The association between mixed symptoms, irritability and functioning measured using smartphones in bipolar disorder.

OBJECTIVE: To (i) validate patient-evaluated mixed symptoms and irritability measured using smartphones against clinical evaluations; (ii) investigate associations between mixed symptoms and irritability with stress, quality of life and functioning, respectively, in patients with bipolar disorder. METHODS: A total of 84 patients with bipolar disorder used a smartphone-based system for daily evaluation of mixed symptoms and irritability for nine months. Clinically evaluated symptoms, stress, quality of life and clinically rated functioning were collected multiple times during follow-up. RESULTS: Patients presented mild affective symptoms. Patient-reported mixed symptoms and irritability correlated with clinical evaluations. In analyses including confounding factors there was a statistically significant association between both mixed symptoms and irritability and stress (P < 0.0001) and between irritability and both quality of life and functioning (P < 0.0001) respectively. There was no association between mixed mood and both quality of life and functioning. CONCLUSION: Mixed symptoms and irritability can be validly self-reported using smartphones in patients with bipolar disorder. Mixed symptoms and irritability are associated with increased stress even during full or partial remission. Irritability is associated with decreased quality of life and functioning. The findings emphasize the clinical importance of identifying inter-episodic symptoms including irritability pointing towards smartphones as a valid tool.

Distance to pig farms as risk factor for community-onset livestock-associated MRSA CC398 infection in persons without known contact to pig farms-A nationwide study.

MRSA CC398 is an emerging MRSA strain found in livestock, mainly in pigs. Direct occupational livestock contact is the principal risk factor for human MRSA CC398 infection. Nonetheless, in recent years, an increasing number of MRSA CC398 cases has been observed in persons without known pig contact. Such cases, referred to as MRSA CC398 of unknown origin (MUO CC398), have, like livestock-onset (LO) MRSA CC398 cases, been found concentrated in rural, livestock-producing areas. The presence of MUO CC398 cases indicates alternative and unknown MRSA CC398 transmission pathways into the community. We performed a nationwide study in Denmark of the geographic distributions of MRSA cases in general and persons with MUO CC398 or LO MRSA CC398 infections (1 January 2006-11 February 2015), with the Danish population as background population. Place of living of study persons was mapped using the ArcGIS software, and information on pig farms was retrieved from the Central Husbandry Register. The incidence of MUO CC398 infections was clearly higher in rural than in urban areas, and such cases lived on average closer to pig farms than the general population. However, within three pig-farming-dense municipalities, patients with MUO CC398 infections did not live closer to pig farms than population controls. This shows that direct environmental spread from neighbouring pig farms of MRSA CC398 is unlikely. Instead, community spread through other means of transmission than direct spread from farms may more likely explain the clustering of MUO CC398 in livestock-dense areas.

Voice analysis as an objective state marker in bipolar disorder.

Changes in speech have been suggested as sensitive and valid measures of depression and mania in bipolar disorder. The present study aimed at investigating (1) voice features collected during phone calls as objective markers of affective states in bipolar disorder and (2) if combining voice features with automatically generated objective smartphone data on behavioral activities (for example, number of text messages and phone calls per day) and electronic self-monitored data (mood) on illness activity would increase the accuracy as a marker of affective states. Using smartphones, voice features, automatically generated objective smartphone data on behavioral activities and electronic self-monitored data were collected from 28 outpatients with bipolar disorder in naturalistic settings on a daily basis during a period of 12 weeks. Depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale 17-item and the Young Mania Rating Scale, respectively, by a researcher blinded to smartphone data. Data were analyzed using random forest algorithms. Affective states were classified using voice features extracted during everyday life phone calls. Voice features were found to be more accurate, sensitive and specific in the classification of manic or mixed states with an area under the curve (AUC)=0.89 compared with an AUC=0.78 for the classification of depressive states. Combining voice features with automatically generated objective smartphone data on behavioral activities and electronic self-monitored data increased the accuracy, sensitivity and specificity of classification of affective states slightly. Voice features collected in naturalistic settings using smartphones may be used as objective state markers in patients with bipolar disorder.

Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial.

BACKGROUND: The number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence. Nevertheless, the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a randomized controlled trial (RCT). The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder. METHOD: A total of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18-60 years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young Mania Rating Scale (YMRS) scores ≤17 were randomized to the use of a smartphone for daily self-monitoring including a clinical feedback loop (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for 6 months. The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS, respectively, between the intervention and control groups. RESULTS: Intention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones on depressive as well as manic symptoms. There was a tendency towards more sustained depressive symptoms in the intervention group (B = 2.02, 95% confidence interval -0.13 to 4.17, p = 0.066). Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group. CONCLUSIONS: These results highlight that electronic self-monitoring, although intuitive and appealing, needs critical consideration and further clarification before it is implemented as a clinical tool.

Predictors of body composition changes during tuberculosis treatment in Mwanza, Tanzania.

BACKGROUND/OBJECTIVES: Gains in fat mass and lean mass during tuberculosis (TB) treatment may determine functional recovery and survival; yet, data are scarce. We aimed to assess predictors of fat and fat-free mass during 2 months of intensive TB treatment in a cohort in Mwanza, Tanzania. SUBJECTS/METHODS: Fat and fat-free mass were determined at the start of TB treatment and repeated after 2 months using the deuterium dilution technique. Gains in fat and fat-free mass were determined and predictors assessed using regression analysis. RESULTS: Data for 116 patients were available at baseline and during follow-up. Of these, 38.8% were females, mean age was 37.3 (s.d. 13.5) years, 69% (81) had sputum-positive TB, 45.7% (53) were HIV infected and 25% (29) were current smokers. The mean weight gain was 3.3 kg (95% confidence interval: 2.7; 3.8), and it did not differ by sex. However, compared with females, males had 1.0 (0.4; 1.6) kg/m(2) lower fat mass but 0.7 (0.2; 1.3) kg/m(2) higher fat-free mass gain. Current smoking was associated with higher fat mass (0.7 kg/m(2), 0.04; 1.4) but lower fat-free mass (-0.5 kg/m(2), -1.2; 0.07) gain. Among HIV-infected patients, antiretroviral therapy (ART) led to a lower fat gain (-1.2 kg/m(2), -2.2; -0.2) but to a higher fat-free mass among sputum-negative (2.9 kg/m(2), 0.8; 5.1) but not sputum-positive patients. CONCLUSIONS: During intensive phase of TB treatment, sex, smoking and ART were predictors of body composition. Larger studies are needed to further understand predictors of body composition during recovery, to help design interventions to improve treatment outcomes.

Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression.

BACKGROUND: Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing. METHOD: In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD-). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals. RESULTS: Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD- individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD- group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals. CONCLUSIONS: Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.

The use of combined heart rate response and accelerometry to assess the level and predictors of physical activity in tuberculosis patients in Tanzania.

SUMMARY: We assessed the role of tuberculosis (TB) disease and HIV infection on the level of physical activity. A combined heart rate and movement sensor was used to assess habitual physical activity in TB patients and non-TB controls. The association between sputum-negative TB, sputum-positive TB, HIV and physical activity estimates were assessed in multivariable linear regression models adjusted for age, sex, haemoglobin and alpha-1-acid glycoprotein (AGP). Sputum-positive [eB 0·43, 95% confidence interval (CI) 0·29-0·64] and sputum-negative (eB 0·67, 95% CI 0·47-0·94) TB as well as HIV infection (eB 0·59, 95% CI 0·46-0·75) were associated with reduced activity compared to controls. Anaemia accounted for a substantial part of the effects of HIV, while elevated AGP primarily mediated the TB effect. The level of physical activity is highly influenced by TB and HIV, and mainly mediated through anaemia of infection and associated with elevated acute phase response.

The role of anthropometric and other predictors for diabetes among urban Tanzanians with tuberculosis.

