Trends in low-density lipoprotein cholesterol goal achievement and changes in lipid-lowering therapy after incident atherosclerotic cardiovascular disease: Danish cohort study.

BACKGROUND: We aimed to investigate trends in low-density lipoprotein cholesterol (LDL-C) goal achievement (LDL-C<1.8 mmol/L, equivalent to 70 mg/dL), initiation of lipid-lowering therapy (LLT) and changes in LLT intensity in individuals with atherosclerotic cardiovascular disease (ASCVD) at very high risk of recurrent cardiovascular disease. METHODS: A cohort study design was used including individuals with incident ASCVD and LDL-C≥1.8 mmol/L in 2010-2015. Data were obtained from national, population-based registers (patient, prescription, income, and laboratory). RESULTS: We included 11,997 individuals. Acute myocardial infarction, ischemic stroke and stable angina pectoris accounted for 79.6% of the qualifying ASCVD events. At inclusion, 37.2% were in LLT. Mean LDL-C before or during ASCVD hospitalization was 3.1 mmol/L (120 mg/dL). LDL-C goal achievement increased within the first two years after inclusion from 40.5% to 50.6%. LLT initiation within the first 90 days increased from 48.6% to 56.0%. Initiation of intensive LLT increased from 9.6% to 32.8%. The largest change in LLT intensity was seen in the period 180 days before to 90 days after discharge with 2.2% in 2010 to 12.1% in 2015. CONCLUSION: LDL-C goal achievement within the first 2 years after inclusion increased from 40.5% in 2010 to 50.6% in 2015. LLT initiation within the first year after inclusion increased, especially for intensive LLT, although only one third initiated intensive LLT in 2015. Despite trends show improvements in LDL-C goal achievement, 49.4% of individuals at very high risk of a CV event did not achieve the LDL-C goal within 2 years after ASCVD hospitalization.

Risk of severe COVID-19 infection in persons with diabetes during the first and second waves in Denmark: A nationwide cohort study.

Objective: Coronavirus disease-2019 (COVID-19) increases risk of hospitalization and death in diabetes and diabetes-related conditions. We examined the temporal trends in COVID-19-related hospitalization and mortality in the total Danish population by diabetes and diabetes-related conditions in the two first waves of COVID-19 in Denmark. Materials and methods: We identified all persons with diabetes in the whole Danish population using national registries. COVID-19-related risks of hospitalization and death were assessed using Cox regression analysis in wave 1 (1 March-31 August 2020) and wave 2 (1 September 2020-28 February 2021) of the pandemic for persons with (n=321,933) and without diabetes (n=5,479,755). Analyses were stratified according to status of hypertension, obesity, cardiovascular and microvascular disease. Results: The cumulative incidence of COVID-19 hospitalization increased from wave 1 to wave 2 in both persons without (from 4 to 10 in 10,000) and with diabetes (from 16 to 54 per 10,000). The relative risk of hospitalization, however, increased more in patients with diabetes compared to persons without (age-, sex- and co-morbidity-adjusted HR [aHR] 1.40 (95% CI 1.27, 1.55) versus 1.76 (1.65, 1.87), p<0.001 for interaction with wave). The mortality rate, according to the whole population, increased similarly in persons without and with diabetes from wave 1 to wave 2 (from 0.63 to 1.5 versus from 4.3 to 10 in 10,000; aHR 1.65; 1.34, 2.03 and 1.64; 1.43, 1.88). However, when mortality was restricted to the hospitalized population, the crude mortality fell from 26.8% to 19.6% in persons with diabetes, while only a minor decrease was seen in persons without diabetes (from 16.7% to 15.5%). Conclusion: The risk of COVID-19-related hospitalization increased more in persons with than without diabetes from wave 1 to wave 2 of the COVID-19 pandemic in the Danish population. However, mortality according to the whole population did not change, due to reduced mortality among hospitalized persons with diabetes.

Clinical procedures used to diagnose inflammatory bowel disease: real-world evidence from a Danish nationwide population-based study.

