Ingrid Becker

Deep Brain Stimulation for Tourette-Syndrome: A Systematic Review and Meta-Analysis

BACKGROUND A significant proportion of patients with Tourette syndrome (TS) continue to experience symptoms across adulthood that in severe cases fail to respond to standard therapies. For these cases, deep brain stimulation (DBS) is emerging as a promising treatment option. OBJECTIVE We conducted a systematic literature review to evaluate the efficacy of DBS for GTS. METHODS Individual data of case reports and series were pooled; the Yale Global Tic Severity Scale (YGTSS) was chosen as primary outcome parameter. RESULTS In total, 57 studies were eligible, including 156 cases. Overall, DBS resulted in a significant improvement of 52.68% (IQR = 40.74, p < 0.001) in the YGTSS. Analysis of controlled studies significantly favored stimulation versus off stimulation with a standardized mean difference of 0.96 (95% CI: 0.36-1.56). Disentangling different target points revealed significant YGTSS reductions after stimulation of the thalamus, the posteroventrolateral part and the anteromedial part of the globus pallidus internus, the anterior limb of the internal capsule and nucleus accumbens with no significant difference between these targets. A significant negative correlation of preoperative tic scores with the outcome of thalamic stimulation was found. CONCLUSIONS Despite small patient numbers, we conclude that DBS for GTS is a valid option for medically intractable patients. Different brain targets resulted in comparable improvement rates, indicating a modulation of a common network. Future studies might focus on a better characterization of the clinical effects of distinct regions, rather than searching for a unique target.

Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry

Uveitis is a major extraarticular quality of life–restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX).

Risk of Serious Infection in Juvenile Idiopathic Arthritis Patients Associated With Tumor Necrosis Factor Inhibitors and Disease Activity in the German Biologics in Pediatric Rheumatology Registry

To examine the effects of tumor necrosis factor inhibitors on the risk for serious infections and other influencing factors in a registry.

Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

Background: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Methods: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na+] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH). Results: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na+] change (Δdaily[Na+]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δdaily[Na+] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived. Conclusions: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH.

Risk of serious infection in juvenile idiopathic arthritis patients associated with TNF-inhibitors and disease activity in the German BIKER registry.

To examine the effects of tumor necrosis factor inhibitors on the risk for serious infections and other influencing factors in a registry.

Association of anemia and hypoalbuminemia in German geriatric inpatients: Relationship to nutritional status and comprehensive geriatric assessment.

BackgroundAnemia and hypoalbuminemia (HA) are acknowledged independent risk factors for morbidity and mortality in geriatric patients and are associated with nutritional status and frailty. Data exist regarding the association between albumin and frailty, anemia and frailty as well as frailty and nutritional status; however, there is a lack of information on the association between HA, anemia and nutritional status in older people.Patients and methodsThis study retrospectively analyzed 626 patients admitted to a German geriatrics department (average age 81.1 years, 68.2 % female and 31.8 % male) for anemia and HA. Data from the comprehensive geriatric assessment (CGA) and from the mini-nutritional assessment (MNA) were available in all patients.ResultsPatients with anemia suffered significantly more often from HA (p < 0.001) than patients without anemia, with an odds ratio (OR) of 1.99 (95 % confidence interval CI: 1.2-3.2) and of 5.41 (CI 95 %: 2.3-12.6) in patients at risk for malnutrition and in malnourished patients, respectively. A moderately significant association was seen between hemoglobin (Hb) and albumin values (Pearson’s correlation r = 0.330; p < 0.001) as well as between albumin values and the Barthel index (Spearman’s correlation r = 0.210; p < 0.001).ConclusionAnemia appears to be a risk factor for HA in inpatients with malnutrition and the observed association between albumin and Hb warrants further research. Geriatric inpatients with anemia should be evaluated in terms of the presence of malnutrition risk and HA.ZusammenfassungHintergrundAnämie und Hypoalbuminämie (HA) sind bei geriatrischen Patienten bekannte unabhängige Risikofaktoren für Morbidität und Mortalität, sie stehen im Zusammenhang mit Ernährungststatus und Frailty. Es gibt Untersuchungen zum Zusammenhang zwischen Albumin und Frailty, Anämie und Frailty, sowie Frailty und dem Ernährungsstatus. Bisher fehlen jedoch Daten zu einem Zusammenhang zwischen HA, Anämie und Ernährungsstatus bei geriatrischen Patienten.Patienten und MethodenRetrospektive Datenanalyse von 626 stationären geriatrischen Patienten (mittleres Alter 81,1 Jahre, 68,2 % Frauen, 31,8 % Männer) hinsichtlich Anämie, HA und einem Zusammenhang mit dem Ernährungsstatus (Mini Nutritional Assessment, MNA) und dem multidimensionalen geriatrischen Assessment (Comprehensive Geriatric Assessment, CGA).ErgebnissePatienten mit Anämie wiesen signifikant häufiger eine HA auf (p < 0,001) als Patienten ohne Anämie, wobei anämische Patienten mit einem Risiko für Mangelernährung eine erhöhte Chance auf eine HA hatten (OR I,9; 95 %-KI: 1,2-3,2) und Patienten mit einer Mangelernährung eine OR von 5,4 (95 %-KI: 2,3-12,6) aufwiesen. Ein moderater signifikanter Zusammenhang konnte gezeigt werden zwischen Hämoglobin (Hb) und Albumin (Pearsons Korrelationskoeffizient r = 0,330; p < 0,001) sowie zwischen Albumin und Barthel Index.SchlussfolgerungenAnämie scheint bei mangelernährten stationär geriatrischen Patienten ein Risikofaktor für HA zu sein, wobei der beobachtete Zusammenhang zwischen Albumin und Hb weiterer wissenschaftlicher Untersuchungen bedarf. Im klinischen Alltag sollte bei stationär geriatrischen Patienten mit Anämie eine Überprüfung auf HA erwogen werden, besonders bei drohender oder bereits bestehender Mangelernährung.

