Patient perspective on remission in rheumatoid arthritis: Validation of patient reported outcome instruments to measure absence of disease activity

ObjectivePatients have identified pain, fatigue and independence as the most important domains that need to be improved to define remission in rheumatoid arthritis (RA). This study identified and validated instruments for these domains and evaluated their added value to the ACR/EULAR Boolean remission definition.MethodsPatients with a 28-joint Disease Activity Score (DAS28) ≤3.2 or in self-perceived remission (declaring their disease activity ‘as good as gone’) from the Netherlands, Portugal, Australia, and Canada, were assessed at 0, 3 and 6 months for patient-reported outcomes and the WHO-ILAR RA core set. Instrument validity was evaluated cross-sectionally, longitudinally and for the ability to predict future good outcome in terms of physical functioning. Logistic regression quantified the added value to Boolean remission.ResultsOf 246 patients, 152 were also assessed at 3, and 142 at 6 months. Most instruments demonstrated construct validity and discriminative capacity. Pain and fatigue were best captured by a simple numerical rating scale (NRS). Measurement of independence proved more complex, but a newly developed independence NRS was preferred. NRS for pain, fatigue and independence, in addition to or instead of patient global assessment did not add enough information to justify modification of the current Boolean definition of remission in RA.ConclusionKey elements of the patient perspective on remission in RA can be captured by NRS pain, fatigue, and independence. Although this study did not find conclusive evidence to improve the current definition of remission in RA, the information from these instruments adds value to the physician's assessment of remission and further bridges the gap between physician and patient.     

Considerations for the definition of remission criteria in psoriatic arthritis

ObjectivesPsoriatic arthritis (PsA) is an autoimmune disease that can cause progressive structural damage of the joints and irreversible disability. The potentially achievable results of biologic therapy for PsA has led to the view that disease remission should be the goal of treatment. However, the heterogeneity of disease manifestations and need for validated outcome measures makes defining remission in PsA challenging. This article evaluates proposed criteria for defining remission in PsA and discusses how these criteria can be applied in clinical practice.MethodsA primary literature search was conducted in PubMed to identify articles discussing potential PsA treatment goals or targets, including minimal disease activity. English-language publications from the last 10 years were included in this assessment.ResultsThere are 5 clinical domains in PsA that must be considered when evaluating remission: synovitis, enthesitis, dactylitis, spondylitis, and psoriasis/nail psoriasis. Due to variability in the completeness of remission and time to achieve remission with different therapies between these domains, remission should be measured clinically through a combination of objective measures, or a composite assessment tool. Composite measures are more efficient than unidimensional instruments in measuring remission, but remission rates differ between the available composite indices.ConclusionAlthough the concept of remission as a treatment goal in PsA is gaining acceptance among rheumatologists, further work is necessary to develop a broadly acceptable definition of remission.     

DAS 28 for defining remission in rheumatoid arthritis in Indian patients

ObjectiveTo establish DAS 28 and DAS 28-3 scores that best define remission in Indian patients with rheumatoid arthritis (RA).Patients and MethodsAll patients diagnosed with RA visiting AIIMS, New Delhi over a period of 3 months were recruited. Clinical assessment included 28 joint counts for swelling and tenderness, duration of early morning stiffness, patient global assessment of disease activity, fatigue, joint pains and ESR. DAS 28 and DAS 28-3 scores were calculated and receiver operating characteristics curve analysis was performed to define cutoff values utilizing ‘ACR 5/6’ and ‘ACR 4/5’ remission criteria.ResultsSubjects included 207 patients (M: 44; F: 163) with mean age of 47.4 ± 12.6 years, median disease duration of 8 [4.12–14] years.‘ACR 5/6’ and ‘ACR 4/5’ criteria for remission were satisfied by 34 (16.42%) and 44 patients (21.25%) patients, respectively. DAS 28 score of 2.94 (sensitivity 84.4%, specificity 85.3%) and DAS 28-3 score of 3.02 (sensitivity 82.1%, specificity 82.4) best defined the ‘ACR 5/6’ remission. Corresponding values using ‘ACR 4/5’ remission were 3.04 (sensitivity 85.9%, specificity 84.1%) for DAS 28 and 3.05 (sensitivity 82.2%, specificity 81.8%) for DAS 28-3.ConclusionsA cutoff value < 3 for both DAS 28 and DAS 28-3 defines remission in RA in Indian patients.     

