Hyvinkää Hospital

In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker.

BACKGROUND: The use of standardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years, but it is unclear whether this approach results in better outcomes than traditional colporrhaphy. METHODS: In this multicenter, parallel-group, randomized, controlled trial, we compared the use of a trocar-guided, transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall (cystocele). The primary outcome was a composite of the objective anatomical designation of stage 0 (no prolapse) or 1 (position of the anterior vaginal wall more than 1 cm above the hymen), according to the Pelvic Organ Prolapse Quantification system, and the subjective absence of symptoms of vaginal bulging 12 months after the surgery. RESULTS: Of 389 women who were randomly assigned to a study treatment, 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy. At 1 year, the primary outcome was significantly more common in the women treated with transvaginal mesh repair (60.8%) than in those who underwent colporrhaphy (34.5%) (absolute difference, 26.3 percentage points; 95% confidence interval, 15.6 to 37.0). The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group (P<0.001 for both comparisons). Rates of bladder perforation were 3.5% in the mesh-repair group and 0.5% in the colporrhaphy group (P=0.07), and the respective rates of new stress urinary incontinence after surgery were 12.3% and 6.3% (P=0.05). Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2% of 186 patients in the mesh-repair group. CONCLUSIONS: As compared with anterior colporrhaphy, use of a standardized, trocar-guided mesh kit for cystocele repair resulted in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events. (Funded by the Karolinska Institutet and Ethicon; ClinicalTrials.gov number, NCT00566917.).

High-frequency ultrasound examination of the thyroid was performed in 253 subjects (130 women and 123 men; age range, 19-50 years) that were randomly selected from the population in an area of Finland where goiter is not endemic. Thyroid echo abnormalities were detected in 69 subjects (27.3%). Prevalence of abnormalities increased with age, and women showed more lesions than did men in each of the 3 decades. The abnormality was solitary in 39 subjects (57%), multiple in 15 (22%), and diffuse in 15 (22%). Of the 68 individual nodules, 48 (70%) were smaller than 1 cm in diameter. Anechoic rounded nodules 1-5 mm in diameter were found in 28 subjects. Fine-needle aspiration biopsy was performed in 30 subjects. Cytologic examination revealed no unequivocal malignancies. In eight subjects (3.2%) with a diffuse echo abnormality, cytologic evaluation indicated lymphocytic thyroiditis. It is concluded that the prevalence of small thyroid echo abnormalities in a randomly selected adult population is rather high, a fact that supports use of a conservative approach to these types of findings.

OBJECTIVES: To evaluate the efficacy and safety of risankizumab, a humanised monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), in patients with active ankylosing spondylitis (AS). METHODS: A total of 159 patients with biological-naïve AS, with active disease (Bath Ankylosing Spondylitis Disease Activity Index score of ≥4), were randomised (1:1:1:1) to risankizumab (18 mg single dose, 90 mg or 180 mg at day 1 and weeks 8, 16 and 24) or placebo over a 24-week blinded period. The primary outcome was a 40% improvement in Assessment in Spondylo Arthritis International Society (ASAS40) at week 12. Safety was assessed in patients who received at least one dose of study drug. RESULTS: At week 12, ASAS40 response rates were 25.5%, 20.5% and 15.0% in the 18 mg, 90 mg and 180 mg risankizumab groups, respectively, compared with 17.5% in the placebo group. The estimated difference in proportion between the 180 mg risankizumab and placebo groups (primary endpoint) was -2.5% (95% CI -21.8 to 17.0; p=0.42). Rates of adverse events were similar in all treatment groups. CONCLUSIONS: Treatment with risankizumab did not meet the study primary endpoint and showed no evidence of clinically meaningful improvements compared with placebo in patients with active AS, suggesting that IL-23 may not be a relevant driver of disease pathogenesis and symptoms in AS. TRIAL REGISTRATION NUMBER: NCT02047110; Pre-results.

