Changes In Clinical Activity Research Articles

Changes in Clinical Activity, Serum Autoantibody Levels, and Chorioretinal Vessels After Systemic Glucocorticoid Therapy in Thyroid Eye Disease.

The aim of this study was to investigate changes in the Clinical Activity Score, serum thyroid-stimulating hormone receptor antibody and thyroid-stimulating immunoglobulin levels, chorioretinal blood vessels, and extraocular muscle thickness in patients with thyroid eye disease following systemic steroid treatment. This prospective observational study enrolled 57 patients with active thyroid eye disease who received systemic intravenous glucocorticoids for 12weeks. Demographics, clinical activity scores, optical coherence tomography images, and serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were assessed at baseline, at 6 and 12weeks after intravenous (IV) GC therapy initiation, and 2months after IV GC therapy termination. The extraocular muscle thickness, choroidal thickness, and choroidal vascularity index were measured. The clinical activity scores showed a significant decrease. Serum thyroid-stimulating immunoglobulin levels dropped continuously for 2months. The thyroid-stimulating hormone receptor antibody level decreased until 12weeks after treatment but returned to within the normal range in 75% of patients after 77 and 126days, respectively. The choroidal thickness decreased at all time points. The thickness of the medial and inferior rectus muscles decreased at 2months after treatment. The clinical activity score decreased to < 3 points in 50% of patients after 78days. Intravenous glucocorticoid therapy improved the clinical activity score, chorioretinal blood flow, and extraocular muscle thickness. The serum autoantibody levels were normalized in patients with active thyroid eye disease 2 months after IV GC termination. The serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels correlated with restoration of chorioretinal capillary perfusion and improved clinical symptoms and muscle thickness. Non-invasive optical coherence tomography findings and serologic factors predict the response to intravenous glucocorticoid therapy.

OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care clinical activity in England during the COVID-19 pandemic.

The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication. With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY. Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month. Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019). Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.

RF35 | PSAT269 Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase 2b Study of Batoclimab in Active and Moderate-to-Severe Thyroid Eye Disease

Abstract Clinical manifestations of thyroid eye disease (TED) are mainly caused by the binding of immunoglobulin G (IgG) thyrotropin receptors (TSHR) autoantibodies (TSHR-Ab) on orbital fibroblasts. Batoclimab (IMVT-1401) is an anti-neonatal Fc receptor (FcRn) human monoclonal antibody that prevents normal IgG recycling, leading to reduced levels of circulating IgG. Thus, batoclimab may provide benefit for patients with TED by reducing pathogenic anti-TSHR-Ab. In this Phase 2b, double-blind, randomized study (NCT03938545), subjects with active and moderate-to-severe TED received weekly subcutaneous (SC) injections of batoclimab (680mg, 340mg, 255mg) or placebo for 12-weeksSixty-five subjects were randomized and received batoclimab (680mg [n=18], 340mg [n=19], 255mg [n=10]) or placebo (n=18). Recruitment and treatment were stopped because of an unanticipated increase in LDL cholesterol levels, not included in subject informed consent. Hence, forty-five of 77 planned subjects completed the 12-week treatment period. Serum IgG and anti-TSHR-Ab were reduced from baseline to Week-12 with batoclimab (680mg [-77.9%; -65.5%], 340mg [-65.8%; -70.1%], 255mg [-56.6%; -42.1%]) versus placebo (-4.67%; -3.23%), respectively. Substantial reductions were also observed at Week-12 in stimulatory anti-TSHR-Ab. Fifty-one of 65 subjects had proptosis ≥ upper level of normal at baseline. At Week-12 (primary outcome), greater proportions of 680mg (30%; p=0.2197) and 340mg (30.8%; p=0.1311) subjects were proptosis responders (≥2mm reduction) versus placebo (8.3%). Absolute risk reduction (ARR [95% CI]) versus placebo was 21.4 (-11.3, 54.1) for 680mg and 24.2 (-4.8, 53.2) for 340mg at Week 12. Earlier proptosis responses were statistically different from placebo for 680mg at Weeks-four (35.7%; ARR [95% CI] 36.0 [10.9, 61.1]), five (42.9%; 43.0 [17.1, 68.9]), and 11 (41.7%; 34.5 [3.4, 65.6]) and for 340mg at Weeks-five (29.4%; 29.6 [7.9, 51.3]), nine(35.7%; 30.6 [3.0, 58.2]), and 11 (46.2%; 40.2 [10.2, 70.1]) (all p&amp;lt;0.05). Changes in clinical activity at Week-12 were not significantly different from placebo.The proportion of subjects with an adverse event (AE) were similar across treatment groups; most were mild or moderate in severity. Two subjects reported serious AEs not related to treatment (optic neuropathy, autoimmune encephalitis [occurring after treatment period]). No subjects withdrew from the study due to an AE during the 12-week treatment period. There was a reversible dose-dependent reduction in serum albumin during the treatment period. Post-hoc lipid analysis demonstrated a reversible increase in mean serum LDL during treatment (680-mg: 58.7%; 340-mg: 30.8%; 255-mg: 19.0%) vs placebo (-3.9%),.In conclusion, batoclimab reduced circulating IgG and especially the pathogenic anti-TSHR-Ab. Although the proptosis response was not statistically significant at the primary endpoint, significance was seen at earlier time points. This is probably related to early study termination which reduced the numbers of patients available for efficacy assessment at the primary endpoint. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:54 p.m. - 12:59 p.m.

