In search of the true inception cohort

Prognostic studies hinge on the assembly of a proper inception cohort. The stepwise assembly of a "true" inception cohort of hypertension complicating pregnancy is reported. Standard assembly procedures would have resulted in the preferential reporting of the severest cases of the prognostically worst categories of disease. The less severe cases would have been missed. Prognostic studies should utilize and report a method for assessing potential missed cases, such as a random selection of records for independent review.     

Enthesitis in an inception cohort of enthesitis-related arthritis

Objective

To describe an enthesitis‐related arthritis (ERA) inception cohort and determine which entheses and joints are most commonly affected.

Methods

We reviewed a retrospective inception cohort study of children with ERA who were diagnosed and treated at The Children's Hospital of Philadelphia between November 2007 and December 2009.

Results

During the study period, there were 32 newly diagnosed ERA patients. Fifty‐nine percent were male, and the median age at the date of initial evaluation was 12.5 years (interquartile range [IQR] 10.2–14.3 years). The median number of tender entheses at presentation was 2 (IQR 0–5), and 21 subjects (66%) had at least 1 tender enthesis. The most prevalent tender entheses were the patellar ligament insertion at the inferior pole of the patella, the plantar fascial insertion at the calcaneus, the Achilles tendon insertion at the calcaneus, and the plantar fascial insertion at the metatarsal heads. Enthesitis was most often symmetric. The median number of active joints was 2 (IQR 0–4). The most commonly affected joints were the sacroiliacs, knees, and ankles. Sacroiliitis, which was defined clinically, was most often symmetric, while peripheral arthritis was most frequently asymmetric. The odds of having active enthesitis at 6 months increased significantly with each additional tender enthesis at the initial evaluation.

Conclusion

Among pediatric patients with ERA, lower extremity enthesitis is prevalent at the time of diagnosis and is likely to persist 6 months later. Future studies should address standardization of the enthesitis examination, the pattern of enthesitis over time, enthesitis response to therapy, and the impact of enthesitis on quality of life.     

Cognitive function in a systemic lupus erythematosus inception cohort

OBJECTIVE: Measurable cognitive impairment occurs in 30-75% of patients with systemic lupus erythematosus (SLE). We compared cognitive functioning in recently-diagnosed SLE patients and normal controls. METHODS: The Automated Neuropsychological Assessment Metrics (ANAM), a repeatable computerized cognitive battery assessing cognitive processing speed and efficiency, was administered to 111 recently diagnosed SLE patients and 79 normal controls. Throughput scores on ANAM subtests were compared using linear regression. RESULTS: After adjusting for age, gender, ethnicity, and education, SLE patients scored significantly lower than controls on throughput measures of 4 ANAM subtests: code substitution immediate recall (p = 0.02), continuous performance (p = 0.02), matching to sample (p = 0.02), and Sternberg subtest (p = 0.0002). CONCLUSIONS:Recently diagnosed SLE patients performed significantly worse than normal controls on 4 of 9 ANAM subtests. ANAM subtests of cognitive efficiency requiring sustained attention/vigilance, visuospatial span of attention/working memory, and simple reaction time showed the greatest impairment. These cognitive deficits were particularly striking, because the SLE patients in this sample were not selected for the presence of neuropsychiatric manifestations, had mild SLE-related disease/damage, and were recently diagnosed with SLE. This suggests that deficits in cognitive efficiency and sustained attention are present early in the course of SLE and in the absence of other significant neuropsychiatric manifestations.     

The impact of new demands for assistance on caregiver depression: tests using an inception cohort

Family caregivers of patients facing high numbers of new demands for assistance following hospital discharge were more likely to experience increased levels of depression in the following six months compared with caregivers facing similar overall demands but few new demands for assistance following hospital discharge. New demands for assistance had a significant independent effect upon the levels of depression and were independent of family relationship (spouse vs nonspouse) and caregiver gender. These findings provide insight into theories of caregiver stress, begin to specify the interaction of time following the onset of a stressful event and caregivers' subsequent reactions, and suggest which caregivers may require some assistance following discharge of their patients.     