BACKGROUND: Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may enhance conventional analgesics in the acute postoperative setting. OBJECTIVES: To evaluate the efficacy and safety of perioperative intravenous ketamine in adult patients when used for the treatment or prevention of acute pain following general anaesthesia. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to July 2018 and three trials registers (metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)) together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: We sought randomised, double-blind, controlled trials of adults undergoing surgery under general anaesthesia and being treated with perioperative intravenous ketamine. Studies compared ketamine with placebo, or compared ketamine plus a basic analgesic, such as morphine or non-steroidal anti-inflammatory drug (NSAID), with a basic analgesic alone. DATA COLLECTION AND ANALYSIS: Two review authors searched for studies, extracted efficacy and adverse event data, examined issues of study quality and potential bias, and performed analyses. Primary outcomes were opioid consumption and pain intensity at rest and during movement at 24 and 48 hours postoperatively. Secondary outcomes were time to first analgesic request, assessment of postoperative hyperalgesia, central nervous system (CNS) adverse effects, and postoperative nausea and vomiting. We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 130 studies with 8341 participants. Ketamine was given to 4588 participants and 3753 participants served as controls. Types of surgery included ear, nose or throat surgery, wisdom tooth extraction, thoracotomy, lumbar fusion surgery, microdiscectomy, hip joint replacement surgery, knee joint replacement surgery, anterior cruciate ligament repair, knee arthroscopy, mastectomy, haemorrhoidectomy, abdominal surgery, radical prostatectomy, thyroid surgery, elective caesarean section, and laparoscopic surgery. Racemic ketamine bolus doses were predominantly 0.25 mg to 1 mg, and infusions 2 to 5 µg/kg/minute; 10 studies used only S-ketamine and one only R-ketamine. Risk of bias was generally low or uncertain, except for study size; most had fewer than 50 participants per treatment arm, resulting in high heterogeneity, as expected, for most analyses. We did not stratify the main analysis by type of surgery or any other factor, such as dose or timing of ketamine administration, and used a non-stratified analysis.Perioperative intravenous ketamine reduced postoperative opioid consumption over 24 hours by 8 mg morphine equivalents (95% CI 6 to 9; 19% from 42 mg consumed by participants given placebo, moderate-quality evidence; 65 studies, 4004 participants). Over 48 hours, opioid consumption was 13 mg lower (95% CI 10 to 15; 19% from 67 mg with placebo, moderate-quality evidence; 37 studies, 2449 participants).Perioperative intravenous ketamine reduced pain at rest at 24 hours by 5/100 mm on a visual analogue scale (95% CI 4 to 7; 19% lower from 26/100 mm with placebo, high-quality evidence; 82 studies, 5004 participants), and at 48 hours by 5/100 mm (95% CI 3 to 7; 22% lower from 23/100 mm, high-quality evidence; 49 studies, 2962 participants). Pain during movement was reduced at 24 hours (6/100 mm, 14% lower from 42/100 mm, moderate-quality evidence; 29 studies, 1806 participants), and 48 hours (6/100 mm, 16% lower from 37 mm, low-quality evidence; 23 studies, 1353 participants).Results for primary outcomes were consistent when analysed by pain at rest or on movement, operation type, and timing of administration, or sensitivity to study size and pain intensity. No analysis by dose was possible. There was no difference when nitrous oxide was used. We downgraded the quality of the evidence once if numbers of participants were large but small-study effects were present, or twice if numbers were small and small-study effects likely but testing not possible.Ketamine increased the time for the first postoperative analgesic request by 54 minutes (95% CI 37 to 71 minutes), from a mean of 39 minutes with placebo (moderate-quality evidence; 31 studies, 1678 participants). Ketamine reduced the area of postoperative hyperalgesia by 7 cm² (95% CI -11.9 to -2.2), compared with placebo (very low-quality evidence; 7 studies 333 participants). We downgraded the quality of evidence because of small-study effects or because the number of participants was below 400.CNS adverse events occurred in 52 studies, while 53 studies reported of absence of CNS adverse events. Overall, 187/3614 (5%) participants receiving ketamine and 122/2924 (4%) receiving control treatment experienced an adverse event (RR 1.2, 95% CI 0.95 to 1.4; high-quality evidence; 105 studies, 6538 participants). Ketamine reduced postoperative nausea and vomiting from 27% with placebo to 23% with ketamine (RR 0.88, 95% CI 0.81 to 0.96; the number needed to treat to prevent one episode of postoperative nausea and vomiting with perioperative intravenous ketamine administration was 24 (95% CI 16 to 54; high-quality evidence; 95 studies, 5965 participants). AUTHORS' CONCLUSIONS: Perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. Results were consistent in different operation types or timing of ketamine administration, with larger and smaller studies, and by higher and lower pain intensity. CNS adverse events were little different with ketamine or control. Perioperative intravenous ketamine probably reduces postoperative nausea and vomiting by a small extent, of arguable clinical relevance.

