Alterations in pituitary adenylate cyclase-activating polypeptide in major depressive disorder, bipolar disorder, and comorbid depression in Alzheimer's disease in the human hypothalamus and prefrontal cortex.

BACKGROUND: Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is involved in the stress response and may play a key role in mood disorders, but no information is available on PACAP for the human brain in relation to mood disorders. METHODS: PACAP-peptide levels were determined in a major stress-response site, the hypothalamic paraventricular nucleus (PVN), of people with major depressive disorder (MDD), bipolar disorder (BD) and of a unique cohort of Alzheimer's disease (AD) patients with and without depression, all with matched controls. The expression of PACAP-(Adcyap1mRNA) and PACAP-receptors was determined in the MDD and BD patients by qPCR in presumed target sites of PACAP in stress-related disorders, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). RESULTS: PACAP cell bodies and/or fibres were localised throughout the hypothalamus with differences between immunocytochemistry and in situ hybridisation. In the controls, PACAP-immunoreactivity-(ir) in the PVN was higher in women than in men. PVN-PACAP-ir was higher in male BD compared to the matched male controls. In all AD patients, the PVN-PACAP-ir was lower compared to the controls, but higher in AD depressed patients compared to those without depression. There was a significant positive correlation between the Cornell depression score and PVN-PACAP-ir in all AD patients combined. In the ACC and DLPFC, alterations in mRNA expression of PACAP and its receptors were associated with mood disorders in a differential way depending on the type of mood disorder, suicide, and psychotic features. CONCLUSION: The results support the possibility that PACAP plays a role in mood disorder pathophysiology.

The Effectiveness of a Nonguided Mindfulness App on Perceived Stress in a Nonclinical Dutch Population: Randomized Controlled Trial.

BACKGROUND: Mindfulness has become increasingly popular, and positive outcomes have been reported for mindfulness-based interventions (MBIs) in reducing stress. These findings make room for innovative perspectives on how MBIs could be applied, for instance through mobile health (mHealth). OBJECTIVE: The aim of this study is to investigate whether a nonguided mindfulness mobile app can decrease perceived stress in a nonclinical Dutch population over the course of 8 weeks, with follow-up at 6 months. METHODS: A randomized controlled trial was performed to compare an experimental group that made use of a structured 8-week mHealth mindfulness program and a control group after 8 weeks, with follow-up after 6 months. Participants were recruited via a national television program. The primary outcome measure was perceived stress as measured by the Perceived Stress Scale, secondary outcomes were symptoms of burnout (measured using the visual analog scale [VAS]) and psychological symptoms (measured using the Four-Dimensional Symptom Questionnaire [4DSQ] at follow-up). Outcomes were analyzed using a multilevel regression model. RESULTS: At baseline, 587 respondents were included. Results showed no postintervention differences between groups for the level of perceived stress. With regard to the secondary outcome measures, the VAS for emotional exhaustion and physical exhaustion showed significantly lower scores for the experimental group after 8 weeks (P=.04 and P=.01, respectively), but not at follow-up. There were no differences between groups for psychological symptoms measured using the 4DSQ. CONCLUSIONS: These findings do not support our hypothesis that using the mindfulness app would reduce stress levels. However, our findings related to diminished exhaustion at 8 weeks are encouraging and require further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05246800; https://clinicaltrials.gov/show/NCT05246800.

Light therapy for mood disorders.

In this chapter, light therapy for mood disorders is discussed, including mood disorders during and after pregnancy. In the introduction, we discuss the symptomatology, etiology, and treatment of a specific type of mood disorder, seasonal affective disorder, since it kick-started the first clinical trials with light therapy. Second, we elaborate on the pathophysiology of mood disorders, in particular in the peripartum period. Next, we present an overview of the proposed working mechanisms of light therapy, followed by a discussion of the clinical trials that have followed after the initial research in seasonal affective disorder. Finally, we also focus on the limitations of these trials, such as considerable heterogeneity among studies and many methodological shortcomings. This is complemented by a number of suggestions for future research. Further studies are needed, which stems from the fact that the results have not always been consistent. Despite this, light therapy may be a promising treatment option for various types of mood disorders, since it shows a significant reduction in symptoms in many patients with few adverse effects.

