Relationship between severity and clinical importance of symptoms in osteoarthritis

Summary Seventeen patients with primary osteoarthritis of the knee were evaluated with respect to the severity and clinical importance of pain, stiffness and physical function during the conduct of a double-blind randomized controlled trial of flurbiprofen SR versus diclofenac sodium SR using the WOMAC Osteoarthritis Index. Mean importance scores were similar for items within the same dimension as well as between items in different dimensions. In general, low levels of correlation were noted between the severity and importance of symptoms. Analysis of individual WOMAC items within a given subscale indicated that, although highly correlated, they differed from one another. Factor analysis further supported the contention that scores from items within a subscale could be summated into subscale scores. These observations are of importance in the weighting and aggregation of items within discrete dimensions and have the potential for reducing sample size requirements for clinical trials in osteoarthritis.     

The comparative risk and predictors of adverse gastrointestinal events in rheumatoid arthritis and osteoarthritis: a prospective 13 year study of 2131 patients

OBJECTIVE: It has been suggested that rheumatoid arthritis (RA) itself may be a risk factor for adverse gastrointestinal (GI) events, but this hypothesis has not been studied in a large sample, nor has the effect of time on risk factors been studied. We investigated rates and risk factors for GI events in RA and osteoarthritis (OA) and assessed the additional risks conveyed by having RA. METHODS: A prospective study of patients with OA and RA from a single center was undertaken using questionnaires mailed at 6 month intervals. The relationship between drug therapy and GI events was assessed in the same 6 month time frame. Over 13 years of biannual assessments, 2,131 patients were studied for serious GI events and adverse GI symptoms during 9,621 patient-years of observation. RESULTS: The incidence rate (IR) for GI hospitalization was 1.56 and 1.28 per 100 patient-years, and for GI bleeding or perforation was 0.50 and 0.58 for RA and OA, respectively. After controlling for age, sex, nonsteroidal antiinflammatory drug (NSAID) and steroid use, the incidence rate ratio (IRR) for RA versus OA did not differ for hospitalization [IRR 1.07 (95% CI 0.66, 1.74)] or for bleeding or perforation [IRR 0.63 (95% CI 0.29, 1.35)]. In multivariate analyses for both groups combined, the IRR was 2.95 (2.05, 4.24) for prednisone use, 1.41 (1.08, 1.85) for NSAID use, and 1.46 (1.22, 1.74) for every 10 year increase in age. In additional multivariate models, Health Assessment Questionnaire disability was also a significant risk factor. During the study period, the odds of NSAID use decreased 2.94 times per 10 year period, while the odds of prednisone use increased by 1.49. Dysphagia [IRR 1.11 (1.00, 1.24)], anorexia [IRR 1.13 (1.03, 1.23)], nausea [IRR 1.13 (1.04, 1.25)], heartburn [IRR 1.12 (1.05, 1.19)], vomiting [IRR 1.20 (1.02, 1.42)], peptic ulcer symptoms [IRR 1.20 (1.11, 1.29)], and abdominal pain [IRR 1.11 (1.01, 1.22)] were associated with NSAID use, but not with steroids. CONCLUSION: Patients with RA and OA do not differ in the rates and risk factors for GI hospitalizations and symptoms after controlling for age, steroid use, NSAID use, or (for OA) body mass index. Prednisone is a more important risk factor among patients with RA than NSAID.     

Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis

OBJECTIVE: To assess the risk of hospitalization for congestive heart failure (CHF) associated with the use of disease-modifying anti-rheumatic drugs (DMARDs) and other medications used in RA. METHODS: We used a case-control design nested within an administrative database cohort of patients with rheumatoid arthritis (RA) who were dispensed a DMARD between September 1998 and December 2001. Subjects identified with a prior history of CHF were excluded. For each hospitalized case of CHF identified during follow-up, 10 controls matched on age and time were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of hospitalizations for CHF associated with the current use of specific drugs, adjusted for sex and co-morbidity. RESULTS: The cohort included 41 885 patients; 75% were women, with an average age at cohort entry of 51 yr. During follow-up, 520 hospitalizations for CHF occurred, for a rate of 10.1 per 1000 per year. The adjusted RR of CHF for current use of any DMARD was 0.7 (95% CI 0.6-0.9) relative to no current use. By DMARD category, there was evidence of a beneficial effect for both tumour necrosis factor-alpha antagonists (RR 0.5, 95% CI 0.2-0.9) and methotrexate monotherapy (RR 0.8, 95% CI 0.6-1.0). For non-DMARD medications, the rate of CHF was not clearly increased or decreased, except for COX-2 inhibitors. The data suggested an increased risk of CHF with rofecoxib (RR 1.3, 95% CI 1.0-3.1) and a decreased risk of CHF with celecoxib (RR 0.6, 95% CI 0.4, 1.0). CONCLUSIONS: The use of DMARDs was associated with a reduction in the risk of hospitalizations for CHF in this RA cohort. The increased risk with rofecoxib alongside a decreased risk with celecoxib suggests the absence of a class effect with respect to COX-II inhibitors for some types of cardiovascular morbidity.     

Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial

BACKGROUND: Many patients with upper gastrointestinal (GI) bleeding have a benign outcome and could receive less intensive and costly care if accurately identified. We sought to determine whether early endoscopy performed shortly after admission in the emergency department could significantly reduce the health care use and costs of caring for patients with nonvariceal upper GI bleeding without adversely affecting the clinical outcome. METHODS: All eligible patients with upper GI bleeding and stable vital signs were randomized after admission to undergo endoscopy in 1 to 2 days (control) or early endoscopy in the emergency department. Patients with low-risk findings on early endoscopy were discharged directly from the emergency department. Clinical outcomes and costs were prospectively assessed for 30 days. RESULTS: We randomized 110 consecutive stable patients with nonvariceal upper GI bleeding during the 12-month study period. The baseline demographic features, endoscopic findings, and the clinical outcomes were no different between the two groups. However the findings of the early endoscopy allowed us to immediately discharge 26 of 56 (46%) patients randomized to that group. No patient discharged from the emergency department suffered an adverse outcome. The hospital stay (median of 1 day [interquartile range of 0 to 3 days] vs. 2 days [interquartile range of 2 to 3 days], p = 0.0001) and the cost of care ($2068 [interquartile range of $928 to $3960] versus $3662 [interquartile range of $2473 to $7280], p = 0.00006) were significantly less for the early endoscopy group. CONCLUSIONS: Early endoscopy performed shortly after admission in the emergency department safely triaged 46% of patients with nonvariceal upper GI bleeding to outpatient care, which significantly reduced hospital stay and costs.     

Evidence of disordered symptom appraisal in fibromyalgia: increased rates of reported comorbidity and comorbidity severity.

OBJECTIVE: Using a large series of unselected consecutive patients, to investigate whether patients with fibromyalgia differ from those with rheumatoid arthritis (RA) or osteoarthritis (OA) in the number of reported comorbid conditions and in their perceived importance, and thereby to investigate differences in symptom appraisal and somatization. METHOD: In a clinical care setting, 1,298 patients with fibromyalgia and 2,396 with RA or OA participating in longitudinal data bank research as part of their routine medical care completed questionnaires concerning the presence or absence of 23 comorbid conditions, and then rated the current importance of each condition to them. Additional information concerning psychological factors and disease severity was also obtained. RESULTS: In analyses adjusted for age and sex, patients with fibromyalgia reported more conditions (4.5 vs. 3.1) than those with RA or OA. In 17 of 23 conditions, the condition was more commonly reported in fibromyalgia than in RA or OA. In 20 of the 23 conditions, the importance attached to the conditions by fibromyalgia patients exceeded that of the importance attributed by RA/OA patients. After adjustment for anxiety, statistical differences between the groups for importance was lost for 6 conditions. CONCLUSIONS: Fibromyalgia patients report more medical conditions and report that they are more important to them than do patients with RA or OA. These differences extend to conditions that might be expected to cause symptoms, as well as to those that are usually symptom free. These data suggest that, on average, patients with fibromyalgia appraise medical symptoms and their importance differently from patients with other rheumatic conditions.     

