Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

Association of placental and umbilical cord characteristics with cerebral palsy: national cohort study.

OBJECTIVES: Cerebral palsy (CP) is a group of movement disorders usually diagnosed in childhood. A substantial proportion are thought to be caused by antenatal events. Abnormalities of the umbilical cord and placenta are associated with an increased risk of adverse neonatal outcomes, but it is unclear whether these conditions also carry an increased risk of CP. We aimed to determine whether abnormalities of the umbilical cord or placenta are associated with CP and assess if these associations differ by sex of the child or gestational age at birth. METHODS: We performed a national cohort study by linking data from The Medical Birth Registry of Norway with other national registries. All liveborn singletons born between 1999 and 2017 (n = 1 087 486) were included and followed up until the end of 2019. Diagnoses of CP were provided by the Norwegian National Insurance Scheme and the Norwegian Patient Register. We used generalized estimating equations and multilevel log binomial regression to calculate relative risks (RR), adjusted for year of birth, and stratified analyses were carried out based on sex and gestational age at birth. Exposures were abnormal umbilical cord (velamentous or marginal insertion, single umbilical artery (SUA), knots and entanglement), and placental abnormalities (retained placenta, placental abruption and previa). RESULTS: A total of 2443 cases with CP (59.8% males) were identified. Velamentous cord insertion (adjusted RR (aRR), 2.11 (95% CI, 1.65-2.60)), cord knots (aRR, 1.53 (95% CI, 1.15-2.04)) and placental abnormalities (placenta previa (aRR, 3.03 (95% CI, 2.00-4.61)), placental abruption (aRR, 10.63 (95% CI, 8.57-13.18)) and retained placenta (aRR, 1.71 (95% CI, 1.32-2.22))) carried an increased risk of CP. Velamentous cord insertion was associated with CP regardless of gestational age or sex. A retained placenta was associated with a 2-fold increased risk for CP in males, while the associations of SUA and cord knot with CP were significant only among females. CONCLUSIONS: The detection of placental and umbilical cord abnormalities may help identify children at increased risk of CP. The associations between placental or umbilical cord abnormalities and the risk of CP do not vary substantially with gestational age at birth or sex of the child. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dietary soy galactooligosaccharides affect the performance, intestinal function, and gut microbiota composition of growing chicks.

The objective of this experiment was to investigate the effects of the dietary soy galactooligosaccharides (GOS), raffinose and stachyose, on performance, gastrointestinal health, and systemic stress in young broilers. Birds were fed a GOS-devoid diet based on soy protein isolate (SPI) or the SPI diet with 0.9, 1.8, 2.7, or 3.6% added stachyose and raffinose in a ratio of 4:1 at the expense of corn starch. These 5 treatments were administered to 10 replicate cages of 8 birds. Performance was measured weekly and excreta moisture, N retention, apparent metabolizeable energy, and complete blood cell counts were determined at 14 and 21 d. At 21 d, 2 birds per cage were orally gavaged with fluorescein isothiocyanate-dextran (FITC-d) and serum samples were analyzed for FITC-d as a marker of gut leakage. Additionally, intestinal morphology, crop presumptive lactic acid bacteria (LAB) counts, crop and cecal pH, and cecal microbiota via16S rRNA microbial sequencing were evaluated at 21 d. From 0 to 21 d, feed intake increased linearly (P < 0.01) as dietary GOS increased, whereas BWG increased (P < 0.05) quadratically. Feed conversion ratio increased (P < 0.01) linearly as GOS increased. There were linear increases (P < 0.05) in excreta moisture as dietary GOS increased at 14 and 21 d, as well as dose-dependent responses (P < 0.05) in N retention, AME, and AMEn. There was a quadratic increase (P < 0.05) in crop LAB recovery and a linear decrease (P < 0.01) in ceca pH as GOS increased. At 14 d, a linear increase (P < 0.05) in blood heterophil to lymphocyte ratio was observed as dietary GOS increased. Serum concentrations of FITC-d increased quadratically (P < 0.01) to dietary GOS. Increasing levels of GOS influenced alpha and beta diversities and composition of gut microbiota, including the abundance of Ruminococcus and Bifidobacterium. Results from this trial indicate that soy-derived GOS exert dose-dependent effects on nutrient utilization and intestinal health in young broilers.