BACKGROUND: As diabetes impairs tuberculosis (TB) treatment outcomes, it is essential to identify diabetes among TB patients. While little is known about predictors of diabetes among healthy individuals in Africa, predictors among TB patients are almost non-existent. OBJECTIVE: To assess potential predictors for diabetes among newly diagnosed pulmonary TB patients in Tanzania. METHODS: TB patients were tested for diabetes using an oral glucose tolerance test, demographic information was collected and anthropometric measurements taken. The association between diabetes and possible predictors were examined using logistic regression analyses. RESULTS: Of 1205 TB patients, 16.4% (n = 197) had diabetes, 9.0% (n = 108) were aged ≥55 years, 3.3% (n = 40) were overweight (body mass index [BMI] ≥ 25 kg/m(2)) and 12.7% (n = 152) severely underweight (BMI < 16 kg/m(2)). Diabetes was most prevalent in the 45-55 year age group, and increasing weight, BMI and waist circumference were associated with diabetes. Severe underweight (BMI < 16 kg/m(2)) among male TB patients (sex-BMI interaction, P = 0.02) was associated with diabetes (OR 2.52, P = 0.004). CONCLUSION: Diabetes is a common comorbidity among TB patients. Although diabetes was associated with obesity and was more prevalent among the middle-aged, the majority of TB patients with diabetes comorbidity were young and lean. With diabetes as a major risk factor for TB, and with the lack of strong predictors for diabetes, universal diabetes screening should be implemented in the TB programme.

Geographical variation of sporadic Legionnaires' disease analysed in a grid model.

The aim was to analyse variation in incidence of sporadic Legionnaires' disease in a geographical information system in three time periods (1990-2005) by the application of a grid model and to assess the model's validity by analysing variation according to grid position. Coordinates of the addresses at time of disease of 606 confirmed cases with Legionnaires' disease were obtained. The incidence was calculated in cells of 10 x 10 km in 25 different grids superimposed on a map of Denmark. A 95% and 99% threshold was applied to identify cells with excess incidence representing potential clusters. Four cells had excess incidence in all three time periods. The analysis in 25 different grid positions indicated a low risk of overlooking cells with excess incidence in a random grid. The coefficient of variation ranged from 0.08 to 0.11 independent of the threshold. By application of a random grid model we demonstrated that it was possible to detect small areas with excess incidence that were not detected in the present surveillance system.

Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis.

The aim of the present study was to evaluate the potential of diagnostic tests based on interferon-gamma inducible protein (IP)-10 and monocyte chemotactic protein (MCP)-2, and compare the performance with the QuantiFERON TB Gold In-Tube (QFT-IT; Cellestis, Carnagie, Australia) test. IP-10 and MCP-2 were determined in supernatants from whole blood stimulated with Mycobacterium tuberculosis-specific antigens. Samples were obtained from 80 patients with culture- and/or PCR-proven tuberculosis (TB), and 124 unexposed healthy controls: 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on receiver operating characteristic curve analysis. TB patients produced significantly higher levels (median) of IP-10 (2158 pg x mL(-1)) and MCP-2 (379 pg x mL(-1)) compared with interferon (IFN)-gamma (215 pg x mL(-1)). The QFT-IT, IP-10 and MCP-2 tests detected 81, 83 and 71% of the TB patients; 0, 3 and 0% of the high school students and 0, 16 and 3% of the staff, respectively. Agreement between tests was high (>89%). By combining IP-10 and IFN-gamma tests, the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students. In conclusion, interferon-gamma inducible protein-10 and monocyte chemotactic protein-2 responses to Mycobacterium tuberculosis-specific antigens could be used to diagnose infection. Combining interferon-gamma inducible protein-10 and interferon-gamma may be a simple approach to increase the detection rate of the Mycobacterium tuberculosis-specific in vitro tests.

Replacement of a severe chronic post-traumatic aneurysm of the ascending aorta with aortic valve conduit--reconstruction of the anterior mitral valve ring and implantation of A-V sequential/biventricular pacemaker.