Delivering multidisciplinary neuromuscular care for children via telehealth

Introduction/AimsIn response to coronavirus disease 2019 (COVID‐19) pandemic restrictions int 2020, our face‐to‐face (F2F) multidisciplinary neuromuscular clinic (NMC) transitioned to widespread use of telehealth (TH). This study aimed to (1) understand parent/guardian, child, and clinician perceptions of TH; (2) examine TH‐related changes in clinical activity; and (3) use these findings to inform a future model of care for the NMC.MethodsA clinical audit was undertaken to examine clinical activity throughout 2018–2020. Online surveys were distributed to clinicians and parents of children attending the NMC via TH in 2020. A working group of clinicians created a checklist to guide a future hybrid model of TH and F2F care.ResultsTotal clinical activity in 2020 was maintained from previous years; 62.8% of all appointments occurred via TH, and 82.3% of patients attended NMC by TH at least once. Ninety‐nine parents (30.6% response rate), 52 children, and 17 clinicians (77% response rate) responded to the survey. All groups reported better interaction when F2F compared to TH. Eighty percent of parents identified advantages of TH and reported lower levels of stress. A lack of “hands‐on” physical assessment was identified by parents and clinicians as a TH limitation. Most families (68.1% of parents; 58.8% of children) and all clinicians indicated a preference for a mix of TH and F2F NMC appointments in the future.DiscussionThis study has informed a checklist to guide future TH use in a new hybrid model of care. Further investigation is required to assess health impacts of TH use in pediatric neuromuscular care.

Dynamics of leukocytic blood parameters depending on the activity of inflammatory bowel disease in children

Aim: to establish the patterns of changes in leukocyte blood parameters to determine their diagnostic significance in the different activity of Crohn’s disease (CD) and ulcerative colitis (UC) in children. Materials and methods. 370 5-18-year children (198 boys, 172 girls) with inflammatory bowel disease (IBD) were examined. Leukocytic blood parameters, concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), faecal calprotectin (FC) levels were determined. Changes in clinical activity in Crohn’s disease (CD) and ulcerative colitis (UC) cases were determined using pediatric activity indices: PCDAI and PUCAI, respectively. Analysis of endoscopic activity in 160 CD and UC patients was determined using the scales: SES-CD and UCEIS, respectively. Results. It was found that with an increase in the clinical activity of CD in children, the absolute numbers of leukocytes, lymphocytes and monocytes did not change significantly. In contrast, a significant increase in neutrophil reactivity was noted. In patients with high endoscopic CD activity an increase in the absolute number of monocytes and neutrophil reactivity was found. In patients with high clinical activity of UC, an increase in the number of leukocytes and the absolute number of neutrophils was found. At the same time, the granularity and reactivity of neutrophils increased from remission to moderate and high clinical activity of UC. In children with high endoscopic UC activity, the number of leukocytes, the absolute number of neutrophils and monocytes increased. At the same time, the granularity of neutrophils significantly increased as the endoscopic activity of UC increased from remission to moderate activity. Leukocyte parameters in UC patients correlated moderately with FC level, and the absolute number of neutrophils was closely related to its content. The granularity and reactivity of neutrophils positively correlated with ESR and CRP levels in children with CD and CRP concentrations in children with UC. Conclusion. The established patterns of changes in the quantitative composition of leukocytes and their functional properties (reactivity and granularity) are directly determined by the different activity of IBD in children and have diagnostic value

