The association of self-reported diabetes with impaired social functioning in low-, middle- and high-income countries: findings from the World Health Survey.

AIM: Epidemiological studies from high-income countries show that diabetes is associated with impaired social functioning. As healthcare systems in middle- and low-income countries offer fewer resources to curtail the potential social impact of diabetes, we performed a comparative study on the diabetes-social impairment link in low-, middle- and high-income countries. METHODS: We use data from the cross-sectional World Health Survey (n = 235 428 from 10 low-income, 29 middle-income and 9 high-income countries). Diabetes was defined by self-reports of a diagnosis. Impaired social functioning was considered present if participants reported severe or extreme difficulties with personal relationships or participation in the community. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) in the overall sample and by income regions. ORs were corrected for demographics and health-related lifestyles, and then additionally adjusted for impairments that may explain any observed association (i.e. impaired vision, mood, cognition and mobility). RESULTS: In the overall sample, we confirmed an association between self-reported diabetes and impaired social functioning (OR = 1.47, 95% CI = 1.18-1.83). The strength of that relationship increased with decreasing country income (e.g. OR in low-income countries = 2.23, 95% CI = 1.14-4.37). Associations were substantially attenuated by further correction for impairments, in particular mood problems, in the overall sample (OR = 0.92, 95% CI = 0.72-1.16) and all income regions. CONCLUSIONS: Self-reported diabetes is associated with impaired social functioning in high- and middle-income countries, and this relationship is even stronger in low-income countries. Associations are largely explained by physical and mental impairments, which may be due to diabetes.

Systemic activity and mortality in primary Sjögren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients.

OBJECTIVE: To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS). PATIENTS AND METHODS: We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological characteristics and level of activity (EULAR-SS Disease Activity Index (ESSDAI) scores) were assessed at diagnosis as predictors of death using Cox proportional hazards regression analysis adjusted for age at diagnosis. The risk of death was calculated at diagnosis according to four different predictive models. RESULTS: After a mean follow-up of 117 months, 115 (11%) patients died. The adjusted standardised mortality ratio for the total cohort was 4.66 (95% CI 3.85 to 5.60), and survival rates at 5, 10, 20 and 30 years were 96%, 90%, 81% and 60%, respectively. The main baseline factors associated with overall mortality in the multivariate analysis were male gender, cryoglobulins and low C4 levels. Baseline activity in the constitutional, pulmonary and biological domains was associated with a higher risk of death. High activity in at least one ESSDAI domain (HR 2.14), a baseline ESSDAI score ≥14 (HR 1.85) and more than one laboratory predictive marker (lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4 and/or cryoglobulins) (HR 2.82) were associated with overall mortality; these HRs increased threefold to 10-fold when the analysis was restricted to mortality associated with systemic disease. CONCLUSIONS: Patients with primary SS, who present at diagnosis with high systemic activity (ESSDAI ≥14) and/or predictive immunological markers (especially those with more than one), are at higher risk of death.

Psychological distress and salivary secretory immunity.

Stress-induced impairments of mucosal immunity may increase susceptibility to infectious diseases. The present study investigated the association of perceived stress, depressive symptoms, and loneliness with salivary levels of secretory immunoglobulin A (S-IgA), the subclasses S-IgA1, S-IgA2, and their transporter molecule Secretory Component (SC). S-IgA/SC, IgA1/SC and IgA2/SC ratios were calculated to assess the differential effects of stress on immunoglobulin transport versus availability. This study involved 113 university students, in part selected on high scores on the UCLA Loneliness Scale and/or the Beck Depression Inventory. Stress levels were assessed using the Perceived Stress Scale. Unstimulated saliva was collected and analysed for total S-IgA and its subclasses, as well as SC and total salivary protein. Multiple linear regression analyses, adjusted for gender, age, health behaviours, and concentration effects (total protein) revealed that higher perceived stress was associated with lower levels of IgA1 but not IgA2. Perceived stress, loneliness and depressive symptoms were all associated with lower IgA1/SC ratios. Surprisingly, higher SC levels were associated with loneliness and depressive symptoms, indicative of enhanced transport activity, which explained a lower IgA1/SC ratio (loneliness and depression) and IgA2/SC ratio (depression). This is the first study to investigate the effects of protracted psychological stress across S-IgA subclasses and its transporter SC. Psychological stress was negatively associated with secretory immunity, specifically IgA1. The lower immunoglobulin/transporter ratio that was associated with higher loneliness and depression suggested a relative immunoglobulin depletion, whereby availability was not keeping up with enhanced transport demand.