We describe 36 patients (six were apparently sporadic cases and 30 were cases from nine families) with amyotrophic lateral sclerosis (ALS) characterized by a distinct phenotype associated with homozygosity for an Asp90Ala mutation in the CuZn-superoxide dismutase gene. The presenting motor manifestation in all patients was paresis in the legs, with slow progression to the upper extremities and finally to the bulbar muscles. The age of ALS onset varied from 20 to 94 years, with a mean of 44 years. Mean survival time was 13 years for the 11 deceased patients. However, this is probably biased and untypical (low) when compared with the disease duration in the surviving patients, and when considering other medical complications in the deceased patients. The rate of progression was highly variable, even within families. All patients showed signs of involvement of both upper and lower motor neurons. Other neurological features included painful muscle spasms and paraesthesiae in the lower extremities. Two-thirds of patients experienced difficulty with micturition. Electrophysiological studies confirmed the slow progression and spatial distribution of clinical symptoms in the peripheral motor system. Furthermore, [corrected] potentials evoked by transcranial magnetic stimulation (MEP) were compared with those evoked by cervical or lumbosacral electrical stimulation and often revealed marked slowing of transmission in central motor pathways. In Sweden and Finland ALS patients homozygous for the Asp90Ala mutation constitute a phenotypically characteristic subset of motor neuron disease.

OBJECTIVE: To explore the impact of an early treatment response on maintenance of work capacity in patients with early, active rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomized to receive either a combination of disease-modifying antirheumatic drugs (DMARDs) with prednisolone or a single DMARD with or without prednisolone for 2 years. Treatment responses were evaluated according to the American College of Rheumatology (ACR) criteria. After a 5-year followup, the cumulative number of days of sick leave and RA-related permanent work disability was calculated for each of the 162 patients who were available for the active work force at baseline. RESULTS: Of the 159 patients assessed at 6 months, 29 were in clinical remission, 66 achieved an ACR50 response but not remission, 29 achieved an ACR20 response but not an ACR50 response, and 35 failed to achieve an ACR20 response. In these 4 groups, the median numbers of work disability days per patient-year from 6 months through 60 months of followup were 0 (interquartile range [IQR] 0-3), 4 (IQR 0-131), 16 (IQR 0-170), and 352 (16-365), respectively (P < 0.001). Pairwise multiple comparisons showed a statistically significant difference between all groups except the ACR50 and ACR20 groups. At 12 months, 30 patients were in remission. None of the 44 patients in remission at 6 or 12 months became permanently work disabled over the 5-year followup, as compared with 15 patients in the ACR50 group (23%), 6 in the ACR20 group (21%), and 19 without an ACR20 response at 6 months (56%). CONCLUSION: Prompt induction of remission translates into maintenance of work capacity. At 6 months, an ACR50 response is no better than an ACR20 response with regard to future productivity, while failure to achieve an ACR20 response carries a high risk for work disability.