The Impact of the First Wave of the COVID-19 Pandemic on Providing Special Care Dentistry: A Survey for Dentists

This study aimed to investigate the impact of COVID-19 on the experiences of special care dentistry providers worldwide. An online survey was administered from 10 to 31 July 2020. Age, sex, years of professional activity, COVID-19 status, geographical area of origin and length of lockdown period were recorded for all participating dentists. The relationships between these variables and the changes in clinical activity, the treated patients’ COVID-19 status and the implementation of protective measures in the dental clinic were analyzed. A total of 436 (70.6% women) dentists from 59 countries responded to the survey. Clinical activity was reduced or stopped for 79.1% of respondents. The most common change was to limit treatment to urgent care only (53.7%). Treatment under general anesthesia or deep sedation was discontinued (51.0%) or reduced (35.8%) for the majority of respondents. Male dentists were more likely to maintain their clinical activity than female dentists (p < 0.001), and respondents from North America were more likely to do so than participants from other geographical regions (p < 0.001). Dentists from Latin America and the Caribbean were more likely to report treatment of confirmed cases of COVID-19 than those from Europe (p < 0.001). The implementation of protective measures in the dental office was determined by the survey participant’s sex, intensity of clinical activity and geographical area of origin. To conclude, the provision of special care dentistry was considerably reduced in response to the pandemic. Service maintenance was mainly related to the geographical area in which the surveyed dentists worked, further exacerbating pre-existing inequalities.

Sentinel joint scoring in rheumatoid arthritis: an individualized power Doppler assessment strategy.

Musculoskeletal ultrasound quantifies the total synovial inflammatory burden in rheumatoid arthritis (RA) but is time consuming when scanning numerous joints. This study evaluated a novel patient-centered method for constructing a longitudinal ultrasound score in RA patients. Fifty-four RA patients starting intravenous tocilizumab were evaluated with power Doppler ultrasound (PDUS) of 34 joints and DAS28-ESR was assessed at baseline and weeks 4, 12, 16, and 24. The sentinel joint score (SJS) was derived from the reduced subset of joints with PDUS ≥ 1 at baseline. Total PDUS (tPDUS) score and US7 were also calculated. Changes in tPDUS and SJS were correlated. Effect sizes were calculated for tPDUS, SJS, and US7. The proportion of "flipped" joints without baseline PDUS signal that later developed PDUS signal was estimated. At baseline, 1236/1829 joints scanned (67.5%) did not have PDUS signal. The proportion of "flipped" joints at 24 weeks was 5.6% for ≥ 1, 2.9% for ≥ 2, and 1.0% for = 3 PD. tPDUS and SJS scores were highly correlated (r = 0.91 to 0.97). Overall the effect sizes for tPDUS, SJS, and US7 increased over 24 weeks, where SJS was the highest (SJS 1.00 4-week, 1.07 12-week, 1.26 24-week) and tPDUS and US7 were comparable (tPDUS 0.32 4-week, 0.52 12-week, 0.84 24-week; US7 0.23 4-week, 0.52 12-week, 0.74 24-week). In RA patients starting a biologic, scanning only joints with baseline PDUS signal can substantially reduce the number of joints requiring follow-up scanning by 67.5% and improves feasibility. "Flipped" joints are infrequently seen after starting therapy. ClinicalTrials.gov NCT01717859 Key messages • Only a small percent of joints develop power Doppler signal after baseline scanning. • Changes in the SJS correlate well with changes in clinical activity measured by DAS28-ESR over time. • The SJS effect size is higher than total PDUS and US7 scores, and may improve examination feasibility.

A prospective study comparing patient-reported outcomes in Crohn's disease.