HLA-DRB1 genotype influences risk for and severity of rheumatoid arthritis.

OBJECTIVE: To examine how HLA-DRB1 genotypes influence rheumatoid arthritis (RA) risk and clinical severity. METHODS: We performed polymerase chain reaction based DRB1 and tumor necrosis factor (TNF) genotyping of 309 Caucasian RA and 283 Caucasian control subjects. For risk analyses, we grouped the DRB1 alleles encoding each specific shared epitope: *0401 alone, *0404 with *0102, *0405 with *0408 and *0101, and *1001 alone. For estimates of RA outcome, we retrospectively obtained data regarding ARA classification criteria, age of disease onset and disease duration, number of slow acting antirheumatic drugs (SAARD) used, and rheumatoid factor (RF). RESULTS: Homozygous shared-epitope DRB1 genotypes, compound heterozygous genotypes, and simple heterozygous genotypes all conferred elevated relative risk (RR) for RA (RR 4.3, 11.7, and 3.5, respectively). However, compound heterozygous genotypes conferred more risk than either simple heterozygous genotype (RR 3.3, p = 0.004) or homozygous genotype (RR 2.8, p = 0.036). There was a trend toward more compound heterozygous genotypes in the male RA group than in the female RA group (p < 0.1), and male sex was associated with higher frequency of rheumatoid nodules (56 vs 35% for female RA). RA outcome was estimated by number of SAARD used; mean SAARD used was higher in male than in female RA (p < 0.01) and higher in genotypes containing one or 2 shared epitope DRB1 alleles than in those negative for shared epitope DRB1 alleles (p < 0.05). Analyses also suggested that shared epitope DRB1 genotype significantly influenced the occurrence of seropositive RA. Seropositive RA fraction was related to either number of shared epitope alleles (0, 1, or 2) represented in the DRB1 genotype, or, alternatively, to the combination of sex with shared epitope DRB1 genotype. The presence of one or 2 shared epitope DRB alleles influenced the occurrence of high titer seropositive RA as defined by sheep cell agglutination test (p < 0.01). TNFab microsatellite markers and TNF promoter polymorphisms did not influence SAARD number, seropositive RA, or high titer seropositive RA. CONCLUSION: Not all shared epitope DRB1 genotypes conferred the same relative risk, and the male RA group tended to have more compound heterozygous genotypes and more severe RA as indicated by rheumatoid nodules and SAARD usage. DRB1 genotypes with one or 2 shared epitope DRB1 alleles influenced the RA outcome as estimated by numbers of SAARD used and RF.     

Extra-articular manifestations of rheumatoid arthritis: risk factors for serious gastrointestinal events.

OBJECTIVES--Serious upper gastrointestinal events are an important threat to patients with arthritis who are treated with non-steroidal anti-inflammatory drugs (NSAIDs). In this study risk factors for serious upper gastrointestinal events are identified in patients with possible or definite rheumatoid arthritis (RA). METHODS--A retrospective analysis of factors that might contribute to the risk of serious upper gastrointestinal events was performed in a cohort of 2315 consecutive patients with possible or definite RA. The relative influences of disease severity, drug treatment, particularly with corticosteroids, and history of peptic ulceration were analysed with a conditional logistic regression model for the 106 patients with serious upper gastrointestinal intestinal events and for an equal number of control patients who were matched for age, gender, number of criteria for RA, and disease duration. RESULTS--The incidence rate for serious upper gastrointestinal events was 4.0/1000 patients in each year. The study reconfirmed that age over 60 years, history of peptic ulceration, and use of corticosteroids are risk factors. The presence of extra-articular manifestations of RA was associated with a two to 11-fold increase in the risk for serious upper gastrointestinal events. This risk was independent of the use of corticosteroids. CONCLUSION--Disease severity, in particular the presence of extra-articular features, may be an important factor in the pathogenesis of upper gastrointestinal ulceration in patients with RA who are treated with NSAIDs.     