Psychological state is related to the remission of the Boolean-based definition of patient global assessment in patients with rheumatoid arthritis

Abstract

Objectives. To evaluate whether the psychological state is related to the Boolean-based definition of patient global assessment (PGA) remission in patients with rheumatoid arthritis (RA).

Methods. Patients with RA who met the criteria of swollen joint count (SJC) ≤ 1, tender joint count (TJC) ≤ 1 and C-reactive protein (CRP) ≤ 1 were divided into two groups, PGA remission group (PGA ≤ 1 cm) and non-remission group (PGA > 1 cm). Anxiety was evaluated utilizing the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), while depression was evaluated with HADS-Depression (HADS-D) and the Center for Epidemiologic Studies Depression Scale (CES-D). Comparison analyses were done between the PGA remission and non-remission groups in HADS-A, HADS-D and CES-D.

Results. Seventy-eight patients met the criteria for SJC ≤ 1, TJC ≤ 1 and CRP ≤ 1. There were no significant differences between the PGA remission group (n = 45) and the non-remission group (n = 33) in age, sex, disease duration and Steinbrocker's class and stage. HADS-A, HADS-D and CES-D scores were significantly lower in the PGA remission group.

Conclusions. Patients with RA who did not meet the PGA remission criteria despite good disease condition were in a poorer psychological state than those who satisfied the Boolean-based definition of clinical remission. Psychological support might be effective for improvement of PGA, resulting in the attainment of true remission.     

Ultrasonography predicts achievement of Boolean remission after DAS28-based clinical remission of rheumatoid arthritis

Abstract

Objectives. To determine whether ultrasonography (US) predicts Boolean remission in rheumatoid arthritis (RA) patients who had achieved disease activity score in 28 joints (DAS28)-based remission criteria.

Methods. Thirty-one RA patients in DAS28-based clinical remission were recruited. US semiquantitatively determined Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and all metacarpophalangeals and proximal interphalangeals. Total GS score and total PD score were calculated as the sum of individual scores for each joint.

Results. Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean remission criteria at the end of study. Both total GS and total PD scores at baseline were significantly lower in Boolean remission group than non-remission group. There was no significant difference in other baseline parameters, including duration of disease, duration of remission, mTSS, and disease activity composite parameters between the two groups. Among the factors for Boolean remission criteria at 2 years, patient global assessment score was associated with total GS score at the entry, while swollen joint count was related to total PD score.

Conclusions. Null or low grade of GS and PD findings in US are associated with achieving Boolean remission. Thus, US is essential for assessment and prediction of “deeper remission” of RA.     

Appropriate maintenance treatment for Crohn's disease: Results of a multidisciplinary international expert panel — EPACT II

IntroductionBiological therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNFα inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating.MethodsA multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7–9), uncertain (4–6 and/or disagreement) and inappropriate (1–3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost.ResultsThree hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNFα antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a “wait-and-see” strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNFα agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial.ConclusionDetailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNFα agents are now freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation.     

Two cases of adult Still’s disease with abnormally high level of telomerase activity in peripheral blood mononuclear cells

Abstract

We report two patients with adult Still’s disease with an abnormally high level of telomerase activity. The first patient was a 61-year-old woman. The mean telomerase activity value for peripheral blood mononuclear cells of healthy adults measured by our method was 0.13 ± 0.03, whereas that in this patient during the active phase was abnormally high, at more than 27.56. The patient was treated by steroid therapy and successfully brought into remission, during which the telomerase activity value for peripheral blood mononuclear cells was reduced to 2.22. The second patient was a 19-year-old man. Although he stayed in remission after steroid therapy, a reduction in the steroid dose resulted in recrudescence, at which time the telomerase activity value peripheral blood mononuclear cells was high, at 11.76. Elevated levels of telomerase activity have been reported in patients with various pathological conditions other than malignant tumors. However, our literature search failed to reveal a report on such a high level of telomerase activity in association with a benign disease.     