OBJECTIVE: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). METHODS: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. RESULTS: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging-evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). CONCLUSION: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.

Abstract In a prospective series of 72 patients, clinical and ultrasonographic examination of the thyroid gland were compared in detail. Normal‐sized lobes were differentiated from enlarged ones both by inspection and by palpation. When lobar size was assessed by palpation, the estimate was most clearly influenced by increase in width. The correlation between two examiners in lobe size assessment was significant. In the classification of thyroid disease as diffuse, solitary, or multinodular, clinical examination and ultrasonography correlated significantly. However, only one third of the clinically solitary nodules proved to be solitary by ultrasound examination. Of 77 separate nodules, 43 escaped detection on clinical examination. Of these 43, 14 nodules exceeded 2 cm in diameter. It is concluded that the use of ultrasonography frequently alters the primary evaluation of thyroid nodularity based on palpation.

PURPOSE: This study explored psychiatric inpatients' experiences of, and their suggestions for, improvement of seclusion/restraint, and alternatives to their use in Finland. METHODS: The data were collected by focused interviews (n= 30) and were analyzed with inductive content analysis. RESULTS: Patients' perspectives received insufficient attention during seclusion/restraint processes. Improvements (e.g., humane treatment) and alternatives (e.g., empathetic patient-staff interaction) to seclusion/restraint, as suggested by the patients, focused on essential parts of nursing practice but have not been largely adopted. PRACTICE IMPLICATIONS: Patients' basic needs have to be met, and patient-staff interaction has to also continue during seclusion/restraint. Providing patients with meaningful activities, planning beforehand, documenting the patients' wishes, and making patient-staff agreements reduce the need for restrictions and offer alternatives for seclusion/restraint. Service users must be involved in all practical development.

OBJECTIVE: To describe the extrarenal symptoms and clinical course of Henoch-Schönlein purpura (HSP). DESIGN: A prospective national multicentre trial with 6-month follow-up. Patients A total of 223 newly diagnosed paediatric HSP patients. RESULTS: Purpura was the initial symptom in 73% of the patients and was preceded by joint or gastrointestinal manifestations in the rest by a mean of 4 days. Joint symptoms, abdominal pain, melena, nephritis and recurrences occurred in 90%, 57%, 8%, 46% and 25% of the patients, respectively. Orchitis affected 17/122 (14%) of the boys. Seven patients developed protein-losing enteropathy characterised by abdominal pain, oedema and serum albumin under 30 g/l, and an additional 49 patients had subnormal albumin levels without any proteinuria. Positive fecal occult blood (26/117, 22%) and α1-antitrypsin (7/77, 9%) suggested mucosal injury even in the patients without gastrointestinal symptoms. HSP was often preceded by various bacterial, especially streptococcal (36%) and viral infections. Previous streptococcal infection did not induce changes in the level of complement component C3. Recurrences were more frequent in patients >8 years of age (OR 3.7, CI 2.0 to 7.0, p<0.001) and in patients with nephritis (OR 4.6, CI 2.3 to 8.9, p<0.001). Patients with severe HSP nephritis had more extrarenal symptoms up to 6 months. There was no difference in the clinical course between the prednisone-treated and non-treated patients during the 6-month follow-up. CONCLUSIONS: Serum albumin is often low in HSP patients without proteinuria, due to protein loss via the intestine. Although corticosteroids alleviate the symptoms, they seem not to alter the clinical course of HSP during 6 months of follow-up.