Responsiveness and interpretation of a symptom severity index specific to upper gastrointestinal disorders.

BACKGROUND AND AIMS: Determining clinically meaningful change of patient-reported outcome measures is important for evaluating effectiveness of treatments for gastrointestinal (GI) diseases. This study evaluates responsiveness of the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) in gastroesophageal reflux disease (GERD) and dyspepsia. METHODS: The PAGI-SYM was based on a review of the published literature and interviews with patients and clinicians. Items were developed to be linguistically and culturally appropriate for multicountry studies. The PAGI-SYM includes 6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Subjects with GERD (n = 810) or dyspepsia (n = 767) participated in this multicountry, observational study. All subjects completed the PAGI-SYM, a global symptom relief questionnaire, and a measure of patient-rated change in GI-related symptoms, the Overall Treatment Effect (OTE) scale. Responsiveness was evaluated at 8 weeks by comparing groups by disease, symptom relief, and OTE (improved, stable, and worsened). RESULTS: Subjects reporting symptom relief reported significantly lower (better) PAGI-SYM scores than those reporting no symptom relief ( P < 0.0001 to P < 0.0005). Subjects with improvements in overall GI symptoms exhibited significant decreases in PAGI-SYM subscale scores compared with those who remained the same or worsened (all P values < 0.0001). Effect sizes ranged from 0.21-1.28, and standard errors of measurement ranged from 0.29-0.63, depending on subscale and disease sample. CONCLUSIONS: The PAGI-SYM is a brief symptom severity instrument that measures common GI symptoms. Results suggest that the PAGI-SYM is responsive and sensitive to change in clinical status in subjects with GERD or dyspepsia.     

Group counseling psychotherapy for patients with functional gastrointestinal disorders: development of new measures for symptom severity and quality of life

Functional gastrointestinal disorders (FGID) can benefit from various psychological interventions. The main objective here was to define the contribution of a new psychotherapeutic intervention, group counseling psychotherapy, for the management of FGID patients. Secondary aims included validation of new measures for gastrointestinal symptoms and quality of life in patients with FGID. Fifty patients seen in a tertiary care center were included in a program of 10 weekly sessions of 2 hr each. Gastrointestinal symptoms, quality of life, and psychological conditions were measured before and after treatment by quantitative indices and by qualitative self-analysis. Gastrointestinal index and quality-of-life index were significantly (P < 0.02) improved at the end of the psychotherapeutic intervention (from 77.5 ± 4.0 to 63.2 ± 4.3 and from 67.7 ± 3.9 to 54.9 ± 3.9, respectively). In a control group of patients observed for a comparable period of time while waiting for the psychotherapy program, gastrointestinal and quality of life indices remained unchanged. The severity of gastrointestinal symptoms and the quality of life deterioration were highly correlated factors (r = 0.8) at entry into the trial, and their improvement with psychotherapy was also correlated (r = 0.6; P < 0.001). Psychological abnormalities were frequent in these patients (anxiety in 31%, somatization in 29%, depression in 26% of the patients). However, no specific disorder could predict the results of the psychotherapeutic intervention. Over the long term (6–24 months after conclusion of treatment), gastrointestinal status, quality of life, and psychological condition were estimated as improved by 53%, 63%, and 67% of the patients, respectively. The gastrointestinal index and quality of life index we developed were validated to detect the disease and to follow its evolution in response to treatment. In conclusion, group counseling psychotherapy offered a significant contribution for the management, improving gastrointestinal symptoms and quality of life, of FGID patients. New measures for symptom severity and quality of life are available.     

Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis

Objective

To determine the effect of quadriceps strength in individuals with knee osteoarthritis (OA) on loss of cartilage at the tibiofemoral and patellofemoral joints (assessed by magnetic resonance imaging [MRI]) and on knee pain and function.

