Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study.

OBJECTIVE: To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism. DESIGN: Nationwide cohort study. SETTING: Denmark through national registries. PARTICIPANTS: All 15-49 year old women living in Denmark between 1996 and 2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment (n=2 029 065). MAIN OUTCOME MEASURE: A first time discharge diagnosis of lower limb deep venous thrombosis or pulmonary embolism. RESULTS: Among 2.0 million women followed for 21.0 million person years, 8710 venous thromboembolic events occurred. Compared with non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 7.2 (95% confidence interval 6.0 to 8.5) in women not using hormonal contraception, 11.0 (9.6 to 12.6) in women using high risk hormonal contraception, 7.9 (5.9 to 10.6) in those using medium risk hormonal contraception, and 4.5 (2.6 to 8.1) in users of low/no risk hormonal contraception. The corresponding numbers of extra venous thromboembolic events per 100 000 women over the first week of NSAID treatment compared with non-use of NSAIDs were 4 (3 to 5) in women not using hormonal contraception, 23 (19 to 27) in women using high risk hormonal contraception, 11 (7 to 15) in those using medium risk hormonal contraception, and 3 (0 to 5) in users of low/no risk hormonal contraception. CONCLUSIONS: NSAID use was positively associated with the development of venous thromboembolism in women of reproductive age. The number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception. Women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly.

Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition.

OBJECTIVE: To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). DESIGN: Nested case-control study. SETTING: The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520,000 participants from 10 western European countries. PARTICIPANTS: 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. MAIN OUTCOME MEASURES: Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. RESULTS: After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. CONCLUSIONS: These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.

Topical anaesthesia in strabismus surgery for Graves' orbitopathy: a comparative study of 111 patients.

PURPOSE: To evaluate the tolerability and usability of topical anaesthesia in single rectus muscle recession for strabismus caused by Graves' orbitopathy (GO). To compare the perioperative pain score and surgical outcome between GO patients and non-GO patients. METHODS: A retrospective comparative study of consecutive single rectus muscle recession performed under topical anaesthesia was carried out. All patients scheduled for one-stage single rectus muscle recession under topical anaesthesia were included. Numerical visual analogue pain score scale (NVAS) points, rates of motor success (horizontal deviation < 8 prism diopters (PD) and vertical deviation ≤ 6 PD) and sensory success (no diplopia without prisms), complications and postoperative adjustment frequencies were compared between GO and non-GO patients. RESULTS: A total of 111 patients were included. The mean perioperative pain scores were 2.3 (SD ± 1.3) in GO and 1.6 (SD ± 1.1) in non-GO patients (p = 0.06 adjusted for gender). The postoperative mean alignments in GO and non-GO patients were 2 versus 3 PD horizontally and 1 versus 1 PD vertically respectively. Both motor and sensory success rates were 98% in GO patients and 94% versus 93% in non-GO patients. Adjustments as a second procedure the day after surgery was performed in 10% of the GO patients and 15% of the non-GO patients. The oculocardiac reflex was not triggered in any of the GO patients. CONCLUSION: Topical anaesthesia in single muscle recession for GO is safe, well-tolerated and gives comparable surgical outcomes to those achieved in non-GO patients.

Nationwide Incidence of Thyroid Eye Disease and Cumulative Incidence of Strabismus and Surgical Interventions in Denmark.

