Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study).

OBJECTIVE: To assess the efficacy and safety of abatacept in patients with early and active primary Sjögren's syndrome (pSS). METHODS: All 15 patients (12 women, three men) included in the open-label Active Sjögren Abatacept Pilot study met the revised American-European Consensus Group criteria for pSS and were biological disease-modifying antirheumatic drug-naive. Patients were treated with eight intravenous abatacept infusions on days 1, 15 and 29 and every 4 weeks thereafter. Follow-up was conducted at 4, 12, 24 (on treatment), 36 and 48 weeks (off treatment). Disease activity was assessed with European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). Several other functional, laboratory and subjective variables were analysed. Generalised estimating equations were used to analyse parameters over time. RESULTS: ESSDAI, ESSPRI, rheumatoid factor and IgG levels decreased significantly during abatacept treatment and increased post-treatment. Salivary and lacrimal gland function did not change during treatment. Fatigue and health-related quality of life (HR-QoL) improved significantly during treatment. No serious side effects or infections were seen. CONCLUSIONS: In this open-label study, abatacept treatment is effective, safe and well tolerated, and results in improved disease activity, laboratory parameters, fatigue and HR-QoL in patients with early and active pSS. TRIAL REGISTRATION NUMBER: 2009-015558-40.

The relationship between self-reported executive performance and psychological characteristics in multiple sclerosis.

BACKGROUND AND PURPOSE: Self-reports of cognitive functioning are not always related to objective measures. We examined psychological characteristics of patients with multiple sclerosis (MS) who underestimate, overestimate or accurately estimate their executive performance. METHODS: The first phase was an inventory of cognitive complaints by means of self-reported (and partner-reported) questionnaires. At the second phase (January-October 2009), 114 of the 128 participants met the inclusion and exclusion criteria and underwent cognitive and neurological assessments. RESULTS: A total of 19% (N = 22) of participants reported subjective executive impairment, whilst 81% (N = 92) reported no subjective executive impairment. Based on Behavioural Assessment of the Dysexecutive Syndrome-Dysexecutive Questionnaire self-reports, 67% (N = 76) of the participants accurately reported no subjective executive impairment, 14% (N = 16) overestimated, and 15% underestimated (N = 17) their executive performance; 78% of the informants accurately reported no subjective executive impairment, 15% overestimated the patient's executive performance, and 4% underestimated the patient's executive performance. Patients with MS underestimating their executive performance were characterized by more depression (F(2,106 = 12.9, P < 0.001), anxiety (F(2,105) = 7.4, P = 0.001) and psychosocial stress (F(2,103) = 17.8, P < 0.001), more often used the coping style 'disclosure of emotions' (H(2) = 12.1, P = 0.002) than accurate estimators and overestimators and displayed a more passive reaction pattern (F(2,104) = 4.4, P = 0.014) than accurate estimators. CONCLUSIONS: Self-reports of executive performance are generally reliable, but 29% of patients with MS underestimated or overestimated their abilities. It is especially important to identify underestimators as they display underlying psychological problems and dysfunctional coping styles in need of further psychological treatment. Informants are valuable in this respect, but should not be seen as the 'gold standard' to identify cognitive impairment.

Treatment effect modifiers for the patient education programme for Parkinson's disease.

AIM: A recent randomised controlled trial showed significant benefits for Parkinson's disease (PD) caregivers' psychosocial problems and need for help and a trend towards significant improvement of patients' quality of life after participation in the Patient Education Programme for Parkinson's disease (PEPP). Large variations in change scores were found, indicating variation in benefit. The aim of this study was to search for treatment effect modifiers. METHODS: Outcome measures were patients' quality of life [Parkinson's Disease Questionnaire (PDQ)-39] and caregivers' psychosocial burden [Belastungsfragebogen Parkinson Angehörigen kurzversion (BELA-A-k)]. Candidate treatment effect modifiers were participants' characteristics and baseline scores on psychological questionnaires (BELA-P/A-k, PDQ-39, EQ-5D, Self-rating Depression Scale) and patients' neuropsychological test scores (Mini Mental State Examination, National Adult Reading Test, Dutch version, Word Test, Behavioural Assessment of the Dysexecutive Syndrome rule shift, Trail Making Test, Stroop). Secondary analyses of data from a randomised controlled trial with 64 patients and 46 caregivers were performed using regression analyses with treatment group interaction terms. RESULTS: No significant modifiers were found for the patients. In the caregiver group, a higher MMSE score of the patient at baseline was found to be a significant predictor of a lower BELA-A-k Bothered by score post-intervention of the caregiver. CONCLUSIONS: A potential predictor of treatment benefit was found for caregivers of PD patients with better cognitive functioning. This study did not find treatment effect modifiers for PD patients: demographics, disease stage and time of diagnosis, cognitive functioning, level of baseline psychosocial burden, participating with or without a caregiver, and caregiver changes did not influence treatment outcome. The PEPP seems suitable for the majority of patients.