Identifying value-based quality indicators for general hospital psychiatry.

OBJECTIVE: To define generic quality indicators for general hospital psychiatry from the perspectives of patients, professionals (physicians, nurses, and managers), and payers (health insurance companies). METHODS: Quality variables were identified by reviewing the relevant literature. A working. group consisting of patients', professionals' and payers' representatives was mandated by their respective umbrella organizations. The working group prioritized the quality variables that were identified. Core values were defined and subsequently linked to preliminary quality indicators. These were tested for feasibility in ten hospitals in a four-week period. Stakeholder consultation took place by means of two invitational conferences and two written commentary rounds. RESULTS: Forty-one quality variables were identified from the literature. After prioritization, seven core values were defined and translated to 22 preliminary indicators. Overall, the feasibility study showed high relevance scores and good implementability of the preliminary quality indicators. A final set of twenty-two quality indicators (17 structure, 3 process and 2 outcome indicators) was then established using a consensus-based approach. CONCLUSION: Consensus on a quality framework for general hospital psychiatry was built by incorporating the perspectives of relevant stakeholders. Results of the feasibility study suggest broad support and good implementability of the final quality indicators. Structural indicators were broadly defined, and process and outcome indicators are generic to facilitate quality measurement across settings. The quality indicator set can now be used to facilitate quality and outcome assessment, stimulate standardization of services, and help demonstrate (cost-) effectiveness.

Antidepressants during pregnancy: Guideline adherence and current practice amongst Dutch gynaecologists and midwives.

BACKGROUND AND OBJECTIVES: prescription rates of antidepressants during pregnancy range from 2-3% in The Netherlands to 6.2% in the USA. Inconclusive evidence about harms and benefits of antidepressants during pregnancy leads to variation in advice given by gynaecologists and midwives. The objective was to investigate familiarity with, and adherence to the Dutch multidisciplinary guideline on Selective Serotonin Reuptake Inhibitor (SSRI) use during pregnancy by gynaecologists and midwives in the Netherlands. METHODS: an online survey was developed and send to Dutch gynaecologists and midwives. The survey consisted mainly of multiple-choice questions addressing guideline familiarity and current practice of the respondent. Also, caregiver characteristics associated with guideline adherence were investigated. FINDINGS: a total of 178 gynaecologists and 139 midwives responded. Overall familiarity with the Dutch guideline was 92.7%. However, current practice and advice given to patients by caregivers differed substantially, both between gynaecologists and midwives as well as within both professions. Overall guideline adherence was 13.9%. Multivariable logistic regression showed that solely caregiver profession was associated with guideline adherence, with gynaecologists having a higher adherence rate (OR 2.10, 95%CI 1.02-4.33) than midwives. KEY CONCLUSION: although reported familiarity with the guideline is high, adherence to the guideline is low, possibly resulting in advice to patients that is inconsistent with guidelines and unwanted variation in current practice. IMPLICATIONS FOR PRACTICE: further implementation of the recommendations as given in the guideline should be stimulated. Additional research is needed to examine how gynaecologists and midwives can be facilitated to follow the recommendations of the clinical guideline on SSRI use during pregnancy.

Influence of hyperoxia on diastolic myocardial and arterial endothelial function.