The early disease stage in axial spondylarthritis: Results from the german spondyloarthritis inception cohort

Objective

Ankylosing spondylitis (AS) is diagnosed late, because radiographs of the sacroiliac joints often do not show definite sacroiliitis at the time of disease onset. The aim of this study was to investigate whether patients without definite radiographically defined sacroiliitis, referred to as nonradiographic axial spondylarthritis (SpA), are different from patients with AS with regard to clinical manifestations and disease activity measures. Moreover, we sought to identify determinants of the development of radiographic sacroiliitis.

Methods

In a cross‐sectional analysis of 462 patients, we compared 226 patients with nonradiographic axial SpA (symptom duration ≤5 years) and 236 patients with AS (symptom duration ≤10 years) who are participants in the German Spondyloarthritis Inception Cohort. Radiographs of the sacroiliac joints and the spine were assessed by 2 readers in a blinded manner. Logistic regression analysis was applied to identify parameters associated with structural damage.

Results

The 2 groups did not differ in the frequency of HLA–B27 positivity, inflammatory back pain, arthritis, enthesitis, and uveitis and had similar levels of disease activity, using measures such as the Bath Ankylosing Spondylitis Disease Activity Index. In both groups, HLA–B27 positivity determined the age at disease onset. Male sex (adjusted odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.19–4.73 [P = 0.014]) and an elevated C‐reactive protein (CRP) level (adjusted OR 1.85, 95% CI 0.96–3.56 [P = 0.066]) were associated with radiographic sacroiliitis. In patients with AS, male sex and an elevated CRP level were also associated with the presence of syndesmophytes.

Conclusion

Clinical manifestations and disease activity measures are highly comparable between patients with early nonradiographic axial SpA and those with early AS, suggesting that these 2 entities are part of the same disease. Male sex and an elevated CRP level are associated with structural damage on radiographs, whereas HLA–B27 positivity determines the age at disease onset.

     

Male systemic lupus erythematosus in a Latin-American inception cohort of 1214 patients

The objective of the study was to evaluate the influence of the male gender in the clinical presentation and outcome of systemic lupus erythematosus in a prospective inception cohort of Latin-American patients. Of the 1214 SLE patients included in the GLADEL cohort, 123 were male. Demographic characteristics as well as clinical manifestations, laboratory profile, activity and damage scores were evaluated at onset and during the course of the disease and compared with female patients. The median age at onset of the male patients was 27 and that at diagnosis 29.2 years. Delay to diagnosis was shorter in males (134 versus 185 days, P = 0.01). At onset, men more frequently showed fever (42.3 versus 27.0%, P = 0.001) and weight loss (23.6 versus 11.8%, P = 0.001). During disease course the incident of symptoms was: fever, 67.8 versus 55.6%, P = 0.012; weight loss, 47.2 versus 24.3%, P = 0.001; arterial hypertension, 37.4 versus 25.8%, P = 0.007; renal disease (persistent proteinuria and/or cellular casts), 58.5 versus 44.6%, P = 0.004); and hemolytic anemia, 19.5 versus 10.9%, P = 0.008. The laboratory results showed that: men more frequently had IgG anticardiolipin antibodies (68.2 versus 49%, P = 0.02) and low C3 (61.3 versus 48.1%, P = 0.03); 5/123 men died (4%) compared with 29/1091 women (2.7%). In conclusion, 10% of GLADEL's cohort patients were male. They showed a distinctive profile with shorter delay to diagnosis, higher incidence of fever, weight loss, arterial hypertension, renal disease, hemolytic anemia, IgG anticardiolipin antibodies and low C3. Although not statistically significant, mortality was higher in men.     