OBJECTIVE: To assess the risk factors for developing Henoch-Schönlein purpura nephritis (HSN) and to determine the time period when renal involvement is unlikely after the initial disease onset. DESIGN: A prospective study of 223 paediatric patients to examine renal manifestations of Henoch-Schönlein purpura (HSP). The patient's condition was monitored with five outpatient visits to the research centre and urine dipstick testing at home. RESULTS: HSN occurred in 102/223 (46%) patients, consisting of isolated haematuria in 14%, isolated proteinuria in 9%, both haematuria and proteinuria in 56%, nephrotic-range proteinuria in 20% and nephrotic-nephritic syndrome in 1%. The patients who developed HSN were significantly older than those who did not (8.2±3.8 vs 6.2±3.0 years, p<0.001, CI for the difference 1.1 to 2.9). Nephritis occurred a mean of 14 days after HSP diagnosis, and within 1 month in the majority of cases. The risk of developing HSN after 2 months was 2%. Prednisone prophylaxis did not affect the timing of the appearance of nephritis. The risk factors for developing nephritis were age over 8 years at onset (OR 2.7, p=0.002, CI 1.4 to 5.1), abdominal pain (OR 2.1, p=0.017, CI 1.1 to 3.7) and recurrence of HSP disease (OR 3.1, p=0.002, CI 1.5 to 6.3). Patients with two or three risk factors developed nephritis in 63% and 87% of cases, respectively. Laboratory tests or blood pressure measurement at onset did not predict the occurrence of nephritis. CONCLUSION: The authors recommend weekly home urine dipstick analyses for the first 2 months for patients with HSP. Patients with nephritis should be followed up for more than 6 months as well as the patients with HSP recurrence.

PURPOSE: Congenital obstructive uropathy can lead to end stage renal disease. Progression to end stage renal disease in childhood is well described but long-term prognosis in adulthood has not been thoroughly investigated. In this study we evaluated the risk of end stage renal disease in patients with posterior urethral valves. MATERIALS AND METHODS: During 1953 to 2003 a total of 200 male patients were treated for posterior urethral valves at our institution and of these 193 could be followed for renal outcome. Followup data on patients treated with dialysis or kidney transplantation were collected from patient records and the Finnish Kidney Transplantation Registry, and data on deceased patients were collected from hospital records and the Finnish Population Register Centre. RESULTS: Median patient age at evaluation was 31 years (range 6 to 69). Of the 193 patients followed 44 (22.8%) had progression to end stage renal disease. According to a Kaplan-Meier analysis the lifetime risk of end stage renal disease was 28.5% (SE 3.8%). No patient had end stage renal disease after the age of 34 years. The lowest serum creatinine value during postoperative year 1 was associated with speed of progression to end stage renal disease. Early presentation, pneumothorax, bilateral vesicoureteral reflux and recurrent urinary tract infections after the abolition of urethral obstruction were associated with an increased risk of end stage renal disease at followup. CONCLUSIONS: Congenital obstructive uropathy can lead to end stage renal disease during childhood or young adulthood. However, the risk of end stage renal disease seems to decrease eventually. Poor kidney function at presentation is associated with worse renal prognosis.

PURPOSE: To prospectively evaluate magnetoencephalography (MEG) and functional magnetic resonance (MR) imaging, as compared with intraoperative cortical mapping, for identification of the central sulcus. MATERIALS AND METHODS: Fifteen patients (six men, nine women; age range, 25-58 years) with a lesion near the primary sensorimotor cortex (13 gliomas, one cavernous hemangioma, and one meningioma) were examined after institutional review board approval and written informed consent from each patient were obtained. At MEG, evoked magnetic fields to median nerve stimulation were recorded; at functional MR imaging, hemodynamic responses to self-paced palmar flexion of the wrist were imaged. General linear model analysis with contextual clustering (P < .01) was used to analyze functional MR imaging data, and dipole modeling was used to analyze MEG data. MEG and functional MR localizations were compared with intraoperative cortical mappings. The distance from the area of functional MR imaging activation to the tumor margin was compared between the patients with discordant and those with concordant intraoperative mapping findings by using unpaired t testing. RESULTS: MEG depicted the central sulcus correctly in all 15 patients, as verified at intraoperative mapping. The functional MR imaging localization results agreed with the intraoperative mappings in 11 patients. In all four patients with a false localization, the primary activation was in the postcentral sulcus region, but it did not differ significantly from the primary activation in the patients with correct localization with respect to proximity to the tumor (P = .38). Furthermore, at functional MR imaging, multiple nonprimary areas were activated, with considerable interindividual variation. CONCLUSION: Although both MEG and functional MR imaging can provide useful information for neurosurgical planning, in the present study, MEG proved to be superior for locating the central sulcus. Activation of multiple nonprimary cerebral areas may confound the interpretation of functional MR imaging results.

