis of early breast cancer. Prior use of hypnotics was defined as one or more prescriptions of hypnotics 13 months to 1 month before diagnosis, and chronic use was defined as four or more prescriptions. Hazard ratios (HRs) for clinical variables, treatment-related factors and sociodemographic factors were calculated. RESULTS: Among women with no prior history of hypnotic use, 17% became new users with 4% on a chronic level. Among prior users, 82% continued their use with one or more prescriptions of hypnotics and 15% increased their use to a chronic level. Significantly increased hazard ratios for use of hypnotics were seen with increasing age [age 50-59 years: HR 1.43 (95% CI 1.31-1.57), age 60-69: HR 1.57 (95% CI 1.44-1.71)], increasing number of tumor positive lymph nodes [1-3 lymph nodes: HR 1.12 (95% CI 1.05-1.09), 4-9 lymph nodes: HR 1.11 (95% CI 1.02-1.29)], chemotherapy [HR 1.25 (95% CI 1.12-1.39)], somatic comorbidity [HR 1.31 (95% CI 1.21-1.42)] and use of antidepressants the year before breast cancer diagnosis [HR 1.97 (95% CI 1.85-2.10)]. CONCLUSION: This study detected a group of patients at great risk for initiating and increasing use of hypnotics and preventive and prophylactic mechanism should be investigated and initiated when this group of patients is seen in the clinical setting.

Working night shifts affects surgeons' biological rhythm.

BACKGROUND: Chronic sleep deprivation combined with work during the night is known to affect performance and compromise residents' own safety. The aim of this study was to examine markers of circadian rhythm and the sleep-wake cycle in surgeons working night shifts. METHODS: Surgeons were monitored prospectively for 4 days: pre call, on call, post call day 1 (PC1), and post call day 2 (PC2). The urinary metabolite of melatonin and cortisol in saliva were measured to assess the circadian rhythm. Sleep and activity were measured by actigraphy. Subjective measures were assessed by the Karolinska Sleepiness Scale and Visual Analog Scale of fatigue, general well-being, and sleep quality. RESULTS: For both metabolite of melatonin and cortisol, a significant difference (P < .05) was found in the measurement period between on call and pre call values. There was increased sleep time during the day on call and on PC1. For all subjective measures, a marked deterioration was seen on PC1. CONCLUSION: Surgeons' circadian rhythm was affected by working night shifts.

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.

Decreased heart rate variability in surgeons during night shifts.

BACKGROUND: Heart rate variability (HRV) has been used as a measure of stress and mental strain in surgeons. Low HRV has been associated with death and increased risk of cardiac events in the general population. The aim of this study was to clarify the effect of a 17-hour night shift on surgeons' HRV. METHODS: Surgeons were monitored prospectively with an ambulatory electrocardiography device for 48 consecutive hours, beginning on a precall day and continuing through an on-call (17-h shift) day. We measured HRV by frequency domain parameters. RESULTS: We included 29 surgeons in our analysis. The median pulse rate was decreased precall (median 64, interquartile range [IQR] 56-70 beats per minute [bpm]) compared with on call (median 81, IQR 70-91 bpm, p < 0.001). Increased high-frequency (HF) activity was found precall (median 199, IQR 75-365 ms2) compared with on call (median 99, IQR 48-177 ms2, p < 0.001). The low-frequency:high-frequency (LF:HF) ratio was lower precall (median 2.7, IQR 1.9-3.9) than on call (median 4.9, IQR 3.7-6.5, p < 0.001). We found no correlation between the LF:HF ratio and performance in laparoscopic simulation. CONCLUSION: Surgeons working night shifts had a significant decrease in HRV and a significant increase in pulse rate, representing sympathetic dominance in the autonomic nervous system. TRIAL REGISTRATION: NCT01623674 (www.clinicaltrials.gov).

CONTEXTE: La variabilité de la fréquence cardiaque (VFC) a été utilisée comme mesure du stress et de l'effort mental chez les chirurgiens. On a établi un lien entre une faible VFC et la mort et le risque accru d'événement cardiaque dans la population générale. Cette étude visait à clarifier l'effet d'un quart de nuit de 17 heures sur la VFC des chirurgiens. MÉTHODES: On a surveillé prospectivement des chirurgiens au moyen d'un appareil d'électrocardiographie ambulatoire pendant 48 heures consécutives en commençant la veille de la période de garde et durant toute la journée de garde (quart de 17 heures). Nous avons mesuré la VFC au moyen de paramètres du domaine fréquentiel. RÉSULTATS: Notre analyse a porté sur 29 chirurgiens. Le pouls médian a diminué avant la période de garde (médiane de 64, plage interquartile [PIQ] de 56 à 70 battements/minute [b/m]) comparativement à la période de garde (médiane de 81, PIQ de 70 à 91 b/m, p < 0,001). On a constaté une activité de haute fréquence (HF) accrue avant la période de garde (médiane de 199, PIQ de 75 à 365 ms2) comparativement à la période de garde (médiane de 99, PIQ de 48 à 177 ms2, p < 0,001). Le ratio basses fréquences:hautes fréquences (BF:HF) était moins élevé avant (médiane de 2,7, PIQ de 1,9 à 3,9) que pendant la période de garde (médiane de 4,9, PIQ de 3,7 à 6,5, p < 0,001). Nous n'avons constaté aucun lien entre le ratio BF:HF et le rendement au cours d'une simulation de laparoscopie. CONCLUSION: Les chirurgiens qui faisaient des quarts de nuit présentaient une diminution importante de la VFC et une augmentation importante du pouls, ce qui représente une domination sympathique du système nerveux autonome. ENREGISTREMENT DE L'ESSAI: NCT01623674 (www.clinicaltrials.gov).