Antibody response in patients with autoimmune inflammatory rheumatic disease after pneumococcal polysaccharide prime vaccination or revaccination.

OBJECTIVE: The aim of the study was to assess the pneumococcal antibody response in autoimmune inflammatory rheumatic disease (AIIRD) patients receiving 23-valent pneumococcal polysaccharide vaccine (PPV23) as a prime vaccination or revaccination. METHOD: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIIRD patients receiving biological disease-modifying anti-rheumatic drug (bDMARD) treatment for rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis. Patients with a non-protective level of pneumococcal antibodies (geometric mean pneumococcal antibody level < 1 µg/mL) were invited to receive vaccination with PPV23 followed by control of antibody titre 3 months later. RESULTS: In total, 224 (74%) of 301 patients were included in the analyses, of whom 126 patients had previously received PPV23 vaccination. Post-vaccination antibody measurement revealed that only 80 patients (36%) achieved a protective level of antibodies. In a multivariable logistic regression analysis, significantly more patients without a previous PPV23 vaccination history achieved a protective antibody level compared with patients with a history of PPV23 vaccination less than 5 years ago (p = 0.005). This difference was not seen when comparing the former group with patients vaccinated 5 years ago or more. Methotrexate (MTX) treatment at the time of vaccination was associated with a non-protective antibody level (p < 0.001). CONCLUSION: Only 36% of patients with a non-protective antibody level achieved a protective level in response to pneumococcal vaccination. Pneumococcal vaccination within the last 5 years and MTX treatment at the time of vaccination were independently associated with a poor antibody response.

A Case of HPV-Associated Oropharyngeal Squamous Cell Carcinoma with Block-Like, Partial Loss of p16 Expression.

BACKGROUND: Oropharyngeal squamous cell carcinoma is frequently associated with high-risk HPV infection, which confers a good prognosis. Immunohistochemistry for p16 is used as a surrogate for HPV status, but discrepant results are occasionally seen. Here, we report a case with a unique pattern of partial loss of p16. METHODS: A 63 year old male presented with a base of tongue nonkeratinizing squamous cell carcinoma and a large metastatic neck mass. The primary lesion and multiple regions of the metastatic mass were assessed with p16 immunohistochemistry, RNA in situ hybridization for high-risk HPV, and HPV16 genome sequencing. RESULTS: The primary lesion was p16 negative, and the metastatic neck mass had large, confluent regions that were either strongly p16 positive or entirely p16 negative. All of these regions were positive for high-risk HPV with identical HPV16 genomes. CONCLUSION: This unusual case illustrates a potential diagnostic pitfall, and it raises important questions regarding molecular mechanisms and prognostic implications of p16 staining in oropharyngeal squamous cell carcinoma.

Incidence of persistent postpartum opioid use by mode of delivery: a 2016 cohort study of Danish women.

BACKGROUND: The use of oral opioids as standard treatment after cesarean delivery has been linked to persistent use in opioid-naïve women in the USA. In Denmark, the use of opioids after cesarean delivery is typically restricted to in-hospital use. The aim of this study was to estimate the incidence of persistent postpartum opioid use in Denmark and compare the incidence by mode of delivery. METHODS: This was a national cohort study of all women giving birth in Denmark in 2016, with one-year follow-up. Data from Danish registries were retrieved and combined using each woman's unique identification number. Persistent use of opioids was defined as ≥3 redeemed opioid prescriptions 31-365 days postpartum. RESULTS: A total of 62 520 births were included in the cohort: 49 859 vaginal deliveries, 5310 intrapartum cesarean deliveries, and 7351 pre-labor cesarean deliveries. For all births, persistent postpartum opioid use occurred in 85 (140 in 100 000) women of whom 36 (42%) had opioid use during pregnancy. The incidence of persistent opioid use was highest in the pre-labor cesarean delivery cohort (n=27; 360 in 100 000) and lowest in the intrapartum cesarean delivery cohort (n=3, 60 in 100 000; P<0.001). Women taking opioids during pregnancy were at increased risk of persistent opioid use (odds ratio 63.3; 95% CI 43.9 to 91.4). CONCLUSIONS: Women giving birth in Denmark, where use of post-discharge opioid treatment is generally restricted, have a low risk of developing persistent use of opioids, with very few women seeking additional analgesic treatment from their general practitioner.