OBJECTIVE: To assess the impact of anemia and iron deficiency on health-related quality of life (HRQoL) in women treated for heavy menstrual bleeding (HMB). DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Five university hospitals in Finland. SAMPLE: A total of 236 women referred for HMB. METHODS: Women were randomized to treatment with hysterectomy or a levonorgestrel-releasing intrauterine system. We defined groups based on women's pretreatment hemoglobin [hemoglobin <120 g/L (anemic) vs. hemoglobin ≥120 g/L (nonanemic)] and serum ferritin (ferritin <15 μg/L vs. ≥15 μg/L) concentrations. HRQoL was compared between groups at baseline, 6 and 12 months after treatment. Hemoglobin and ferritin were followed for 5 years. MAIN OUTCOME MEASURES: HRQoL was measured by the RAND 36-item health survey (RAND-36), 5-Dimensional EuroQol and two questionnaires of mental wellbeing. RESULTS: At baseline, 63 women (27%) were anemic and 140 (60%) were severely iron deficient (ferritin <15 μg/L). Only 8% of the anemic women had taken iron supplementation. Twelve months after treatment hemoglobin had increased in both hemoglobin groups, but was still significantly lower (p < 0.001) in initially anemic women (128 g/L) compared with nonanemic women (136 g/L). Twelve months after treatment three domain scores of RAND-36 increased more (energy, p = 0.002; physical functioning, p = 0.04; social functioning, p = 0.05), and anxiety (p = 0.02) and depression scores (p = 0.002) decreased more in anemic compared with nonanemic women. Serum ferritin took 5 years to reach normal levels. CONCLUSIONS: Improved HRQoL after treatment of HMB is associated with correction of anemia. Clinicians should actively screen for anemia in women with HMB and emphasize early iron substitution as an integral part of treatment.

Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 × 10-8) with GDM, mapping to/near MTNR1B (P = 4.3 × 10-54), TCF7L2 (P = 4.0 × 10-16), CDKAL1 (P = 1.6 × 10-14), CDKN2A-CDKN2B (P = 4.1 × 10-9) and HKDC1 (P = 2.9 × 10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.

BACKGROUND AND AIMS: Deep remission, meaning clinical remission with mucosal healing (MH), with anti-tumor necrosis factor-alpha (TNF-α) agents is a new target for therapy in inflammatory bowel disease (IBD). Our aim was to study how often patients on TNF-α blocking therapy actually achieve deep remission. METHODS: The total of 252 IBD patients retrospectively included (183 Crohn's disease (CD), 62 ulcerative colitis (CU) or 7 inflammatory bowel disease unclassified-type colitis (IBDU)) received TNFα-antagonists (177 infliximab, 75 adalimumab) for at least 11 months and underwent ileocolonoscopy. We reviewed endoscopic and histological findings, clinical symptoms, C-reactive protein (CRP), and fecal calprotectin (FC) levels, and data on TNF-α blocking therapy. Defining deep remission as no clinical symptoms with endoscopic remission (the simple endoscopic score for Crohn's disease, SES-CD 0-2 or Mayo endoscopic subscore 0-1). RESULTS: Of the 252 patients, 168 (67%) were in clinical remission and 122 (48%) in deep remission after a median of 23 months of maintenance therapy. Of the 183 CD patients, 117 (64%) reached clinical remission and 79 (43%) deep remission. Of the UC patients, 52 (75%) were in clinical remission and 43 (62%) in deep remission. The majority of patients in deep remission (n=99, 81%) also had histologically inactive disease. Both median CRP and FC levels were significantly lower in patients with deep remission. CONCLUSION: Reassuringly, half of the IBD patients on the TNFα-blocking maintenance therapy achieved deep remission. The majority of patients in deep remission also achieved histological remission.