Impact of musculoskeletal disorders on quality of life: an inception cohort study

OBJECTIVE: To assess longitudinally the impact of new onset musculoskeletal (MSK) disorders on quality of life (QoL). METHODS: An inception cohort of 1202 subjects in France aged 45-60 years was determined to be free of MSK problems at baseline. Over 28 months of follow up between 1996 and 1998, 310 were diagnosed with MSK disorders and matched for age and sex with 620 healthy controls. The impact of the MSK disorder onset on QoL was assessed by the change in SF-36 dimension scores over time, using a linear mixed ANOVA model to compare the groups. RESULTS: The incidence of MSK disorder was 13.6% per person-year in the spine, 4.2% per person-year in a joint, and 4.6% per person-year at an extra-articular site. The greatest change in QoL was a 10 point drop in the 100 point SF-36 bodily pain dimension scale in the MSK group. Compared with controls, subjects with an MSK disorder had significantly greater reductions in the following dimensions: bodily pain (a -7.4 point difference in change), vitality (-2.7), general health (-1.8), and physical functioning (-1.3). Within the MSK group, chronic disorders had a greater impact than acute ones on the physical functioning (-2.1), role emotional (-8.4), and social functioning (-5.9) dimensions. CONCLUSION: New onset MSK disorders have a marked deleterious effect on QoL in the physical domain, with lesser effects on social and mental functioning. This evidence of an early significant impact on their QoL reinforces recent recommendations for early treatment and primary prevention.     

Five-year outcome of a primary-care-based inception cohort of patients with inflammatory polyarthritis plus psoriasis

OBJECTIVES: To establish whether patients with inflammatory arthritis plus psoriasis have a different outcome from those who do not have psoriasis. METHODS: Seventy-nine patients with inflammatory arthritis plus psoriasis were recruited by the Norfolk Arthritis Register (NOAR) in 1990-94 and followed for 5 yrs. Their outcome was compared with the remainder (n = 755) of the NOAR cohort. We then restricted the analysis to subjects who were rheumatoid factor (RF)-negative, and compared those with and without psoriasis. Outcomes studied included remission, deformed joint count, the presence and extent of erosive damage and physical function. RESULTS: Patients with psoriasis were younger, more likely to be male, less likely to be RF-positive and more likely to have been treated with disease-modifying drugs than patients without psoriasis. After adjustment for age, gender and treatment, the only differences between the psoriasis and non-psoriasis groups were in RF positivity (adjusted odds ratio 0.44; 95% CI 0.25, 0.78) and in the Larsen score in patients with erosions. CONCLUSIONS: Patients with inflammatory arthritis plus psoriasis have a similar outcome to other RF-negative patients with arthritis.     

Comparison of three classification criteria of rheumatoid arthritis in an inception early arthritis cohort

The aim of this study is to compare the three classification criteria for rheumatoid arthritis (RA) in a large cohort of early arthritis patients. Patients who had at least one clinically swollen joint with disease duration no more than 1 year and age more than 18 years were enrolled. The clinical and laboratory parameters were recorded. The patients were diagnosed by two experienced rheumatologists. Undiagnosed patients were followed up every 3 months until 1 year. The sensitivity, specificity, and predictive value were compared among the early RA (ERA) criteria, the 1987 ACR criteria, and the 2010 ACR/EULAR criteria in this inception cohort of early arthritis patients. A total of 417 patients with inflammatory arthritis were recruited. By the end of 1 year follow-up, there were 399 patients (95.7 %) with a definitive diagnosis and 18 (4.3 %) patients remained as undifferentiated arthritis. Among the patients with definitive diagnosis, 202 (50.6 %) patients were diagnosed with RA and 197 (49.4 %) with non-RA. The sensitivity of ERA criteria was equal to 2010 ACR/EULAR criteria (both were 72.3 %), but much higher than 1987 ACR criteria (72.3 vs. 39.1 %, P?<?0.001); the specificity of ERA criteria was comparable to 2010 ACR/EULAR criteria (87.8 vs. 83.2 %) and slightly lower than 1987 ACR criteria (87.8 vs. 92.4 %, P?<?0.001). Unlike the complicated scoring system of 2010 criteria, the ERA criteria were more feasible to use in practice with five criteria only. The ERA criteria have a high sensitivity and more clinically feasibility in daily practice for early RA diagnosis.     