An evaluation of the patient education programme for Parkinson's disease in clinical practice.

AIM: The Patient Education Programme for Parkinson's disease (PEPP) was assessed in a recent randomised controlled trial (RCT). In this study, a trend was identified towards significant improvement of patients' quality of life (Qol) as well as a significant reduction of caregivers' psychosocial burden and need for help. This study is aimed at evaluating the effectiveness of the PEPP in clinical practice as compared with the RCT in an academic setting. The second aim is to assess its effectiveness in clinical practice at 6-month follow-up. METHODS: Fifty-five patients and 50 caregivers from nine clinical settings participated in the PEPP consisting of eight weekly sessions of 90 min. Self-report questionnaires were used to assess patients' Qol (PDQ-39) and caregivers' psychosocial burden and need for help (BELA-A-k) at baseline, directly after the programme and at 6-month follow-up. To compare the baseline data and short-term effects, data were used from an RCT study which included 64 Parkinson's disease patients and 46 caregivers. RESULTS: Compared with the RCT control group, significant effects, after Bonferoni adjustment, were found for patients' Qol as well as for caregivers' psychosocial burden and need for help. No significant changes were found between baseline scores compared with 6-month follow-up. Scores returned to baseline levels at 6-month follow-up. CONCLUSIONS: Effects from the RCT study were replicated and the effect on patients' Qol was now significant. However, at 6-month follow-up, scores returned to baseline levels, indicating the need for some form of a booster session.

Immunofluorescence serration pattern analysis as a diagnostic criterion in antilaminin-332 mucous membrane pemphigoid: immunopathological findings and clinical experience in 10 Dutch patients.

BACKGROUND: Antilaminin-332 mucous membrane pemphigoid (anti-LN-332 MMP) is a chronic subepidermal blistering disease characterized by IgG anti-epidermal basement membrane zone (BMZ) autoantibodies against laminin-332 (LN-332). PATIENTS: with anti-LN-332 MMP have an increased relative risk of malignancy. Laboratory techniques that are difficult to obtain are needed for diagnosis of anti-LN-332 MMP. Objectives To incorporate direct immunofluorescence (DIF) serration pattern analysis of IgG depositions in the diagnostic criteria of anti-LN-332 MMP. METHODS: Patients who met our revised inclusion criteria for anti-LN-332 MMP were selected from our biobank over the period 1997-2009. Inclusion criteria were clinical symptoms, DIF serration pattern analysis, indirect immunofluorescence (IIF) on salt-split skin, and antigen-specificity analysis of the serum including immunoblotting and/or immunoprecipitation and/or enzyme-linked immunosorbent assay (ELISA) against native LN-332. RESULTS: Ten patients met the inclusion criteria. A malignancy was found in two patients (20%). In all patients in whom it was performed (n = 9), DIF showed linear IgG deposition along the BMZ in an n-serrated pattern. Nine sera reacted by salt-split skin analysis and bound to the dermal side of the split skin. ELISA against native LN-332 was positive in 78% of the tested sera. CONCLUSIONS: Anti-LN-332 MMP can clinically resemble other forms of pemphigoid. Although state-of-the-art laboratory diagnostics are necessary for definite diagnosis, the combination of simple DIF serration pattern and IIF salt-split skin analysis will exclude other forms of MMP and epidermolysis bullosa acquisita from the differential diagnosis. Because of the increased risk for malignancy patients should be thoroughly oncologically screened.

Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjögren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. METHODS: Patients with active primary SS, as determined by the revised American-European Consensus Group criteria, and a rate of stimulated whole saliva secretion of > or =0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. RESULTS: Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean +/- SD age of the patients receiving rituximab was 43 +/- 11 years and the disease duration was 63 +/- 50 months, while patients in the placebo group were age 43 +/- 17 years and had a disease duration of 67 +/- 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness-like disease. CONCLUSION: These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS.

Caregiver education in Parkinson's disease: formative evaluation of a standardized program in seven European countries.

PURPOSE: The formative evaluation of a standardized psychosocial education program for patients with Parkinson's disease (PD) and their caregivers. The results of the participation of the caregivers are presented next to the data of the patients. METHODS: Caregivers (n = 137) and patients with PD (n = 151) participated in the 8-week program in separate groups. Measurements were performed on psychosocial problems (BELA-P/A-k), health state (EQ-5D VAS), quality of life (PDQ-39) and depression (SDS) 1 week before and 1 week after the program. Participants rated their mood on a visual analogue scale before and after each session, and they filled in an evaluation questionnaire after the last session. RESULTS: Scores on the BELA-P/A-k improved significantly on the 'bothered by scale' as well as the 'need for help scale'. No improvements were found on EQ-5D VAS, PDQ-39 and SDS. Mood ratings improved significantly after each session. Most participants evaluated the program as positive. Feedback led to improvements in the program, which are incorporated in a final manual. CONCLUSIONS: The program was feasible to run in the different countries. This exploratory study led to improvements in the program and recommendations for further research. A study on the effectiveness of the program is the next step.

The benefits of a standardized patient education program for patients with Parkinson's disease and their caregivers.

The Patient Education Program Parkinson (PEPP) is a standardized psychosocial intervention aiming at improving the health-related quality of life (Hr-Qol) of patients with Parkinson's disease (PD) and caregivers. A randomized controlled trial was performed to assess its effectiveness. Sixty-four PD patients and 46 caregivers were allocated to either the intervention group (PEPP) or the control group (usual care). The intervention consisted of eight weekly sessions of 90-minute duration. Assessments were performed on psychosocial problems (BELA-P/A-k), Hr-Qol (PDQ-39/EQ-5D) and depression (SDS) at baseline and one week after the end of the PEPP. Participants rated their mood on a visual analogue scale before and after each session. A significant effect for the caregivers on psychosocial problems and need for help was found and a trend for significance for patients' quality of life. Patients' and caregivers' mood improved significantly after each session. This study provides indications that PD patients and caregivers benefit from the PEPP.

[Techniques for posterior lamellar keratoplasty through a scleral incision]. / Techniken der posterioren lamellären Keratoplastik über einen skleralen Zugang.

PURPOSE: To describe several techniques for posterior lamellar keratoplasty through a scleral incision, for management of corneal endothelial disorders like pseudophacic bullous keratopathy and Fuchs' endothelial dystrophy, and to report the mid-term clinical results. METHODS: Three techniques have been developed to perform a posterior lamellar keratoplasty procedure through a scleral incision, i.e. to replace the posterior corneal layers while leaving the anterior corneal surface intact and without the use of corneal sutures. In the first technique, a 9.0 mm scleral incision is made to accommodate an intracorneal trephine and spoon-shaped glide to insert a 7.5 mm donor posterior lamellar disc into the anterior chamber. In the second technique, the procedure is performed through a 5.0 mm scleral tunnel incision using microscissors and by folding a 8.5 mm donor posterior disc prior to insertion. In the third technique, a 4.0 mm tunnel incision is made to perform a descemetorhexis in the host cornea, i.e. Descemet's membrane is selectively excised from the recipient eye, and a 9.0 mm donor Descemet's membrane is inserted. In eyes with a minimal postoperative follow-up of 3-5 years ( n=16), we documented the best spectacle corrected visual acuity (BSCVA), keratometry readings, endothelial cell counts, and clinical events. RESULTS: In all cases, the graft adhered to the recipient posterior cornea without suture fixation. In patients without concomitant ocular disease, BSCVA was 0.7-1.0 in all eyes. The astigmatism averaged 2.1+/-0.7 D, endothelial cell counts averaged 2126+/-529 cells/mm(2) at 6 months, 1839+/-473 cells/mm(2) at 12 months, 1418+/-434 cells/mm(2) at 24 months, and 1137+/-420 cells/mm(2) at 36 months. In two patients, an irido-corneal adhesiolysis was performed within days after the procedure. In one patient, residual visco-elastic adherence was present at the donor-to-recipient interface, and a penetrating keratoplasty was performed 1 month postoperation. One patient developed significant interface haze, requiring a penetrating keratoplasty 13 months after the first surgery. CONCLUSION: Posterior lamellar keratoplasty can be an effective surgical technique to manage corneal endothelial disorders. An improved visual acuity can be obtained within the first weeks after surgery, and the visual perfomance of the graft is stable up to 5 years postoperation.