BACKGROUND: Overlap syndrome of asthma and chronic obstructive pulmonary disease (COPD) is a common condition, which is not well understood. This study describes the characteristics and hospital impact of patients suffering from this condition. METHODS: The data are comprised of the hospital discharge registry data maintained by National Institute for Health and Welfare [Terveyden ja hyvinvoinnin laitos (THL)] between 1972 and 2009 covering the entire Finnish population (5.35 million inhabitants in 2009). In THL, treatment periods for patients with the primary or secondary diagnosis of asthma or COPD were selected. From that data, patients over 34 years and their treatment periods starting and ending 2000-2009 with a principal or secondary diagnosis of asthma [International Classification of Diseases (ICD) 10: J45-J46] or COPD (ICD 10: J41-J44) were picked up. There were 105 122 such patients who had 343 420 treatment periods altogether. RESULTS: Patients with asthma were younger than patients with COPD and overlap syndrome, while COPD and overlap syndrome patients' age distribution was very similar. Patients with both asthma and COPD had 30.4% of all treatment periods, even though the percentage of all patients in this group was only 16.1%. These patients had an increased number of hospitalisation episodes across all age groups. Average number of treatment periods during 2000-2009 was 2.1 in asthma, 3.4 in COPD and 6.0 in overlap syndrome. Hospital impact of the same period in asthma was 939 900 days in COPD 1 517 308 and 1 000 724 days in overlap syndrome. CONCLUSION: Overlap syndrome of asthma and COPD is a common condition with high hospital impact for patients with this condition.

Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. In 2012–2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80·4 months in R0/1-resected (HR 0·15; CI95% 0·12–0·19), 39·1 months in R2-resected/LAT (0·39; 0·29–0·53) patients, and 20·8 months in patients treated with “systemic therapy alone” (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. The funders had no role in the study design, analysis, and interpretation of the data or writing of this report.

INTRODUCTION: The cesarean rates are low but increasing in most Nordic countries. Using the Robson classification, we analyzed which obstetric groups have contributed to the changes in the cesarean rates. MATERIAL AND METHODS: Retrospective population-based registry study including all deliveries (3 398 586) between 2000 and 2011 in Denmark, Finland, Iceland, Norway and Sweden. The Robson group distribution, cesarean rate and contribution of each Robson group were analyzed nationally for four 3-year time periods. For each country, we analyzed which groups contributed to the change in the total cesarean rate. RESULTS: Between the first and the last time period studied, the total cesarean rates increased in Denmark (16.4 to 20.7%), Norway (14.4 to 16.5%) and Sweden (15.5 to 17.1%), but towards the end of our study, the cesarean rates stabilized or even decreased. The increase was explained mainly by increases in the absolute contribution from R5 (women with previous cesarean) and R2a (induced labor on nulliparous). In Finland, the cesarean rate decreased slightly (16.5 to 16.2%) mainly due to decrease among R5 and R6-R7 (breech presentation, nulliparous/multiparous). In Iceland, the cesarean rate decreased in all parturient groups (17.6 to 15.3%), most essentially among nulliparous women despite the increased induction rates. CONCLUSIONS: The increased total cesarean rates in the Nordic countries are explained by increased cesarean rates among nulliparous women, and by an increased percentage of women with previous cesarean. Meanwhile, induction rates on nulliparous increased significantly, but the impact on the total cesarean rate was unclear. The Robson classification facilitates benchmarking and targeting efforts for lowering the cesarean rates.