Remission in axial spondyloarthritis: Developing a consensus definition

ObjectiveTo reach a consensus on the tools available to evaluate disease activity in patients with axial spondyloarthritis (axSpA), and to develop a consensus definition of remission in axSpA.MethodsA modified Delphi method was used. A scientific committee proposed statements addressing the assessment of axSpA in clinical practice and the definition of remission. The questionnaire was evaluated in 2 rounds by rheumatologists from GRESSER (GRupo de Estudio de ESpondiloartritis de la Sociedad Española de Reumatología).ResultsAfter 2 rounds of evaluation, a panel of 81 rheumatologists reached agreement on 56 out of the 80 proposed items (72.0%). There was agreement that the definition of remission in axSpA should include: disease activity, pain, fatigue, peripheral involvement, extra-articular manifestations, laboratory tests, functional impairment, mobility, quality of life, need for treatment, radiographic progression, and patient and physician global assessments. It is recommended to set a therapeutic goal when starting a treatment. The ideal goal is remission although low disease activity may also be an acceptable alternative. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred tool to assess disease activity. The panel made a proposal for clinical remission in axSpA based on the ASDAS cut-off value for inactive disease, the absence of extra-articular (acute anterior uveitis, psoriasis, inflammatory bowel disease) and peripheral (arthritis, enthesitis, dactylitis) manifestations, plus normal C-reactive protein levels and absence of radiographic progression.ConclusionThis work offers consensus recommendations and a proposal of clinical remission that may be useful in the management of patients with axSpA.     

Prevalence of functional dyspepsia-like symptoms in ulcerative colitis patients in clinical remission and overlap with irritable bowel syndrome-like symptoms

Abstract

Objective: Quiescent ulcerative colitis (UC) patients often have irritable bowel syndrome (IBS)-like symptoms and we recently showed that the prevalence of IBS-like symptoms in UC patients in clinical remission was significantly higher as compared to healthy control subjects. However, the prevalence of functional dyspepsia (FD)-like symptoms in quiescent UC patients remains unknown. The purpose of this study was to evaluate the prevalence of FD-like symptoms and the overlap with IBS-like symptoms in such patients.

Materials and Methods: We reanalyzed the records of UC patients in remission using the subject cohort from our previous study. Clinical remission was defined as a clinical activity index (CAI) value ≤4 for at least 6?months. Diagnoses of FD- and IBS-like symptoms were evaluated by questionnaire according to the Rome III criteria.

Results: One hundred seventy-two UC patients in clinical remission and 330 healthy control subjects were analyzed. Of the 172 patients, 9 (5.2%) met the criteria of FD, which was comparable with the controls (22/330, 6.7%). The prevalence rate of FD-like symptoms in UC patients with IBS-like symptoms (7/46, 15.2%) was lower as compared to that of the control subjects (6/16, 37.5%). On the other hand, a high percentage of the UC patients with FD-like symptoms also had IBS-like symptoms (7/9, 77.8%).

Conclusions: Although the prevalence of FD-like symptoms in quiescent UC patients with IBS-like symptoms was low, UC patients with FD-like symptoms frequently had IBS-like symptoms.     

A multicenter phase II prospective clinical trial of glucocorticoid for patients with untreated IgG4-related disease

Objective: Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established.

Patients and methods: Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6?mg/kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events.

Results: This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed.

Conclusions: Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.     

Familial hemophagocytic lymphohistiocytosis in a neonate: Case report and literature review

Rationale:Familial hemophagocytic lymphohistiocytosis (FHL) is a potentially fatal disease that rarely presents in the neonatal period. Timely diagnosis is a key challenge owing to the atypical clinical manifestations. Here, we describe a case of FHL type 3 with disease onset in the early neonatal period and review the relevant literature. Our findings may provide insights into the diagnosis and treatment of this rare disease.Patient concerns:A 6-day-old male neonate presented with fever, hepatosplenomegaly, cytopenia, hyperferritinemia, hypofibrinogenemia, hemophagocytosis, and hypertriglyceridemia.Diagnosis:Considering the clinical picture (prolonged fever, progressive hepatosplenomegaly, high triglycerides, low fibrinogen, and high ferritin), along with abnormal natural killer-cell activity, combining sequence analysis of genomic DNA results (compound heterozygous mutations of UNC13D), the patient was finally diagnosed with FHL type 3 (FHL3).Interventions:The patient was initially treated with HLH-1994 protocol and subsequently switched to an oral regimen of ruxolitinib due to incomplete remission of the disease.Outcomes:The trend of change in weekly cytokine levels, neutrophil counts, hemoglobin, and platelet counts indicated that the complete remission was not achieved after the treatment of HLH-1994 protocol. The platelet counts fluctuated within the normal range after oral administration of ruxolitinib. But soon after, the patient did not respond to treatment and eventually died of respiratory failure.Lesson:Timely diagnosis of FHL is challenging. This case report illustrates that thrombocytopenia can be the first clinical sign of FHL with neonatal onset. Genetic testing, detection of cytokines, and flow cytometry should be performed as soon as possible to confirm the diagnosis. Given the high morbidity and mortality of FHL, pediatricians should have a high suspicion index for this disease.     