Vagal Nerve Stimulation-Modulation of the Anti-Inflammatory Response and Clinical Outcome in Psoriatic Arthritis or Ankylosing Spondylitis.

OBJECTIVES: The vagal nerve exerts an essential pathway in controlling the cholinergic anti-inflammatory reflex. Thus, the study is aimed at investigating the acute effect of a noninvasive transcutaneous vagus nerve stimulation on clinical disease activity and systemic levels of inflammation in patients with psoriatic arthritis or ankylosing spondylitis. METHODS: Twenty patients with psoriatic arthritis (PsA) and 20 patients with ankylosing spondylitis (AS) were included and stimulated bilaterally with a handheld vagal nerve stimulator for 120 seconds 3 times a day for 5 consecutive days. All patients were in remission. Cardiac vagal tone, clinical scores, CRP, and cytokine levels were assessed. RESULTS: In PsA and AS, decreased heart rate was observed, confirming compliance. Furthermore, in PsA, a clear reduction of clinical disease activity associated with a 20% reduction in CRP was shown. In AS, a reduction in interferon-γ, interleukin- (IL-) 8, and 10 was shown. No side effects were described. CONCLUSION: This open-label study provides support for an anti-inflammatory effect of transcutaneous vagus nerve stimulation in patients with psoriatic arthritis and ankylosing spondylitis. The modulated immune response and reduced disease activity and CRP-levels raise the fascinating possibility of using neuromodulation as an add-on to existing pharmacological treatments.

Prediction of preterm pre-eclampsia according to NICE and ACOG criteria: descriptive study of 597 492 Danish births from 2008 to 2017.

OBJECTIVE: The aim of this national study was to examine the incidence of preterm pre-eclampsia (PE) and the proportion of women with risk factors for PE, according to the criteria suggested by the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), during a 10-year period in Denmark. METHODS: Data from The Danish National Patient Registry and the Danish Medical Birth Registry were used to obtain the incidence of preterm PE with delivery < 37 weeks' gestation and risk factors for PE for all deliveries in Denmark from 1 January 2008 to 31 December 2017. The proportion of women with at least one high-risk factor and/or at least two moderate-risk factors for PE, according to the NICE and ACOG criteria, and the detection rate for preterm PE were examined. Race, socioeconomic status and the woman's weight at birth were not available from the registries used, and information on Type-2 diabetes was found to be invalid. RESULTS: Of the 597 492 deliveries during the study period, any PE was registered in 3.2%, preterm PE < 37 weeks in 0.7% and early-onset PE < 34 weeks' gestation in 0.3%. These proportions remained largely unchanged from 2008 to 2017. Overall, the NICE criteria were fulfilled in 7.5% of deliveries and the ACOG criteria in 17.3%. In the total population, the NICE criteria identified 47.6% of those with preterm PE and the ACOG criteria identified 60.5%. The current criteria for offering aspirin treatment in Denmark largely correspond to having at least one NICE high-risk factor. In 2017, a total of 3.5% of deliveries had at least one NICE high-risk factor, which identified 28.4% of cases that later developed preterm PE. CONCLUSIONS: The incidence of preterm PE remained largely unchanged in Denmark from 2008 to 2017. Prediction of PE according to high-risk maternal factors could be improved by addition of moderate-risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The anatomy of past abrupt warmings recorded in Greenland ice.