Targeting ß2 adrenergic receptors regulate human T cell function directly and indirectly.

It is well-established that central nervous system activation affects peripheral blood mononuclear cell (PBMCs) function through the release of the catecholamines (Epi) and norepinephrine (NE), which act on ß2-adrenergic receptors (ß2AR). However, most studies have used non-specific stimulation of cells rather than antigen-specific responses. Likewise, few studies have parsed out the direct effects of ß2AR stimulation on T cells versus indirect effects via adrenergic stimulation of antigen presenting cells (APC). Here we report the effect of salmeterol (Sal), a selective ß2AR agonist, on IFN-γ(+) CD4 and IFN-γ(+) CD8 T cells following stimulation with Cytomegalovirus lysate (CMVL-strain AD169) or individual peptides spanning the entire region of the HCMV pp65 protein (pp65). Cells were also stimulated with Staphylococcal enterotoxin B. Additionally, we investigated the effect of Epi and Sal on cytotoxic cell killing of transfected target cells at the single cell level using the CD107a assay. The results show that Sal reduced the percentage of IFN-γ(+) CD4 and IFN-γ(+) CD8 T cells both when applied directly to isolated T cells, and indirectly via treatment of APC. These inhibitory effects were mediated via a ß2 adrenergic-dependent pathway and were stronger for CD8 as compared to CD4 T cells. Similarly, the results show that Sal suppressed cytotoxicity of both CD8 T and NK cells in vitro following stimulation with Chinese hamster ovary cell line transfected with MICA(*009) (T-CHO) and the human erythromyeloblastoid leukemic (K562) cell line. The inhibitory effect on cytotoxicity following stimulation with T-CHO was stronger in NK cells compared with CD8 T cells. Thus, targeting the ß2AR on lymphocytes and on APC leads to inhibition of inflammatory cytokine production and target cell killing. Moreover, there is a hierarchy of responses, with CD8 T cells and NK cells inhibited more effectively than CD4 T cells.

Negative affectivity predicts decreased pain tolerance during low-grade inflammation in healthy women.

INTRODUCTION: Experimental animal studies provided evidence for a synergistic effect of immunological and psychological stressors on subsequent sickness behaviours. Up to now, little corroborating evidence for such synergy exists for humans, in whom it may provide a mechanism leading to the expression of functional somatic symptoms. The aim of the present study was to determine an interaction between stress(-vulnerability) and an immunological activation on experimental pain sensitivity, i.e., pressure pain threshold and tolerance in healthy humans. METHODS: In healthy female participants (n=25, mean age 22.3 years), negative affectivity (NA) and experienced stress were assessed by questionnaire before receiving a Salmonella typhi vaccine or saline control in a randomized blinded cross-over design. Pressure pain threshold was assessed at the lower back and calves and pain tolerance was assessed at the thumbnail, before and six hours after each injection. RESULTS: Vaccination induced leukocytosis (+100%) and increased serum IL-6 (+670%). NA predicted decreased pain tolerance after vaccination (ß=-.57, p=.007), but not after placebo (ß=.25, p=.26). Post-hoc analyses also demonstrated an association with administration order. DISCUSSION: NA moderated the effects of inflammation on pain tolerance. This finding is consistent with a synergistic model whereby inflammation may lower the threshold for pain reporting in individuals with increased vulnerability for somatic symptom reporting.