Improvement of facial affect recognition in children and adolescents with attention-deficit/hyperactivity disorder under methylphenidate

Introduction and Hypothesis Some authors draw a connection between the dopaminergic pathways and emotional perception. The present study is based on that association and addresses the question whether methylphenidate and the resulting amelioration of the disturbed dopamine metabolism lead to an improvement of the facial affect recognition abilities in children with attention-deficit/hyperactivity disorder (ADHD). Methods A computer test was conducted on 21 participants, aged 7–14 years and with a diagnosis of ADHD – some with comorbid oppositional defiant disorder – conducted the FEFA (Frankfurt Test and Training of Facial Affect), a computer test to examine their facial affect recognition abilities. It consists of two subtests, one with faces and one with eye pairs. All participants were tested in a double-blind cross-over study, once under placebo and once under methylphenidate. Results and Discussion The collected data showed that methylphenidate leads to amelioration of facial affect recognition abilities, but not on a significant level. Reasons for missing significance may be the small sample size or the fact that there exists some overlapping in cerebral connections and metabolic pathways of the site of action of methylphenidate and the affected dopaminergic areas in ADHD. However, consistent with the endophenotype concept, certain gene locations of the dopaminergic metabolism as both an aetiological factor for ADHD and the deficient facial affect recognition abilities with these individuals were considered. Consulting current literature they were found to be not concordant. Therefore, we conclude that the lacking significance of the methylphenidate affect on facial affect recognition is based on this fact.