Occupational IgE sensitisation to phytase, a phosphatase derived from Aspergillus niger.

OBJECTIVE: Phytase is a phosphatase derived from Aspergillus niger that enhances phosphate bioavailability in the gut, and therefore has been increasingly used as an animal feed additive since the early 1990s. The aim of this study was to assess whether work related respiratory symptoms among workers in a so called premix factory producing animal feed additives, could be due to type I (mediated by immunoglobulin E (IgE) allergic sensitisation to phytase. METHODS: Preparations of specific IgE against phytase as used in the factory were assessed by enzyme immunoassay (EIA) in serum samples of 11 exposed workers who regularly handled the enzyme, in 11 office and laboratory workers of the same plant (non-exposed internal controls), and in 19 laboratory animal workers as external controls. The factory workers also completed a questionnaire on common and work related respiratory symptoms. RESULTS: Depending on the cut off level in the EIA for IgE, and the preparation used as coated allergen, antiphytase sensitisation was found in one to four of the 19 external controls, in one to five of the 11 internal controls, and in four to 10 of the 11 exposed workers. Strongest IgE reactions were found in four exposed workers who reported work related respiratory symptoms, particularly wheezing, and in one internal control who possibly had become sensitised because the structure of the factory building did not preclude airborne exposure in the offices and corridors of the plant. Experiments with inhibition EIA for IgE showed that (a) phytase of another commercial source was only partially cross reactive with phytase as used in the premix factory, and (b) phytase used as an animal feed additive did not cross react with common mould extracts, except for extracts from the species of origin, Aspergillus niger. The amount of IgE binding phytase in Aspergillus niger was estimated to be between 0.1% and 1% of the extractable mould proteins. CONCLUSIONS: Phytase is a potentially important new occupational allergen causing specific IgE immune responses among exposed workers. Such IgE sensitisation could probably be the cause of work related asthmatic and other respiratory symptoms if no effective measures are taken to prevent airborne occupational exposure at sites where phytase is handled, particularly during addition of enzyme preparations to animal feed.

Shape of the craniofacial complex in children with Turner syndrome.

The shape of the craniofacial complex was established in 69 children with Turner syndrome aged between 3.5 and 16.6 years. The children had not been treated with growth hormone (GH) or anabolic steroids. On a standardized lateral roentgenencephalogram 13 linear and 7 angular variables were measured. Data of all variables were available from normal Dutch children for comparison. The main abnormalities were located in the cranial base and in the mandible and consisted of a short posterior cranial base, all increased cranial base angle and a short, retrognathic and posteriorly rotated mandible. The maxilla was smaller than normal and also slightly posteriorly rotated. The abnormalities were already present in young children with Turner syndrome. Indications were found that in Turner syndrome interstitially as well as appositionally growing cartilage is affected. The changes in the maxilla can be explained in various ways. They may be due to defective growth of the nasal cartilage or to a disorder in the intramembranous ossification of the maxilla or they may be adaptive to the changes in the cranial base and the mandible. From this study it can be concluded that patients with Turner syndrome exhibit several craniofacial abnormalities, probably due to a cartilage disorder.