OBJECTIVE: Although clinical guidelines exist, the diagnostic work-up for diagnosing inflammatory bowel disease (IBD) is complex and varies in clinical practice. This study used real-life data to characterise the current diagnostic procedures used to establish IBD diagnoses in a Danish nationwide setting. DESIGN: Person-level data on patients diagnosed with IBD between 1 January 2014 and 30 June 2018 were linked between Danish health registers. Information on age, sex, registration of other gastrointestinal diseases, and diagnostic procedures (endoscopies, biopsies, and imaging) performed in relation to the first IBD hospital admission was analysed for the total study population and was stratified by IBD type, sex, and age. RESULTS: The majority of the 12 871 patients with IBD included underwent endoscopy (84%), had a biopsy taken (84%), and/or underwent imaging procedures (44%). In total, 7.5% of the population (6% for Crohn's disease and 8% for ulcerative colitis) were diagnosed with IBD despite not undergoing any of these diagnostic procedures. Patients with Crohn's disease underwent more procedures than patients with ulcerative colitis (94% vs 92%, p<0.001). Children underwent slightly fewer diagnostic procedures than adults (92% vs 93%, p=0.004). Slightly more men underwent at least one procedure than women (92% vs 94%, p<0.001). CONCLUSION: For 7.5% of patients with IBD, this study did not detect any registrations of the recommended diagnostic procedures for establishing an IBD diagnosis. Further research is needed to examine whether these findings are mainly explained by limitations of the register data or also indicate shortcomings of the general approach to IBD.

Type 1 diabetes in 2017: global estimates of incident and prevalent cases in children and adults.

AIMS/HYPOTHESIS: Data on type 1 diabetes incidence and prevalence are limited, particularly for adults. This study aims to estimate global numbers of incident and prevalent cases of type 1 diabetes in 2017 for all age groups, by country and areas defined by income and region. METHODS: Incidence rates of type 1 diabetes in children (available from 94 countries) from the IDF Atlas were used and extrapolated to countries without data. Age-specific incidence rates in adults (only known across full age range for fewer than ten countries) were obtained by applying scaling ratios for each adult age group relative to the incidence rate in children. Age-specific incidence rates were applied to population estimates to obtain incident case numbers. Duration of diabetes was estimated from available data and adjusted using differences in childhood mortality rate between countries from United Nations demographic data. Prevalent case numbers were derived by modelling the relationship between prevalence, incidence and disease duration. Sensitivity analyses were performed to quantify the impact of alternative assumptions and model inputs. RESULTS: Global numbers of incident and prevalent cases of type 1 diabetes were estimated to be 234,710 and 9,004,610, respectively, in 2017. High-income countries, with 17% of the global population, accounted for 49% of global incident cases and 52% of prevalent cases. Asia, which has the largest proportion of the world's population (60%), had the largest number of incident (32%) and prevalent (31%) cases of type 1 diabetes. Globally, 6%, 35%, 43% and 16% of prevalent cases were in the age groups 0-14, 15-39, 40-64 and 65+ years, respectively. Based on sensitivity analyses, the estimates could deviate by ±15%. CONCLUSIONS/INTERPRETATION: Globally, type 1 diabetes represents about 2% of the estimated total cases of diabetes, ranging from less than 1% in certain Pacific countries to more than 15% in Northern European populations in 2017. This study provides information for the development of healthcare and policy approaches to manage type 1 diabetes. The estimates need further validation due to limitations and assumptions related to data availability and estimation methods.

Forecasting lung cancer incidence, mortality, and prevalence to year 2030.

BACKGROUND: Lung cancer incidence and prevalence is increasing worldwide and there is a focus on prevention, early detection, and development of new treatments which will impact the epidemiological patterns of lung cancer. The clinical characteristics and the trends in incidence, mortality, and prevalence of lung cancer in Denmark from 2006 through 2015 are described and a model for predicting the future epidemiological profile of lung cancer through 2030 is introduced. METHODS: The study population comprised all cases of lung cancer, registered in the Danish Cancer Registry, who were alive on January 1, 2006 or had a first-time ever diagnosis of lung cancer during 2006 through 2015. Information on morphology, stage of the disease, comorbidity and survival was obtained from other Danish health registers. Based on NORDCAN data and estimated patient mortality rates as well as prevalence proportions for the period 2006 through 2015, future case numbers of annual incidence, deaths, and resulting prevalence were projected. RESULTS: A total of 44.291 patients were included in the study. A shift towards more patients diagnosed with lower stages and with adenocarcinoma was observed. The incidence increased and the patient mortality rate decreased significantly, with a doubling of the prevalence during the observation period. We project that the numbers of prevalent cases of lung cancer in Denmark most likely will increase from about 10,000 at the end of 2015 to about 23,000 at the end of 2030. CONCLUSIONS: Our findings support that lung cancer is being diagnosed at an earlier stage, that incidence will stop increasing, that mortality will decrease further, and that the prevalence will continue to increase substantially. Projections of cancer incidence, mortality, and prevalence are important for planning health services and should be updated at regular intervals.