Outcomes of off-label drug uses in hospitals: a multicentric prospective study.

PURPOSE: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. METHODS: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. RESULTS: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (33-62) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.9-5,872.54). CONCLUSIONS: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed.

Challenging the evidence for pre-emptive coil embolisation of the internal iliac artery during endovascular aneurysm repair.

OBJECTIVES: We retrospectively analysed the results of a strategy in which coverage of the internal iliac artery (IIA) during endovascular aneurysm repair (EVAR) was routinely performed without coil embolisation. METHODS: From January 2010 until May 2012, 32 patients (96.9% men; mean age 73.0 years, range 52-89 years) underwent EVAR with stent grafts extended into the external iliac artery (EIA), all without prior coil embolisation. Aneurysm morphology was determined on preoperative computed tomography (CT) images. During follow-up, patients were interviewed about buttock claudication, and the occurrence of endoleaks and evolution of aneurysm diameter were recorded. RESULTS: At baseline, the mid-common iliac artery (CIA) diameter was 33.5 ± 16.8 mm and seven patients presented with ruptured aneurysms. Mean follow-up was 14.3 ± 7.4 months. There were eight deaths, none related to IIA coverage. Buttock claudication occurred in seven (22.6%) patients, which persisted after 6 months in two cases of bilateral IIA coverage. No Type-I or -II endoleaks occurred related to IIA coverage. Aneurysm growth was not observed. CONCLUSION: Endovascular treatment of aortoiliac and iliac aneurysm without pre-emptive coil embolisation of the IIA appears safe and effective. No IIA-related endoleaks or re-interventions occurred in our series. This approach saves operating time, contrast load and costs and may reduce complications. However, a larger population and longer follow-up is required to confirm our findings.

Available evidence and outcome of off-label use of rituximab in clinical practice.

PURPOSE: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. METHODS: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. RESULTS: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30 months) in 69.2 % of patients showing a short-term response. Median cost per patient was €5,187.5 (IQR €5,187.5-7,781.3). CONCLUSIONS: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Plasma levels of matrix metalloproteinase-9: a possible diagnostic marker of successful endovascular aneurysm repair.

OBJECTIVE: The aim of the study was evaluating the diagnostic value of plasma matrix metalloproteinase- (MMP)-2 and -9 and tissue inhibitor of MMP-1 (TIMP-1) for endoleak detection after endovascular aneurysm repair (EVAR). REPORT: Consecutive EVAR patients (n = 17) with endoleak and matched controls without endoleak (n = 20) were prospectively enrolled. Increased levels of MMP-9 were observed in patients with endoleak (P < 0.001). Regression analysis showed no significant influence of age, sex or abdominal aortic aneurysm (AAA) size. The receiver operating characteristic (ROC) curve of plasma MMP-9 levels showed that a cut-off value of 55.18 ng ml(-1) resulted in 100% sensitivity and 96% specificity with an AUC value of 0.988 (P < 0.001) to detect endoleak. CONCLUSIONS: Plasma MMP-9 levels appear to discriminate between patients with and without an endoleak with high sensitivity and specificity.

Acute stress reactivity and intrusive memory development: a randomized trial using an adjusted trauma film paradigm.