Overall and cause-specific mortality in ulcerative colitis: meta-analysis of population-based inception cohort studies

OBJECTIVES: It remains debated whether patients with ulcerative colitis (UC) are at greater risk of dying and whether a possible alteration in mortality can be attributed to specific causes of death. We aimed to clarify this issue by conducting a meta-analysis of population-based inception cohort studies on overall and cause-specific mortality in patients with UC. METHODS: The MEDLINE search engine and abstracts from international conferences were searched for relevant literature by use of explicit search criteria. STATA meta-analysis software was used to calculate pooled risk estimates (SMR, standardized mortality ratio, observed/expected deaths) of overall mortality and specific causes of death and to conduct metaregression analyses of the influence of specific variables on SMR. RESULTS: Ten papers fulfilled the inclusion criteria, reporting SMRs varying from 0.7 to 1.4. The overall pooled estimate was 1.1 (95% confidence interval [CI] 0.9-1.2, P= 0.42). However, greater risk of dying was observed during the first years of follow-up, in patients with extensive colitis, and in patients from Scandinavia. Metaregression analysis showed an increase in SMR by increasing cohort size. UC-related mortality accounted for 17% of all deaths. Mortality from gastrointestinal diseases, nonalcoholic liver diseases, pulmonary embolisms, and respiratory diseases was increased whereas mortality from pulmonary cancer was reduced. CONCLUSIONS: The overall risk of dying in patients with UC did not differ from that of the background population, although subgroups of patients were at greater risk of dying. The cause-of-death distribution seemed to differ from that of the background population.     

Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis

Objective

To investigate mortality rates, causes of death, time trends in mortality, prognostic factors for mortality, and the relationship between disease activity and mortality over a 23‐year period in an inception cohort of rheumatoid arthritis (RA) patients.

Methods

A prospective inception cohort of RA patients diagnosed between January 1985 and October 2007 was followed for up to 23 years after diagnosis. Excess mortality was analyzed by comparing the observed mortality in the RA cohort with the expected mortality based on the general population of The Netherlands, matched for age, sex, and calendar year. Period analysis was used to examine time trends in survival across calendar time. Prognostic factors for mortality and the influence of the time‐varying Disease Activity Score in 28 joints (DAS28) on mortality were analyzed using multivariable Cox proportional hazards models. Causes of death were analyzed.

Results

Of the 1,049 patients in the cohort, 207 patients died. Differences in observed and expected mortality emerged after 10 years of followup. No improvement in survival was noted over calendar time. Significant baseline predictors of survival were sex, age, rheumatoid factor, disability, and comorbidity. Higher levels of DAS28 over time, adjusted for age, were associated with lower survival rates, more so in men (hazard ratio [HR] 1.58, 95% confidence interval [95% CI] 1.35–1.85) than in women (HR 1.21, 95% CI 1.04–1.42).

Conclusion

Excess mortality in RA emerged after 10 years of disease duration. Absolute survival rates have not improved in the last 23 years and a trend toward a widening mortality gap between RA patients and the general population was visible. Higher disease activity levels contribute to premature death in RA patients.     