End-of-life anticancer treatment - a nationwide registry-based study of trends in the use of chemo-, endocrine, immune-, and targeted therapies.

BACKGROUND: Anticancer treatments near the end of a patient's life should generally be avoided, as it leaves the patient with no significant anticancer effect but increases the risk of severe side effects. We described the pattern of all end-of-life anticancer treatment in a population of Danish cancer patients. METHODS: Using the Danish national health registries, we identified all patients deceased due to cancer 2010-2015. Anticancer treatment registered in the last 30 days of life was categorized as end-of-life treatment. Predictors of such treatment were investigated using logistic regression models. RESULTS: We identified 42,277 patients (median age 70 years) of whom 16% received end-of-life anticancer treatment. This proportion did not change during the study period (p = .09). Chemotherapy alone was the most frequent treatment, accounting for 78% of all end-of-life treatment in 2010, decreasing to 71% in 2015. In contrast, end-of-life use of immunotherapy, targeted therapy and endocrine therapy increased during the study period. Breast cancer as index cancer was associated with the highest frequency of end-of-life treatment (23%), followed by malignant melanoma (21%), and prostate cancer (18%). Factors associated with lower odds for end-of-life treatment were female sex, older age, high burden of comorbidity, and being diagnosed >6 months prior to death. CONCLUSIONS: We found a stable overall rate at 16% of patients receiving anticancer treatment within one month prior to death in this nationwide sample of cancer deaths. Further research is needed to assess whether this level of end-of-life treatment is justified or reflects inappropriate use.

Chronic Inflammatory Diseases - Diabetes Mellitus, Rheumatoid Arthritis, Coeliac Disease, Crohn's Disease, and Ulcerative Colitis Among the Offspring of Affected Parents: A Danish Population-Based Registry Study.

BACKGROUND: Chronic inflammatory diseases (CIDs) may share aetiological factors across diseases. We used registry data to evaluate the risk of developing five common childhood CIDs dependent on the parents' disease status. METHODS: We performed a national population-based registry study by linking data from the national Danish health registers from January 1973 to March 2016 to evaluate any potential associations between parents' disease and development of CIDs among the offspring. Results were adjusted for parental age at birth, the decade of birth, gender of the child, and type of birth. A cohort of 2,699,449 liveborn children was established for investigating the primary outcome measures: diabetes mellitus (DM), rheumatoid arthritis (RA), coeliac disease, Crohn's disease (CD), and ulcerative colitis (UC) and all diseases combined (CID). RESULTS: Children with one CID affected parent (Hazard ratio (HR), 95% confidence interval (95% CI)=1.75 (1.72-1.79, p<0.001)), one multiple CID affected parent (HR=2.23 (2.11-2.34), p<0.001), and both parents affected (HR=3.10 (2.98-3.22), p<0.001) were at higher risk than children without CID affected parents. Children with DM, RA, and COE affected parents were at increased risk of three specific diseases (DM, RA and COE), whereas children with CD and UC affected parents were at increased risk of two specific diseases (CD and UC). CONCLUSION: Children with CID affected parents were at increased risk of the same CID as their parents as well as other specific CIDs dependent on the parents' CID. Future studies should address the aetiology underlying these findings to support the development of new strategies for prevention, treatment, and cure.

Primary care visits can reduce the risk of potentially avoidable hospitalizations among persons with diabetes in France.

BACKGROUND: Diabetes is a frequent chronic condition, which can lead to costly complications if not managed well in the primary care setting. Potentially avoidable hospitalizations (PAH) are considered as an indirect measure of primary care. However, the association between primary care use and PAH in diabetic patients has not been investigated in France. METHODS: We investigate the association between primary care indicators and PAH at an individual level among persons with diabetes in a population-based cohort study on the French national health insurance database (EGB sample). PAH occurrence in 2013 was modeled as a function of primary care use and access, health status and socio-economic indicators over the exposure period 2011-12 using a cause-specific hazards model with death as a competing event. RESULTS: We included 25 293 diabetics in our cohort, among which 385 (1.5%) experienced at least 1 PAH in 2013. After adjustment on health status indicators, primary care use had a protective effect against PAH. Diabetic patients who had seen a general practitioner (GP) 10-14 times had a reduced hazard of PAH compared to less frequent encounters (HR=0.49, P<0.001). The effect size decreased when the number of encounters increased, suggesting a remaining confounding effect of health status. CONCLUSIONS: For the first time in France, this study shows a protective effect of the number of GP encounters against PAH at an individual level and highlights the importance of a frequent monitoring of diabetic patients in the primary care setting to prevent PAH occurrence.