Patient reported outcomes are important in Crohn's disease. In this prospective cohort, we investigated the performance of the Bristol Stool Form Scale (BSFS) and a visual analog scale (VAS) for abdominal pain as outcome measures in Crohn's disease. Patients with active Crohn's disease starting glucocorticoids or anti-tumor necrosis factor were included. Before treatment and 10 weeks later we collected: clinical activity [Harvey Bradshaw Index (HBI) and Crohn's-Disease-Activity-Index (CDAI)], serum C-reactive protein (CRP) and fecal calprotectin, and BSFS (1-7) and a 100-mm VAS based on a 7-day diary. Clinical response was defined as a reduction by at least 3 and at least 100 of HBI and CDAI, respectively. Fecal calprotectin-response and CRP-response were defined as reduction of at least 50%. Thirty-eight patients completed follow-up. At baseline, BSFS-parameters correlated more strongly with clinical activity (range: rs: 0.31-0.74) than with CRP (rs: -0.01 to 0.16) and fecal calprotectin (rs: 0.14-0.26). VAS scores correlated very weakly to moderately with clinical activity (rs: 0.18-0.45), and weakly to moderately with CRP (rs: 0.24-0.34) and fecal calprotectin (rs: 0.35-0.43). Changes in VAS scores correlated moderately to strongly (rs: 0.55-0.71) with changes in clinical activity, and weakly with changes in CRP and fecal calprotectin (rs: 0.21-0.35). Changes in BSFS parameters correlated weakly to moderately (rs: 0.23-0.53) with changes in clinical activity, and very weakly to weakly (rs: 0.01-0.35) with changes in CRP and fecal calprotectin. Responsiveness of VAS and BSFS was moderate to high (Guyatt's statistic 0.41-2.17) and highly dependent on the definition of response. The BSFS and a VAS appear to be responsive with moderate-to-strong construct validity to monitor patients with Crohn's disease.

P012 Successful Use of Combination Biologic Therapy in Medically Refractory Pediatric Crohn's Disease and Sacroiliitis

CASE: We present a patient with medically refractory Crohn’s disease, sacroiliitis and growth failure who showed remarkable response to combination therapy using two different biological agents along with an immunomodulator and no significant adverse events. A 14-year old male presented for 2nd opinion regarding management of refractory ileocolonic Crohn’s disease. He was diagnosed with Crohn’s disease at an outside center at 9 years of age. Initial treatment with systemic steroids and azathioprine was unsuccessful. He had sub-optimal clinical improvement on anti-tumor necrosis factor (TNF) therapy that included infliximab for 1 year, followed by adalimumab for 1.5 years. He subsequently struggled with repeated episodes of Clostridium difficile (CDI) requiring prolonged vancomycin taper. His therapy was then switched to vedolizumab, systemic steroids and azathioprine which provided some symptomatic relief, but he was noted to be persistently anemic with elevated inflammatory markers and poor growth. At the time of presentation to our center he was steroid dependent on prednisone 5 mg daily for 6 months while still on vedolizumab and azathioprine. He had mildly active clinical disease but severe growth failure and was negative for CDI. Repeat disease assessment noted severe granulomatous colitis and terminal ileitis with worsening disease in the distal colon. He was treated with Budesonide MMX and mesalamine enemas with no improvement. Vedolizumab levels were noted to be low and therefore therapy escalated to every 4-week intervals. Azathioprine was stopped due to lack of efficacy despite adequate levels. Due to body mass index (BMI) z-score of -2.4, exclusive enteral therapy was implemented for 3 months followed by transition to regular diet. His weight improved but there was no change in clinical activity or laboratory abnormalities. He subsequently developed leg and hip pain. Rheumatology evaluation was pursued, and he was diagnosed with sacroiliitis based on physical examination and a lumbosacral MRI. At this point a decision was made to use combination of two biologicals due to prior history of GI disease refractory to anti-TNF therapy. Adalimumab and oral methotrexate were given in addition to vedolizumab. He has been on this combination for last 9 months with no adverse events. Patient has shown excellent clinical response with normalization of inflammatory markers and resolution of anemia. His BMI z-score improved to 0.76 with weight gain of 25 kilograms in the past year. Combination biologicals are rarely utilized due to concerns for side effects and high cost making it difficult to obtain insurance approval. When used judiciously in patients with medically refractory disease it can be safe and effective. A paucity of literature exists regarding the use of combination biologicals especially in children.