Causes of death in systemic lupus erythematosus,long-term followup of an inception cohort

Objective. To describe the causes of death in a cohort of patients with systemic lupus erythematosus (SLE), and to determine if the major causes of death differ according to patient age, sex, race, socioeconomic status, and the duration of SLE. Methods. We examined survival in a cohort of 408 patients with SLE. During a median of 11 years of followup, 144 patients died. The cause of death was determined for 134 patients (93%). Results. SLE was the most common cause of death, occurring in 49 patients (34%), followed by in- fection (n = 32; 22%), cardiovascular disease (n = 23; 16%), cerebrovascular disease (n = 8; 6%), and cancer (n = 8; 6%). Deaths due to SLE and due to infections were more common among younger patients, and deaths due to cancer were more common among older patients. Although the risk of death due to SLE was greatest during the first 3 years after diagnosis, deaths due to SLE occurred throughout the course of disease. Conclusion. In this study of patients with SLE who were followed up for an extended period of time beginning soon after diagnosis, SLE was the most common cause of death, and deaths due to SLE occurred throughout the course of illness.     

Infliximab in ankylosing spondylitis: a prospective observational inception cohort analysis of efficacy and safety

OBJECTIVE: Infliximab, a neutralizing antibody to tumor necrosis factor-alpha, appears to be effective therapy in ankylosing spondylitis (AS), although treatment is costly and serious infections are an increasing concern. We investigated the efficacy and tolerability of infliximab in a prospective observational inception cohort of patients with nonsteroidal antiinflammatory drug-refractory AS seen in both university and community based practice. We also used a lower dose, 3 mg/kg, than has been evaluated to date in AS. METHODS: We included all consecutive patients with AS starting infliximab therapy 3 mg/kg i.v. at 0, 2, and 6 weeks and q 2 months between April 2000 and October 2001. Data were systematically collected at baseline, 14 weeks, and 1 year, or at withdrawal, and included demographic characteristics, Bath AS indexes (BASDAI, BASFI, BASGI, BASMI), adverse events, and reasons for withdrawal. Laboratory measures included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum matrix metalloproteinases (MMP) 1 and 3, and serum human cartilage glycoprotein-39 (YLK-40). The first 6 consecutive patients were also studied by several magnetic resonance sequences, including dynamic MRI with gadolinium augmentation of affected joints. Maximal rate of augmentation was determined at baseline and 84 days. Analysis was by intention-to-treat. RESULTS: Twenty-one patients (m:f = 17:4), mean age 42.5 years (range 24-66), mean disease duration 13.8 years (range 3-26), were studied: 13 had active peripheral synovitis at baseline. Mean followup was 47.5 weeks (range 10-77). Four patients withdrew, 2 for serious adverse events (septic osteomyelitis and severe hypersensitivity after 3 and 2 infusions, respectively), one for lack of efficacy, and one lost to followup. Three patients required an increased dose to 5 mg/kg after 14 weeks. Efficacy data were available on 17 patients at 14 weeks; mean BASDAI improved significantly from baseline (6.2) to 14 weeks (2.8) (p < 0.001), with 10 patients (58.8%) showing at least 50% improvement (range 0-99.6%). Significant reduction in mean BASFI (43.4%; p < 0.001), BASGI (44%; p = 0.001), ESR (55%; p < 0.001), and CRP (63.5%; p = 0.01) was evident. Complete remission of peripheral joint disease was seen in 5 of 11 (45.4%) patients evaluated at 14 weeks and maximal rate of MRI defined gadolinium augmentation was significantly decreased (p = 0.04). Reductions in serum YKL-40 and MMP-1 and 3 were nonsignificant, but significant correlations were observed between changes in BASDAI, ESR, CRP, and changes in serum levels of MMP-3 and YKL-40 (p < 0.005 to p < 0.05). Followup data on 8 patients completing 1 year of therapy revealed continued efficacy at a dose of 3 mg/kg every 8 weeks. CONCLUSION: Infliximab appears to be effective and well tolerated for both axial and peripheral joint disease in AS even at lower doses than those examined to date. Suppression of markers of cartilage degradation/turnover commensurate with reductions in clinical and laboratory measures of disease activity suggests that these markers should be further validated as surrogates for structural damage in AS. Controlled trials are warranted to further assess the potential of this agent in ameliorating structural damage.