Importance: Thyroid eye disease (TED) is a serious condition that can cause proptosis and strabismus and, in rare cases, lead to blindness. Incidence data for TED and strabismus and surgical interventions after TED are sparce. Objective: To investigate the nationwide incidence of TED, strabismus, and surgical interventions associated with TED. Design, Setting, and Participants: A Danish nationwide registry-based cohort study between 2000, which marks the beginning of uniform coding for the decompression surgery nationwide, and 2018. The cohort consisted of a mean 4.3 million people aged 18 to 100 years with no prior TED diagnosis each year. Total observation time was 8.22 × 107 person-years (women, 4.18 × 107 person-years; men, 4.04 × 107 person-years). Main Outcome Measures: The annual numeric and age-standardized incidence of hospital-treated TED and cumulative incidence of strabismus, strabismus surgery, and orbital decompression surgery in patients with TED. The incidence was stratified by sex, thyroid diagnosis, and age. Results: A total of 4106 incident diagnoses of TED were identified during 19 years among 3344 women (81.4%) and 762 men (18.6%). The mean numeric annual nationwide incidence rate of TED was 5.0 per 100 000 person-years overall, 8.0 per 100 000 person-years in women, and 1.9 per 100 000 person-years in men, resulting in a 4:1 ratio of women to men with TED. The age-standardized incidence was similar. The mean (SD) age at onset was 51.3 (14.5) years. At the time of TED diagnosis, 611 patients (14.9%) were euthyroid, 477 (11.6%) were hypothyroid, and 3018 (73.5%) were hyperthyroid. In patients with TED who were euthyroid, the 4-year cumulative incidence was 41% for antithyroid medication and 13% for L-thyroxine. In patients with TED, the 4-year cumulative incidence for strabismus was 10%. The 4-year cumulative incidence of surgical interventions after TED was 8% for strabismus surgery and 5% for orbital decompression. At 4 years, strabismus surgery was more common in men (13.3%; 95% CI, 10.75-15.86) than in women (7.2%; 95% CI, 6.24-8.08), and the absolute difference was 6.1% (95% CI, 3.42-8.14; P < .001). Conclusions and Relevance: This study in Denmark provides nationwide empirical incidence of TED and strabismus and surgical interventions after TED that required inpatient or outpatient hospital treatment, and might be used for patient information and health care planning.

Assessing absolute stroke risk in patients with atrial fibrillation using a risk factor-based approach.

AIM: To assess the risk of stroke and thromboembolism in patients with atrial fibrillation (AF) based on risk factor combinations of the CHA2DS2-VASc score. METHODS AND RESULTS: Using nationwide Danish registries, patients with AF were included from 1997 to 2015 in this retrospective observational study. A multiple logistic regression, including interactions of history of stroke with age at AF, calendar year of AF, and the CHA2DS2-VASc score risk factors (congestive heart failure, hypertension, diabetes, vascular disease, and female sex) were used to predict the personalized risks of stroke within 1 year. A total of 147 842 patients with AF were included in the study cohort (median age 76 years, range 20-100 years, 51% females). Within the first year, 6% of the cohort were diagnosed with stroke. The predicted personalized 1-year absolute risk of stroke varied widely within each CHA2DS2-VASc score. To estimate the personalized risk of stroke an online calculator was created, the Calculator of Absolute Stroke Risk (CARS), which allows calculation of all the possible combinations of the CHA2DS2-VASc score (https://hjerteforeningen.shinyapps.io/riskvisrr/). CONCLUSION: Calculation of the individual risk using a risk factor-based approach as opposed to using average risk for a particular CHA2DS2-VASc score can improve risk estimates. Furthermore, CARS can assist in the communication of the stroke risk for a more evidence-based shared decision-making of whether to initiate oral anticoagulation therapy.

Correlation between retinal vein occlusion and cancer - a nationwide Danish cohort study.

PURPOSE: To explore the association between retinal vein occlusion (RVO) and incident cancer. METHODS: All Danish citizens with a first-time diagnosis of RVO and no previous diagnosis of cancer in the period from 1 January 2004 to 31 December 2014 were included. Five likewise cancer-free, age- and gender-matched controls were included in a control cohort. All were followed up for 5 years or until either first diagnosis of cancer or death. Proportional hazards models with adjustment for age, gender, year of diagnosis and covariates and death as competing risk were used to estimate the risk of being diagnosed with cancer. RESULTS: There were 7963 RVO patients without cancer at the time of diagnosis, and all could be matched to likewise cancer-free controls. Half of RVO patients were male, and the median age at RVO diagnosis was 70 years (61-79). The control cohort was similar in terms of gender and age. The risk of cancer within 1 year was 1.8 among RVO patients and 1.5 among controls. The crude risk of cancer was 1.22 (1.11;1.34) and upon full adjustment 1.15 (1.05;1.27). No time dependency was detected, and the types of cancer developed in RVO patients and controls were similar. CONCLUSION: Retinal vein occlusion (RVO) diagnosis is associated with an increased risk of being diagnosed with cancer. This risk is likely to reflect shared risk factors rather than a causal association.