Methods

We studied 265 subjects (154 men and 111 women, mean ± SD age 67 ± 9 years) who met the American College of Rheumatology criteria for symptomatic knee OA and who were participating in a prospective, 30‐month natural history study of knee OA. Quadriceps strength was measured at baseline, isokinetically, during concentric knee extension. MRI of the knee at baseline and at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and patellofemoral joints, with medial and lateral compartments assessed separately. At baseline and at followup visits, knee pain was assessed using a visual analog scale, and physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index.

Results

There was no association between quadriceps strength and cartilage loss at the tibiofemoral joint. Results were similar in malaligned knees. However, greater quadriceps strength was protective against cartilage loss at the lateral compartment of the patellofemoral joint (for highest versus lowest tertile of strength, odds ratio 0.4 [95% confidence interval 0.2, 0.9]). Those with greater quadriceps strength had less knee pain and better physical function over followup (P < 0.001).

Conclusion

Greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint, including in malaligned knees. We report for the first time that greater quadriceps strength protected against cartilage loss at the lateral compartment of the patellofemoral joint, a finding that requires confirmation. Subjects with greater quadriceps strength also had less knee pain and better physical function over followup.

     

Burden and risk factors for gastrointestinal symptom distress in HIV patients in the modern antiretroviral era

In the modern antiretroviral (ARV) era, there is limited knowledge about the prevalence and risk factors for HIV patient-reported gastrointestinal (GI) symptoms (diarrhoea/soft stool, nausea/vomiting, bloating/painful abdomen, loss of appetite, and weight loss/wasting) and distress. We prospectively analysed data (2007–2014) on distressing GI symptoms from the Ontario HIV Treatment Network Cohort Study, which follows people attending HIV clinics. Using generalized estimating equations with a logit link, we estimated the associations of psychosocial, demographic, behavioural, and clinical factors with each GI symptoms compared to asymptomatic and non-bothersome symptoms. Among 1532 included participants, 80.4% were male, mean age was 45 years, and 64.6% reported being men who have sex with men. Most were Caucasian (56.3%), a median time since HIV diagnosis of 9.8 years (interquartile range (IQR): 4.1–16.9), and 83.1% were on ARV. More than two-thirds (68.7% (95% confidence intervals (CI): 63.1% to 69.2%)) reported one or more symptoms with a median of 1.2 (IQR: 0–1.7). The proportion remained stable over time since HIV diagnosis and ARV initiation. Risk factors varied for multivariable models. A strong association with Centre for Epidemiologic Studies Depression scale scores of ≥23 was found for all symptoms. Adjusted odds ratios (95% CI) were 1.72 (1.39–2.12), 2.95 (2.33–3.72), 2.20 (1.81–2.68), 4.97 (3.99–6.19), and 2.98 (2.52–3.82) for diarrhoea, nausea/vomiting, bloating, loss of appetite, and weight loss, respectively. With the exception of bloating, odds were significantly lower for those on ARV containing integrase inhibitors and greater for patients reporting current cannabis use. GI symptoms in the modern ARV era are highly prevalent and may arise as a common pathway of distress in response to psychosocial vulnerabilities, regardless of the stage of diagnosis. These findings support the need for integrated approaches to address psychological and physical distress in HIV disease.     

The impact of rheumatoid arthritis and osteoarthritis: the activities of patients with rheumatoid arthritis and osteoarthritis compared to controls

We measured the impact of rheumatoid arthritis (RA) and osteoarthritis (OA) by comparing the activities of patients with these illnesses to controls matched for age, sex, and community of residence. Our results indicate that patients with RA experience more losses than controls in every domain of human activity and that patients with OA experience more losses in the performance of household chores, shopping and errands, and leisure activities. The methods described here provide a simple, reliable way to assess the impacts of illness in the same terms for all dimensions of human activity.     

