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.

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.

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.

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.

Three out of four disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients meet 28-joint Disease Activity Score remission at 12 months: results from the FIN-ERA cohort.

OBJECTIVE: To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland. METHOD: Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites. Repeated measures were analysed using a mixed models approach with appropriate distribution and link function. RESULTS: In total, 611 patients were recruited at five sites: 67% were female; the mean (sd) age was 57 (16) years; 71% and 68% were positive for rheumatoid factor and anti-cyclic citrullinated peptides, respectively; and 23% had radiographic erosions. A total of 506 (83%) fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for rheumatoid arthritis for further analyses. DAS28-3 remission was met by 68% and 75% at 3 and 12 months, respectively. The clinical site had no effect on remission when adjusted for confounders. At baseline, 68% used methotrexate-based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine, and sulphasalazine (the Fin-RACo regimen). In multivariate analysis, the only independent predictors of DAS28-3 remission at 12 months were lower baseline DAS28-3 and triple therapy as the initial treatment. CONCLUSION: Three out of four DMARD-naïve ERA patients in Finland are in remission during the first year from the diagnosis. High remission rates were achieved for most patients with the use of conventional synthetic DMARDs in combination. Treatment of DMARD-naïve ERA patients with the FIN-RACo regimen is a predictor of DAS28-3 remission in real-life rheumatology settings.

Effects of low and high fluoride levels on rat dental caries and simultaneous dentine apposition.

The effects of various fluoride levels in drinking water on the development of enamel and dentinal caries and on dentine apposition were determined in Osborne-Mendel rats fed ad libitum either on a 43% sucrose diet and distilled water supplemented with 0, 1, 7 or 19 parts/10(6) fluoride, or on a non-cariogenic diet. The jaws were sectioned sagittally and fissure caries was assessed. The areas of the dentinal lesions and simultaneously formed dentine were quantified after tetracycline staining. There were fewer and smaller caries lesions in all fluoride groups than in the non-fluoride groups. The anti-caries effects of fluoride at 1 and 7 parts/10(6) were similar, but both had significantly less effect than 19 parts/10(6) fluoride. Much smaller dentinal lesions were seen with 19 parts/10(6) fluoride, which appears to have been accompanied by an even greater reduction in dentine apposition. Dentine formation in the third molars was significantly reduced in the rats fed a cariogenic diet. These observations suggest that a high-sucrose diet interferes with the formation of dentine in the developing tooth. Fluoride has a multiple effect; besides reducing the formation and progression of caries, it may also affect the dentinal response normally seen in the development of a caries lesion.

Effect of fluoride on caries progression and dentin apposition in rats fed on a cariogenic or non-cariogenic diet.

The effect of fluoride in drinking water on the progression of dentinal caries and dentin apposition was studied in Wistar rats. The initiation of enamel caries lesions was first induced for 2 wk with S. sobrinus and a 43% sucrose diet after weaning. Thereafter the animals were fed on either a cariogenic or a non-cariogenic diet and distilled water supplemented with 0, 1, 7 or 19 ppm fluoride. The areas of dentinal caries and dentin apposition were quantified after tetracycline staining. Fluoride reduced dentinal caries progression after the initiation of lesions in the presence of a cariogenic diet at a concentration of 19 ppm F, and without sucrose at 1 ppm F. The effect of fluoride in reducing dentin apposition with a cariogenic diet was dose-dependent, whereas fluoride in non-cariogenic groups had practically no effect on dentin formation. These results suggest that fluoride together with a high concentration of sucrose in the diet might have an odontoblast-mediated effect on the regulation of the progression of dentinal caries.

Effect of fluoride on the rate of dentin apposition and caries progression in young and old Wistar rats.

The effect of fluoride in drinking water on the progression of dentinal caries and dentin apposition was studied separately in young and old Wistar rats. The animals were inoculated with Streptococcus sobrinus and fed ad libitum on a 43% sucrose diet and distilled water supplemented with 0, 1, or 19 ppm fluoride. After a 7-wk (young) or 13-wk (adult) cariogenic challenge, the areas of dentinal caries and dentin apposition were quantified after tetracycline staining. Fluoride in the drinking water reduced the progression of dentinal caries and the speed of dentin formation in the young animals but only the progression of dental caries in the adult ones. Both the progression of carious lesions in the dentin and the rate of dentin apposition were 10 times faster during primary dentinogenesis.