2925 Effect of Short Bowel Syndrome on Disease Activity in Patients With Crohn's Disease

INTRODUCTION: Despite advancements in medical therapies a significant number of Crohn's disease (CD) patient's end up requiring surgical intervention, often leading to short bowel syndrome (SBS). We aimed to assess the changes in clinical activity in CD patients before and after the diagnosis of SBS and assess the association between endoscopic disease activity and length of remaining bowel. METHODS: Using our home parenteral nutrition (PN) database all patients with the diagnosis of CD and SBS requiring PN or IV fluid support between January 1990 and June 2018 were identified. Data on baseline demographics, co-morbidities and concomitant medications was collected. Laboratory data, Simple Endoscopy score [SES], patient reported outcomes (PROs) and medications at baseline and 6-12 months after SBS diagnosis were collected. We also assessed exacerbation of IBD, hospitalization and adverse events after SBS diagnosis. RESULTS: A total of 86 patients were included in the final analysis. Out cohort consisted of 58% females and 87% were Caucasians. At the time of SBS surgery, nearly 60% were current or ex-smokers, 38% had perianal disease and 17% had fistulas. After the surgery leading to SBS, mean bowel length was 154.0 ± 68 cms. stoma was present in 77%, colon in 63%, ileocecal valve in 12.5% and 92% of them were PN-dependent. At baseline and after 6-12 months of diagnosis of SBS, there were no significant changes in BMI, laboratory data, endoscopic disease activity or extraintestinal manifestations (P &gt; 0.05 for all). In terms of symptoms, there was a trend towards more diarrhea after the diagnosis of SBS (P = 0.06) but no significant change in abdominal pain and bleeding (P &gt; 0.05) were noted. The use of salicylates decreased after SBS (38% vs. 22%, P = 0.02) but more patients were on vedolizumab after SBS diagnosis (0 vs. 13%, P = 0.001), there were no significant changes in other medications (Table 1). Overall, 59% required hospitalizations after the diagnosis of SBS, but only 15% had CD-exacerbation. There was no significant association between endoscopic disease activity and intestinal length before and after the diagnosis of SBS (Figure 1a,b). CONCLUSION: Our study suggests that contrary to common belief of less medication requirement in CD after SBS, some patient might need aggressive medical therapy as there is no significant co-relation between endoscopic disease activity and bowel length. Further studies with longer follow-up are required to confirm these findings.

The perceived effect of serious adverse perinatal events on clinical practice. Can it be objectively measured?

ObjectiveObstetrics involves a high degree of clinical risk. While serious adverse events resulting in substantial maternal or neonatal morbidity or mortality are relatively rare it has been shown that exposure to a such an event can have a predominantly negative personal and professional impact on the healthcare professionals who are involved. There is little in the published literature to show an objective change in clinical practice as a result of an adverse event.The aim of this study was to identify if it was feasible to design a study that could objectively demonstrate if a change in labour ward clinical activity occurred in the 28 days following a serious adverse perinatal event. If this proved possible, the second aim was to identify if these changes could be attributed to the preceding adverse event. Study designThis study was conducted in a large tertiary teaching hospital in Ireland. This was a retrospective observational study conducted using data from a 25-month period from August 2013 to September 2015.Six of the most serious adverse perinatal events that occurred over that time period were identified from the hospital’s clinical risk register. Various outcome variables in the form of aggregate data on all deliveries that occurred in CUMH for the 28 days preceding and succeeding the events were collected by the lead author. The medical records for each severe adverse perinatal event were reviewed and the clinical case details recorded. Based on these clinical details individual hypotheses were created for each event. Data was analysed using IBM-SPSS. ResultsAggregate data relating to 6180 deliveries was collected and analysed. Data analysis revealed some statistically significant changes in clinical activity in the 28 days following five of the six adverse events. These changes in clinical activity did not, however, always match what we had expected from our original hypotheses. ConclusionThis novel study aimed to identify if it was possible to objectively demonstrate this practice change. We identified some statistically significant changes in clinical activity in the 28 days following five of the six adverse events but were unable to definitively conclude if the change in activity was a direct result of each event.