Lipid-lowering therapy and low-density lipoprotein cholesterol goal attainment after acute coronary syndrome: a Danish population-based cohort study.

BACKGROUND: Patients with acute coronary syndrome (ACS) are at high risk of recurrent cardiovascular (CV) event. The European guidelines recommend low-density lipoprotein cholesterol (LDL-C) levels < 1.8 mmol/L and early initiation of intensive lipid-lowering therapy (LLT) to reduce CV risk. In order to reduce the risk of further cardiac events, the study aimed to evaluate LDL-C goal attainment and LLT intensity in an incident ACS population. METHODS: A cohort study of patients with residency at Funen in Denmark at a first-ever ACS event registered within the period 2010-2015. Information on LLT use and LDL-C levels was extracted from national population registers and a Laboratory database at Odense University Hospital. Treatments and lipid patterns were evaluated during index hospitalization, at 6-month and 12-month follow-up. RESULTS: Among 3040 patients with an LDL-C measurement during index hospitalization, 40.7 and 39.0% attained the recommended LDL-C target value (< 1.8 mmol/L) within 6- and 12-month follow-up, respectively. During 6- and 12-month follow-up, a total of 89.2% (20.2%) and 88.4% (29.7%) used LLT (intensive LLT). Of the intensive LLT users, 43.4 and 47.7% reached the LDL-C target value at 6- and 12-month follow-up. The frequency of lipid monitoring was low: 69.5, 77.7 and 53.6% in patients with a first-ever ACS during index hospitalization, 6- and 12-month follow-up, respectively. CONCLUSION: Using national health registers and laboratory data, a considerably gap was observed between treatment guidelines and clinical practice in the management of dyslipidemia leaving very high-risk patients without adequate lipid management strategy. Therefore, improved lipid management strategies aimed at reaching treatment targets are warranted.

Serum vitamin K1 associated to microangiopathy and/or macroangiopathy in individuals with and without diabetes.

OBJECTIVE: Vitamin K has proposed beneficial effects on cardiovascular health. We investigated whether serum vitamin K1 was associated with prevalence of microangiopathy and/or macroangiopathy. RESEARCH DESIGN AND METHODS: Serum vitamin K was quantified in 3239 individuals with and 3808 without diabetes enrolled in Vejle Diabetes Biobank (2007-2010). Each individual was assessed for microangiography and macroangiopathy at enrollment based on registered diagnoses in the Danish National Patient Registry according to the International Classification of Disease 8 (1977-1993) and 10 (since 1994). Using multinomial logistic regression, relative risk ratios (RRRs) were calculated within each group of individuals with and without diabetes. RRRs were estimated for microangiopathic/macroangiopathic status compared with individuals without complications as a function of 1 nmol/L increments in K1. Adjustment for potential confounders was also performed. RESULTS: Vitamin K1 (median) varied 0.86-0.95 nmol/L depending on diabetes, microangiopathic and macroangiopathic status. In individuals with diabetes, the crude RRR for only having microangiopathy was 1.05 (95% CI 0.98 to 1.12) and was found significant when adjusting 1.10 (95% CI 1.01 to 1.19). RRR for having only macroangiopathy was 0.89 (95% CI 0.77 to 1.03) and was again significant when adjusting 0.79 (95% CI 0.66 to 0.96). In individuals without diabetes, adjustments again led to similar estimates that was not significant. The adjusted RRR for having only macroangiopathy was 1.08 (95% CI 0.98 to 1.19). CONCLUSIONS: Serum vitamin K1 levels were associated with microangiopathic and macroangiopathic status in individuals with diabetes, but considered of no clinical relevance. The clinical value of other candidate markers for vitamin K status needs to be evaluated in future studies.

Caesarean Delivery and Risk of Chronic Inflammatory Diseases (Inflammatory Bowel Disease, Rheumatoid Arthritis, Coeliac Disease, and Diabetes Mellitus): A Population Based Registry Study of 2,699,479 Births in Denmark During 1973-2016.