Understanding the neurobiological and cognitive processes underlying the development of posttraumatic stress disorder (PTSD) and its specific symptoms may facilitate preventive intervention development. Severe traumatic stress and resulting biological stress system activations can alter contextual memory processes. This may provide a neurobiological explanation for the occurrence of intrusive memories following trauma. Investigating the associations between temporal aspects and individual variation in peri- and post-traumatic hypothalamic pituitary adrenal (HPA) axis and sympathetic nervous system (SNS) stress reactivity and memory processing may increase our understanding of intrusive symptom development. The experimental trauma film paradigm is commonly used for this purpose but lacks robust SNS and HPA axis activation. Here, we performed an RCT to investigate the effect of an adjusted trauma film paradigm containing an added brief psychosocial stressor on HPA and SNS stress reactivity throughout the experiment and intrusive memory frequency in the following week in healthy males (N = 63, mean age = 22.3). Secondary, we investigated effects on film-related declarative memory accuracy and intrusion-related characteristics, and associations between acute HPA and SNS stress reactivity, film-related memory, glucocorticoid receptor functioning and intrusion frequency and characteristics. Participants were randomized to the socially-evaluated cold pressor test (seCPT n = 29) or control condition (warm water n = 34) immediately prior to a trauma film. Linear Mixed Models revealed increased acute SNS and cortisol reactivity, lower recognition memory accuracy and more intrusions that were more vivid and distressing during the following week in the seCPT compared to control condition. Linear regression models revealed initial associations between cortisol and alpha amylase reactivity during the experimental assessment and subsequent intrusions, but these effects did not survive multiple comparison corrections. Thus, with this adjustment, we increased the translational value of the trauma film paradigm as it appears to elicit a stronger stress response that is likely more comparable to real-life trauma. The adapted paradigm may be useful to investigate individual variation in biological and cognitive processes underlying early post-trauma PTSD symptoms and could advance potential preventive interventions.

EVAR suitability is not a predictor for early and midterm mortality after open ruptured AAA repair.

OBJECTIVE: The reported mortality reduction of emergency endovascular aneurysm repair (eEVAR) compared with open repair in patients with a ruptured abdominal aortic aneurysm (rAAA), as observed in observational studies, might be flawed by selection bias based on anatomical suitability for eEVAR. In the present study, we compared mortality in EVAR suitable versus non-EVAR-suitable patients with a ruptured AAA who were all treated with conventional open repair. MATERIALS AND METHODS: In all patients presenting with a suspected rAAA, computed tomography angiography (CTA) scanning was performed. All consecutive patients with a confirmed rAAA on preoperative CTA scan and treated with open repair between April 2002 and April 2008 were included. Anatomical suitability for eEVAR was determined by two blinded independent reviewers. Outcomes evaluated were mortality (intra-operative, 30-day, and 6-month), morbidity, complications requiring re-intervention and length of hospital stay. RESULTS: A total of 107 consecutive patients presented with a rAAA and underwent preoperative CTA scanning. In 25 patients, eEVAR was performed. In the 82 patients who underwent open repair, CTA showed an EVAR-suitable rAAA in 33 patients (41.8%) and a non-EVAR-suitable rAAA in 49 patients. Thirty-day and 6-month mortality rate was 15/33 (45.5%; 95% confidence interval (CI) 28.1-63.7) and 18/33 (54.5%; 95% CI 36.4-71.9) in the EVAR-suitable group versus 24/49 (49.0%; 95% CI 34.4-63.7) (P=0.75) and 29/49 (59.2%; 95% CI 44.2-73.0) (P=0.68) in the non-EVAR-suitable group, respectively. CONCLUSIONS: The present study suggests that anatomical suitability for EVAR is not associated with lower early and midterm mortality in patients treated with open ruptured AAA repair. Therefore, the reported reduction in mortality between eEVAR and open repair is unlikely due to selection bias based on anatomical AAA configuration.

Treatment of a coronal shear injury of the trochlea using a modified hedgehog-based technique through an anterior neurovascular interval approach: A case report.