Clinical meaning and implications of serum hemoglobin levels in patients with rheumatoid arthritis.

Anemia is a common problem in rheumatoid arthritis (RA), associated with radiographic progression and disability. We explored the association of hemoglobin with a comprehensive set of variables in RA patients. We included RA outpatients in the routine setting. For each patient we performed measurements (clinical measures, blood tests including serology, markers of acute phase response and iron metabolism, including hepcidin, and circulating hematopoietic precursor levels) at baseline and 12 weeks thereafter, and analyzed their changes in patients with a treatment adaptation at baseline. We performed principal component analysis (PCA) to identify thematic groups hemoglobin was related to. Then we constructed multivariable linear models to assess the contribution of individual variables to the variability of hemoglobin. In total, 88 patients were included (age: 58 ± 12; disease duration: 9.3 ± 9.6 years). Cross-sectionally (at baseline and week 12) hemoglobin levels were tied to iron metabolism and hematopoiesis, but not to clinical activity, based on thematic groups extracted from the PCA. In contrast, longitudinal changes in hemoglobin levels were closely linked to changes in clinical activity. Conversely, hepcidin reflected iron metabolism cross-sectionally, but changes in acute phase response longitudinally. In multivariable analysis variability components of hemoglobin were explainable by ferritin, ESR, evaluator global assessment (EGA), and iron levels, while components of hemoglobin changes were explained by changes in EGA mostly. Hepcidin was not independently associated with hemoglobin. Besides its dependence on body iron status, changes in hemoglobin levels are strongly tied to disease activity, possibly revealing more about disease activity than other laboratory markers.

The lupus impact tracker is responsive to changes in clinical activity measured by the systemic lupus erythematosus responder index.

Objective The lupus impact tracker (LIT) is a 10-item patient reported outcome tool to measure the impact of systemic lupus erythematosus or its treatment on patients' daily lives. Herein, we describe the responsiveness of the LIT and LupusQoL to changes in disease activity, using the systemic lupus erythematosus responder index (SRI). Methods A total of 325 adult systemic lupus erythematosus patients were enrolled in an observational, longitudinal, multicentre study, conducted across the USA and Canada. Data (demographics, LIT, LupusQoL, BILAG, SELENA-SLEDAI) were obtained three months apart. Modified SRI was defined as: a decrease in SELENA-SLEDAI (4 points); no new BILAG A, and no greater than one new BILAG B; and no increase in the physician global assessment. Standardised response mean and effect size for LIT and LupusQoL domains were calculated among SRI responders and non-responders. Wilcoxon's test was used to compare the LIT and LupusQoL variation by SRI responder status. Results Of the participants 90% were women, 53% were white, 33% were of African descendant and 17% were Hispanic. Mean (SD) age and SELENA-SLEDAI at baseline were 42.3 (16.2) years and 4.3 (3.8), respectively. Mean (SD) LIT score at baseline was 39.4 (22.9). LIT standardised response mean (effect size) among SRI responders and non-responders were -0.69 (-0.36) and -0.20 (-0.12), respectively ( P = 0.02). For LupusQoL, two domains were responsive to SRI: standardised response mean (effect size) for physical health and pain domains were 0.42 (0.23) and 0.65 (0.44), respectively. Conclusions LIT is moderately responsive to SRI in patients with systemic lupus erythematosus. Inclusion of this tool in clinical care and clinical trials may provide further insights into its responsiveness. This is the first systemic lupus erythematosus patient reported outcome tool to be evaluated against composite responder index (SRI) used in clinical trials.

Modulation of plasma cytokines and its association with clinical response to treatment with the JAK2-selective inhibitor SAR302503 in myelofibrosis (MF).