A comparison of physician-rated disease severity and patient reported outcomes in mild to moderately active ulcerative colitis

Background and aimsThe aim was to derive health state utility scores in ulcerative colitis (UC) by establishing the relationship between the physician-rated ulcerative colitis disease activity index (UCDAI) and a patient reported EQ-5D by statistically mapping the two instruments.MethodsIn a randomised controlled trial comparing oral plus enema mesalazine treatment with oral mesalazine treatment alone (PINCE), UCDAI and EQ-5D scores were collected in parallel from patients with active UC. From these data, multinomial logistic regression was used to estimate response probabilities to each of the five domains of the EQ-5D index from assessment of UC disease severity using original and abbreviated (no endoscopy) versions of the UCDAI. Predicted EQ-5D responses were converted by Monte Carlo simulation to the EQ-5D index for predicting health-related quality of life (HRQoL). The reliability of the algorithm was tested using UCDAI scores from a second mesalazine RCT (PODIUM).ResultsThe abbreviated-UCDAI showed comparable explanatory performance to the full UCDAI. For patients in remission, mean utility was 0.939, 0.944, and 0.940 U for PINCE_estimated, PINCE_observed, and PODIUM, respectively. Mild/moderate and relapsing cases showed mean utilities of 0.801, 0.811, and 0.775, respectively; whilst for those in severe relapse, the mean utilities were 0.630, 0.700 and 0.660 units, respectively. The mean squared error between actual and predicted utilities from observations in PINCE was 0.019.ConclusionResponse mapping of UC activity to EQ-5D domains produced reliable estimates of patient-rated health state utility consistent with UCDAI rated severity. Comparing abbreviated-UCDAI and full UCDAI suggests that inclusion of endoscopy scores has limited predictive value in estimating patient HRQoL.     

Revising DAS28 scores for remission in rheumatoid arthritis

Current initiatives to treat rheumatoid arthritis (RA) to target remission have resulted in the widespread use of composite outcome measures to quantify disease activity. Simplified Disease Activity Index (SDAI) ≤3.3 is the gold standard of remission. Previous work has suggested that the remission threshold of DAS28-ESR or DAS28-CRP ≤2.6 is known to be not strict enough and should be revised. There is no previous study that looks at the equivalent DAS28-CRP value that best reflects SDAI remission in a real-life cohort. Consecutive cases fulfilling ACR/EULAR classification criteria for RA from one centre were included if they had an optimum number of visits with recording of all raw data to calculate DAS28-ESR, DAS28-CRP and SDAI. Data from seven visits each of 76 patients, providing 532 data points was examined. Spearman’s correlation between DAS28-ESR, DAS28-CRP and SDAI was 0.91–0.97 (p?<?0.001). A Bland-Altman plot demonstrated a mean difference of 0.37 units between DAS28-ESR and DAS28-CRP (p?<?0.001). ROC and kappa analysis provided values of 2.58 and 2.55 for DAS28-ESR4V and 2.09 and 2.05 for DAS28-CRP4V for SDAI value of 3.3, respectively. The two versions of DAS28 using ESR and CRP and SDAI correlate but are not equivalent or interchangeable for an individual patient. The DAS28-CRP overestimates remission and should be revised downwards to a proposed value of 2.1.     

Diabetes reversal: Update on current knowledge and proposal of prediction score parameters for diabetes remission

Background and aimThe field of diabetes reversal is continuously evolving. Strategies for implementing diabetes care towards diabetes reversal are still being worked out. We aim to analyse data from available literature to ascertain factors allowing patient centric dietary approach to achieve diabetes reversal in clinical practice.MethodsIn this exploratory review, an update on current knowledge is presented to delineate factors driving diabetes remission in an individual based on major studies in the field. This knowledge is then applied to subtypes of type 2 diabetes to optimise dietary approach for reversal of diabetes.Results and conclusionShorter duration of diabetes, lesser number of medicines needed to achieve euglycemia and 15 kg weight loss are common factors favouring diabetes remission in all major studies. A patient centric approach to diabetes reversal taking into account the recently described diabetes subtypes is being proposed to improve the proportion of patients achieving remission. We also propose the parameters of a novel diabetes remission prediction score, based on patient motivation, interaction with the care-team, level of diabetes self-care and the intent of the care-team.     

