The diagnostic trajectories of Danish patients with autoimmune rheumatologic disease associated interstitial lung disease: an interview-based study.

Background: Autoimmune rheumatologic disease associated interstitial lung diseases (ARD-ILD) are rare conditions and the association between ARDs and respiratory symptoms often goes unrecognised by ARD patients and general practitioners (GPs). The diagnostic trajectory from the first respiratory symptoms to an ARD-ILD diagnosis is often delayed and may increase the burden of symptoms and allow further disease progression.The aim of this study was to 1) characterise the diagnostic trajectories of ARD-ILD patients and to 2) identify barriers for obtaining a timely ILD diagnosis based on the experiences and perceptions of both patients and healthcare professionals. Method: Semi-structured qualitative interviews were conducted with Danish ARD-ILD patients, rheumatologists, pulmonologists and ILD nurses. Results: Sixteen patients, six rheumatologists, three ILD nurses and three pulmonologists participated. Five characteristics of diagnostic trajectories were identified in the patient interviews: 1) early referral to lung specialists; 2) early delay; 3) delay or shortcut depending on specific circumstances; 4) parallel diagnostic trajectories connected late in the process; 5) early identification of lung involvement without proper interpretation. With the exception of early referral to lung specialists, all of the diagnostic trajectory characteristics identified led to delayed diagnosis. Delayed diagnostic trajectories resulted in patients experiencing increased uncertainty. Inconsistent disease terminology, insufficient knowledge and lack of awareness of ARD-ILD among central healthcare professionals and delayed referral to ILD specialists were main contributors to the diagnostic delay identified by the informants. Conclusion: Five characteristics of the diagnostic trajectories were identified, four of which led to diagnostic delay of ARD-ILD. Improved diagnostic trajectories can shorten the diagnostic trajectory and increase early access to appropriate specialist medical care. Improved awareness and expertise in ARD-ILD across different medical specialties, especially among GPs, may contribute to more efficient and timely diagnostic trajectories and improved patient experiences.

Tibial plateau fractures are associated with a long-lasting increased risk of total knee arthroplasty a matched cohort study of 7,950 tibial plateau fractures.

OBJECTIVE: This study aims to investigate the risk of total knee replacement (TKR) following tibia plateau fractures. Secondary the study aims to investigate the risk of knee arthroscopy following tibial plateau fractures. METHOD: The study was designed as a matched cohort study. All patients who sustained a tibial plateau fracture in Denmark between January 1, 1996, and December 31, 2000, were included and followed until December 31, 2015. For each patient with a tibial plateau fracture, 10 matched citizens without a tibial plateau fracture were included as a reference group. RESULTS: 7,950 patients sustained a tibial plateau fracture in Denmark during the study period. The median age of patients was 52.6 (IQR: 32.4-71.5) years. The mean observational period was 13.9 years. 5.7% were treated with a TKR (N = 452), and 2.0% of patients from the reference group were treated with a TKR (N = 1,623). Patients with a tibial plateau fracture had a 3.5 (95%CI: 3.1-3.9) times higher hazard ratio (HR) compared to patients from the reference group. 7.6% of patients with a tibial plateau fracture were treated with a secondary knee arthroscopy (N = 603) and 2.0% of patients from the reference group were treated with a knee arthroscopy (N = 1,565). Patients with a tibial plateau fracture presented with a 5.0 (95%CI: 4.5-5.6)) times higher HR compared to patients in the reference group. CONCLUSIONS: Tibial plateau fractures are associated with a 3.5 times increased risk of TKR compared with an age- and gender-matched reference group with a mean follow-up of 13.9 years.

Patellar fractures are associated with an increased risk of total knee arthroplasty: A Matched Cohort Study of 6096 Patellar Fractures with a mean follow-up of 14.3 Years.