OBJECTIVE: Hyperoxia is known to influence cardiovascular and endothelial function, but it is unknown if there are differences between younger and older persons. The aim of this study was to monitor changes in myocardial diastolic function and flow-mediated dilatation (FMD) in younger and elderly volunteers, before and after exposure to relevant hyperbaric hyperoxia. METHODS: 51 male patients were separated into two groups for this study. Volunteers in Group 1 (n=28, mean age 26 ±6, "juniors") and Group 2 (n=23, mean age 53 ±9, "seniors") received standard HBO2 protocol (240kPa oxygen). Directly before and after hyperoxic exposure in a hyperbaric chamber we took blood samples (BNP, hs-troponin-t), assessed the FMD and echocardiographic parameters with focus on diastolic function. RESULTS: After hyperoxia we observed a high significant decrease in heart rate and systolic/diastolic FMD. Diastolic function varied in both groups: E/A ratio showed a statistically significant increase in Group 1 and remained unchanged in Group 2. E/e' ratio showed a slight but significant increase in Group 1, whereas e'/a' ratio increased in both groups. Deceleration time increased significantly in all volunteers. Isovolumetric relaxation time remained unchanged and ejection fraction showed a decrease only in Group 2. There were no changes in levels of BNP and hs-troponin-t in either group. CONCLUSION: Hyperoxia seems to influence endothelial function differently in juniors and seniors: FMD decreases more in seniors, possibly attributable to pre-existing reduced vascular compliance. Hyperoxia-induced bradycardia induced a more pronounced improvement in diastolic function in juniors. The ability of Group 1 to cope with hyperoxia-induced effects did not work in the same manner as with Group 2.

Interventions to treat mental disorders during pregnancy: A systematic review and multiple treatment meta-analysis.

BACKGROUND: For women suffering from an antepartum mental disorder (AMD), there is lack of evidence-based treatment algorithms due to the complicated risk-benefit analysis for both mother and unborn child. We aimed to provide a comprehensive overview of pharmacological and non-pharmacological interventions to treat AMD and performed a meta-analysis of the estimated treatment effect on the psychiatric symptoms during pregnancy. METHODS: MedLine, PsycINFO and Embase databases were searched by two independent reviewers for clinical trials with a control condition on treatment of women with AMD, i.e. major depressive (MDD), anxiety, psychotic, eating, somatoform and personality disorders. We inventoried the effect of the treatment, i.e. decrease of psychiatric symptoms at the end of the treatment or postpartum. We adhered to the PRISMA-protocol. FINDINGS: Twenty-nine trials were found involving 2779 patients. Trials studied patients with depressive disorders (k = 28), and anxiety disorders (k = 1). No pharmacological trials were detected. A form of psychotherapy, like Cognitive Behavioural Therapy (g = -0.61; 95%CI:-0.73 to -0.49, I2 = 0%; k = 7) or Interpersonal Psychotherapy (g = -0.67; 95%CI:-1.27 to -0.07; I2 = 79%; k = 4), holds robust benefit for pregnant women with MDD. Body-oriented interventions (g = -0.43; 95%CI:-0.61 to -0.25; I2 = 17%; k = 7) and acupuncture (g = -0.43; 95%CI:-0.80 to -0.06; I2 = 0%; k = 2) showed medium sized reduction of depressive symptoms. Bright light therapy (g = -0.59; 95%CI:-1.25 to 0.06; I2 = 0%; k = 2), and food supplements (g = -0.51; 95%CI:-1.02 to 0.01; I2 = 20%; k = 3) did not show significant treatment effects. One study was found on Integrative Collaborative Care. CONCLUSIONS: This meta-analysis found a robust moderate treatment effect of CBT for MDD during pregnancy, and to a lesser extent for IPT. As an alternative, positive results were found for body-oriented interventions and acupuncture. No evidence was found for bright light therapy and food supplements. Only non-pharmacological trials on women with MDD were found. Research on a wider range of AMD is needed.

Bright light therapy in pregnant women with major depressive disorder: study protocol for a randomized, double-blind, controlled clinical trial.

BACKGROUND: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. METHODS: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. DISCUSSION: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. TRIAL REGISTRATION: Netherlands Trial Register NTR5476 . Registered 5 November 2015.

Current and remitted depression and anxiety disorders as risk factors for medication nonadherence.

