Causes and predictors of death among Finnish patients with systemic sclerosis.

OBJECTIVE: The aim of this study was to assess causes and predictors of death among Finnish patients with systemic sclerosis (SSc). METHOD: Medical records of patients registered with the ICD-10 code M34 from 1996 to 2018 in two university hospitals were reviewed retrospectively. Clinical data were collected until the end of 2020. Death certificates were obtained from Statistics Finland up to August 2021. Using death certificates and patient records, the cause of death for each patient was determined. The mean age at death, median time from SSc diagnosis, and factors predicting death were analysed. RESULTS: Among 313 SSc patients, 91 deaths occurred between April 2000 and September 2020. Overall 5 and 10 year survival rates were 88.4% and 80.2%, respectively. SSc was the most common primary cause of death (n = 35) and interstitial lung disease (ILD) was the most common SSc-related cause of death (n = 13). Moreover, 52% of the patients with diffuse SSc and 33% of those with limited cutaneous SSc died as a result of SSc itself. Patients who died because of SSc were significantly younger [mean ± sd age 65.6 ± 12.7 years, 95% confidence interval (CI) 61.2-70.1] than those who died from other causes (74.2 ± 9.6 years, 95% CI 71.5-76.9) (p = 0.0006). ILD, pulmonary arterial hypertension, gastrointestinal involvement, male gender, and older age at disease onset predicted death. CONCLUSION: The disease itself was the major cause of death among Finnish SSc patients, in both diffuse and limited forms of SSc.

Systemic sclerosis: changes in the incidence rates in the Finnish population during the years 1999-2018.

OBJECTIVE: The aim of our study was to examine changes in the incidence of systemic sclerosis (SSc) in Finland using two different classification criteria. METHOD: Medical records of patients who had been registered with ICD-10 code M34 from 1999 to 2018 in two university hospitals were reviewed retrospectively. This period was divided into 5 year periods: 1999-2003, 2004-2008, 2009-2013, and 2014-2018. Using American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 criteria and clinical findings, we reclassified patients into four groups: diffuse SSc, limited SSc, sine SSc, or early SSc. In the same population, we also investigated whether the ACR 1980 criteria were fulfilled. RESULTS: In 1999-2018, 246 new patients with SSc and 45 patients with early SSc were identified using ACR/EULAR 2013 criteria. Of these patients, 70 fulfilled the ACR 1980 criteria. Using ACR/EULAR 2013 criteria, the increase in new diagnoses was statistically significant when comparing the fourth period with the first period (p = 0.0012). The increase was due to a rise in limited SSc. Mean annual incidence rates in these groups were 0.9, 1.2, 1.9, and 2.8 per 100 000 inhabitants ≥ 16 years old. An increasing trend was also seen when using ACR 1980 criteria, but this was not statistically significant. CONCLUSION: The incidence of SSc increased during the period between 1999-2003 and 2014-2018 using ACR/EULAR 2013, but not using ACR 1980 criteria. The increase was detected within a limited SSc subclass, owing to more sensitive classification criteria.

The feasibility of existing JADAS10 cut-off values in clinical practice: a study of data from The Finnish Rheumatology Quality Register.

BACKGROUND: The ten-joint juvenile arthritis disease activity score (JADAS10) is designed to measure the level of disease activity in non-systemic juvenile idiopathic arthritis by providing a single numeric score. The clinical JADAS10 (cJADAS10) is a modification of the JADAS10 that excludes erythrocyte sedimentation rate (ESR). Three different sets of JADAS10/cJADAS10 cut-offs for disease activity states have been published, i.e., the Backström, Consolaro, and Trincianti cut-offs. The objective of this study was to investigate the performance of existing JADAS10 cut-offs in real-life settings using patient data from The Finnish Rheumatology Quality Register (FinRheuma). METHODS: Data were collected from the FinRheuma register. The proportion of patients with an active joint count (AJC) above zero when classified as being in clinically inactive disease (CID) or low disease activity (LDA) groups according to existing JADAS10/cJADAS10 cut-off levels were analyzed. RESULTS: A significantly larger proportion of the patients classified as being in CID had an AJC > 0 when using the JADAS10/cJADAS10 cut-offs by Trincianti et al. compared to those for the other cut-offs. In the LDA group, a significantly larger proportion of the polyarticular patients (35%/29%) had an AJC of two when Trincianti JADAS10/cJADAS10 cut-offs were used compared with when Backström (11%/10%) and Consolaro (7%/3%) JADAS10/cJADAS10 cut-offs were used. CONCLUSIONS: We found the cut-offs proposed by Consolaro et al. to be the most feasible, since these cut-off levels for CID do not result in the misclassification of active disease as remission, and the proportion of patients with AJC > 1 in the LDA group is lowest using these cut-offs.

The validity of systemic sclerosis diagnoses in two university hospitals in Finland.