AIMS: The aim of this study was to investigate the incidence of knee arthroplasty and arthroscopy following patellar fractures, and to compare this with an age- and gender-matched group without a prior patellar fracture. PATIENTS AND METHODS: A national matched cohort study based on the Danish National Patient Register including all citizens of Denmark (approximately 5.3 million) was undertaken. A total of 6096 patients who sustained a patellar fracture in Denmark between 1 January 1996 and 31 December 2000 were included. The median age of these patients was 50.6 years (interquartile range (IQR) 28.5 to 68.9); 49.1% were women. Patients were followed-up until 31 December 2015, with regard to treatment with knee arthroplasty and/or knee arthroscopy. RESULTS: Patients with a patellar fracture had an increased risk of knee arthroplasty (hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.57 to 2.13) compared with citizens without a patellar fracture, and the effect was strongest during the first five years (HR 3.02, 95% CI 2.26 to 4.03). Patients with a patellar fracture also had a higher risk of knee arthroscopy (HR 3.94, 95% CI 3.49 to 4.46), and the effect was highest during the first five years after the fracture (HR 7.40, 95% CI 6.32 to 8.66). CONCLUSION: Patellar fractures are associated with an increased risk of knee arthroplasty and knee arthroscopy. The consequences of a patellar fracture may be more severe than previously considered, and patients must expect a lifelong increased risk of knee arthroplasty. Cite this article: Bone Joint J 2018;100-B:1477-81.

Nucleophilic fluorination facilitated by a CsF-CaF2 packed bed reactor in continuous flow.

A simple to prepare, dry and handle packed bed reactor carrying CsF on CaF2, towards nucleophilic fluorinations in continuous flow, is reported. The reactor also proved adaptable for silyl-ether deprotection and trifluoromethylations with Ruppert's reagent. The study includes reactor stability and scale-up investigations.

Beneficial effect of n-3 polyunsaturated fatty acids on inflammation and analgesic use in psoriatic arthritis: a randomized, double blind, placebo-controlled trial.

OBJECTIVE: This study aimed to investigate the effects of marine n-3 polyunsaturated fatty acids (PUFAs) on disease activity, use of analgesics, and inflammatory biomarkers in patients with psoriatic arthritis (PsA). METHOD: Patients with established PsA (n = 145) were investigated in a randomized, double-blind, placebo-controlled study. The participants received a supplement of 3 g n-3 PUFA/day or 3 g olive oil/day (control) for 24 weeks. Outcome measures for disease activity, use of analgesics, and leukotriene formation from activated granulocytes were assessed at baseline and at study end. RESULTS: In total, 145 patients were included and 133 completed the study. After 24 weeks, the n-3 PUFA group showed a decrease in Disease Activity Score (DAS28-CRP), 68 tender joint count, enthesitis score, and psoriasis area and severity index, although not significantly different from the controls. There was a significant reduction in non-steroidal anti-inflammatory drug (NSAID) and paracetamol use compared with controls (p = 0.04). In addition, the participants in the n-3 PUFA group had significantly lower formation of leukotriene B4 (p = 0.004) from stimulated granulocytes and significantly higher formation of leukotriene B5 (p < 0.001) compared with controls. CONCLUSION: The n-3 PUFA-supplemented group showed improvement in outcome measures for disease activity, although the difference between the groups was not statistically significant. However, use of NSAIDs and paracetamol was significantly reduced in the n-3 PUFA group compared to the control group. Finally, there was a significant decrease in leukotriene B4 formation in the n-3 PUFA group compared with controls.

Mortality in elderly ICU patients: a cohort study.