We present the case of a 23-year-old African professional footballer who was admitted on April 1, 1999 to the Cardiology Department of the University Hospital in Magdeburg, on an emergency basis, from a regional lung clinic. According to the history, he was involved in a collision with an opposing player during a football match in his country (in Africa). He lost consciousness for a short time, but continued playing to the end of the match. About two months later he was invited by a German football club for a check-up, with the view to ultimately playing for the club. The team did not find him physically fit enough to play professional football, so he decided to go to Paris by bus on March 31, 1999. During the journey he suddenly became cardio-pulmonary decompensated and had to undergo cardio-pulmonary resuscitation (CPR). He was intubated and placed on a respirator and immediately transferred to a nearby lung clinic. From the lung clinic he was transferred to the Intensive Care Unit of the Cardiology Department of the Magdeburg University Hospital, on April 1, 1999 as an emergency case. He was intensively treated with catecholamines, intravenous ACE inhibitors and diuretics. His clinical condition did not improve appreciably. His chest X-ray showed extreme dilatation of the right and left heart as well as extreme pulmonary congestion.

Cardiopulmonary effects of non-invasive positive pressure ventilation (NPPV)--a controlled, prospective study.

BACKGROUND: This study was undertaken to investigate the haemodynamic effect of non-invasive positive pressure ventilation (NPPV) in patients after cardiac surgery. NPPV has recently become popular as method for treating acute respiratory failure. Its influence on cardiopulmonary haemodynamics is still unknown. METHODS: 30 extubated low-risk patients were included in four study intervals after cardiac surgery. During the first and the third interval, the patients breathed spontaneously and received oxygen via face mask for 45 min. Both intervals were followed by 45 min on NPPV. RESULTS: Cardiac index increased significantly from 2.8 to 3.1 ml/min/m2 during NPPV (p < 0.001) and from 2.7 to 3.2 ml/ min/m2 (p < 0.001). Mixed venous saturation rose significantly from 72.4 to 74.8 % (p < 0.001) and from 72.1 to 75.4 % (p < 0.001) during NPPV while the oxygen extraction ratio decreased from 25.5 and 26.1 % to 23.0 (p < 0.001) and 22.6 % (p < 0.001) during NPPV. At the same time, urine production increased significantly from 182 to 328 ml/h and from 186 to 285 ml/h (p < 0.001). Heart rate and mean arterial blood pressure rose significantly during NPPV. There were no significant changes in systemic and pulmonary haemodynamics, oxygenation or CO 2 elimination. CONCLUSIONS: NPPV improves CI significantly in stable cardiac surgery patients. Factors other than blood pressure, vascular resistance or blood gases must exert an additional influence on CI. They are still not identified. Changes in transmural pressure during NPPV may play an important role.

Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat.

Stevioside, a glycoside present in the leaves of the plant, Stevia rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro. Its potential antihyperglycemic and blood pressure-lowering effects were examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat. Rats were fed 0.025 g x kg(-1) x d(-1) of stevioside (purity > 99.6%) for 6 weeks. An intra-arterial catheter was inserted into the rats after 5 weeks, and conscious rats were subjected to arterial glucose tolerance test (2.0 g x kg(-1)) during week 6. Stevioside had an antihyperglycemic effect (incremental area under the glucose response curve [IAUC]): 985 +/- 20 (stevioside) versus 1,575 +/- 21 (control) mmol/L x 180 minutes, (P <.05), it enhanced the first-phase insulin response (IAUC: 343 +/- 33 [stevioside] v 136 +/- 24 [control] microU/mL insulin x 30 minutes, P <.05) and concomitantly suppressed the glucagon levels (total AUC: 2,026 +/- 234 [stevioside] v 3,535 +/- 282 [control] pg/mL x 180 minutes, P <.05). In addition, stevioside caused a pronounced suppression of both the systolic (135 +/- 2 v 153 +/- 5 mm Hg; P <.001) and the diastolic blood pressure (74 +/- 1 v 83 +/- 1 mm Hg; P <.001). Bolus injections of stevioside (0.025 g x kg(-1)) did not induce hypoglycemia. Stevioside augmented the insulin content in the beta-cell line, INS-1. Stevioside may increase the insulin secretion, in part, by induction of genes involved in glycolysis. It may also improve the nutrient-sensing mechanisms, increase cytosolic long-chain fatty acyl-coenzyme A (CoA), and downregulate phosphodiesterase 1 (PDE1) estimated by the microarray gene chip technology. In conclusion, stevioside enjoys a dual positive effect by acting as an antihyperglycemic and a blood pressure-lowering substance; effects that may have therapeutic potential in the treatment of type 2 diabetes and the metabolic syndrome.