The effect of a combination of chlorhexidine diacetate, sodium fluoride and xylitol on plaque wet weight and periodontal index scores in military academy cadets refraining from mechanical tooth cleaning for 7-day experimental periods.

45 subjects participated in a double-blind cross-over mouthwash study where a new tablet-form combination of chlorhexidine, fluoride and xylitol (XYLIHEX) was studied together with solutions of chlorhexidine (CHX) and sodium fluoride (NaF). The preparation XYLIHEX was developed as a dental chemotherapeutic that could easily be added to the soldiers' kit to be used under circumstances where practising normal oral hygiene habits is restricted. For comparative purposes, XYLIHEX was prediluted in this study to make a solution. Before starting, professional prophylaxis was given to the subjects to bring their gingivitis index scores as close to 0 as possible. The subjects refrained from mechanical tooth cleaning for three 7-day test periods. Plaque wet weight and periodontal index scores were recorded before and after the test periods. The results showed that the preparations XYLIHEX and CHX did not statistically differ from each other in reducing plaque wet weight values and the recorded periodontal index scores. Both these preparations were statistically highly significantly more effective antiplaque agents than NaF, as expected.

Odontoblast-mediated regulation of the progression of dentinal caries.

Osteoblasts and odontoblasts are both derived from the same mesenchymal cell line. Our aim was to investigate whether the processes of bone destruction and dentinal caries are biologically similar. The working hypothesis was that after the initiation of caries in the enamel, its rate of progression in the dentine is regulated by cell-mediated factors. Experimental caries was induced in the rat with a high sucrose diet combined with Streptococcus sobrinus infection. Both destruction of dentine and its apposition in the pulp under the carious lesions were measured after vital staining with tetracycline. Caries progression and dentine apposition were higher in developing teeth prior to apex "closure" than in adult, fully-formed teeth. Rats placed on a cariogenic diet during tooth development had an increased rate of caries progression. Fluoride administration via the drinking water was associated with decreased dentine apposition and little progression of dentine caries during the developmental stages. Dentine apposition was enhanced in adult rats placed on fluoride administration, while caries progression was reduced, whereas in animals subjected to metabolic acidosis dentine caries progression was enhanced, with reduced dentine apposition. In contrast, alkalotic animals had less dentinal lesions and smaller ones than the controls. Three theories are advanced to explain the observed changes: (i) They may be associated with changes in alkaline phosphatase activity in the pulpo-dentinal complex, (ii) they may be mediated by ionic changes in the dentinal fluid, or (iii) they may reflect the liberation of growth factors from dentinal matrix.

Pregnancy outcome in carriers of fragile X.

OBJECTIVE: To evaluate pregnancy outcome in women who are carriers of fragile X. DESIGN: Cross-sectional case-control study. SETTING: Department of Obstetrics and Gynaecology, Kuopio University Hospital, Finland. SAMPLE: Sixty-three singleton pregnancies in carriers of fragile X who were referred for genetic counselling and prenatal diagnosis to Kuopio University Hospital. METHODS: Logistic regression analysis was used to compare pregnancy outcome in women who are fragile X carrier with outcome of the general obstetric population. RESULTS: Carriers of fragile X often experienced more bleeding in late pregnancy than did the reference group. Otherwise, the course and outcome of pregnancy were comparable in both groups. CONCLUSION: Pregnancy outcome in women who are carriers of fragile X is favourable. There is no need to initiate special fetal monitoring because of the fragile X status of the woman.

Reduction of venous sequelae of i.v. diazepam with a fat emulsion as solvent.

Venous sequelae were studied in 93 female patients undergoing minor gynaecological procedures. They were premedicated with diazepam i. v. dissolved in a fat emulsion (Diazemuls) injected to a superficial vein of the right hand. The patients observed the site of injection for 14 days and recorded their findings. Twenty-eight per cent reported mild tenderness and 7.5% mild or moderate swelling of short duration. Signs of thrombophlebitis were found in 2.2%. Thrombophlebitis after injection can be prevented effectively and safely using fat emulsion as a solvent for diazepam.