Insulin-like Factor 3, Basal and Human Chorionic Gonadotropin-Stimulated Testosterone as Biomarkers to Predict the Effect of Testosterone Replacement in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency.

INTRODUCTION: Mild Leydig cell insufficiency affects a substantial proportion of testicular cancer survivors. Previous studies have not shown a beneficial effect of testosterone replacement therapy, however, with a pronounced interindividual effect. Thus, biomarkers identifying the subgroups that might benefit are wanted. We aimed to determine if insulin-like factor 3 (INSL3), basal and human chorionic gonadotropin (hCG)-stimulated testosterone can predict the effect of testosterone replacement therapy in testicular cancer survivors with mild Leydig cell insufficiency. PATIENTS AND METHODS: We randomized adult testicular cancer survivors with mild Leydig cell insufficiency 1:1 to 12 months of transdermal testosterone replacement therapy (Tostran gel 2%) or placebo. INSL3, basal, and hCG-stimulated testosterone were measured at baseline. Outcomes (glucose, insulin, HbA1C, lipids, blood pressure, and body composition) were measured at baseline, 6 and 12 months. We applied a linear mixed-effect model comparing patients receiving testosterone with placebo in subgroups by biomarker. RESULTS: We included and randomized 69 patients between October 2016 and February 2018. Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had a -1.7 kg (95% CI: -3.1, -0.4) and -2.0 kg (95% CI: -3.5, -0.6) change in fat mass after 12 months of testosterone replacement therapy compared with placebo. This was not the case in patients with INSL3 and hCG-stimulated testosterone above the median. We did not find any effect of these biomarkers on glucose, insulin, HbA1c, or lipids. CONCLUSION: Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had decreased fat mass after 12 months of testosterone replacement therapy compared with placebo. It should be evaluated in larger trials if these biomarkers can be used as predictive markers identifying testicular cancer patients with mild Leydig cell insufficiency who might benefit from testosterone substitution.

Bipolar disorder and regretted behavior in relation to use of social media and online dating.

OBJECTIVES: Individuals with bipolar disorder are prone to risk-taking behavior that is subsequently regretted. Here, we investigated whether this also occurs in relation to the use of social media and online dating. METHODS: A questionnaire-based survey focusing on the use of social media and online dating was conducted among individuals attending an outpatient clinic for bipolar disorder, and among individuals attending two general practices in the same region (controls). The association between bipolar disorder and self-reported regretted behavior on social media/online dating sites was investigated using logistic regression with adjustment for age and sex. RESULTS: A total of 124 individuals with bipolar disorder and 196 individuals without affective disorder from the general practices (controls) formed the study sample. Among the individuals with bipolar disorder who used social media, 66% reported regretted behavior as a consequence of this use, whereas only 31% of the controls reported such behavior. The corresponding numbers for individuals who used online dating were 65% for those with bipolar disorder and 31% for the controls. Following adjustment for age and sex, bipolar disorder was associated with elevated risk of regretted behavior in relation to the use of both social media (adjusted odds ratio: 3.6, 95% CI: 2.2, 5.9) and online dating (adjusted odds ratio: 4.1, 95% CI: 2.1, 8.0). CONCLUSIONS: These findings suggest that risk-taking behavior and subsequent regret among individuals with bipolar disorder extend to social media and online dating. Cautious use of these platforms may be particularly relevant for individuals with bipolar disorder.

Use of social media and online dating among individuals with a history of affective disorder.

OBJECTIVES: To investigate how individuals with a history of affective disorder use and perceive their use of social media and online dating. METHODS: A questionnaire focusing on affective disorders and the use of social media and online dating was handed out to outpatients from unipolar depression and bipolar disorder clinics and general practice patients with or without a history of affective disorders (latter as controls). The association between affective disorders and use of social media and online dating was analysed using linear/logistic regression. RESULTS: A total of 194 individuals with a history of unipolar depression, 124 individuals with a history of bipolar disorder and 196 controls were included in the analysis. Having a history of unipolar depression or bipolar disorder was not associated with the time spent on social media compared with controls. Using the controls as reference, having a history bipolar disorder was associated with use of online dating (adjusted odds ratio: 2.2 (95% CI: 1.3; 3.7)). The use of social media and online dating had a mood-congruent pattern with decreased and more passive use during depressive episodes, and increased and more active use during hypomanic/manic episodes. Among the respondents with a history of affective disorder, 51% reported that social media use had an aggravating effect on symptoms during mood episodes, while 10% reported a beneficial effect. For online dating, the equivalent proportions were 49% (aggravation) and 20% (benefit), respectively. CONCLUSION: The use of social media and online dating seems related to symptom deterioration among individuals with affective disorder.

Typical Versus Atypical Antipsychotics for Acute Mania.