Effect of topical nasal pharmaceuticals on sodium and chloride transport by human airway epithelia.

The human airway epithelium lines the respiratory tract from the nasal mucosa to the bronchioles. Electrolyte transport by these epithelia is crucial in maintaining the appropriate volume and salt composition of the airway surface fluid. When this epithelium becomes functionally impaired, the airways are more prone to respiratory infections. We studied the effect of six common topical agents that are commonly used to treat rhinorrhea and nasal inflammation on the transepithelial resistance, sodium, and chloride transport of primary cultures of human airway epithelia grown at the air-liquid interface. The pharmaceuticals fluticasone propionate, cromolyn sodium, ipratropium bromide, azelastine, oxymetazoline, and normal saline were used and the electrical function of the epithelia was studied in Ussing chambers. Azelastin and ipratropium bromide-treated epithelia were found to have a significant decrease in transepithelial resistance. Both normal saline and fluticasone propionate resulted in significant increases in amiloride-sensitive short circuit currents that reflect sodium transport. Finally, normal saline resulted in a significant increase in bumetanide-sensitive short circuit current that reflects chloride transport across the epithelia. The data presented may explain a mechanism by which some topical pharmaceuticals help reduce rhinorrhea, and may point to some unwanted side effects of some pharmaceuticals on the electrolyte transport of the airway epithelia. In summary, several of the common topical nasal agents alter the electrolyte transport of the nasal airway epithelia. The in vivo significance of these findings is to be determined.

The European Society for Medical Oncology (ESMO) and its activities through the Central Eastern European Task Force.

The article describes the history and organization of the European Society for Medical Oncology. The society, founded in 1975, aims at advancing medical oncology on a pan-European basis. Postgraduate training and education constitute a major part of ESMO's activities through a current CME programme of courses and other activities. Each year the ESMO Examination is held, and every other year ESMO organizes its congresses with the latest attendance of more than 6000 delegates. ESMO has a continuous increase of members, also from outside Europe. In 1996 ESMO created the Central Eastern European Programme with the aim to support the needs of the countries of the former Eastern Europe. A task force (CEE TF) with members from 16 Central Eastern European countries meets twice a year to discuss key areas. An e-mail communication system has been launched, courses are planned for 1998-1999, exchange programmes are in progress, and support in setting up national guidelines will follow. A Central Eastern European Oncology Group (CEE OG), which performs clinical trials on a cooperative basis, has been established with ESMO guidance.

[Results after surgery of incisional hernias]. / Resultater efter operation for hernia incisionalis.

The purpose of this paper is to describe the subjective results after operation for ventral hernia. Patients operated for ventral hernia in the period from January 1, 1988 to December 31, 1992 were sent a questionnaire with a response rate of 87%. Forty-five percent had lasting discomfort, 30% were absent due to illness more than eight weeks after the operation and 22% were not able to go to work. These factors increase with the number of hernia operations. Regardless of the number of operations, about 70% of the patients wanted a new operation should the hernia recur. It is therefore important to give the patient an objective and detailed information to prevent from unrealistic expectations of the results of ventral hernia operation.

Rectangular surface-relief transmission gratings with a very large first-order diffraction efficiency (~95%) for unpolarized light.

Computer optimization shows that the first-order diffraction efficiency of a lossless-transmission surface-relief grating with a rectangular surface profile can be made very large (~95%) simultaneously for light of TE and TM polarizations incident near the Bragg angle by the proper choice of the fill factor. The case for visible light incident close to the Bragg angle on unslanted gratings with periodicities corresponding to Bragg angles of 30 degrees , 37.5 degrees , and 45 degrees is presented. The refractive index of the grating material was chosen in the range between 1.2 and 2.