Data availability and temporal resolution make it challenging to unravel the anatomy (duration and temporal phasing) of the Last Glacial abrupt climate changes. Here, we address these limitations by investigating the anatomy of abrupt changes using sub-decadal-scale records from Greenland ice cores. We highlight the absence of a systematic pattern in the anatomy of abrupt changes as recorded in different ice parameters. This diversity in the sequence of changes seen in ice-core data is also observed in climate parameters derived from numerical simulations which exhibit self-sustained abrupt variability arising from internal atmosphere-ice-ocean interactions. Our analysis of two ice cores shows that the diversity of abrupt warming transitions represents variability inherent to the climate system and not archive-specific noise. Our results hint that during these abrupt events, it may not be possible to infer statistically-robust leads and lags between the different components of the climate system because of their tight coupling.

Short-term transcutaneous non-invasive vagus nerve stimulation may reduce disease activity and pro-inflammatory cytokines in rheumatoid arthritis: results of a pilot study.

Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA. Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS. Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = -0.37, p = 0.03). Overall, n-VNS was well tolerated. Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.

Long-term outcomes after perioperative treatment with omega-3 fatty acid supplements in colorectal cancer.

BACKGROUND: This study aimed to evaluate the effect of perioperative supplementation with omega-3 fatty acids (n-3 FA) on perioperative outcomes and survival in patients undergoing colorectal cancer surgery. METHODS: Patients scheduled for elective resection of colorectal cancer between 2007 and 2010 were randomized to either an n-3 FA-enriched oral nutrition supplement (ONS) twice daily or a standard ONS (control) for 7 days before and after surgery. Outcome measures, including postoperative complications, 3-year cumulative incidence of local or metastatic colorectal cancer recurrence and 5-year overall survival, were compared between the groups. RESULTS: Of 148 patients enrolled in the study, 125 (65 patients receiving n-3 FA-enriched ONS and 60 receiving standard ONS) were analysed. There were no differences in postoperative complications after surgery (P = 0·544). The risk of disease recurrence at 3 years was similar (relative risk 1·66, 95 per cent c.i. 0·65 to 4·26).The 5-year survival rate of patients treated with n-3 FA was 69·2 (95 per cent c.i. 56·5 to 78·9) per cent, compared with 81·7 (69·3 to 89·4) per cent in the control group (P = 0·193). After adjustment for age, stage of disease and adjuvant chemotherapy, n-3 FA was associated with higher mortality compared with controls (hazard ratio 1·73, 95 per cent c.i. 1·06 to 2·83; P = 0·029). The interaction between n-3 FA and adjuvant chemotherapy was not statistically significant. CONCLUSION: Perioperative supplementation with n-3 FA did not confer a survival benefit in patients undergoing colorectal cancer surgery. n-3 FA did not benefit the subgroup of patients treated with adjuvant chemotherapy or decrease the risk of disease recurrence.

ANTECEDENTES: Este estudio tuvo como objetivo evaluar el efecto de la suplementación perioperatoria con ácidos grasos omega-3 (omega-3 fatty acids, n-3 FA) sobre los resultados perioperatorios y la supervivencia en pacientes sometidos a cirugía de cáncer colorrectal (colorectal cáncer, CRC). MÉTODOS: Los pacientes programados para una resección electiva de CRC entre 2007 y 2010 fueron asignados al azar a recibir dos veces al día un suplemento nutricional oral (oral nutrition supplement, ONS) enriquecido con n-3 FA o un ONS estándar (control) durante siete días antes y después de la cirugía de CRC. Los grupos se compararon mediante análisis estadísticos. Las medidas de resultado incluyeron las complicaciones postoperatorias, la incidencia acumulada de recidivas locales o metastásicas de CCR a los 3 años y la supervivencia global a los 5 años. RESULTADOS: De 148 pacientes reclutados, se analizaron 125 pacientes (65 que recibieron el ONS enriquecido con n-3 FA y 60 que recibieron el ONS estándar). No hubo diferencias en las complicaciones postoperatorias después de la cirugía (P = 0,544). El riesgo de recidiva de la enfermedad a los 3 años no fue diferente entre los grupos (riesgo relativo, RR = 1,66; i.c. del 95% (0,65; 4,26)). La supervivencia a los 5 años para los pacientes tratados con n-3 FA fue del 69,2% (i.c. del 95% (56,5; 78,9)) en comparación con el 81,7% (i.c. del 95% (69,4; 89,4)) en el grupo control (P = 0,193). Después del ajuste por edad, estadio de la enfermedad y quimioterapia adyuvante, n-3 FA se asoció con una mayor mortalidad (cociente de riesgos instantáneos, hazard ratio, HR = 1,73; i.c. del 95% (1,05; 2,83); P = 0,029) en comparación con los controles. Sin embargo, la interacción entre n-3 FA y la quimioterapia adyuvante no fue estadísticamente significativa. CONCLUSIÓN: La suplementación perioperatoria con n-3 FA no confirió un beneficio de supervivencia en pacientes sometidos a cirugía de CRC. El n-3 FA tampoco benefició al subgrupo de pacientes tratados con quimioterapia adyuvante, ni disminuyó el riesgo de recidiva de la enfermedad.

Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group.

STUDY QUESTION: Is the risk of imprinting disorders increased in children conceived after ART? SUMMARY ANSWER: We found an adjusted odds ratio (AOR) of 2.84 [95% CI: 1.34-6.01] for Beckwith-Wiedemann syndrome in ART children, while the risk of Prader-Willi syndrome, Silver-Russell syndrome or Angelman syndrome was not increased in children conceived after ART. WHAT IS KNOWN ALREADY: Earlier studies, most of them small, have suggested an association between ART and imprinting disorders. STUDY DESIGN, SIZE, DURATION: This was a binational register-based cohort study. All children conceived by ART in Denmark (n = 45 393, born between 1994 and 2014) and in Finland (n = 29 244, born between 1990 and 2014) were identified. The full background populations born during the same time periods in the two countries were included as controls. Odds ratios of imprinting disorders in ART children compared with naturally conceived (NC) children were calculated. The median follow-up time was 8 years and 9 months for ART children and 11 years and 9 months for NC children. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the national health registries in Denmark and Finland, we identified all children diagnosed with Prader-Willi syndrome (n = 143), Silver-Russell syndrome (n = 69), Beckwith-Wiedemann syndrome (n = 105) and Angelman syndrome (n = 72) born between 1994/1990 and 2014, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a total of 388 children diagnosed with imprinting disorders; 16 of these were conceived after ART. The overall AOR for the four imprinting disorders in ART children compared with NC children was 1.35 [95% CI: 0.80-2.29], but since eight ART children were diagnosed with Beckwith-Wiedemann syndrome, the AOR for this specific imprinting disorder was 2.84 [95% CI: 1.34-6.01]. The absolute risk of Beckwith-Wiedemann syndrome in children conceived after ART was still low: 10.7 out of 100 000 newborns. The risks of Prader-Willi syndrome, Silver-Russell syndrome and Angelman syndrome were not increased in children conceived after ART. LIMITATIONS, REASONS FOR CAUTION: Imprinting disorders are rare events and our results are based on few ART children with imprinting disorders. The aetiology is complex and only partly clarified, and the clinical diagnoses are challenged by a broad phenotypic spectrum. WIDER IMPLICATIONS OF THE FINDINGS: In the existing studies, results on the risk of imprinting disorders in children conceived after ART are ambiguous. This study adds that the risk of imprinting disorders in ART children is very small and perhaps restricted to Beckwith-Wiedemann syndrome. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (grant number: 71450), the Nordic Federation of Obstetrics and Gynecology (grant numbers: NF13041, NF15058, NF16026 and NF17043) and the Interreg Öresund-Kattegat-Skagerak European Regional Development Fund (ReproUnion project). The authors have no conflicts of interest related to this work. TRIAL REGISTRATION NUMBER: N/A.

Pneumococcal antibody protection in patients with autoimmune inflammatory rheumatic diseases with varying vaccination status.