Association of anemia and hypoalbuminemia in German geriatric inpatients

BackgroundAnemia and hypoalbuminemia (HA) are acknowledged independent risk factors for morbidity and mortality in geriatric patients and are associated with nutritional status and frailty. Data exist regarding the association between albumin and frailty, anemia and frailty as well as frailty and nutritional status; however, there is a lack of information on the association between HA, anemia and nutritional status in older people.Patients and methodsThis study retrospectively analyzed 626 patients admitted to a German geriatrics department (average age 81.1 years, 68.2 % female and 31.8 % male) for anemia and HA. Data from the comprehensive geriatric assessment (CGA) and from the mini-nutritional assessment (MNA) were available in all patients.ResultsPatients with anemia suffered significantly more often from HA (p < 0.001) than patients without anemia, with an odds ratio (OR) of 1.99 (95 % confidence interval CI: 1.2-3.2) and of 5.41 (CI 95 %: 2.3-12.6) in patients at risk for malnutrition and in malnourished patients, respectively. A moderately significant association was seen between hemoglobin (Hb) and albumin values (Pearson’s correlation r = 0.330; p < 0.001) as well as between albumin values and the Barthel index (Spearman’s correlation r = 0.210; p < 0.001).ConclusionAnemia appears to be a risk factor for HA in inpatients with malnutrition and the observed association between albumin and Hb warrants further research. Geriatric inpatients with anemia should be evaluated in terms of the presence of malnutrition risk and HA.ZusammenfassungHintergrundAnämie und Hypoalbuminämie (HA) sind bei geriatrischen Patienten bekannte unabhängige Risikofaktoren für Morbidität und Mortalität, sie stehen im Zusammenhang mit Ernährungststatus und Frailty. Es gibt Untersuchungen zum Zusammenhang zwischen Albumin und Frailty, Anämie und Frailty, sowie Frailty und dem Ernährungsstatus. Bisher fehlen jedoch Daten zu einem Zusammenhang zwischen HA, Anämie und Ernährungsstatus bei geriatrischen Patienten.Patienten und MethodenRetrospektive Datenanalyse von 626 stationären geriatrischen Patienten (mittleres Alter 81,1 Jahre, 68,2 % Frauen, 31,8 % Männer) hinsichtlich Anämie, HA und einem Zusammenhang mit dem Ernährungsstatus (Mini Nutritional Assessment, MNA) und dem multidimensionalen geriatrischen Assessment (Comprehensive Geriatric Assessment, CGA).ErgebnissePatienten mit Anämie wiesen signifikant häufiger eine HA auf (p < 0,001) als Patienten ohne Anämie, wobei anämische Patienten mit einem Risiko für Mangelernährung eine erhöhte Chance auf eine HA hatten (OR I,9; 95 %-KI: 1,2-3,2) und Patienten mit einer Mangelernährung eine OR von 5,4 (95 %-KI: 2,3-12,6) aufwiesen. Ein moderater signifikanter Zusammenhang konnte gezeigt werden zwischen Hämoglobin (Hb) und Albumin (Pearsons Korrelationskoeffizient r = 0,330; p < 0,001) sowie zwischen Albumin und Barthel Index.SchlussfolgerungenAnämie scheint bei mangelernährten stationär geriatrischen Patienten ein Risikofaktor für HA zu sein, wobei der beobachtete Zusammenhang zwischen Albumin und Hb weiterer wissenschaftlicher Untersuchungen bedarf. Im klinischen Alltag sollte bei stationär geriatrischen Patienten mit Anämie eine Überprüfung auf HA erwogen werden, besonders bei drohender oder bereits bestehender Mangelernährung.

Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: A systematic review and meta-analysis of randomized clinical trials

Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto’s method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.

Fluorescence optical imaging and musculoskeletal ultrasonography in juvenile idiopathic polyarticular disease before and during antirheumatic treatment - a multicenter non-interventional diagnostic evaluation

BackgroundValid detection of inflamed joints is essential for correct classification, therapeutic decisions, prognosis and assessment of treatment efficacy in juvenile idiopathic arthritis (JIA). Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis of finger and hand joints and might be used for monitoring.MethodsA 24-week observational study in polyarticular JIA patients newly starting treatment with methotrexate or an approved biologic was performed in three centers. Patients were evaluated clinically, by gray-scale ultrasonography (GSUS), power-Doppler ultrasonography (PDUS) and FOI at baseline, week 12 and week 24.ResultsOf 37 patients enrolled, 24 patients started methotrexate and 13 patients a biologic for the first time (etanercept n = 11, adalimumab and tocilizumab n = 1 each). Mean JADAS 10 decreased significantly from 17.7 at baseline to 12.2 and 7.2 at week 12 and 24 respectively. PedACR 30/50/70/100 response rates at week 24 were 85%/73%/50%/27%. The total number of clinically active joints in hand and fingers at baseline/week 12/week 24 was 262 (23.6%)/162 (16.4%)/162 (9.0%). By GSUS, at baseline/week 12/week 24, 192 (19.4%)/135 (16.1%)/83 (11.5%) joints showed effusions and 186 (18.8%)/107 (12.7%)/69 (9.6%) showed synovial thickening, and by PDUS 68 (6.9%)/15 (1.8%)/36 (5%) joints showed hyperperfusion. Any sign of arthritis was detected by US in a total of 243 joints (24.5%) at baseline, 161 joints (19.2%) at week 12 and 123 joints (17%) at week 24. By FOI at baseline/week 12/week 24, 430 (38.7%)/280 (29.2%)/215 (27.6%) showed a signal enhancement in at least one phase.Summarizing all three points of time, the highest numbers of signals were detected by FOI with 32% of joints, especially in phase 2, while by US 20.7% and by clinical examination 17.5% of joints were active. A high number of joints (21.1%) had FOI signals but were inactive by clinical examination. A total 20.1% of joints with signals in FOI did not show effusion, synovial thickening or hyperperfusion by US.Because of the high number of negative results, specificity of FOI compared with clinical examination/US/PD was high (84–95%), and sensitivity was only moderate.ConclusionFOI and US could detect clinical but also subclinical inflammation. FOI detected subclinical inflammation to a higher extent than US. Improvement upon treatment with either methotrexate or a biologic can be visualized by FOI and US.Trial registrationDeutsches Register Klinischer Studien DRKS00011579. Registered 10 January 2017.