Trends in assisted ventilation and outcome for obstructive pulmonary disease exacerbations. A nationwide study.

BACKGROUND: Non-invasive ventilation (NIV) has been used for decades in treatment of exacerbations of chronic obstructive pulmonary disease (COPD). The impact of the changing use of assisted ventilation in acute exacerbations on outcomes has not been fully elucidated and we aimed to describe these changes in the Danish population and describe their consequences for mortality. METHODS: A register-based study was conducted of a cohort of 12,847 patients admitted for acute exacerbation of COPD (AECOPD) from 2004 through 2011, treated with invasive mechanical ventilation (IMV) or NIV for the first time. Age, sex, in-hospital mortality rates, time to death or readmission for AECOPD were established and changes over time tracked. RESULTS: The number of admissions for AECOPD where assisted ventilation was used was 1,130 in 2004 and had increased by 145% in 2011. First time ventilations increased by 88%. This was mainly due to an increase in use of NIV accounting for 36% of the total number of assisted ventilations in 2004 and 67% in 2011. The number of IMV with or without NIV treatments remained constant. The mean age of NIV patients increased from 71.5 to 73.6 years, but remained constant at 70.0 years in IMV patients. Mortality rates both in hospital and after discharge for patients receiving NIV remained constant throughout the period. In-hospital mortality following IMV increased from 30% to 38%, but mortality after discharge remained stable. CONCLUSION: Assisted ventilation has been increasingly used in a broader spectrum of AECOPD patients since the introduction of NIV. The changes in treatment strategies have been followed by shifts in in-hospital mortality rates following IMV.

Assisted ventilation in COPD - association between previous hospitalizations and mortality.

BACKGROUND: In general, previous studies have shown an association between prior exacerbations and mortality in COPD, but this association has not been demonstrated in the subpopulation of patients in need of assisted ventilation. We examined whether previous hospitalizations were independently associated with mortality among patients with COPD ventilated for the first time. PATIENTS AND METHODS: In the Danish National Patient Registry, we established a cohort of patients with COPD ventilated for the first time from 2003 to 2011 and previously medicated for obstructive airway diseases. We assessed the number of hospitalizations for COPD in the preceding year, age, sex, comorbidity, mode of ventilation, survival to discharge, and days to death beyond discharge. RESULTS: The cohort consisted of 6,656 patients of whom 66% had not been hospitalized for COPD in the previous year, 18% once, 8% twice, and 9% thrice or more. In-hospital mortality was 45%, and of the patients alive at discharge, 11% died within a month and 39% within a year. In multivariate models, adjusted for age, sex, mode of ventilation, and comorbidity, odds ratios for in-hospital death were 1.26 (95% confidence interval [CI]: 1.11-1.44), 1.43 (95% CI: 1.19-1.72), and 1.56 (95% CI: 1.30-1.87) with one, two, and three or more hospitalizations, respectively. Hazard ratios for death after discharge from hospital were 1.32 (95% CI: 1.19-1.46), 1.76 (95% CI: 1.52-2.02), and 2.07 (95% CI: 1.80-2.38) with one, two, and three or more hospitalizations, respectively. CONCLUSION: Preceding hospitalizations for COPD are associated with in-hospital mortality and after discharge in the subpopulation of patients with COPD with acute exacerbation treated with assisted ventilation for the first time.

Association between hemoglobin and prognosis in patients admitted to hospital for COPD.