Laparoscopic skills and cognitive function are not affected in surgeons during a night shift.

OBJECTIVE: To monitor surgeons' performance and cognition during night shifts. DESIGN: Surgeons were monitored before call and on call (17-hour shift). Psychomotor performance was assessed by laparoscopic simulation and cognition by the d2 test of attention. The surgeons performed the laparoscopic simulation and the d2 test of attention at 8 a.m. before call and at 4 a.m. on call. Sleep was measured by wrist actigraphy and sleepiness by the Karolinska sleepiness scale. SETTING: Department of Surgery at Herlev Hospital, Denmark. PARTICIPANTS: Overall, 30 interns, residents, and attending surgeons were included and completed the study. One participant was subsequently excluded owing to myxedema. RESULTS: The surgeons slept significantly less on call than before call. There was increasing sleepiness on call; however, no significant differences were found in the precall laparoscopic simulation values compared with on-call values. The d2 test of attention showed significantly improved values on call compared with before call. CONCLUSION: Sleep deprivation during a 17-hour night shift did not impair surgeons' psychomotor or cognitive performance.

Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial.

Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30-75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077-0.80]), giving a NNT of 3.0 [95 % CI 1.7-11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery.

Pharmacological treatment of depression in women with breast cancer: a systematic review.

The objective of this study is to review the literature on pharmacological treatment of depression in women with breast cancer. According to the PRISMA guidelines, we conducted a systematic review of randomized, controlled clinical trials and open label prospective studies on antidepressants effects on depression in women with breast cancer up to January 14, 2013. In this analysis, a total of 213 studies were identified, and six studies met the inclusion criteria. Of the six studies, three were placebo-controlled randomized controlled clinical trials with fluoxetine, a selective serotonin reuptake inhibitor; and Mianserin­a noradrenergic and specific serotonergic antidepressant. Both studies found that fluoxetine and mianserin significantly improved depressive symptoms and quality of life (QOL) compared with placebo. Conversely, desipramine, a tricyclic antidepressant, and the SSRI, paroxetine, showed no significant effects on depression compared with placebo. A double-blind, parallel group study comparing a tricyclic antidepressant, amitriptyline, and paroxetine showed a significant and comparable improvement in depression and QOL. Two open label, prospective studies found that escitalopram and the norepinephrine reuptake inhibitor, reboxetine, significantly improved depression and QOL compared with baseline values. In conclusion, depression is a clinical problem in patients with breast cancer. Pharmacological treatment with antidepressants may improve depression and QOL. However, the evidence is limited, and the studies are too heterogeneous to recommend one regimen or drug over another. Further antidepressant studies are needed to guide depression treatment in patients with breast cancer.

No increased risk of perforation during colonoscopy in patients undergoing Nurse Administered Propofol Sedation.

OBJECTIVE: Nurse Administered Propofol Sedation (NAPS) contributes to a deeper sedation of the patients, making them unable to respond to pain and an increased incidence of perforations has been speculated. The objective of this study was to evaluate the risk of perforations during colonoscopies performed with either NAPS or conventional sedation regimes. MATERIAL AND METHODS: Data were retrospectively retracted from medical journals from 1 January 2007 to 31 December 2011. All journals were examined and cross-referenced to reveal any perforations. We analyzed all colonoscopies in regard to nature of the procedure (diagnostic vs therapeutic), experience of the endoscopist and ASA-classification of the patients. RESULTS: A total of 6371 colonoscopies were performed, of which 3155 were performed under propofol sedation. There were 16 perforations (0.25%); 10 of these performed during NAPS and 6 during conventional colonoscopy (p = 0.454, OR: 1.7 (95% CI: 0.6-5.7)). There were 4874 diagnostic and 1497 therapeutic colonoscopies, with a majority of the perforations (94%) occurring during a diagnostic procedure (p = 0.389). No statistically difference was found in the incidence of perforations caused by an experienced or less experienced endoscopist (p = 0.589). CONCLUSION: The risk of colonic perforations during colonoscopy was not found to be significantly higher in patients undergoing NAPS compared to patients undergoing conventional sedation, although a tendency may exist. Furthermore, we found no correlation to neither experience of the endoscopist, nature of the procedure nor sex of the patients. Larger and prospective studies are needed to further evaluate on this subject.