E-Health intervention for subthreshold depression: Reach and two-year effects of a randomized controlled trial.

BACKGROUND: There is evidence for e-Health interventions for full-blown depression. Little is known regarding commonly untreated subthreshold depression in primary care. This randomized controlled multi-centre trial assessed reach and two-year-effects of a proactive e-Health intervention (ActiLife) for patients with subthreshold depression. METHODS: Primary care and hospital patients were screened for subthreshold depression. Over 6 months, ActiLife participants received three individualized feedback letters and weekly messages promoting self-help strategies against depression, e.g., dealing with unhelpful thoughts or behavioural activation. The primary outcome depressive symptom severity (Patient Health Questionnaire;PHQ-8) and secondary outcomes were assessed 6, 12 and 24 months. RESULTS: Of those invited, n = 618(49.2 %) agreed to participate. Of them, 456 completed the baseline interview and were randomized to ActiLife (n = 227) or assessment only (n = 226). Generalised estimation equation analyses adjusting for site, setting and baseline depression revealed that depressive symptom severity declined over time, with no significant group differences at 6 (mean difference = 0.47 points; d = 0.12) and 24 months (mean difference = -0.05 points; d = -0.01). Potential adverse effects were observed at 12 months, with higher depressive symptom severity for ActiLife than control participants (mean difference = 1.33 points; d = 0.35). No significant differences in rates of reliable deterioration or reliable improvement of depressive symptoms were observed. ActiLife increased applied self-help strategies at 6 (mean difference = 0.32; d = 0.27) and 24 months (mean difference = 0.22; d = 0.19), but not at 12 months (mean difference = 0.18; d = 0.15). LIMITATIONS: Self-report measures and lack of information on patients' mental health treatment. DISCUSSION: ActiLife yielded satisfactory reach and increased the use of self-help strategies. Data were inconclusive in terms of depressive symptom changes.

Introducing a gatekeeping system for amyloid status assessment in mild cognitive impairment.

BACKGROUND: In patients with mild cognitive impairment (MCI), enhanced cerebral amyloid-ß plaque burden is a high-risk factor to develop dementia with Alzheimer's disease (AD). Not all patients have immediate access to the assessment of amyloid status (A-status) via gold standard methods. It may therefore be of interest to find suitable biomarkers to preselect patients benefitting most from additional workup of the A-status. In this study, we propose a machine learning-based gatekeeping system for the prediction of A-status on the grounds of pre-existing information on APOE-genotype 18F-FDG PET, age, and sex. METHODS: Three hundred and forty-two MCI patients were used to train different machine learning classifiers to predict A-status majority classes among APOE-ε4 non-carriers (APOE4-nc; majority class: amyloid negative (Aß-)) and carriers (APOE4-c; majority class: amyloid positive (Aß +)) from 18F-FDG-PET, age, and sex. Classifiers were tested on two different datasets. Finally, frequencies of progression to dementia were compared between gold standard and predicted A-status. RESULTS: Aß- in APOE4-nc and Aß + in APOE4-c were predicted with a precision of 87% and a recall of 79% and 51%, respectively. Predicted A-status and gold standard A-status were at least equally indicative of risk of progression to dementia. CONCLUSION: We developed an algorithm allowing approximation of A-status in MCI with good reliability using APOE-genotype, 18F-FDG PET, age, and sex information. The algorithm could enable better estimation of individual risk for developing AD based on existing biomarker information, and support efficient selection of patients who would benefit most from further etiological clarification. Further potential utility in clinical routine and clinical trials is discussed.

The association of cognitive distortions and the type of gambling in problematic and disordered gambling.

BACKGROUND: Previous studies have shown that particular types of gambling are related to the development of gambling-related problems. Further, gambling-related cognitive distortions contribute to the development of disordered gambling. The aim of the present study is to compare different gambling types with respect to cognitive distortions and the development of disordered gambling. METHODS: Based on a proactively screened sample of vocational school students (N = 6718), 309 students were selected to undergo an in-depth interview. We assessed the Gamblers-Belief-Questionnaire (GBQ) to measure gambling-related cognitive distortions and the Stinchfield questionnaire for assessing gambling-related problems. Associations between cognitive distortions, gambling-related symptoms, and types of gambling were analysed using logistic regression analyses. RESULTS: Higher scores on the GBQ subscale "belief in luck/perseverance" led to a significantly higher chance to be classified as a person with Gambling Disorder (Conditional Odds Ratio (COR) = 1.05, Confidence Interval (CI) = 1.02-1.08) as well as problematic gambling (COR = 1.04, CI = 1.01-1.06). Higher scores on the subscale "illusion of control" were also associated with problematic gambling (COR = 1.04, CI = 1.00-1.08). The multivariate analyses of the gambling types identified only sports betting as a predictor for problematic gambling (COR = 1.91, CI = 1.05-3.49). When controlling for cognitive distortions, sports betting was not significant anymore. With respect to disordered gambling, gambling on electronic gambling machines (EGMs) turned out to be a risk factor besides cognitive distortions (COR = 2.59, CI = 1.04-6.49). DISCUSSION: The present study confirmed the high relevance of cognitive distortions for problematic and disordered gambling especially for sports betting and gambling on EGMs. Preventive measures and psychotherapy should take these relationships into account.