A multicenter study of hospitalization in rheumatoid arthritis: effect of health care system, severity, and regional difference

During 1981, centers in Phoenix, Saskatoon, Stanford and Wichita monitored hospitalizations for 816 patients with rheumatoid arthritis. Admission rates varied 2-fold, and admissions for evaluation and treatment 10-fold across centers. Admissions were related primarily to disease severity, but in US centers, were reduced by a factor of 3 by prepaid health care. Length of stay was shortest in California (7.3 days), and longest in Saskatoon (16.3) where designated arthritis beds and government prepaid health care existed. Average charges for surgery were as high as $10,000 in Phoenix and as low as $4550 in Wichita. Charges and length of stay were unrelated to disease severity, but were responsive to health care delivery system, availability of facilities, and geographic and center variation.     

Assessing severity of adult asthma and need for hospitalization

Exacerbations of asthma requiring emergency treatment are common but, fortunately, asthma is rarely life threatening. In the course of treating acute asthmatics, however, the question of whether to admit the patient often is raised. With the current costs of hospitalization and morbidity associated with the disease, it is advantageous to be able to separate accurately those who require in-hospital treatment from those who can be treated as outpatients. The choice to hospitalize the asthmatic patient must be based on objective findings, including spirometry alone, spirometry plus history and physical signs, or index scoring (Figure). The best method awaits elucidation by prospective study. The most objective indicator of asthma severity is the indirect measurement of airways obstruction by spirometry, either by FEV1.0 or PEFR. FEV1.0 and PEFR yield comparable results. Simple, inexpensive devices for these measurements are available. An FEV1.0 less than 0.8 to 1.0 L (less than 25% predicted in women and men ages 25 to 65 years) or a PEFR less than 100 L/min (less than 20% predicted in women and men ages 25 to 65 years) accurately indicates a severe asthma exacerbation. The percentage predicted is utilized in those individuals who lack average stature. An increase in FEV1.0 to greater than 1.6 to 2.1 L (greater than 60% predicted) or a PEFR improvement to greater than 300 L/min (greater than 60% predicted) after therapy negates the need for hospitalization. In order to gain such improvement the patient may require approximately four to six hours of outpatient treatment. Some will treat patients for longer periods. Evidence of worsening obstruction or impending respiratory failure during this period mandates admission.(ABSTRACT TRUNCATED AT 250 WORDS)     

肠易激综合征患者肠外症状评价

目的评析肠易激综合征患者（irritable bowel syndrome,IBS）结肠外症状,特别是精神症状及其不同亚型表现的差异以及精神症状和消化道症状的关系。方法对71例IBS患者采用Rome官方网站调查表进行症状问卷。采用精神心理自评表（SCL-90）进行心理因素测评,对结果进行统计学分析。结果71例患者除结肠症状外较易合并腰痛（74.6%）,对异性兴趣减退（50.7%）、睡眠不好（62%）、头痛（40.8%）、头昏（38%）,食欲不振（32.4%）,肌肉酸痛（62%）。与腹泻型IBS患者相比较,胃排空障碍在便秘型IBS较为常见（P〈0.05）。IBS患者SCL-90各因子评分均高于中国常模组（P〈0.05）,其中焦虑和精神因子差异非常显著（P〈0.01）。女性患者较男性患者在人际关系敏感、焦虑和抑郁等方面表现差异显著（P〈0.05）,其中焦虑非常显著（P〈0.01）,SCL-90各因子积分在便秘型IBS与腹泻型IBS之间无明显差异。将SCL-90各因子与消化道症状严重性进行相关性分析,其中躯体化（R：0.303,P=0.04）,焦虑（R：0.56,P=0.008）及睡眠饮食（R：0.275,P=0.02）有明显相关性,其余因子无明显统计学意义。结论IBS患者除结肠症状外易合并结肠外症状。便秘型IBS患者较腹泻型患者易并发上消化道症状,以胃排空障碍为主。精神心理因素与IBS患者的症状关系密切,精神症状方面女性患者较男性更易表现为焦虑,抑郁及人际关系敏感。消化道症状的严重性与心理因素有关,其中焦虑呈明显相关。