INTRODUCTION AND IMPORTANCE: Surgical treatment for dislocated trochlear shear injuries is recommended due to its articular nature. However, the surgical exposure is often limited and large cartilaginous fragments with lack of subchondral bone stock makes a stable fixation technically challenging. Rapid swelling of the traumatized cartilage induces a size misfit between the cartilage of the fragment and the defect site. The use of a "modified hedgehog"-based technique might be a solution in these cases. However, this technique has only been described in chondral shear lesions of the knee. CASE PRESENTATION: A fifteen-year-old boy fell out of the still rings during gymnastics at school and suffered trauma to his elbow. A CT-scan of the right elbow showed a coronal shear injury of the trochlea with accompanied lateral condyle fracture of the humerus. The patient was treated throughout an anterior neurovascular approach with a modified hedgehog-based technique with triple fixation by creating an interlocking match of the cartilage, application of fibrin glue and additional screw fixation. CLINICAL DISCUSSION: The anterior neurovascular interval approach provides a clear exposure of the fracture site which is useful for anatomic reduction and triple fixation. The subsequent modified hedgehog-based technique has only been described once in children with shear-off chondral fragments of the knee, without additional screw fixation. Adding a screw fixation of the fragment creates some collateral damage to the cartilage and might not be necessary in future cases. CONCLUSION: The anterior neurovascular approach seems elegant and provides adequate exposure. Furthermore, a modified hedgehog-based technique delivers a stable triple fixation of the osteochondral fragment.

Maternal long-chain polyunsaturated fatty acid status during early pregnancy: Association with child behavioral problems and the role of autonomic nervous system activity.

BACKGROUND & AIMS: The prenatal environment, including availability of critical nutrients, has a profound impact on offspring development. The present study examined the association between maternal long-chain polyunsaturated fatty acid (LC-PUFA) status during pregnancy and later child behavioral problems at the age of 5-6 years. In light of evidence of autonomic nervous system (ANS) dysregulation in some behavioral problems, study further tested if the above association is statistically mediated by cardiac ANS activity. METHODS: Data was collected as part of the Amsterdam Born Children and their Development-study and complete data were available for 1717 mothers and their offspring. Maternal LC-PUFA status was assessed during early pregnancy (mean gestation = 12.7, SD = 2.5 weeks) and quantified as levels of docosahexenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), as well as the ratio of n-6:n-3 fatty acids. Child emotional problems and peer problems (internalizing problems), as well as conduct problems and inattention/hyperactivity (externalizing problems), were assessed using the Strengths and Difficulties Questionnaire as rated by the mother and teacher at 5-6 years. Child cardiac respiratory sinus arrhythmia (RSA), pre-ejection period (PEP), and heart rate (HR) were utilized as measures of ANS activity at 5-6 years. RESULTS: The results confirmed an association between maternal LC-PUFA status and internalizing behavioral problems as rated by the mother, as shown for DHA (ß = -0.11;p < 0.01), EPA (ß = -0.22;p < 0.05), and n-6:n-3 LC-PUFA (ß = 0.17;p < 0.01). Statistical mediation was only demonstrated for HR. No associations were observed between LC-PUFA status and externalizing behavioral problems. CONCLUSIONS: The present results are consistent with a role of maternal LC-PUFA status in internalizing behavioral problems as rated by the mother. These results were not observed when problem behavior was rated by the teacher. Analyses did not yield strong evidence supporting ANS activity as a possible mediator in this relationship.

Work-related stress, inability to relax after work and risk of adult asthma: a population-based cohort study.