OBJECTIVE: This study aimed to determine the validity of systemic sclerosis (SSc) diagnoses in Finnish university hospitals. METHOD: Electronic medical records for 385 patients with a registered diagnosis of SSc (ICD-10 code M34) in two Finnish university hospitals from 2008 to 2018 were reviewed to assess whether each patient's diagnosis was correct. RESULTS: The positive predictive value (PPV) of a diagnosis of SSc was 0.66 when fulfilment of the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc was required; the PPV was 0.75 if patients meeting the 2001 LeRoy and Medsger classification criteria for early SSc were also included. When a diagnosis of SSc was made in a department of rheumatology, the PPV was 0.78, and 0.90 when including patients with early SSc. For the more specific diagnosis of limited cutaneous SSc (lcSSc), the PPV was 0.80, and 0.95 when including early SSc. For an lcSSc diagnosis made in rheumatology, the PPV was 0.81, and 0.97 with early SSc included. CONCLUSION: These results demonstrate that in these two Finnish university hospitals, the diagnostic validity of a diagnosis of SSc was good if it was diagnosed in the department of rheumatology. For a more specific diagnosis of lcSSc, the most prevalent form of SSc in Finland, the validity was good even when registered in any department.

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.

Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: A double blind placebo controlled multicenter study.

BACKROUND: Venous thromboembolism (VTE) after primary intracerebral hemorrhage (ICH) worsens patient prognosis. Administering low-molecular weight heparins (LMWH) to prevent VTE early (24 h) may increase the risk of hematoma enlargement, whereas administering late (72 h) after onset may decrease its effect on VTE prevention. The authors investigated when it is safe and effective to start LMWH in ICH patients. METHODS: In the setting of double blinded, placebo controlled randomization, patients >18 years of age with paretic lower extremity, and admitted to the emergency room within 12 h of the onset of ICH, were randomized into two groups. Patients in the enoxaparin group received 20 mg twice a day 24 h (early) after the onset of ICH and in the placebo group 72 h (late) after onset respectively. Both groups immediately received intermittent pneumatic compression stockings at the ER. Patients were prospectively and routinely screened for VTE and hemorrhagic complications 1 day after entering the study and again before discharge. RESULTS: 139 patients were included for randomization in this study. Only 3 patients developed VTE, 2 in the early enoxaparin group and one in the late enoxaparin group. No patients developed PE. Thromboembolic events (p = 0.901), risk of hematoma enlargement (p = 0.927) and overall outcome (P = 0.904) did not differ significantly between the groups. CONCLUSION: Administering 40 mg/d LMWH for prevention of VTE to a spontaneous ICH patient is safe regardless of whether it is started 24 h (early) or 72 h (late) after the hemorrhage. Risk of hemorrhage enlargement is not associated with early LMWH treatment. Administering LMWH late did not increase VTEs.

Better than expected survival after primary intracerebral hemorrhage in patients with untreated hypertension despite high admission blood pressures.

BACKGROUND: Hypertension is the most important modifiable risk factor for primary intracerebral hemorrhage (ICH), but little is known of the effect of preceding hypertension on outcome. Because high mean arterial blood pressure (MABP) at admission is an independent predictor of early death in patients with ICH, we explored its role on survival and poor outcome separately in normotensive subjects and subjects with treated and untreated hypertension. METHODS: We assessed clinical data and the 3-month outcome of patients with spontaneous ICH (n = 453) admitted to the stroke unit of Oulu University Hospital between 1993 and 2004. Standard medical treatment was used to lower MABP from levels >127 mmHg to <120 mmHg. RESULTS: Overall mortality within 3 months was 28%. Patients with untreated hypertension had significantly lower mortality (6%) than those with treated hypertension (36%, P < 0.001) or those without hypertension (25%, P < 0.01). High admission MABP associated with early death in normotensive subjects (P < 0.05) and those on medication for hypertension (P < 0.01) but not in those with untreated hypertension. Patients with untreated hypertension were younger and had less frequently cardiac disease, diabetes, and/or warfarin or aspirin medications, but they showed the highest blood pressures (BPs) at admission. Amongst patients with high admission MABP, favorable outcome was seen most frequently in those who had untreated hypertension. Hematoma growth did not associate with high MABP amongst them. CONCLUSION: Despite their higher BP values at admission, subjects with untreated hypertension showed better survival and more frequently favorable outcome after BP-lowering therapy than other patients.

Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y.

The negative regulation of the human parathyroid hormone (PTH) gene by biologically active vitamin D3 (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) was studied in rat pituitary GH4C1 cells, which express factors needed for the negative regulation. We report here that NF-Y binds to sequences downstream of the site previously reported to bind the vitamin D receptor (VDR). Additional binding sites for NF-Y reside in the near vicinity and were shown to be important for full activity of the PTH gene promoter. VDR and NF-Y were shown to exhibit mutually exclusive binding to the VDRE region. According to our results, sequestration of binding partners for NF-Y by VDR also affects transcription through a NF-Y consensus binding element in GH4C1 but not in ROS17/2.8 cells. These results indicate that 1,25(OH)2D3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y.