OBJECTIVE: To investigate the impact of current and remitted depression and anxiety disorders and sociodemographic and other related factors on medication nonadherence in a large cohort study. METHOD: The Medication Adherence Rating Scale was used to assess medication nonadherence of 1,890 medication users in the 4-year follow-up assessment of the Netherlands Study of Depression and Anxiety, which was conducted between 2008 and 2011. Psychiatric diagnoses according to the DSM-IV, sociodemographic and clinical characteristics, and medication use were determined. Medication nonadherence was defined by the tendency to forget a dose, change the dose, stop for a while, skip 1 dose, or take a smaller dosage than prescribed. RESULTS: Overall medication nonadherence was 44%. In multivariate analyses, all current and remitted depression and anxiety diagnoses were risk factors for medication nonadherence as compared to subjects never having had a depressive or anxiety diagnosis (P < .05). Age (OR = 0.85, P < .001) and antidepressant use (OR = 0.66, P = .001) were associated with less medication nonadherence. Alcohol dependence (OR = 1.67, P = .05) and the number of dietary supplements (OR = 1.18, P = .02) proved risk factors for medication nonadherence. Associations of anxiety diagnosis with medication nonadherence were mainly driven by depression diagnosis. CONCLUSIONS: All current and remitted depression and anxiety disorders were risk factors for medication nonadherence. Since these disorders are highly comorbid with other medical conditions, health care workers should address medication nonadherence in patients with depression and/or anxiety disorders, even in those who are in symptomatic remission.

Dose-time dependency of hyperbaric hyperoxia-induced DNA strand breaks in human immune cells visualized with the comet assay.

PURPOSE: Hyperbaric oxygen exposure may induce dose-dependent DNA damage in peripheral blood mononuclear cells (PBMCs), and repetitive exposures of man may have protective cellular effects. METHOD: PBMCs, freshly isolated from non-divers and pure oxygen divers, were exposed to ambient air (21kPa) and hyperoxia at different levels: 100kPa, 240kPa, 400kPa and 600kPa) for up to 6.5 hours in an experimental pressure chamber. DNA double-strand breaks were studied in the comet assay by calculating the "tail moment" and an alternative "Yes or No" method for damaged nuclei. Previously, the experimental procedure had been optimized for human cell experiments: Pre-tests assured that DNA damage could be considered to be oxygen-induced; and cell viability remained over 95% during exposure time. RESULTS: Visible DNA damage increased with the partial pressure of oxygen (pO2) and exposure time dose-dependently. Linear regressions revealed r2 between 0.61 and 0.98 with the Yes/No method, and significant differences in slopes from control. Tail moment showed similar results, but with less accuracy. The PBMCs of oxygen divers exposed to 400kPa pO2 (up to six hours) showed a significant lower slope in the linear regression. CONCLUSION: Oxygen induces dose-dependent DNA double-strand breaks, and the Yes/No discrimination is superior to the tail moment in linearity and accuracy. Oxygen diver PBMCs seem to be more resistant to hyperbaric oxygen.

Influence of hyperoxia and physical exercise on *OH-radical stress in humans as measured by dihydroxylated benzoates (DHB) in urine.

BACKGROUND: Hyperoxia and physical exercise are known to produce reactive oxygen species (ROS), and the *OH radical is the most aggressive among them. However, knowledge is limited about *OH stress during physical work under hyperoxic conditions. METHODS: This study monitored *OH stress in human volunteers before and after a total of 135 exposures to ambient air (control), different levels of hyperoxia at rest and challenging open-water closed-circuit dives by measurement of dihydroxylated benzoates (DHB) with HPLC by electrochemical detection in urine. RESULTS: Changes in DHB in urine after control were only 3.43 +/- 4.8% (n = 9). After exposures to 100 kPa oxygen (O2) for 110 minutes DHB revealed increases in urine of 23.14 +/- 5.12% (n = 9); exposures to 240 kPa O2 for 90 minutes increases of 22.38 +/- 8.91% (n = 8); and 280 kPa 02 for 30 minutes of 21.92 +/- 10.76% (n = 17). Closed-circuit dives in open water (45-54 minutes of 125-160 kPa O2) revealed DHB increases of 66.34 +/- 25.73% (n = 92). All results differed significantly from control (p < 0.001). The closed-circuit dives also differed significantly from all exposures to hyperoxia without exercise (p < 0.001). Standardization of "oxygen burden" during each exposure (pO2 x exposure time x VO2) allowed for comparison of different exposures vs. DHB changes and revealed goodness of linear fit of r2 = 0.432 (p < 0.0001). CONCLUSIONS: Increases in urine DHB after exposures to different levels of hyperoxia at rest and during exercise are consistent with *OH stress that is greater during exercise than at rest, although other interpretations are possible. Standardization of the individual "oxygen burden" for a given exposure may become useful in future for the estimation of *OH stress.

Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial.

CONTEXT: Major depressive disorder (MDD) in elderly individuals is prevalent and debilitating. It is accompanied by circadian rhythm disturbances associated with impaired functioning of the suprachiasmatic nucleus, the biological clock of the brain. Circadian rhythm disturbances are common in the elderly. Suprachiasmatic nucleus stimulation using bright light treatment (BLT) may, therefore, improve mood, sleep, and hormonal rhythms in elderly patients with MDD. OBJECTIVE: To determine the efficacy of BLT in elderly patients with MDD. DESIGN: Double-blind, placebo-controlled randomized clinical trial. SETTING: Home-based treatment in patients recruited from outpatient clinics and from case-finding using general practitioners' offices in the Amsterdam region. PARTICIPANTS: Eighty-nine outpatients 60 years or older who had MDD underwent assessment at baseline (T0), after 3 weeks of treatment (T1), and 3 weeks after the end of treatment (T2). Intervention Three weeks of 1-hour early-morning BLT (pale blue, approximately 7500 lux) vs placebo (dim red light, approximately 50 lux). MAIN OUTCOME MEASURES: Mean improvement in Hamilton Scale for Depression scores at T1 and T2 using parameters of sleep and cortisol and melatonin levels. RESULTS: Intention-to-treat analysis showed Hamilton Scale for Depression scores to improve with BLT more than placebo from T0 to T1 (7%; 95% confidence interval, 4%-23%; P = .03) and from T0 to T2 (21%; 7%-31%; P = .001). At T1 relative to T0, get-up time after final awakening in the BLT group advanced by 7% (P < .001), sleep efficiency increased by 2% (P = .01), and the steepness of the rise in evening melatonin levels increased by 81% (P = .03) compared with the placebo group. At T2 relative to T0, get-up time was still advanced by 3% (P = .001) and the 24-hour urinary free cortisol level was 37% lower (P = .003) compared with the placebo group. The evening salivary cortisol level had decreased by 34% in the BLT group compared with an increase of 7% in the placebo group (P = .02). CONCLUSIONS: In elderly patients with MDD, BLT improved mood, enhanced sleep efficiency, and increased the upslope melatonin level gradient. In addition, BLT produced continuing improvement in mood and an attenuation of cortisol hyperexcretion after discontinuation of treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00332670.

Bright light in elderly subjects with nonseasonal major depressive disorder: a double blind randomised clinical trial using early morning bright blue light comparing dim red light treatment.

BACKGROUND: Depression frequently occurs in the elderly. Its cause is largely unknown, but several studies point to disturbances of biological rhythmicity. In both normal aging, and depression, the functioning of the suprachiasmatic nucleus (SCN) is impaired, as evidenced by an increased prevalence of day-night rhythm perturbations, such as sleeping disorders. Moreover, the inhibitory SCN neurons on the hypothalamus-pituitary adrenocortical axis (HPA-axis) have decreased activity and HPA-activity is enhanced, when compared to non-depressed elderly. Using bright light therapy (BLT) the SCN can be stimulated. In addition, the beneficial effects of BLT on seasonal depression are well accepted. BLT is a potentially safe, nonexpensive and well accepted treatment option. But the current literature on BLT for depression is inconclusive. METHODS/DESIGN: This study aims to show whether BLT can reduce non-seasonal major depression in elderly patients. Randomized double blind placebo controlled trial in 126 subjects of 60 years and older with a diagnosis of major depressive disorder (MDD, DSM-IV/SCID-I). Subjects are recruited through referrals of psychiatric outpatient clinics and from case finding from databases of general practitioners and old-people homes in the Amsterdam region. After inclusion subjects are randomly allocated to the active (bright blue light) vs. placebo (dim red light) condition using two Philips Bright Light Energy boxes type HF 3304 per subject, from which the light bulbs have been covered with bright blue- or dim red light- permitting filters. Patients will be stratified by use of antidepressants. Prior to treatment a one-week period without light treatment will be used. At three time points several endocrinological, psychophysiological, psychometrically, neuropsychological measures are performed: just before the start of light therapy, after completion of three weeks therapy period, and three weeks thereafter. DISCUSSION: If BLT reduces nonseasonal depression in elderly patients, then additional lighting may easily be implemented in the homes of patients to serve as add-on treatment to antidepressants or as a stand-alone treatment in elderly depressed patients. In addition, if our data support the role of a dysfunctional biological clock in depressed elderly subjects, such a finding may guide further development of novel chronobiological oriented treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00332670.

Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial.

CONTEXT: Cognitive decline, mood, behavioral and sleep disturbances, and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers. Circadian rhythm disturbances have been associated with these symptoms. OBJECTIVE: To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system: bright light and melatonin. DESIGN, SETTING, AND PARTICIPANTS: A long-term, double-blind, placebo-controlled, 2 x 2 factorial randomized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherlands; mean (SD) age, 85.8 (5.5) years; 90% were female and 87% had dementia. INTERVENTIONS: Random assignment by facility to long-term daily treatment with whole-day bright (+/- 1000 lux) or dim (+/- 300 lux) light and by participant to evening melatonin (2.5 mg) or placebo for a mean (SD) of 15 (12) months (maximum period of 3.5 years). MAIN OUTCOME MEASURES: Standardized scales for cognitive and noncognitive symptoms, limitations of activities of daily living, and adverse effects assessed every 6 months. RESULTS: Light attenuated cognitive deterioration by a mean of 0.9 points (95% confidence interval [CI], 0.04-1.71) on the Mini-Mental State Examination or a relative 5%. Light also ameliorated depressive symptoms by 1.5 points (95% CI, 0.24-2.70) on the Cornell Scale for Depression in Dementia or a relative 19%, and attenuated the increase in functional limitations over time by 1.8 points per year (95% CI, 0.61-2.92) on the nurse-informant activities of daily living scale or a relative 53% difference. Melatonin shortened sleep onset latency by 8.2 minutes (95% CI, 1.08-15.38) or 19% and increased sleep duration by 27 minutes (95% CI, 9-46) or 6%. However, melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale, both for positive affect (-0.5 points; 95% CI, -0.10 to -1.00) and negative affect (0.8 points; 95% CI, 0.20-1.44). Melatonin also increased withdrawn behavior by 1.02 points (95% CI, 0.18-1.86) on the Multi Observational Scale for Elderly Subjects scale, although this effect was not seen if given in combination with light. Combined treatment also attenuated aggressive behavior by 3.9 points (95% CI, 0.88-6.92) on the Cohen-Mansfield Agitation Index or 9%, increased sleep efficiency by 3.5% (95% CI, 0.8%-6.1%), and improved nocturnal restlessness by 1.00 minute per hour each year (95% CI, 0.26-1.78) or 9% (treatment x time effect). CONCLUSIONS: Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia. To counteract the adverse effect of melatonin on mood, it is recommended only in combination with light. TRIAL REGISTRATION: controlled-trials.com/isrctn Identifier: ISRCTN93133646.

Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report.

BACKGROUND: Elevated arginine vasopressin (AVP) plasma levels have been observed in major depression, particularly in relation to the melancholic subtype. Two hypothalamic structures produce plasma vasopressin: the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The aim of this study was to establish which structure is responsible for the increased vasopressin plasma levels in depression. METHODS: Using in situ hybridization, we determined the amount of vasopressin messenger ribonucleic acid (mRNA) in the PVN and SON in postmortem brain tissue of nine depressed subjects (six with the melancholic subtype) and eight control subjects. RESULTS: In the SON, a 60% increase of vasopressin mRNA expression was found in depressed compared with control subjects. In the melancholic subgroup, AVP mRNA expression was significantly increased in both the SON and the PVN compared with control subjects. CONCLUSIONS: We found increased AVP gene expression in the SON in depressed subjects. This might partly explain the observed increased vasopressin levels in depression.

