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.

Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy: 5-year outcomes of merged data from two randomized clinical trials (SLEEVEPASS and SM-BOSS).

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB) are both effective surgical procedures to achieve weight reduction in patients with obesity. The trial objective was to merge individual-patient data from two RCTs to compare outcomes after LSG and LRYGB. METHODS: Five-year outcomes of the Finnish SLEEVEPASS and Swiss SM-BOSS RCTs comparing LSG with LRYGB were analysed. Both original trials were designed to evaluate weight loss. Additional patient-level data on type 2 diabetes (T2DM), obstructive sleep apnoea, and complications were retrieved. The primary outcome was percentage excess BMI loss (%EBMIL). Secondary predefined outcomes in both trials included total weight loss, remission of co-morbidities, improvement in quality of life (QoL), and overall morbidity. RESULTS: At baseline, 228 LSG and 229 LRYGB procedures were performed. Five-year follow-up was available for 199 of 228 patients (87.3 per cent) after LSG and 199 of 229 (87.1 per cent) after LRYGB. Model-based mean estimate of %EBMIL was 7.0 (95 per cent c.i. 3.5 to 10.5) percentage points better after LRYGB than after LSG  (62.7 versus 55.5 per cent respectively; P < 0.001). There was no difference in remission of T2DM, obstructive sleep apnoea or QoL improvement; remission for hypertension was better after LRYGB compared with LSG (60.3 versus 44.9 per cent; P = 0.049). The complication rate was higher after LRYGB than LSG (37.2 versus 22.5 per cent; P = 0.001), but there was no difference in mean Comprehensive Complication Index value (30.6 versus 31.0 points; P = 0.859). CONCLUSION: Although LRYGB induced greater weight loss and better amelioration of hypertension than LSG, there was no difference in remission of T2DM, obstructive sleep apnoea, or QoL at 5 years. There were more complications after LRYGB, but the individual burden for patients with complications was similar after both operations.

Outcomes of treatment of faecal incontinence with sacral nerve stimulation - a Finnish multicentre study.

AIM: The aim of this multicentre study is to report the results of sacral nerve stimulation (SNS) treatment for faecal incontinence (FI) in Finland and determine factors that could influence SNS treatment outcomes. METHOD: This is a national multicentre study, involving all patients tested for SNS implantation in Finland from 1999 to 2017. Data were collected retrospectively from electronic patient archives and analysed for possible effects on treatment outcome. RESULTS: Of the 432 patients with FI tested for SNS, 365 were women. Three hundred and thirteen (72.5%) of the tested patients advanced to permanent implantation of a stimulator. A successful final treatment outcome, with subjective alleviation of FI, was reported by 59.3% of the patients at the end of follow-up (mean 2.4 years, range 8 days to 13.3 years). Patients with obstetric sphincter injury and idiopathic FI had more permanent stimulator implantations than patients with iatrogenic injury (P = 0.012). Male patients had significantly worse test phase outcomes than female patients (P < 0.001). Age did not influence treatment outcome (P = 0.446) CONCLUSION: Subjective final success of SNS treatment for FI was achieved in 59.3% of patients at a mean of 2.4 years. Gender and the aetiology of FI influenced the test phase and final treatment outcome of SNS treatment.

Hospital admissions and surgical treatment of children with lower-limb deficiency in Finland.

BACKGROUND AND AIMS: There are no population-based studies about hospital admissions and need for surgical treatment of congenital lower-limb deficiencies. The aim is to assess the impact children with lower-limb deficiencies pose to national hospital level health-care system. MATERIALS AND METHODS: A population-based study was conducted using the national Register of Congenital Malformations and Care Register for Health Care. All 185 live births with lower-limb deficiency (1993-2008) were included. Data on hospital care were collected until 31 December 2009 and compared to data on the whole pediatric population (0.9 million) live born in 1993-2008. RESULTS: The whole pediatric population had annually on average 0.10 hospital admissions and the mean length of in-patient care of 0.3 days per child. The respective figures were 1.5 and 5.6 in terminal lower-limb amputations (n = 7), 1.1 and 3.9 in long-bone deficiencies (n = 53), 0.6 and 1.9 in foot deficiencies (n = 26) and 0.4 and 2.6 in toe deficiencies (n = 101). Orthopedic surgery was performed in 72% (5/7) of patients with terminal amputations, in 62% (33/53) of patients with long bone, in 58% (14/24) of patients with foot and in 25% (25/101) of patients in toe deficiencies. Half (54%) of all procedures were orthopedic operations. CONCLUSION: In congenital lower-limb deficiencies the need of hospital care and the number of orthopedic procedures is multiple-fold compared to whole pediatric population. The burden to the patient and to the families is markedly increased, especially in children with terminal amputations and long-bone deficiencies of lower limbs.

Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial).

BACKGROUND: Based on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70-80%) or complicated (20-30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis. METHODS: APPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients. Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin. DISCUSSION: To our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03236961, retrospectively registered on the 2nd of August 2017.

Humoral response to John Cunningham virus during pregnancy in multiple sclerosis.

BACKGROUND: Pregnancy induces an immunosuppressive state in the mother to ensure immunological acceptance of the foetus. Impairment of cell-mediated immune responses may render the mother susceptible to intracellular pathogens. It is not presently known whether pregnancy alters the immunosurveillance for John Cunningham virus (JCV), an opportunistic pathogen associated with natalizumab treatment for multiple sclerosis (MS). OBJECTIVE: To evaluate whether the humoral immune response to JCV is altered during pregnancy among MS patients and healthy controls to get insight to potential pregnancy-induced alterations related to immune response to JCV during pregnancy. METHODS: Serum anti-JCV-antibody-indices (JCV-Ab-index) were determined by a two-step second-generation enzyme-linked immunosorbent assay in 49 MS patients during and after pregnancy and in 49 healthy controls during pregnancy. For comparison, total IgG levels and antibodies against Epstein-Barr, cytomegalo and measles viruses were similarly measured. RESULTS: The JCV-Ab-indices of MS patients were not altered during the pregnancy (1st vs. 3rd trimester, 0.62 vs. 0.77, p = 0.99). Contrary to this, in the healthy controls JCV-Ab-indices (p = 0.005), antibody levels to the other viruses, and total IgG levels (p < 0.0001) decreased significantly during pregnancy. CONCLUSIONS: JCV-Ab levels remain unaltered during MS pregnancy, while the total IgG concentration is reduced/diluted due to increasing plasma volumes during the course of pregnancy. This may imply a biologically significant alteration in the immune response to JCV during MS pregnancy.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

BACKGROUND: An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. METHODS: The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. RESULTS: Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P < 0·001). When the age and sex of the patient as well as the hospital were controlled for simultaneously, the operative treatment generated significantly more costs in all models. CONCLUSION: Patients receiving antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery.

Effect of antenatal growth and prematurity on brain white matter: diffusion tensor study.

BACKGROUND: White matter maturation is characterised by increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD). Contradictory results have been published on the effect of premature birth on white matter maturation at term-equivalent age. OBJECTIVE: To assess the association of gestational age and low birth-weight-for-gestational-age (z-score) with white matter maturation. MATERIALS AND METHODS: Infants (n = 76, 53 males) born at different gestational ages were imaged at term-equivalent age. Gestational age and birth weight z-score were used as continuous variables and the effect on diffusion parameters was assessed. Brain maturation was studied using regions-of-interest analysis in several white matter areas. RESULTS: Gestational age showed no significant effect on white matter maturation at term-equivalent age. Children with low birth weight z-score had lower FA in the genu and splenium of the corpus callosum (regression, P = 0.012 and P = 0.032; correlation, P = 0.009 and P = 0.006, respectively), and higher MD in the splenium of the corpus callosum (regression, P = 0.002; correlation, P = 0.0004) compared to children whose birth weight was appropriate for gestational age. CONCLUSION: Children with low birth weight relative to gestational age show delay and/or anomaly in white matter maturation at term-equivalent age.