BACKGROUND: There is an extensive literature linking stressful work conditions to adverse health outcomes. Notwithstanding, the relationship with asthma has not been examined, although various other measures of psychological stress have been associated with asthma. Therefore, we aimed to investigate the relation between work stress and asthma prevalence and incidence. METHODS: We used data from a population-based cohort study (n = 5114 at baseline in 1992-1995 and n = 4010 at follow-up in 2002/2003). Asthma was measured by self-reports. Two scales that assessed psychologically adverse work conditions were extracted from a list of work-condition items by factor analysis (these scales were termed 'work stress' and 'inability to relax after work'). For each scale, the derived score was employed both as continuous z-score and as categorized variable in analyses. Associations with asthma were estimated by prevalence ratios (PRs) and risk ratios (RRs) using Poisson regression with a log-link function adjusting for demographics, health-related lifestyles, body mass index and family history of asthma. Analyses were restricted to those in employment (n = 3341). RESULTS: Work stress and inability to relax z-scores were positively associated with asthma prevalence (PR = 1.15, 95%CI = 0.97, 1.36 and PR = 1.43, 95%CI = 1.12, 1.83, respectively). Prospective analyses using z-scores showed that for each 1 standard deviation increase in work stress and inability to relax, the risk of asthma increased by approximately 40% (RR for work stress = 1.46, 95%CI = 1.06, 2.00; RR for inability to relax = 1.39, 95%CI = 1.01, 1.91). Similar patterns of associations were observed in analyses of categorized exposures. CONCLUSIONS: This is the first study to show a cross-sectional and longitudinal association of work stress with asthma.

Predictors of walking distance after supervised exercise therapy in patients with intermittent claudication.

OBJECTIVE: To identify predictor variables for results after supervised exercise therapy (SET), and to develop a clinical prediction model that aims to predict a target walking distance for individual patients. DESIGN: Retrospective analyses on prospectively collected data. MATERIALS: Patients with intermittent claudication who participated in a SET programme. METHODS: SET was conducted according to the guidelines of the Royal Dutch Society for Physiotherapy. The main outcome measurement was the absolute claudication distance (ACD) after 6 months of SET. Linear regression analyses were conducted to identify independent predictor variables for ACD. RESULTS: In this cohort, 437 patients were analysed. Independent predictor variables for post-treatment ACD were baseline ACD (P<0.001), smoking behaviour (P=0.012) and body-mass index (P=0.041). A better baseline ACD was associated with a longer post-treatment ACD whereas current smoking and a higher body-mass index were associated with a shorter post-treatment ACD. The final regression equation included baseline ACD, age, body-mass index, smoking and pulmonary disease, and was translated into several clinical prediction models. However, only 24.8-33.6% of the patients had an ACD within the calculated target range. CONCLUSIONS: Predictive variables for post-treatment ACD after SET are baseline ACD, age, body-mass index, pulmonary disease and smoking behaviour. However, translating the regression equation into a clinical prediction model did not lead to a valid model for use in clinical practice.

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential.

BACKGROUND: Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited. OBJECTIVE: In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings. METHODS: Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe. RESULTS: P3 amplitude was not affected by tVNS (Experiment 1A: N = 24; Experiment 1B: N = 20; Bayes factor supporting null model = 4.53), nor was pupil size (Experiment 2: N = 16; interaction of treatment and time: p = .79). However, tVNS increased SAA (Experiments 1A and 2: N = 25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N = 17), as indicated by significant interactions involving treatment and time (p = .023 and p = .040, respectively). CONCLUSION: These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function.

How are we treating our systemic patients with primary Sjögren syndrome? Analysis of 1120 patients.

OBJECTIVE: To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjögren syndrome (pSS) in daily practice, focusing on the adequacy of therapies for the level of systemic activity measured by ESSDAI score. PATIENTS AND METHODS: By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine (HCQ) and/or low dose glucocorticoids (GCS) (<20mg/day), high dose GCS (>20mg/day) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins [IVIG] and/or rituximab [RTX]). RESULTS: There were 1048 (94%) women and 72 (6%) men , with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic pSS during follow-up were HCQ in 282 (25%) patients, GCS in 475 (42%, at doses >20mg/day in 255-23%), immunosuppressive agents in 148 (13%), IVIG in 25 (2%) and RTX in 35 (3%) patients. HCQ was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34-0.95). We classified 16 (7%) of the 255 patients treated with >20mg GCS and 21/148 (14%) treated with immunosuppressive agents as patients inadequately treated, mainly associated with articular involvement of low/moderate activity. CONCLUSION: The management of pSS should be organ-specific, using low dose GCS in patients with moderate systemic activity, limiting the use of high dose GCS and second-line therapies to refractory or potentially severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted.