BACKGROUND: Chronic inflammatory diseases in childhood and early adult life share aetiological factors operating from birth and onwards. In this study, we use data from the national Danish health registers to evaluate the risk of developing four common, immune-mediated hospital-diagnosed childhood chronic inflammatory diseases. METHODS: A national population-based registry study. Data from the Danish Medical Birth Registry and the Danish National Patient Registry from January 1973 to March 2016 were linked at a personal level to evaluate any potential associations between caesarean section and development of Inflammatory bowel diseases, rheumatoid arthritis, coeliac disease and diabetes mellitus among the offspring. A model adjusted for parental age at birth, decade of birth, gender of child, and parents' chronic inflammatory disease status was used. RESULTS: This register-based national cohort study of 2672708 children with information on delivery mode found an increased risk of diabetes, arthritis, coeliac disease, and inflammatory bowel disease for both girls and boys after caesarean section compared with vaginal delivery. The higher risk was present at least 40 years after delivery. In a subgroup analysis, both acute and elective caesarean section was associated with an increased risk of developing a chronic inflammatory disease. CONCLUSIONS: Being born by caesarean section leads to increased host susceptibility for chronic inflammatory diseases that last for decades. This finding should be further addressed in future studies with the aim to support the development of new strategies for prevention, treatment, and maybe even cure.

Characteristics of finasteride users in comparison with nonusers: A Nordic nationwide study based on individual-level data from Denmark, Finland, and Sweden.

PURPOSE: Published epidemiological studies on the association between finasteride use and the risk of male breast cancer have been inconclusive due to methodological limitations including a few male breast cancer cases included. Determinants of male breast cancer have been studied, but it remains unexplored whether these are also related to finasteride use and thereby constitute potential confounders. This study aimed to assess whether there are differences between finasteride users and nonusers with regard to numerous potential confounders. METHODS: In total, 246 508 finasteride users (≥35 years) were identified in the prescription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). An equal number of nonusers were sampled. The directed acyclic graph (DAG) methodology was used to identify potential confounders for the association between finasteride and male breast cancer. A logistic regression model compared finasteride users and nonusers with regard to potential confounders that were measurable in registries and population surveys. RESULTS: Finasteride users had higher odds of testicular abnormalities (odds ratio [OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exogenous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabetes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry or in high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), living in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70; 0.50-0.99) compared to nonusers. CONCLUSIONS: Systematic differences between finasteride users and nonusers were found emphasizing the importance of confounder adjustment of associations between finasteride and male breast cancer.

Long-Term Outcome of Patients Operated with Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment.

PURPOSE: To determine the long-term outcome of patients operated with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD) and to identify potential predictors for poor visual outcome. METHODS: Prospective, observational 30-month study of patients operated for primary RRD with PPV. Examinations were performed preoperatively and after months 2, 6, and 30. RESULTS: Eighty-four patients (84 eyes) were included and 73 (86.9%) participated at month 30. The macula was attached in 30 (35.7%) patients at primary operation. The majority of patients (n = 59, 80.8%) achieved a good final best corrected visual acuity (BCVA ≤0.3 logMAR, ≥0.5 Snellen) with a better outcome in patients with the macula attached than detached (0.02 vs. 0.17 logMAR, p = 0.007). Variables associated with poor visual outcome were baseline BCVA >0.3 logMAR (p = 0.03), female gender (p = 0.02), silicone oil (p = 0.03), and larger areas of retinal detachment (p = 0.01). In multivariable regression analysis, female gender (OR = 8.5 [95% CI 1.8-39.8]) was the strongest risk factor for poor visual outcome. CONCLUSION: The majority of patients operated for primary RRD achieved a reasonable long-term visual outcome. Notably, female gender was associated with poor visual outcome, indicating a need for closer follow-up.

Finasteride Use and Risk of Male Breast Cancer: A Case-Control Study Using Individual-Level Registry Data from Denmark, Finland, and Sweden.