The analgesic effect of continuous subacromial bupivacaine infusion after arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: The benefits of subacromial local anesthetic infusion are controversial. The aim of this study was to evaluate the efficacy of subacromial bupivacaine infusion after arthroscopic acromionplasty and rotator cuff procedures. METHODS: Ninety patients with subacromial impingement disease scheduled for elective shoulder arthroscopy were enrolled in this randomized, prospective and placebo-controlled study. The patients received subacromially either 5.0 mg/ml bupivacaine or 9.0 mg/ml saline at the rate of 2 ml/h post-operatively for 48 h. The primary outcome measure was the use of rescue oxycodone. The consumption of opioids, ibuprofen, paracetamol and codeine, and the intensity of pain were recorded. RESULTS: Patients receiving bupivacaine infusion used significantly less oxycodone compared with patients receiving saline [15 vs. 20 mg (median) oxycodone intravenously on the day of surgery, 0 vs. 10 mg (median) perorally on the first post-operative day]. There was no significant difference in the use of ibuprofen, paracetamol and codeine, except that paracetamol was used more in patients receiving saline during the day of surgery (P = 0.009). The pain scores of patients receiving bupivacaine were lower at 18 h (P = 0.008). Average pain scores for the worst pain experienced did not differ between the groups. There were three (4%) premature discontinuations because of technical problems. CONCLUSIONS: Considering the low need of opioids, expenses and technical problems in these patients, subacromial 5.0 mg/ml bupivacaine infusion 2 ml/h confers only moderate and probably clinically insignificant efficacy compared with placebo. This efficacy might be overweighed by the disadvantages.

Quality of life after surgery for rectal cancer with special reference to pelvic floor dysfunction.

AIM: Conventional outcomes such as survival, tumour recurrence and complication rates after surgery for rectal cancer have been rigorously assessed, but the importance of maintaining quality of life (QOL) after surgery for rectal cancer has received less attention. The aim of the current study was to analyse QOL and the occurrence of pelvic dysfunction after the surgical treatment of rectal cancer. METHOD: Between May 2005 and May 2008, 150 patients with rectal cancer underwent abdominoperineal resection (APR) or anterior resection (AR). Seventy-four answered two preoperative questionnaires. At a follow up of 1 year, 65 were alive without sign of recurrence and answered the same questionnaires: (a) validated RAND 36-item health survey QOL questionnaire; and (b) self-administered disease-related questionnaire with special reference to anorectal and urogenital function. RESULTS: The postoperative general QOL was similar after surgery, and mental functioning was better (P < 0.001). Problems with physical functions were associated with anal dysfunction after AR (P < 0.001) and problems with social functioning were associated with urinary dysfunction (P = 0.038). At 1 year after surgery, urinary incontinence was worse (P = 0.026) after all operations, and the incidence of dysuria was higher after APR than AR (P = 0.001). Male sexual function also worsened (P = 0.060). Anorectal dysfunction caused more inconvenience among patients who underwent AR (P = 0.028). Preoperative radiation was associated with postoperative ejaculation problems (P = 0.028) and anal incontinence (P = 0.012). CONCLUSION: Factors affecting QOL and pelvic floor function should be taken into account when making treatment decisions in rectal cancer.

Plasma levels of bupivacaine and its metabolites after subacromial infusions in concentrations 2.5 or 5.0 mg/ml.

BACKGROUND: We studied plasma bupivacaine concentrations in patients with a continuous subacromial bupivacaine infusion after an ambulatory arthroscopic shoulder surgery to evaluate whether it is feasible to discharge patients with an on-going infusion early on the operation day. METHODS: Sixteen ASA I-III patients undergoing elective arthroscopic shoulder surgery were randomized in 1:1 ratio to receive a continuous infusion of either 2.5 or 5.0 mg/ml bupivacaine subacromially for 48 h post-operatively. Before the commencement of the infusion, 20 ml of 5.0 mg/ml bupivacaine was injected subacromially in both groups. Plasma bupivacaine concentrations were defined as the primary endpoint and concentrations of its metabolites, side effects and pain scores as the secondary endpoints. RESULTS: The mean total plasma bupivacaine concentration increased up to 48 h, the highest mean being 0.87 (SD 0.30) µg/ml during the 5.0 mg/ml treatment and 0.24 (0.10) µg/ml during the 2.5 mg/ml bupivacaine treatment. After 48 h, there was a significant difference between the groups in the plasma levels. The highest mean 4-hydroxy-bupivacaine and desbutylbupivacaine concentrations were 0.11 and 0.22 µg/ml, respectively. In the pain scores, no significant difference was found. No clear signs of toxicity were observed. CONCLUSIONS: The concentrations of total bupivacaine and its metabolites remained below toxic levels. Excluding patients with renal or liver diseases, both 2.5 and 5.0 mg/ml bupivacaine as subacromial infusion 2 ml/h for 48 h following shoulder arthroscopy seem to be well tolerated, enabling patient discharge with an on-going infusion on the operation day. Because of similar side effects and pain scores in both groups, 2.5 mg/ml may be preferable.