Technetium-99m-HMPAO brain SPECT in Behçet's disease.

UNLABELLED: Behçet's disease (BD) is an idiopathic multisystem disorder. Involvement of the central nervous system (CNS) occurs in 4%-48% of cases. The aim of this study was to evaluate 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT findings in BD patients and eventually to detect CNS involvement by depicting cerebral blood flow disturbances. METHODS: Technetium-99m-HMPAO brain SPECT was performed on 33 consecutive BD patients. Qualitative and quantitative evaluation of the cortical uptake was done using an automatic program that generated 32 regions of interest (ROIs). An uptake index for each ROI was obtained. Reference values were obtained from a healthy control group (n = 20). Twenty-five patients also had an MRI study. RESULTS: Twelve of 32 patients (36%) presented with a clinical neurological disorder. SPECT and visual evaluation revealed that 17 patients (51.5%) had abnormalities; 9 of 25 MRI studies (36%) were abnormal. Using the quantitative approach for SPECT, 23 patients (69.7%) had abnormally low values. Six of 12 patients with neurological symptoms had a visually abnormal SPECT scan, whereas quantitative analysis showed abnormalities in 11 patients. Of the 21 patients with no neurological findings, 9 had abnormal SPECT results, and 12 had low uptake indexes. CONCLUSION: HMPAO brain SPECT shows high rates of cerebral blood flow abnormalities in BD patients presenting with neuropsychiatric symptoms, and it also is frequently abnormal in asymptomatic BD patients who have no abnormalities on MR scans. Compared with visual analysis, quantitative analysis detects an even higher rate of SPECT changes in BD patients.

Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy.

UNLABELLED: Salivary gland dysfunction has been described in patients undergoing radioiodine therapy but associated lacrimal gland dysfunction (sicca syndrome) has never been reported. We conducted a prospective cohort study with follow-up for up to 3 y in a tertiary care university center to determine the prevalence of sicca syndrome in patients after high-dose radioiodine treatment. METHODS: From January 1990 to December 1995, all patients undergoing radioiodine therapy (n = 79) with a standard dose of 925 MBq to 18.5 GBq (25-500 mCi) were interviewed using a standardized questionnaire to determine subjective ocular and oral dryness and were examined for objective lacrimal and salivary gland dysfunction. RESULTS: After radioiodine treatment, 32.9% of the patients reported subjective xerostomia and 25.3% reported subjective xerophthalmia in the first year of follow-up. Xerostomia persisted to the second year of follow-up in 20.3% of cases and was still present >3 y after the last dose of radioiodine in 15.2% of cases. Xerophthalmia persisted to the second year of follow-up in 17.7% of cases and was still present in the third year of follow-up in 13.9% of cases. Severe xerostomia occurred in 4 patients. Reduced salivary and lacrimal gland function was documented in 40 (50.6%) and 14 (17.7%) of the 79 cases, respectively, in the first year of follow-up. Objective xerostomia persisted in 13.9% of cases to the second year of follow-up and was still present in all patients >3 y after the last radioiodine application. Keratoconjunctivitis sicca persisted in 11 patients (13.9%) to the second year of follow-up but was only present in 6 patients (7.6%) >3 y after the last radioiodine application. Additionally, 28/79 patients (35.4%) who had a normal salivary gland scintigraphy previously showed reduced salivary gland function in the third year of follow-up. No significant dependence on cumulative treatment was found for objective xerostomia or xerophthalmia, but doses >11.1 GBq (300 mCi) were related to stage 3 dysfunction on salivary gland scintigraphy. CONCLUSION: Salivary and lacrimal gland dysfunction (sicca syndrome) is relatively frequent after radioiodine therapy. In most cases this is a transient side effect, but in some patients it may persist for a long period or appear late.