BACKGROUND: Mania is challenging to treat. Typical antipsychotics may be more efficient compared with atypical antipsychotics, however, with unfavorable side effects. STUDY QUESTION: To investigate the courses of acute manic episodes and correlations between changes of severity during manic episodes and type of antipsychotic treatment. STUDY DESIGN: This case record study included patients admitted with mania (International Classification of Diseases 10th revision code F30, F31.0, F31.1, F31.2 or F31.6) at the Department of Affective Disorders, Aarhus University Hospital from June 1, 2013 to April 1, 2016. MEASURES AND OUTCOMES: The doses of typical and atypical antipsychotics were standardized as defined daily dose according to the World Health Organization's guidelines. The severity of mania was measured up to 3 times daily with the Modified Bech-Rafaelsen Mania Scale (MAS-M), a nurse administered scale. We applied a linear regression in a mixed model approach to compare MAS-M score over time under the influence of typical plus atypical antipsychotics and atypical antipsychotics only. We further analyzed by mania with and without psychosis and by concomitant use of lithium and/or antiseizure medication. RESULTS: We included 56 admissions on 46 patients. The courses of the manic episodes measured by MAS-M varied between patients-both daily variations and changes over time. Patients receiving typical antipsychotics had higher baseline MAS-M, more recent admissions, and were mechanically constrained more often compared with patients receiving atypical antipsychotics only. Adjusted for age, gender, mechanical constraint, and dosage of antipsychotics, the difference in reduction of mania was -0.02 MAS-M points/d (95% confidence interval, -0.05 to 0.01) higher in the group receiving atypical antipsychotics only; however, it is not statistically or clinically significant. CONCLUSIONS: The rate of improvement of mania was similar in the two groups which supports that atypical antipsychotics can be recommended over typical antipsychotics to reduce risk of severe side effects.

No Impact of Preadmission Anti-Inflammatory Drug Use on Risk of Depression and Anxiety After Critical Illness.

OBJECTIVES: Risk of depression and anxiety is elevated after intensive care. Drugs with anti-inflammatory properties may have antidepressant and anxiolytic effects. The aim of this study was to investigate the association between preadmission use of drugs with anti-inflammatory effects and risk of new-onset depression and anxiety among adult patients admitted to an ICU. DESIGN: Propensity score-matched, population-based cohort study. SETTING: All ICUs in Denmark from 2005 to 2013. PATIENTS: Adults receiving mechanical ventilation in an ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 48,207 ICU patients were included. Exposures were preadmission single-agent or combined use of statins, nonsteroidal anti-inflammatory drugs, or glucocorticoids. Outcomes were cumulative incidence (risk) and risk ratio of new-onset psychiatrist-diagnosed depression or anxiety or prescriptions for antidepressants or anxiolytics. Propensity score matching yielded 6,088 statin user pairs, 2,886 nonsteroidal anti-inflammatory drug user pairs, 1,440 glucocorticoid user pairs, and 1,743 combination drug user pairs. The cumulative incidence of anxiety and depression during the 3 years following intensive care was 18.0% (95% CI, 17.0-19.0%) for statin users, 21.3% (95% CI, 19.8-22.9%) for nonsteroidal anti-inflammatory drug users, 17.4% (95% CI, 15.4-19.5%) for glucocorticoid users, and 19.0% (95% CI, 16.3-20.2%) for combination users. The cumulative incidence was similar in nonusers compared with users in all drug groups. The risk ratio of depression and anxiety 3 years after admission to ICU was 1.04 (95% CI, 0.96-1.13) for statin users, 1.00 (95% CI, 0.90-1.11) for nonsteroidal anti-inflammatory drug users, 0.97 (95% CI, 0.82-1.14) for glucocorticoid users, and 1.05 (95% CI, 0.90-1.21) for combination users, compared with nonusers. Results were consistent across subgroups (gender, age, preadmission diseases, type of admission) and sensitivity analyses (depression and anxiety separately). CONCLUSIONS: Preadmission use of statins, nonsteroidal anti-inflammatory drugs, glucocorticoids, or combinations did not alter the risk of depression and anxiety after critical illness.

Improving quality of life and physical health in patients with schizophrenia: A 30-month program carried out in a real-life setting.

BACKGROUND: Patients with schizophrenia experience low quality of life (QoL) and poor physical health, which is explained, in part, by unhealthy lifestyle, tobacco smoking, poor diet and sedentary behavior. AIM: To measure QoL and physical health in patients with schizophrenia and to quantify associations between QoL and physical health. METHODS: This was a naturalistic longitudinal 30-month follow-up study including individual guidance, group sessions and treatment as usual. RESULTS: We included 190 patients. QoL was low among newly diagnosed patients. Higher body mass index was significantly associated with lower QoL. Newly diagnosed male patients showed lower QoL compared with females. Newly diagnosed patients experienced worsened health during the study period. In contrast, long-term schizophrenic patients started with worse physical health but improved with regard to weight, waist circumferences, intake of fast food and soft drinks, and light physical activity level. Newly diagnosed patients improved their QoL ( p = .056), and the psychological domain improved by 8.0 points ( p = .003). The number of interventions was positively associated with QoL. CONCLUSION: Patients with schizophrenia presented with low QoL and elevated risk factors for poor physical health. The intervention added onto 'treatment as usual' improved some risk factors for poor physical health among long-term patients. The number of interventions had an elevating effect on QoL in patients.