Philadelphia chromosome-positive B-lymphoblastic lymphoma successfully treated with chemotherapy regimen containing imatinib: A rare case report and literature review

Rationale:B-lymphoblastic lymphoma (B-LBL) with BCR/ABL mutation (Ph+ B-LBL) is a rare type of cancer in both childhood and adults. Its clinical manifestations are similar to those of other types lymphoma. However, the targeted therapy can substantially improve the outcome of Ph+ B-LBL.Patient concerns:A 19-year-old male with blood type O, Rh+ was admitted into our hospital on August 14, 2018, due to a recurrent fever and hypocytosis for 6 months.Diagnoses:Routine blood exam showed pancytopenia. Bone marrow sample flow cytometry (FCM) exam showed abnormal cells were 2.27% of the nucleated cells, and was classified as the abnormal early B-lineage lymphoblastic cells. FISH testing showed the BCR/ABL positive cells were 13.6%. Karyotype analysis showed the 46, XY, t(9;22)(q34;q11). Molecular analysis of BCR/ABL mutation on ABL kinase showed that BCR/ABL T315I mutation. Patient was diagnosed with B-LBL with BCR/ABL mutation (Ph+ B-LBL).Interventions:The patient was given chemotherapy with VDPI regimen (Vinorelbine, daunorubicin, prednisone, imatinib).Outcomes:The patient achieved complete remission after 2 courses’ treatment, followed by one course of clarithromycin regimen and another two courses of VDPI regimen. Patient remains in complete remission as of March 10, 2021.Lessons:In B-LBL, a BCR/ABL mutation can happen in some of these patients. It is important to guide the pathologist to perform appropriate gene mutation detection, in addition to routine Immunohistochemistry test, to ensure an accurate diagnosis and use the targeted agent for treatment. According to the literature and our results, it seems that intensive chemotherapy plus TKI regimen is effective in inducing complete remission, and allo-SCT should be used as a long-term strategy.     

Low-dose smoking resumption in ex-smokers with refractory ulcerative colitis

Background and aimUlcerative colitis (UC) is primarily a disease of non-smokers. Ex-smokers may have a more refractory disease course and anecdotal evidence in non-controlled clinical trials have suggested that smoking resumption, or the administration of nicotine, may ameliorate signs and symptoms of UC in ex-smokers. We report outcomes of ex-smokers with refractory UC who resumed low-dose cigarette smoking.Methods17 ex-smokers with refractory UC were identified. Clinical remission was defined as a disease activity index score of 0.ResultsTwo out of 17 patients refused the recommendation to resume smoking. Of the 15 patients who resumed smoking, the mean daily number of cigarettes was 8.6. Fourteen out of those 15 patients who resumed smoking were able to maintain prolonged clinical remission off steroids. One out of the 15 patients failed to improve and required oral steroids. Another patient was compelled to quit smoking since he became addicted. His disease flared after maintaining a prolonged remission of 3 years and he eventually underwent surgery. Three out of these 15 patients switched from cigarettes smoking to nicotine compounds and continued to maintain remission.ConclusionResumption of low dose smoking in a selected group of ex-smokers with refractory UC may ameliorate signs and symptoms. Quality of life, medication side effects, and smoking risk factors should all be considered and discussed with patients. Smokers should be meticulously followed for compliance with “low-dose” regimen and all associated smoking risks.     