Low concentrations of hemoglobin have previously been demonstrated in many patients with COPD. There is evidence of anemia as a prognostic factor in acute exacerbations, but the detailed relationship between concentrations of hemoglobin and mortality is not known. A register-based cohort of patients admitted for the first time to Danish hospitals for acute exacerbations of COPD from 2007 through 2012 was established. Age, sex, comorbidities, medication, renal function, and concentrations of hemoglobin were retrieved. Sex-specific survival analyses were fitted for different rounded concentrations of hemoglobin. The cohort encompassed 6,969 patients. Hemoglobin below 130 g/L was present in 39% of males and below 120 g/L in 24% of females. The in-hospital mortality rates for patients with hemoglobin below or above these limits were 11.6% and 5.4%, respectively. After discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22-1.73), adjusted HR 1.37 (95% CI 1.15-1.64). Compared to hemoglobin 120 g/L, the HR for females with hemoglobin 110 g/L was 1.4 (95% CI 1.17-1.68), adjusted HR 1.28 (95% CI 1.06-1.53). In conclusion, low concentrations of hemoglobin are frequent in COPD patients with acute exacerbations, and predict long-term mortality.

Prehospital treatment with continuous positive airway pressure in patients with acute respiratory failure: a regional observational study.

BACKGROUND: Patients with acute respiratory failure are at risk of deterioration during prehospital transport. Ventilatory support with continuous positive airway pressure (CPAP) can be initiated in the prehospital setting. The objective of the study is to evaluate adherence to treatment and effectiveness of CPAP as an addition to standard care. METHODS: In North Denmark Region, patients with acute respiratory failure, whom paramedics assessed as suffering from acute cardiopulmonary oedema, acute exacerbation of chronic obstructive pulmonary disease or asthma were treated with CPAP using 100 % O2 from 1 March 2014 to 3 May 2015. Adherence to treatment was evaluated by number of adverse events and discontinuation of treatment. Intensive care admissions and mortality were reported in this cohort. Effectiveness was evaluated by changes in peripheral oxygen saturation (SpO2) and respiratory rate during transport and compared to a historical control (non-CPAP) group treated with standard care only. Values were compared by hypothesis testing and linear modelling of SpO2 on arrival at scene and ΔSpO2 stratified according to treatment group. RESULTS: In fourteen months, 171 patients were treated with CPAP (mean treatment time 35 ± 18 min). Adverse events were reported in 15 patients (9 %), hereof six discontinued CPAP due to hypotension, nausea or worsening dyspnoea. One serious adverse event was reported, a suspected pneumothorax treated adequately by an anaesthesiologist called from a mobile emergency care unit. Among CPAP patients, 45 (27 %) were admitted to an intensive care unit and 24 (14 %) died before hospital discharge. The non-CPAP group consisted of 739 patients. From arrival at scene to arrival at hospital, CPAP patients had a larger increase in SpO2 than non-CPAP patients (87 to 96 % versus 92 to 96 %, p < 0.01) and a larger decrease in respiratory rate (32 to 25 versus 28 to 24 breaths/min, p < 0.01). In a linear model, CPAP was superior to non-CPAP in patients with initial SpO2 ≤90 % (p < 0.05). One CPAP patient (0.6 %) and eight non-CPAP patients (1.1 %) were intubated in the prehospital setting. DISCUSSION: The study design reflects the daily prehospital working environment including long transport timesand paramedics educated in treating symptoms of acute respiratory failure, rather than treating one specific diagnosis. The study population was included consecutively and few patients were lost to follow-up. However, the study was too small to allow assessment of any effect of prehospital CPAP on mortality, nor could the effectiveness in specific disease conditions be examined. CONCLUSIONS: In an emergency medical service including physician backup, adherence to CPAP treatment administered by paramedics was high and treatment was effective in patients with acute respiratory failure.

[Statins can maybe reduce the risk of venous thromboembolism]. / Statiner kan måske reducere risikoen for venøs tromboemboli.

Recent reports suggest beneficial effects of statin treatment on risk of venous thromboembolism (VTE). This review studies the existing literature on statins and VTE: one meta-analysis, one randomized controlled trial, four cohort studies and eight case-control studies. The hypothesis of a risk reducing effect of statins on recurrent VTE is supported, but the included studies are heterogeneous; and there is a risk of uncontrolled confounding. Randomized clinical trials aimed at clarifying whether statins can prevent recurrent VTE or not are warranted.