BACKGROUND: The population is aging. We examined changes in the proportion of elderly (≥ 80 years) intensive care unit (ICU) patients during 2005-2011 and the association between age and mortality controlling for preexisting morbidity. METHODS: Through the Danish National Patient Registry, we identified a cohort of 49,938 ICU admissions (47,596 patients) in Northern Denmark from 2005 to 2011. Patients were subdivided in age groups (15-49, 50-64, 65-79 and ≥ 80 years) and calendar year. We estimated 30-day and 31-365-day mortality and mortality rate ratios (MRRs), stratified by admission type (medical and elective/acute surgical patients). Mortality was compared between age groups adjusting for sex and preexisting morbidity using 50-64-year-olds as reference. RESULTS: The proportion of elderly patients increased from 11.7% of all ICU patients in 2005 to 13.8% in 2011. Among the elderly, the 30-day mortality was 43.7% in medical, 39.6% in acute surgical, and 11.6% in elective surgical ICU patients. The corresponding adjusted 30-day MRRs compared with the 50-64-year-olds were 2.7 [95% confidence interval (CI) 2.5-3.0] in medical, 2.7 (95% CI 2.4-3.0) in acute surgical, and 5.2 (95% CI 4.1-6.6) in elective surgical ICU patients. The 31-365-day mortality among elderly patients was 25.4% in medical, 26.9% in acute, and 11.9% in elective surgical ICU patients, corresponding to adjusted MRRs of 2.5 (95% CI 2.1-2.9), 2.2 (95% CI 1.9-2.5), and 1.9 (95% CI 1.6-2.3), respectively. CONCLUSIONS: During 2005-2011, there was an 18% increase in the proportion of elderly ICU patients. Advancing age is associated with increased mortality even after controlling for preexisting morbidity.

Effects of an expressive writing intervention on cancer-related distress in Danish breast cancer survivors - results from a nationwide randomized clinical trial.

OBJECTIVE: To examine the effects of an expressive writing intervention (EWI) on cancer-related distress, depressive symptoms, and mood in women treated for early stage breast cancer. METHODS: A nationwide sample of 507 Danish women who had recently completed treatment for primary breast cancer were randomly assigned to three 20-min home-based writing exercises, one week apart, focusing on either emotional disclosure (EWI group) or a non-emotional topic (control group). Cancer-related distress [Impact of Event Scale (IES)], depressive symptoms (Beck Depression Inventory-Short Form), and negative (37-item Profile of Moods State) and positive mood (Passive Positive Mood Scale) were assessed at baseline and at 3 and 9 months post-intervention. Choice of writing topic (cancer versus other), alexithymia (20-item Toronto Alexithymia Scale), and social constraints (Social Constraints Scale) were included as possible moderators. RESULTS: Significant (p<0.01) group differences in mood change from before to immediately after each session suggested successful manipulation. Reductions over time in psychological symptoms were seen in both groups (p<0.05), but no time × group interactions were found. Choice of writing topic moderated effects on IES, with women writing about other themes showing greater reductions in cancer-related avoidance than women writing about their cancer. Fewer depressive symptoms and higher levels of positive mood were seen 3 months post-intervention in women writing about their cancer when compared with the control group. Difficulties describing feelings and externally oriented thinking (20-item Toronto Alexithymia Scale) moderated effects on positive mood and IES-total, while no moderating effects were found of social constraints. CONCLUSIONS: In concordance with the majority of previous results with cancer patients, no main effects of EWI were found for cancer-related distress, depressive symptoms, and mood. Moderator analyses suggested that choice of writing topic and ability to process emotional experiences should be studied further.

Quality of ICD-10 colorectal cancer diagnosis codes in the Danish National Registry of Patients.

This study examined the quality of International Classification of Diseases-10 colorectal cancer (CRC) diagnosis coding in the Danish National Registry of Patients (DNRP), using the Danish Cancer Registry (DCR) as a reference. We included all patients in Denmark with a CRC diagnosis in the DNRP and/or in the DCR from 2001 through 2006. Data quality was evaluated by estimating completeness and positive predictive value (PPV) of data in different subcategories of patients. We estimated mortality and date of diagnosis, to evaluate the effect of potential differences in data quality. Overall completeness of data in the DNRP for CRC was 93.4% [95% confidence interval (CI): 93.1-93.7] and the PPV was 88.9% (95% CI: 88.5-89.2). Completeness and PPV improved during the study period. However, the completeness of data for patients >75 years in the 2001-2003 period [88.8% (95% CI: 87.8-89.6)] was lower than average, and cancers in more unspecific locations and cancers in the colorectal junction also had lower estimates (below 90%). There were no differences in survival estimates in the DNRP compared to the DCR. In conclusion, this study shows high CRC data quality in the DNRP measured by completeness and PPV, except in a few subgroups.

Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation.

BACKGROUND: Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel. AIM: To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) with stent implantation, using time-varying drug exposure ascertainment. METHODS: We conducted this population-based cohort study in Western Denmark (population 3 million) using medical databases. We identified all 13,001 patients with coronary stent implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12-month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders. RESULTS: During follow-up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non-use was 0.57 [95% confidence interval (CI): 0.44-0.74] among PPI users and 0.47 (95% CI: 0.42-0.53) among PPI non-users, yielding an interaction effect (i.e. relative rate increase) of 1.20 (95% CI: 0.91-1.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non-users, independent of clopidogrel use [adjusted HR = 1.24 (95% CI: 0.97-1.58) for clopidogrel users and 1.26 (95% CI: 0.97-1.63) for clopidogrel non-users]. CONCLUSIONS: The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention.

The impact of pre-admission morbidity level on 3-year mortality after intensive care: a Danish cohort study.

BACKGROUND: Chronic diseases are common among intensive care unit (ICU) patients and may worsen their prognosis. We examined the prevalence and impact of pre-admission/index morbidity among ICU patients compared with a general population cohort. METHODS: Our study encompassed all 28,172 adult patients admitted to ICUs in northern Denmark in 2005-2007 and 281,671 age- and sex-matched individuals from the general population. We used a nationwide hospital registry to obtain a 5-year history of 19 chronic diseases and computed Charlson Comorbidity Index (CCI) for each study participant and grouped them into low (CCI=0), moderate (CCI=1-2), and high (CCI=3+) morbidity levels. We computed mortality and mortality rate ratios (MRRs) adjusted for confounders, and compared the mortality between ICU patients and the general population cohort. RESULTS: Low, moderate, and high pre-admission morbidity levels were present in 51.5%, 34.1%, and 14.4% of ICU patients, respectively. In these groups, 30-day mortality was 10.8%, 18.4%, and 26.7%, respectively. Three-year mortality was 21.3%, 43.1%, and 63.2%, respectively. The adjusted 30-day MRR was 1.30 [95% confidence intervals (CI): 1.21-1.39] and 1.86 (95% CI: 1.71-2.01) for ICU patients with moderate and high morbidity levels, both compared with a low morbidity level. The general population had a lower morbidity level and mortality at all morbidity levels throughout the study period. Interaction between ICU admission and high morbidity level added 5.1% to the mortality during the second and third year of follow-up. CONCLUSION: A high pre-admission morbidity level was frequent among ICU patients and associated with a worsened prognosis. Morbidity had more impact on mortality among ICU patients compared with a general population cohort.

Antiplatelet drugs and risk of subarachnoid hemorrhage: a population-based case-control study.