A rare case series of concomitant inflammatory bowel disease,sporadic adenomas,and serrated polyposis syndrome

Background and aimsInflammatory bowel disease (IBD) involving the colon is associated with an increased risk of colon cancer. Patients may develop sporadic adenomas further increasing their risk of colorectal cancer. Current knowledge of IBD with concomitant serrated polyposis syndrome (SPS) is limited. We describe four patients with both IBD and SPS.MethodsFour patients with inflammatory bowel disease and hyperplastic polyps referred to Beth Israel Deaconess Medical Center meeting the World Health Organization (WHO) criteria for SPS were identified.ResultsFour patients with long standing IBD involving the colon were identified. All of these patients' IBD were in clinical remission. Additionally, 2 of the 4 patients were also noted to have sporadic adenomas. Each patient was also found to have multiple sessile serrated adenomas and hyperplastic polyps meeting the WHO criteria for SPS. Two of the patients had colonoscopy with chromoendoscopy which improved polyp detection. Discussions were held with each patient regarding the potentially increased risk of colorectal cancer with the combination of IBD and SPS. Patients were advised that colectomy would be the safest method to reduce the risk of cancer. None of the patients opted for colectomy and instead planned on a repeat colonoscopy with chromoendoscopy at 3–12 month intervals.ConclusionSerrated polyposis syndrome develops in patients with IBD. It is unclear how high the risk of colon cancer is in patients who have both IBD and SPS and what the recommendations should be regarding the frequency of surveillance or surgery. Further studies are necessary to identify the optimal management of these patients.     

Ankylosing spondylitis assessment group preliminary definition of short‐term improvement in ankylosing spondylitis

Objective

To develop criteria for symptomatic improvement in patients with ankylosing spondylitis (AS), using outcome domain data from placebo‐controlled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs).

Methods

Patient data from 5 short‐term, randomized, controlled trials were used to assess equivalence, reliability, and responsiveness of multiple items in the 5 outcome domains for AS treatment: physical function, pain, spinal mobility, patient global assessment, and inflammation. At least one measure per domain was responsive (standardized response mean of >0.5), except for the spinal mobility domain, which was omitted from the criteria. We developed and tested candidate improvement criteria in a random two‐thirds subset from the 3 largest trials and used the remaining one‐third for validation. These 3 largest trials included 923 patients (631 receiving NSAIDs, 292 in placebo groups). We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi‐square test and that had a placebo response rate of ≤25%.

Results

Candidate definitions were changes in single domains and in multiple measure indices, as well as combinations of improvements in multiple domains. Worsening in a domain was defined as a change for the worse of ≥20% and a net change for the worse of ≥10 units on a scale of 0–100. Partial remission (for comparison purposes) was defined as an end‐of‐trial value of <20/100 in each of the 4 domains. Among 20 candidate criteria, change of ≥20% and ≥10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset (51% of patients improved with NSAIDs, 25% with placebo; χ² = 36.4, P < 0.001). Results were confirmed in the validation subset. Almost all patients satisfying the definition of partial disease remission at the end of the trial had also improved by this criterion. Among all 923 patients, improvement rates using this criterion were 49% for NSAID‐treated patients and 24% for placebo‐treated patients.

Conclusion

Although further validation using data from new trials is still needed, we conclude that we have developed a clinically valid, easy‐to‐use measure of short‐term improvement in AS.

     

Nosocomial Pneumonia: A Cost-of-Illness Analysis

Background: We investigated incremental cost of nosocomial pneumonia (NP) from the perspective of a hospital and health insurance funds. Patients and Methods: The incremental cost was determined by calculating total costs for pneumonia patients and controls using prospective and retrospective matched-pairs analysis with 29 and 37 matched pairs, respectively. Results: Compared to controls, patients who developed pneumonia had to be on artificial ventilation 5 days longer, needed markedly more intensive care with 6.55 additional days in intensive care. Excess cost per pneumonia patient amounted to DM 14,606 (95% CI: DM 5,285–23,927) from the hospital's perspective and to DM 7,988 (95% CI: DM 5,281–10,894) according to statutory insurance charges. According to the retrospective analysis carried out on the neurosurgical and neurological intensive care wards, pneumonia patients were ventilated 5 days longer than patients without pneumonia, needed more intensive care over 30 days and had an additional 14.03 days of intensive care and 10.14 more days in hospital. Excess cost per patient was DM 29,610 (95% CI: DM 23,054–36,174) from the hospital's perspective and DM 18,000 (95% CI: 14,855–21,020) according to the statutory insurance criteria. Conclusion: The study gives insight into the structure of incremental cost caused by NP and shows that based on a conservative cost calculation the incremental cost per NP patient is higher for the hospital than for health insurance funds which indicates a significant financial deficit for the hospital. Antibiotics and microbiology together only contribute 6.8% to incremental cost. Therefore in a cost saving initiative their close relationship to length of hospitalization must be considered. Received: July 5, 2000 · Revision accepted: January 9, 2002