7110 Background: Abnormal cytokine expression may represent an inflammatory response that contributes to the clinical phenotype of MF. Some constitutional symptoms (eg. fever, fatigue, pruritus, cachexia) are thought to be caused by elevated cytokines. In phase I/II studies, SAR302503 reduced splenomegaly and constitutional symptoms in patients with MF. Here, we report the effects of SAR302503 on the expression of 97 cytokines in MF patients enrolled in a Phase II study (NCT01420770) and the relationship to clinical response (spleen size), pharmacokinetic (PK) exposure, and body weight changes. Methods: Thirty-one patients were randomized to receive 300, 400, or 500 mg of SAR302503 orally, once daily, continuously in 4-week cycles. Plasma cytokines were measured at baseline and at the end of 4, 8, and 12 weeks of treatment using a microsphere-based immuno-multiplex assay (Rules Based Medicine). Results: Complete sample sets were available for 29/31 patients. A total of 28 cytokines predominantly involved in immune/inflammation pathways were regulated ≥1.5-fold (ANOVA P&lt;0.05) and of these, 19 were regulated at all time points, indicating rapid and sustained modulation by JAK2 inhibition. At 4 weeks, 16 cytokines were down-regulated, including TNFα, IL-1RA, and IL-18, and 6 were up-regulated, including leptin, EPO, and adiponectin. Hierarchical clustering of the 22 regulated cytokines enriched patients into spleen responder (≥35% reduction in spleen volume by MRI) and non-responder groups, suggesting a link between cytokine modulation and clinical response. Moderate correlations (P&lt;0.05) with spleen volume reduction at the end of week 12 were seen for a subset of regulated cytokines, including adiponectin and TNFα. Levels of the majority of the regulated cytokines tended to correlate with steady state PK exposure at week 4. A positive association with weight changes at week 24 were observed for leptin and adiponectin at week 4 (P&lt;0.05). Conclusions: This analysis shows that SAR302503 treatment modulated the expression of circulating cytokines in MF patients in association with changes in clinical activity, PK exposure, and symptom improvement (weight gain). Clinical trial information: NCT01420770.

Change in the clinical activity of multiple sclerosis after treatment switch for suboptimal response

Therapy for multiple sclerosis (MS) has a partial efficacy, and a significant proportion of treated patients will develop a suboptimal response with first-line disease-modifying drugs (DMD). Therapy switch in patients with MS can be a strategy after a treatment failure. We studied the change in clinical activity after switching of first-line DMD because of a treatment failure. Relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon-beta (IFNB) or glatiramer acetate (GA) were divided into (i) patients without change in DMD, (ii) patients with a change in DMD because of a poor response, and (iii) those with a change in DMD without relation with response. Annualized relapse rate (ARR) and relapse-free proportions were analyzed. We identified 923 patients with RRMS. Of the 180 who experienced a change because of suboptimal response, 90 switched to another first-line DMT, 38 to mitoxantrone, and 52 to natalizumab. Median ARR in the pre-DMD period on first DMD and second DMD was the following: 1, 1, and 0 for switchers from IFNB to another IFNB (P = 0.0001); 0.67, 1, and 0 for switchers from GA to IFNB (P = 0.01); 1, 1, and 0 for switchers from an IFNB to GA (P = 0.02); 1.1, 1.5, 0.2 for switchers from IFNB or GA to mitoxantrone (P = 0.0001); 0.9, 1, 0 for switchers from IFNB or GA to natalizumab (P = 0.0001). In patients with RRMS who have a poor response, switch to another DMD may reduce the clinical activity of the disease.

Health‐related quality of life in paediatric patients with inflammatory bowel disease related to disease activity

Impaired health-related quality of life (HRQoL) and an increased risk of psychosocial problems may encounter children and adolescents with inflammatory bowel disease (IBD). Generic HRQoL questionnaires, 15D designed for subjects over 16 years of age, 16D for adolescents aged 12-15 and 17D for younger children, allow comparison to healthy peers and have not been used in children with IBD before. Further, in paediatric IBD patients, HRQoL has not been related to disease activity. We evaluated the applicability of 15D, 16D and 17D questionnaires in the paediatric IBD population and examined how HRQoL is influenced by changes in clinical activity of IBD. The study subjects recruited at their scheduled, routine appointment in the outpatient clinic of the children's hospital completed the HRQoL questionnaire at baseline and again after 3-5 months. Disease activity was estimated by a three-level scale. The HRQoL of the study population was compared with that of the age-standardised general population. Fifty-five children, aged 7-19 years, were recruited. The HRQoL scores strongly correlated with the activity of the disease (P < 0.001). The two oldest age groups with IBD had lower HRQoL scores than age-standardised peers (P= 0.001/0.04). There was no gender difference in HRQoL scores. IBD has a considerable impact on the HRQoL of children and adolescents. The generic HRQoL instruments used appeared to be promising tools for examining HRQoL in paediatric IBD patients in different age groups, but larger studies to establish their usefulness in the follow-up of young patients are still warranted.