Use of a gamma-2 herpesvirus as a vector to deliver antibodies to rhesus monkeys.

The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated in vivo delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture. Two RRV-negative rhesus monkeys were experimentally infected with recombinant RRV-4L6 and two with recombinant RRV-5L7. Following infection, the appearance of the delivered antibody was readily detected in all four animals. However, the levels of the delivered antibody were considerably lower than what has been typically observed following intramuscular AAV delivery. Furthermore, three of the four monkeys had an antibody response to the delivered antibody as had been observed previously with intramuscular AAV delivery of these same antibodies. We conclude that this recombinant herpesvirus has no inherent advantage over AAV for delivery of potentially therapeutic monoclonal antibodies in a rhesus monkey model.

Genome-wide association study of pathological gambling.

BACKGROUND: Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence. METHODS: Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence. RESULTS: No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value=6.63×10(-3)); 5'-adenosine monophosphate-activated protein kinase signalling (P-value=9.57×10(-3)); and apoptosis (P-value=1.75×10(-2)) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status. CONCLUSIONS: The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.

Long-term outcomes after endothoracic sympathetic block at the T4 ganglion for upper limb hyperhidrosis.

BACKGROUND: The aim of this study was to evaluate long-term results, quality of life, satisfaction and compensatory sweating after endothoracic sympathetic block at T4 (ESB4). METHODS: Patients who underwent an ESB4 procedure for palmar or palmoaxillary hyperhidrosis between 2001 and 2008 were included in a prospective study at a university hospital. Questionnaires devised by Keller and Milanez de Campos were applied to evaluate disease-specific quality of life. RESULTS: A total of 189 patients underwent 374 ESB4 procedures. Of 174 evaluated patients, 54 (31·0 per cent) had palmar and 120 (69·0 per cent) had palmoaxillary hyperhidrosis. Median follow-up was 92 months. In both groups, treatment successfully reduced hyperhidrosis (P < 0·001) and quality of life increased significantly after ESB4 (P < 0·001), remaining stable after 5 years. Overall satisfaction rates decreased owing to the development of compensatory sweating and recurrence during follow-up. Compensatory sweating affected 41 patients (23·6 per cent), and was severe in 11 (6·7 per cent) of 163 patients at 5-year follow-up; eight of these 11 patients had been treated for palmoaxillary sweating. The severity of compensatory sweating did not deteriorate with time. The severe recurrence rate increased to 11·0 per cent during follow-up, and was twice as common in patients treated for palmoaxillary sweating as in those treated for palmar sweating (13·2 versus 6·1 per cent respectively). Nine reoperations (5·2 per cent) were performed for persistent sweating, recurrence or compensatory sweating. CONCLUSION: T4 endothoracic sympathetic clip application is safe and effective in patients with upper limb hyperhidrosis, with stable long-term improvements in quality of life.

Changes in drinking behavior among control group participants in early intervention studies targeting unhealthy alcohol use recruited in general hospitals and general practices.

BACKGROUND: This study aims to analyze the influence of setting variables on drinking behavior in patients with unhealthy alcohol consumption recruited proactively in general medical practices (GP) and internal and surgical wards of two general hospitals (GH) assigned to control groups. METHOD: This analysis compared two control groups of RCTs targeting unhealthy alcohol consumption: one outpatient sample (GP; n=99) with one inpatient sample (GH; n=173). Both groups were recruited via systematic screening of all patients aged between 18 and 64 years and were included in the studies if drank above the at-risk criteria of the British Medical Association (20/30 g alcohol/daily) and/or fulfilled criteria of alcohol abuse or - dependence according to DSM-IV. Both samples received a non-alcohol specific brochure on healthy living after study inclusion and were re-assessed 12 months later. RESULTS: GH patients were significantly older, included of more males, had received less schooling and had a higher readiness to change at baseline than GP patients. Groups did not differ concerning alcohol-related diagnoses or smoking status. At the 12-month follow-up, significantly more GH patients revealed abstinence or drinking below the inclusion criteria (50.0% vs. 26.1%, p<.001). In a multivariate analysis, medical setting (GH vs. GP) remained a significant predictor for non-problematic drinking or abstinence even after controlling for baseline differences between groups. CONCLUSIONS: Findings suggest that untreated change from problematic alcohol use may be more intense after non-alcohol-related inpatient treatment than after having been a GP patient. Implications for brief interventions in inpatients are discussed.