[Reproducibility of a German scale for assessing the need for inpatient treatment in surgery]. / Reproduzierbarkeit eines deutschsprachigen Instruments zur Erfassung der Notwendigkeit von stationären Behandlungen in der Chirurgie.

During the past years, the assessment of the appropriateness of hospital utilization has become increasingly important in the German health care system. Previous evaluations by regional review organizations in several states demonstrated the need for a standardized, reliable, and valid instrument to evaluate the appropriateness of inpatient care. Objective of the study is to test the reliability of a German adaptation of the "Appropriateness Evaluation Protocol" (AEP). Among all 2672 admissions from the department of surgery of a regional medical center during one calendar year, 54 patients were randomly selected to evaluate the inter-rater reliability and 51 patients to test intra-rater reliability. Overall agreement, specific agreement and Kappa statistics were estimated for every hospital admissions and all consecutive hospital days. The German AEP showed an inter-rater agreement of 74% (62-86%) for hospital admissions (Kappa = 0.44) and 84% (79%-88%) for all hospital days (K = 0.55). Intra-rater reliability was 88% (79%-97%) for hospital admissions (K = 0.60) and 88% (85%-92%) for all hospital days (K = 0.70). The observed agreement is independent of length of hospital stay and proportion of appropriate days. A standardized instrument with known metric properties is essential for quality management in hospitals to prepare for an increasingly consolidating health care market in Germany. The German AEP is a reliable instrument, which will allow to identify inefficiencies in the management of surgical inpatients.

[Is total thyroidectomy and lymph node excision as therapy of differentiated thyroid gland carcinomas in childhood justified?]. / Ist die totale Thyreoidektomie und Lymphknotendissektion zur Therapie differenzierter Schilddrüsenkarzinome im Kindesalter angezeigt?

The extent of radical resection of differentiated thyroid carcinomas in children (< 18 years) is discussed controversially because of good prognosis, on the one hand, but a high rate of lymph node metastases, greater tumor size, lung metastases and tumor recurrences on the other. Because of our data we advocate thyroidectomy, cervical lymph node dissection and postoperative 131J-therapy as the treatment of choice in patients with manifest disease in order of further detection and/or treatment of lung metastases. Limited radicality (i.e. hemithyroidectomy) should be reserved for children with small and occult tumors.

[Lactic acidosis--recognition and treatment of an important complication of perioperative parenteral nutrition]. / Lactatacidose--Erkennung und Behandlung einer wichtigen Komplikation unter perioperativer parenteraler Ernährung.

We report 5 cases of acute vitamin B-1 induced lactic acidosis in surgical patients receiving parenteral nutrition. In all patients treatment with vitamin B-1 induced a dramatical improvement of clinical findings. 4 patients recovered completely, 1 patient died from already developed irreversible cardiocirculatory failure. These cases underline the need for regular vitamin B-1 substitution in patients with parenteral nutrition and preoperatively in alcoholics and in patients, in whom a sufficient food intake can not be assured.

Current status of anti-bradycardial electrotherapy.

A review of the current status of cardiac pacing in the treatment of cardiac bradyarrhythmias is presented. The article describes the indications, haemodynamic principles of differentiated treatment and the technical potential of a new generation of (multi-mode and multi-parameter programmable, rate responsive) devices.

[Malnutrition and anemia in children hospitalized in Martinique]. / Malnutrition et anémie chez des enfants hospitalisés en Martinique.

In order to assess prevalences, characteristics and risk factors of malnutrition and anemia, a clinical and biological study was undertaken at Lamentin hospital in 100 hospitalized children aged 6 months to 6 years. Forty seven p. cent of children were underweight and 38 p. cent were anemic. Anemia and iron deficiency predominated in the under-24-month age group, whereas wasting was the dominate finding in older children. Under 2 years of age, risk factors for wasting and anemia were associated with method of breastfeeding. Over 2 years of age, low birthweight was the only risk factor of wasting identified. In Martinique, nutritional deficiency is common in children admitted to hospital and a high index of suspicion is indicated in the hospitalized population. Following the resolution of infections, supplemental iron therapy must be considered for a great number of children under 2 years of age.