Development of standardized methods for analysis of changes in antibacterial use in hospitals from 18 European countries: the European Surveillance of Antimicrobial Consumption (ESAC) longitudinal survey, 2000–06

Our objective was to develop and test standardized methods for collection and statistical analysis of longitudinal data on hospital antibacterial use from different countries. We collected data on monthly supply of antibiotics from pharmacies in one hospital from each of 18 European countries. We applied a standardized method to classify drugs, measure use in defined daily doses and compare the effect of using occupied bed-days (OBDs) or admissions as denominators for longitudinal analysis. Antibiotic use increased in 14 (78%) hospitals and decreased in 4 hospitals. For 16 (89%) hospitals, adjustment of antibiotic use with OBDs resulted in larger changes over time than adjustment with admissions. Inclusion of all hospital clinical activity variables (admissions, length of stay and OBDs) in multivariate time series analysis identified distinct hospital groups. Nine (50%) hospitals had statistically significant changes in antibiotic use (six increasing and three decreasing) that were not explained (n = 3) or only partially explained (n = 6) by change in clinical activity. Three (17%) hospitals had no significant change in antibiotic use. In the remaining six hospitals, apparent changes in antibiotic use were largely explained by changes in clinical activity. This is the first study to use a standardized method for data collection and longitudinal analysis of antibiotic use in different hospitals. These data suggest that determination of changes in antibiotic exposure of hospital patients over a period of time is unreliable if only one clinical activity variable (such as OBDs) is used as the denominator. We recommend inclusion of admissions, OBDs and length of stay in statistical, time series analysis of antibiotic use. This model is also relevant to longitudinal analysis of infections in hospitals.

Extracorporeal leukocyte removal therapy for patients with ulcerative colitis

The purpose of the present paper was to investigate efficacy of leukocytapheresis (LCAP) or granulocytapheresis (GCAP) in pediatric patients with ulcerative colitis (UC), including reduction of the total dose and side-effects of corticosteroids. Courses of five Japanese adolescents with UC were analyzed. Four patients had recurrent UC with repeated remissions and exacerbations despite therapy including 5-aminosalicylic acid in combination with a corticosteroid. The other patient had a first attack. Effectiveness of adding LCAP or GCAP was assessed with regard to short-term changes in clinical activity, complications, and longer-term outcome. Clinical improvement was attained in three patients, while the other two did not improve and underwent colectomy. One of the two patients had moderately severe complications from LCAP and showed increased clinical activity during LCAP. The other, who began therapy with LCAP alone, had moderate improvement only after addition of a corticosteroid. Additional studies are needed to determine optimum timing of LCAP or GCAP and initiation of remission-maintenance therapy.

The Fort Bragg Sniper Attack and Mental Health Response

In October 1995, a U.S. Army sergeant opened fire on a formation of fellow soldiers at Fort Bragg, North Carolina. The authors describe the efforts of mental health providers to assist command, reduce psychological stress among affected units, and treat longer-term cases of post-traumatic stress disorder. Findings of critical-incident stress debriefings are discussed. Changes in clinical activity at the Division Mental Health Clinic following the sniper attack are presented. Recommendations are made for mental health interventions in future military community crises.

IgG and IgM anti-snRNP reactivity in sequentially obtained serum samples from patients with connective tissue diseases.

Sequentially obtained serum samples from 30 patients with connective tissue disease positive for antibody to ribonucleoprotein (RNP) were examined to determine the specificities of IgG and IgM antibodies to snRNP during the disease course using immunoblotting of nuclear extracts. The antibody patterns were correlated with disease activity. The patterns of antibody to snRNP of individual patients were mainly stable during the study but changes in levels of antibody to snRNP were seen corresponding to changes in clinical activity. These results indicate that increased reactivity of serum IgM antibodies against the B/B' proteins seems to precede a clinically evident exacerbation of disease whereas IgG antibody reactivity to the 70 K protein peaks at the time of a disease flare.