Altered expression of p120catenin predicts poor outcome in invasive breast cancer.

PURPOSE: The study focuses on p120catenin, a regulator of cell adhesion, which has previously been described in many malignancies and suggested with a role in invasion and metastatic behaviour. In this study, we investigate the role of altered immunoexpression of p120catenin isoforms in the prognosis of invasive breast cancer (n = 351). METHODS: We used cDNA microarrays to screen differences in gene expression in invasive breast cancer in general, and between local and metastasized disease particularly. On this basis, we performed p120catenin immunohistochemistry in order to confirm the prognostic value of p120catenin isoforms on tissue microarrays comprising 341 patients from the era of mammographic screening, directed to modern surgical and oncological treatments, and followed-up for maximum of 20 years. RESULTS: In cDNA microarray analysis, p120catenin was discovered down-regulated along with E-cadherin and alpha-catenin. In addition, p120catenin distinguished metastasized breast cancer from local disease. Immunohistochemistry confirmed the value of p120catenin as an independent prognosticator of breast cancer survival. In our results, p120catenin was associated with 3.7-fold risk of breast cancer death in multivariate Cox's regression analyses adjusted for the established prognosticators of breast cancer (p = 0.039). Particularly, the long isoform of p120catenin predicted metastatic disease (p = 0.029). CONCLUSION: The present paper is the first report on p120catenin in invasive breast cancer based on a well-characterized patient material with long-term follow-up. We observed altered expression of p120catenin isoforms in invasive breast cancer and, in our material, the decrease in p120 immunoexpression was significantly associated with poor outcome of disease.

Securin promotes the identification of favourable outcome in invasive breast cancer.

BACKGROUND: Securin is a recently recognised oncogene with multiple known functions in initiation, progression and cell cycle regulation in several malignant diseases, including breast carcinoma. METHODS: In this paper, the prognostic value of securin is evaluated by immunohistochemistry in 310 patients diagnosed with invasive breast cancer during a mammographic screening programme in Central Finland. All patients were directed to modern surgical and oncological treatments and were followed up for a maximum of 20 years. RESULTS: Our results suggest that securin immunopositivity is an independent prognosticator of invasive breast cancer. In our study, securin predicted breast cancer-specific survival among all cases of invasive breast cancer and subgroups divided according to histological type, Ki-67 proliferation status and tumour size. Especially in a multivariate analysis standardised for axillary lymph node status, patient's age and tumour size at the time of diagnosis, securin immunopositivity indicated a 13.1-fold risk of breast cancer death (P=0.024) among invasive ductal breast carcinomas with low Ki-67 positivity. CONCLUSION: Our present and previous results suggest that securin could be useful in clinical pathology to intensify the power of the established prognosticators of invasive breast cancer and, especially, to assist in identifying patients with a more favourable outcome than that indicated by Ki-67 alone.

Utility of C-reactive protein in assessing the disease severity and complications of community-acquired pneumonia.

Previous studies on the usefulness of C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) have yielded somewhat inconsistent results. Our aim was to assess the value of CRP in estimating the severity and complications of CAP. CRP levels during the first 5 days of hospitalization were measured in 384 adult patients with CAP, and the data were evaluated using comprehensive statistical analyses. Significantly higher CRP levels on admission were detected in Pneumonia Severity Index (PSI) classes III-V than in classes I and II (p <0.001). An increment of 50 mg/L CRP on admission was associated with a 1.22-fold odds for a patient to be in PSI classes III-V as compared with classes I and II (OR 1.22, 95% CI 1.11-1.34; p <0.001). CRP levels were significantly higher in bacteraemic pneumonia than in non-bacteraemic pneumonia (p <0.001). An increment of 50 mg/L CRP was associated with a 1.67-fold odds for a patient to be bacteraemic (OR 1.67, 95% CI 1.46-1.92; p <0.001). CRP levels >100 mg/L on day 4 after the admission were significantly associated with complications (p <0.01). There was a trend for an association between the level of CRP on admission and the time to reach clinical stability (p <0.01). In conclusion, CRP may be valuable for revealing the development of complications in CAP. It may also be useful to assess the disease severity, thus being complementary to the assessment of the PSI. In our patients, high CRP levels were associated with a failure to reach clinical stability.