SUMMARY BACKGROUND: Antiplatelet drug use increases bleeding risk, but its role in precipitating subarachnoid hemorrhage remains unclear. OBJECTIVES: We examined whether the use of low-dose acetylsalicylic acid (LDA), clopidogrel or dipyridamole increased the risk of subarachnoid hemorrhage. PATIENTS/METHODS: This population-based case-control study was conducted in northern Denmark. We used the Danish National Patient Registry to identify all persons admitted to neurosurgery or neurology departments with a first diagnosis of subarachnoid hemorrhage between 1997 and 2008 (n = 1186). Using risk-set sampling, we selected 10 population controls (n = 11 840) for each case, matched by age and sex. We obtained data on prescriptions for antiplatelet drugs, use of other medications and comorbidity from medical databases. We used conditional logistic regression to compute odds ratios with 95% confidence intervals (CIs), controlling for confounding factors. RESULTS: One hundred and nine cases (9.2%) and 910 controls (7.7%) used antiplatelet drugs. Among cases, 104 (8.8%) used LDA and 11 (0.9%) used dipyridamole. Among controls, 891 (7.5%) used LDA and 48 (0.4%) used dipyridamole. As compared with not using any antiplatelet drugs during the study period, the adjusted odds ratios were 1.03 (95% CI 0.81-1.32) for long-term LDA use, 2.52 (95% CI 1.37-4.62) for new LDA use, and 2.09 (95% CI 1.04-4.23) for long-term dipyridamole use. Owing to the low number of users, data were inconclusive for clopidogrel. CONCLUSIONS: Long-term dipyridamole use and new LDA use were associated with an increased risk of subarachnoid hemorrhage. Because of the limited precision of these risk estimates, however, caution is advised in their interpretation. Long-term LDA use was not associated with subarachnoid hemorrhage.

Methotrexate compliance among patients with rheumatoid arthritis: the influence of disease activity, disease duration, and co-morbidity in a 10-year longitudinal study.

OBJECTIVE: To assess methotrexate (MTX) compliance among rheumatoid arthritis (RA) patients. METHODS: Using prescription data, we conducted a 10-year longitudinal study among RA patients who were first-time MTX users. MTX compliance was expressed as the continuous measure of medication gaps (CMG), that is the proportion of treatment gaps compared with the total observation period stratified by age, sex, C-reactive protein (CRP), haemoglobin, co-morbidity, concurrent medication, and disease duration. Multiple linear regression analysis was used to assess the influence of disease activity, disease duration, and co-morbidity on compliance. RESULTS: A total of 941 RA patients redeemed 7501 MTX prescriptions during our study period. Overall, the patients had gaps in 12.3% of the observation period corresponding to a mean period not covered with MTX of 1.5 months/year if all participants were followed for 1 year. Patients with CRP > 32 mg/L had a lower mean CMG than patients with CRP < 8 mg/L [adjusted CMG difference -0.04, 95% confidence interval (CI) -0.07 to - 0.02]. Patients with a disease duration < 1 year had a lower mean CMG than patients with a disease duration between 1 and 5 years (adjusted CMG difference 0.01, 95% CI -0.01 to 0.04). Patients with a diagnosis of ulcer/mild liver disease had a higher mean CMG than patients without this diagnosis (adjusted CMG difference 0.04, 95% CI 0.004-0.084). CONCLUSION: MTX compliance was generally high among RA patients. Compliance decreased with increasing disease duration, low to moderate disease activity, and the presence of a diagnosis of ulcer/mild liver disease.

End-cretaceous brachiopod extinctions in the chalk of denmark.

The results of a detailed study of the brachiopods of the most complete Cretaceous-Tertiary boundary in Denmark, Nye Klslashed circlev, show an extinction pattern for this marine invertebrate group compatible with that reported for pelagic foraminifera and coccoliths and with the impact scenario. The extinction is abrupt, coinciding with the Maastrichtian-Danian boundary. There is no warning in the form of decreasing density, decreasing diversity, or early extinction of specialized groups. The basal few meters of the Danian are almost devoid of brachiopods, and a Danian brachiopod fauna starts almost as abruptly as the Maastrichtian fauna disappeared. The new fauna is similar to the Maastrichtian as regards density and diversity, and at maximum six species are common to both stages. The northwest European Masstrichtian chalk is composed mainly of the remains of coccoliths and pelagic foraminifera. The mass extinction of these groups led to a total cessation of chalk production. The chalk is overlain by a thin clay bed deposited partly under anoxic conditions. This combination of anoxia and clay deposition coupled with a cessation of productivity led to the extinction of specialized groups such as the chalk brachiopods. The surviving species included forms that could survive in well-aerated shallow marine waters on substrates other than chalk.