Is there a role for dynamic swallowing MRI in the assessment of gastroesophageal reflux disease and oesophageal motility disorders?

OBJECTIVES: To evaluate the diagnostic value of dynamic MRI swallowing in patients with symptoms of Gastroesophageal Reflux Disease (GERD). METHODS: Thirty-seven patients (17 m/20f) with typical signs of GERD underwent MR swallowing in the supine position at 1.5 T with a phased-array body coil. Using dynamic, gradient echo sequences (B-FFE) in the coronal, sagittal and axial planes, the bolus passages of buttermilk spiked with gadolinium chelate were tracked. MRI, pH-metry and manometry were performed within 31 days and results were compared. RESULTS: MRI results were concordant with pH-metry in 82% (23/28) of patients diagnosed with abnormal oesophageal acid exposure by pH-metry. Five patients demonstrated typical symptoms of GERD and had positive findings with pH monitoring, but false negative results with MRI. In four of six patients (67%), there was a correct diagnosis of oesophageal motility disorder, according to manometric criteria, on dynamic MRI. The overall accuracy of MRI diagnoses was 79% (27/34). A statistically significant difference was found between the size of hiatal hernia, grade of reflux in MRI, and abnormal acid exposure on pH-monitoring. CONCLUSIONS: MR fluoroscopy may be a promising radiation-free tool in assessing the functionality and morphology of the GE junction. KEY POINTS: • Swallowing MRI can assess anatomy and function of the gastroesophageal-junction • Swallowing MRI can help identifying reflux and motility disorders • Definition of the size of hiatal hernias is possible in all three planes in MR. • Short duration of swallowing MRI enables its application in routine clinical practice.

[Assessment of problematic alcohol use]. / Erfassung problematischen Alkoholkonsums.

An overview with respect to the identification of patients with risky drinking, alcohol abuse or alcohol dependence is given. As a first step, a simple screening questionnaire should be used. Self-statements in standardized questionnaires are more valid than standard laboratory markers. A useful instrument is for example BASIC. In screening positive patients, an in-depth diagnosis is necessary and helps to distinguish between different forms of problematic alcohol use. Depending on the severity of the alcohol problem, brochures, internet-programs, counselling or referral to treatment services is helpful.

New epidemiological aspects of patients with severe hyperhidrosis presenting for sympathetic surgery.

BACKGROUND: Epidemiological data on individuals suffering from severe primary hyperhidrosis are scarce. OBJECTIVE: This study aims to prospectively assess disease-specific characteristics of patients with severe, mostly therapy-resistant hyperhidrosis presenting for sympathetic surgery. METHODS: We evaluated a total of 227 patients (69.6% women) with a mean age of 30 years (standard deviation, 9.5 years) using a standardized questionnaire. Severity of disease was rated on a visual analogue scale (VAS) graded between 0 (no symptoms) and 10 (worst symptom). Age, sex, previous therapies, hormonal therapies and body mass index were analysed for their possible influence on severity of the disease and on hyperhidrosis sites. In addition, allergies were investigated for the first time in this patient population. RESULTS: There was a positive correlation between age of onset and sites of hyperhidrosis. The most commonly affected areas were palmar-axillary-plantar (51.1%) and palmar-plantar (15.0%), with sex-specific differences. Two hundred and twelve patients (93.4%) had previous conservative therapies; 219 patients (96.5%) reported VAS scores between 8 and 10. Female patients stated higher VAS scores for palmar (P = 0.009) and axillary (P = 0.012) sites. Type IV allergies were found to be much higher than in the general Austrian female population. Hormonal therapies and the body mass index had no influence on severity of hyperhidrosis after analysis of VAS scores. CONCLUSION: Sex-dependent aspects can be found in patients strongly affected by primary upper limb hyperhidrosis.

Alcohol screening in general practices using the AUDIT: how many response categories are necessary?