Objectives: The aims of this cross-sectional study were to assess the pneumococcal antibody coverage in patients with autoimmune inflammatory rheumatic disease (AIRD) and to identify predictors associated with inadequate protective antibody levels. Method: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIRD patients with a diagnosis of rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis attending the Department of Rheumatology at the North Denmark Regional Hospital. Immunization against pneumococcal infection was defined as a geometric mean level ≥ 1 µg antibodies/mL. Clinical information about vaccination status and disease/treatment history was retrieved from the medical file system. Results: Results of antibody measurement and vaccination status were available from 346 AIRD patients, of whom 200 (58%) were registered as receiving pneumococcal vaccination, whereas the remaining 146 patients (42%) were not. Of all 346 patients, only 61 (18%) were measured with an adequate level of protective antibodies (30% vs 1%, respectively). Methotrexate treatment at the time of vaccination and increasing age were identified as predictors of poor vaccination outcome in multiple logistic regression analysis. Conclusions: This post-vaccination study showed that less than one-fifth of the AIRD patients are adequately protected against pneumococcal infection, although the immunization programme had been implemented in more than half of the study population. Development of improved vaccination strategies is required to achieve a higher immunization coverage rate and more efficient lasting antibody response.

Cost-effectiveness of 12 weeks of supervised treatment compared to written advice in patients with knee osteoarthritis: a secondary analysis of the 2-year outcome from a randomized trial.

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA). DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost). RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY). CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.

Complications after benign hysterectomy, according to procedure: a population-based prospective cohort study from the Danish hysterectomy database, 2004-2015.

OBJECTIVE: To compare the risk of complications associated with benign hysterectomy according to surgical procedure. DESIGN: Register-based prospective cohort study. SETTING: Danish Hysterectomy Database, 2004-2015. POPULATION: All Danish women with benign elective hysterectomy (n = 51 141). METHODS: Multivariate log-binomial regression to compute relative risks (RRs) stratified by calendar period, and adjusted for age, height, weight, smoking habits, use of alcohol, comorbidity, indications, uterine weight and adhesions. Multiple imputation and 'intention to treat' analyses were performed. MAIN OUTCOME MEASURES: Major (grades III-V) and minor (grades I-II) Clavien-Dindo modified complications within 30 days. RESULTS: Overall, major complications occurred in 3577 (7.0%) hysterectomies and minor complications occurred in 4788 (9.4%). The proportions of major and minor complications according to type of hysterectomy were: 10.3 and 9.6% for abdominal hysterectomy (AH); 4.1 and 12.1% for laparoscopic hysterectomy (LH); and 4.9 and 8.0% for vaginal hysterectomy (VH) for non-prolapse, and 2.3 and 6.4% for prolapse. In multivariate analyses, compared with VH for non-prolapse, the risk of major complications was higher for AH (RR 1.82, 95% CI 1.63-2.03) but lower for both LH (RR 0.78, 95% CI 0.68-0.90) and VH for prolapse (RR 0.55; 95% CI 0.41-0.75). For LH, the risk of major complications reduced from a RR of 0.96 (95% CI 0.75-1.22) in the time period 2004-2009 to an RR of 0.72 (95% CI 0.60-0.87) between 2010 and 2015. CONCLUSION: Laparoscopic hysterectomy and VH for uterine prolapse are associated with fewer major complications, and AH is associated with more major complications, compared with VH performed in the absence of uterine prolapse. TWEETABLE ABSTRACT: Laparoscopic hysterectomy has fewer major complications compared with vaginal hysterectomy, in the absence of uterine prolapse.

Adhesive bowel obstruction: Incidence, recurrence and 30-day mortality in Danish women 1984-2013 - A national cohort study.

BACKGROUND: Adhesive bowel obstruction is a serious complication to abdominal surgery. It is unknown whether incidence and mortality rates have changed as new surgical procedures were introduced. METHODS: In a nationwide cohort of Danish women from 1984 to 2013, incidence of adhesive bowel obstruction and 30 days mortality were presented as standardized rates. Impact of treatment was analyzed by Cox regression and recurrent disease characterized by Kaplan Meyer estimates. RESULTS: Incidence of adhesive bowel obstruction increased 50% among women with no prior abdominal surgery. These women had 3-5 times lower incidence than those with a surgical record. 30-day mortality rate was 13%, highest in patients treated non-operatively. The mortality declined in recent years. Recurrent disease had lower mortality rates compared to the first episode. CONCLUSIONS: The incidence of adhesive bowel obstruction increased during the last 30 years, mortality after the first episode is high, while recurrent disease shows declining mortality rates.