BACKGROUND: In case reports, concerns have been raised as to whether finasteride use increases the risk of male breast cancer. Previous epidemiologic evidence on the potential link is conflicting. This study aimed to assess whether an association between finasteride use and male breast cancer exists after accounting for potential confounders. METHODS: The source population consisted of all men (≥35 years) from Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). Cases with incident male breast cancer were identified in the cancer registries and matched with 50 density-sampled, age, and country-matched male population controls per case. Exposure information on finasteride use was derived from the prescription registries. Potential confounders were identified using the directed acyclic graph methodology and measured by use of information from nation-wide registries. RESULTS: The study population comprised 1,005 male breast cancer cases and 43,058 controls. Confounder-adjusted odds of finasteride exposure were not statistically significantly increased [OR, 1.09; 95% confidence interval (CI), 0.77-1.54] in breast cancer cases relative to controls. There was no evidence of a dose-response relationship, as the group with greatest exposure to finasteride was associated with lowest OR of male breast cancer [OR, 0.72 (95% CI, 0.40-1.30)]. Sensitivity analyses did not reveal marked changes in results with different exposure definitions or for specific subgroups. CONCLUSIONS: Results from this study provided no evidence that finasteride use was associated with male breast cancer. IMPACT: This large confounder-adjusted study supports the view that exposure to finasteride is not associated materially with male breast cancer risk.

Patient reported outcome data as performance indicators in surgically treated lung cancer patients.

OBJECTIVE: Quality in lung cancer care is in Denmark routinely evaluated using quality indicators. The indicators are reported from national registries and are based on data from health care professionals. However, data based on the patients' perspective are rarely reported. The aim of this study was to propose a model for the use of patient reported outcomes (PROs) as quality indicators, enabling us to compare PROs across the surgical departments in Denmark. METHODS: All patients registered in the Danish Lung Cancer Registry (DLCR) from 1 October 2013 until 30 September 2015 who received surgical treatment were eligible (N = 1718). They were asked to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire six months after surgery. From QLQ-C30 we chose global health status (GHS) and role function (RF) as indicators to be tested. An indicator threshold for good performance was set to ≥ 65 points (on a scale 0-100 where 100 was the best). Results were compared between the four thoracic surgical departments in Denmark. RESULTS: Of 1615 patients alive six months after surgery, questionnaires were completed by 1002 patients (62.0%). The patients from the four departments differed significantly in clinical variables at diagnosis, and the departments differed significantly in the surgical procedures performed. After adjustment for case-mix, the patients in Department 2 had a better RF than patients from the other departments. CONCLUSION: Significant differences in RF and in the fulfilment of the indicator requirement for RF were observed. Since these findings might indicate differences in the quality of performance between participating departments, subsequent audit is recommended. The analyses and results indicate that it is feasible to use PROs as supplementary outcome indicators in the evaluation of the quality of surgical treatment for lung cancer. Our model could serve as a useful foundation for further research.

Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease.

BACKGROUND: Anti-tumor necrosis factor-α (TNF-α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti-TNF therapy among patients with CD or UC. AIM: A new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti-TNF response. METHODS: Fifty-three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender). RESULTS: Ten SNPs were associated with anti-TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02-3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00-1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02-1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33-0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24-4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27-0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06-2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44-0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01-2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65-0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01-1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57-0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66-1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04)). CONCLUSIONS: The results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF-α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti-TNF therapy. Our multi-SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.

Patient-reported outcomes (PROs) in lung cancer: Experiences from a nationwide feasibility study.

OBJECTIVES: Our objectives were to examine the feasibility of a nationwide collection of patient-reported outcomes (PROs) in a lung cancer population as well as in various sub-populations, and to describe the characteristics of responders compared to non-responders. MATERIALS AND METHODS: All patients diagnosed with lung cancer in Denmark are registered in the Danish Lung Cancer Registry (DLCR). The 7,295 patients registered in DLCR from 1 October 2013 until 30 September 2015 who had received treatment were eligible. Using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 questionnaires, we employed two different methods of delivery, resulting in two different project parts. In project part 1, the baseline questionnaire was handed out at the hospital departments before treatment. The following questionnaires were sent out as paper versions three times within one year. In project part 2, all questionnaires were electronic versions delivered in association with planned hospital visits. RESULTS: Of the 7,295 lung cancer patients 4,229 (58%) completed at least one questionnaire, and 2,459 completed two or more. Only 562 baseline questionnaires were returned before treatment (7.7%), whereas 43.4%-57.4% of the potential responders completed the following questionnaires. The best response rates were achieved among patients treated with surgery and among patients who discussed their questionnaires with health care personnel. When comparing patient characteristics, responders had a significantly better health and a higher socioeconomic position than non-responders. CONCLUSION: A decentralised model used for delivering the initial questionnaire to the patients was insufficient. It is our estimation that sending out electronic versions of the baseline questionnaires, as was done with the following questionnaires, would result in a significantly better patient coverage. Despite the severe morbidity and high mortality rate in lung cancer, reasonable response rates were achieved at follow-ups to this method, and PRO collection in this population was feasible.

Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.