The validity of rheumatoid arthritis diagnoses in Finnish biobanks

Objective The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. Method We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. Results The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. Conclusion These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.Peer reviewe

The validity of rheumatoid arthritis diagnoses in Finnish biobanks

Objective The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. Method We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. Results The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. Conclusion These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.Peer reviewe

Clinical presentations and outcomes of Filipino juvenile systemic lupus erythematosus

<p>Abstract</p> <p>Objective</p> <p>Juvenile Systemic Lupus Erythematosus (SLE) varies by location and ethnicity. This study describes the clinical, laboratory profile and outcome of juvenile SLE seen at Philippine General Hospital (PGH) from 2004-2008.</p> <p>Method</p> <p>Medical charts of all Filipino Juvenile SLE cases admitted at PGH during the 5-year period were reviewed collecting demographic profile, clinical and laboratory manifestations and treatment during disease course.</p> <p>Results</p> <p>Seventy-eight cases of juvenile SLE were reviewed. There were 7 boys and 71 girls. The mean age at diagnosis was 14 years (SD 2.7) with a range of 8-18 years. Fever (52.5%) and malar rash (41.0%) were the most common features at disease onset. At the time of diagnosis, the most common features were malar rash (65.3%), renal involvement (62.8%) and photosensitivity (55.1%). Mucocutaneous (92.3%), renal (71.7%) and hematologic (69.2%) involvement were the most common features during the entire course of illness. Infection (34.5%) and neurologic (19.0%) complications were observed most frequently. Corticocosteroid treatment was given in most of the patients in the form of prednisone (97.4%) and concomitant methylprednisolone intravenous pulses (29.4%). Nine patients died during the study period. The overall 5-year mortality rate was 11.5%. Infection (77.0%) was the most frequent cause of death.</p> <p>Conclusion</p> <p>Malar rash was a common feature at disease onset and at diagnosis among Filipinos with juvenile SLE. Throughout the disease course, renal involvement occurs in 71.7% of patients. Infection was the leading cause of complication and death. The clinical presentations of Filipinos with juvenile SLE were similar to juvenile SLE in other countries.</p

The validity of rheumatoid arthritis diagnoses in Finnish biobanks

Objective: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks.Method: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland.Results: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98.Conclusion: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.</p

Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis

Key messages Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.Peer reviewe

Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis

Key messages Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

First international descriptive and interventional survey for cholesterol and non-cholesterol sterol determination by gas- and liquid- chromatography–Urgent need for harmonisation of analytical methods

Serum concentrations of lathosterol, the plant sterols campesterol and sitosterol and the cholesterol metabolite 5α-cholestanol are widely used as surrogate markers of cholesterol synthesis and absorption, respectively. Increasing numbers of laboratories utilize a broad spectrum of well-established and recently developed methods for the determination of cholesterol and non-cholesterol sterols (NCS). In order to evaluate the quality of these measurements and to identify possible sources of analytical errors our group initiated the first international survey for cholesterol and NCS. The cholesterol and NCS survey was structured as a two-part survey which took place in the years 2013 and 2014. The first survey part was designed as descriptive, providing information about the variation of reported results from different laboratories. A set of two lyophilized pooled sera (A and B) was sent to twenty laboratories specialized in chromatographic lipid analysis. The different sterols were quantified either by gas chromatography-flame ionization detection, gas chromatography- or liquid chromatography-mass selective detection. The participants were requested to determine cholesterol and NCS concentrations in the provided samples as part of their normal laboratory routine. The second part was designed as interventional survey. Twenty-two laboratories agreed to participate and received again two different lyophilized pooled sera (C and D). In contrast to the first international survey, each participant received standard stock solutions with defined concentrations of cholesterol and NCS. The participants were requested to use diluted calibration solutions from the provided standard stock solutions for quantification of cholesterol and NCS. In both surveys, each laboratory used its own internal standard (5α-cholestane, epicoprostanol or deuterium labelled sterols). Main outcome of the survey was, that unacceptably high interlaboratory variations for cholesterol and NCS concentrations are reported, even when the individual laboratories used the same calibration material. We discuss different sources of errors and recommend all laboratories analysing cholesterol and NCS to participate in regular quality control programs