Seasonal variations in hospital admissions for mania: Examining for associations with weather variables over time.

BACKGROUND: Bipolar disorder is characterized by a seasonal pattern with emerging evidence that weather conditions may trigger symptoms. Thus, our aims were to investigate if year-to-year variations in admissions with mania correlated with year-to-year variations in key meteorological variables, if there was a secular trend in light of climate change and if gender or admission status influenced the seasonal pattern. METHODS: We undertook a Danish register-based nationwide historical cohort study. We included all adults hospitalized to psychiatric care from 1995 to 2012 with mania using the Danish Psychiatric Central Research Register. The Danish Meteorological Institute provided the meteorological variables. The association between weather and admissions was tested using linear regression. RESULTS: Our database comprised 24,313 admissions with mania. There was a seasonal pattern with admission rates peaking in summer. Higher admission rates were associated with more sunshine, more ultraviolet radiation, higher temperature and less snow but were unassociated with rainfall. We did not find a secular trend in the seasonal pattern. Finally, neither gender nor admission status impacted on the overall seasonal pattern of admissions with mania. LIMITATIONS: Only patients in psychiatric care were included. We could not subdivide by type of bipolar disorder. CONCLUSION: This cohort study based on more than 24,000 admissions identified a distinct seasonal pattern in hospital admissions for those with mania. We found no secular trend. This could indicate that the climate change is not impacting on seasonal patterns, that there is no link between the proposed variables or that change is currently not sufficiently distinctive.

Quality of life and clinical characteristics in a nonselected sample of patients with schizophrenia.

BACKGROUND: Patients with schizophrenia experience low quality of life (QOL). AIMS: To examine QOL in these patients and the relation between QOL and illness duration, adjusted daily doses (ADDs) of antipsychotics, body mass index (BMI), waist circumference and smoking. METHODS: In this naturalistic, cross-sectional study, 82 patients were interviewed about smoking habits. Patients completed a QOL questionnaire (World Health Organization Quality of Life-Bref) consisting of physical, psychological, social and environmental domains and had height, weight and waist circumference measured. The characteristics and QOL were correlated using multiple regression analysis. RESULTS: QOL was significantly lower in the patients than in the general population (p < .01). In first-ever diagnosed patients, QOL was associated with BMI (regression coefficient (RC): physical -0.73, psychological -1.44 and environmental -0.55; all p < .05), ADD (RC: physical 3.71, psychological 4.37 and environmental 2.94; all p < .10) and smoking (RC: physical -0.69; p < .01). In the long-term ill patients, QOL was associated with BMI (RC: physical -1.19 and psychological -1.28; all p < .05) and illness duration (RC: physical 1.38; p < .05). CONCLUSION: Patients experienced low QOL. Lower QOL was associated with high BMI, low ADD and smoking in first-ever diagnosed patients and with high BMI and short illness duration in long-term ill patients.

Mortality and secular trend in the incidence of bipolar disorder.

BACKGROUND: The world-wide interest in bipolar disorder is illustrated by an exponential increase in publications on the disorder registered in Pubmed since 1990. This inspired an investigation of the epidemiology of bipolar disorder. METHODS: This was a register-based cohort study. All first-ever diagnoses of bipolar disorder (International Classification of Diseases-10: F31) were identified in the nationwide Danish Psychiatric Central Research Register between 1995 and 2012. Causes of death were obtained from The Danish Register of Causes of Death. Age- and gender standardized incidence rates, standardized mortality ratio (SMR) and Kaplan-Meier survival estimates were calculated. RESULTS: We identified 15,334 incident cases of bipolar disorder. The incidence rate increased from 18.5/100,000 person-years (PY) in 1995 to 28.4/100,000 PY in 2012. The mean age at time of diagnosis decreased significantly from 54.5 years in 1995 to 42.4 years in 2012 (p<0.001). The mean time from first affective diagnosis to diagnosis of bipolar disorder was 7.9 years (SD 9.1). The SMR was 1.7 (95%-CI 1.2-2.1). Causes of death were mainly natural; 9% died from suicide. LIMITATIONS: Only patients in psychiatric care were included. The outpatient registry opened in 1995. Patients treated solely in outpatient units are not recorded previously. Systematic studies validating all the clinical diagnoses of the registry do not exist. CONCLUSIONS: The incidence of bipolar disorder has increased in the last 10 years. The SMR was significantly increased. Half of the patients were known to have another affective disorder. This should be considered in future decisions regarding the healthcare organization.