AIMS: The Alcohol Use Disorders Identification Test (AUDIT) is a common screening instrument. This study analyses if response categories of the AUDIT might be dichotomized without affecting the psychometric properties of the questionnaire. METHODS: Participants between 18 and 65 years were recruited from general practices in two northern German cities. In total, 10,803 screenings were conducted (refusal rate: 5.9%). For those who were screened positive, the Munich-Composite International Diagnostic Interview (M-CIDI) was used for identification of 12-month Alcohol Use Disorders and at-risk consumption (exceeding 20/30 g per day). Abstinent subjects and screening positives without diagnostic interview were excluded from the analysis, leaving a sample of 7,112 subjects. ROC-Curves were calculated separately for each item in order to identify an optimal cut-off value. Finally, a version of the AUDIT based on dichotomized items was compared to the original version and its short-form, the AUDIT version based on three questions dealing with consumption AUDIT-C. RESULTS: As an optimal cut-off value for items on consumption, drinking at least once a week, having more than 1-2 drinks per occasion, and drinking 6 or more drinks in one sitting at least once a month were identified. For all questions on alcohol-related problems or dependence symptoms, having 'ever occurred' differed best between subjects with and without Alcohol Use Disorders or at-risk consumption. Sensitivity and specificity of the dichotomized version of the AUDIT did not differ from the original version, and both full versions performed superior compared to the AUDIT-C. CONCLUSION: Data indicate that the AUDIT response categories may be dichotomized without affecting its validity.

Postoperative pain and quality of life after laparoscopic and open inguinal hernia repair: results of a prospective randomized trial.

BACKGROUND: As part of a large prospective randomized Austrian multicenter trial evaluating recurrence rates and complications of open and laparoscopic unilateral inguinal hernia repairs we assessed postoperative pain and quality of life. METHODS: Approximately 151 patients were randomized to Shouldice repair, Bassini operation, or laparoscopic transabdominal preperitoneal hernioplasty (TAPP). Pain was recorded preoperatively and on the first four postoperative days. Quality of life was recorded preoperatively and 1 month postoperatively. RESULTS: Patients having Shouldice repairs had significantly higher visual analog-scale scores for pain on the fourth postoperative day (P=0.048) and significantly higher scores in McGill pain questionnaires on the first four postoperative days (P=0.046) compared with the other groups. Apart from a significantly lower score in postoperative bodily pain in the Shouldice group (P=0.039), no significant differences in quality of life were apparent among the three methods. CONCLUSIONS: The TAPP and Bassini repairs result in less short-term postoperative pain.

Improved quality of life after sympathetic block for upper limb hyperhidrosis.

BACKGROUND: The aim of the study was to assess two disease-specific quality of life (QoL) instruments after limited endoscopic thoracic sympathetic block (TS) at T4 for upper limb hyperhidrosis. METHODS: : Between 2001 and 2005, 112 patients underwent 223 TS procedures in a prospective study. Some 103 patients (92.0 per cent) had palmar, 87 (77.7 per cent) had axillary and 75 (67.0 per cent) had combined hyperhidrosis. QoL questionnaires devised by Keller et al. and Milanez de Campos et al. were employed before and after treatment. Mean(s.d.) follow-up was 21.9(10.1) months. RESULTS: A total of 106 patients (94.6 per cent) were evaluated. All patients with palmar hyperhidrosis were completely or almost dry after surgery. Side-effects of compensatory sweating and gustatory sweating were observed in 17.0 and 28.3 per cent of patients respectively. QoL improved after TS in 100 per cent (Keller) and 97.3 per cent (Milanez de Campos) of patients illustrated by ameliorated scores of 78.7 and 67.8 per cent, respectively (both P < 0.001). Both questionnaires showed that compensatory sweating resulted in reduced postoperative QoL (P = 0.011, Keller; P = 0.032, Milanez de Campos). CONCLUSION: Endoscopic sympathetic block at T4 leads to improved QoL. Both current questionnaires fulfilled validation criteria for disease-specific QoL instruments in upper limb hyperhidrosis.

The relationship between impaired decision-making, sensation seeking and readiness to change in cigarette smokers.

OBJECTIVE: The study investigated whether impaired decision-making as measured by the Gambling Task and Sensation Seeking, on one hand, and nicotine-dependence and readiness to change, on the other hand, show mutual influences in cigarette smokers. METHODS: Cigarette smokers were classified as dependent or non-dependent smokers. Assessment included stages of change (RCQ), decisional balance (DBS), Sensation Seeking Scale Form-V (SSS-V), and performance on the Gambling Task (GT). RESULTS: With the exception of a significant higher score in the SSS-V subscale Experience Seeking in dependent smokers, correlations between nicotine-dependence and cognitive features were not significant. The directions of the non-significant differences were not consistent. No significant relationship was found between the SSS-V and the GT, on one hand, and the readiness to change smoking behaviour, on the other hand. CONCLUSIONS: The results of the present study suggest that impaired performance on the GT and high scores in Sensation Seeking do not play an important role in nicotine-dependence and readiness to change smoking behaviour or vice versa.