Inflammatory bowel disease: new therapies from antisense oligonucleotides

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract encompassing two main clinical entities: Crohn’s disease (CD) and ulcerative colitis (UC). These disorders are characterized by various grades of tissue damage and development of local complications and extra-intestinal manifestations. The cause of IBD remains unknown but accumulating evidence indicates that both CD and UC arise in genetically predisposed individuals as a result of the action of multiple environmental factors, which ultimately trigger excessive and poorly controlled immune response against antigens of the luminal flora. Despite this realization, a full understanding of IBD pathogenesis is still out of reach and, consequently, treatment is far from optimal. However, in recent years, several pathways of intestinal damage have been delineated and the improved knowledge has contributed to the development of new therapies. Various approaches have been used to either inhibit the expression and/or function of inflammatory molecules or enhance counter-regulatory mechanisms. This review summarizes the available pre-clinical and clinical data for antisense oligonucleotides and oligonucleotide-based therapy to provide a comprehensive understanding of the rationale and mechanism of action of these compounds in IBD.

• Key messages

• Preclinical studies and clinical trials show that antisense oligonucleotide (ASO)-based therapy could be of benefit in inflammatory bowel diseases.

• ASOs have an excellent safety profile.

• Technical issues emerged from clinical trials suggest that changes in drug formulation and/or route of administration could improve ASO efficacy.

     

Rheumatologic and extraintestinal manifestations of inflammatory bowel diseases

Inflammatory bowel diseases (IBDs) often present as a complex inflammatory process wherein colon lesions (ulcerative colitis, UC) or widespread ulceration and fissure (Crohn’s disease, CD) might be accompanied by ancillary extraintestinal manifestations (EIMs) that could involve almost every organ system, but also by autoimmune disorders ranging from psoriasis and rheumatoid arthritis to connective tissue diseases. Certain EIMs are more common related to the activity of the IBD (joint, skin, ocular and oral manifestations), other EIMs typically run a course independent of the IBD activity (hepatobiliary disorders) and some are non-specific disorders (osteoporosis and amyloidosis). This paper reviews the most common extraintestinal and rheumatologic manifestations of UC and CD. They may produce greater morbidity than the underlying intestinal disease and may even be the initial presenting symptoms of the IBD. Thus, early recognition of these manifestations should help guide therapy that will reduce overall morbidity in affected patients.

• Key Message

• A complete review on the most common extraintestinal and rheumatologic manifestations of ulcerative colitis and Crohn’s disease.

     

Subclinical carotid atherosclerosis in patients with chronic obstructive pulmonary disease: a meta-analysis of literature studies

Background: Chronic obstructive pulmonary disease (COPD) patients have an increased cardiovascular (CV) morbidity and mortality. Common carotid intima-media thickness (CCA-IMT) and carotid plaques are surrogate markers of subclinical atherosclerosis and predictors of CV events.

Methods and results: We performed a meta-analysis to evaluate the association between COPD and subclinical atherosclerosis. Studies evaluating the impact of COPD on CCA-IMT and on the prevalence of carotid plaques were systematically searched.

Results: Twenty studies (2082 COPD patients and 4844 controls) were included, 12 studies with data on CCA-IMT (13 data-sets on 1180 COPD patients and 2312 controls) and 12 studies reporting on the prevalence of carotid plaques (1231 COPD patients and 4222 controls). Compared to controls, COPD patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.201?mm; 95%CI: 0.142, 0.260; p?p?Conclusions: COPD is significantly associated with subclinical atherosclerosis. These findings may be useful to plan adequate CV prevention strategies.

• Key messages

• COPD patients show a higher CCA-IMT and an increased prevalence of carotid plaques compared with controls.

• A more severe pulmonary disease is associated with a higher prevalence of carotid plaques in COPD patients.

• Screening for subclinical atherosclerosis may be worthy in COPD patients to plan specific prevention strategies.

     

Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease

Dermatitis herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased.

• Key messages

• Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent.

• Gastrointestinal symptoms and the degree of villous atrophy are less obvious in dermatitis herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients

• Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in dermatitis herpetiformis mainly B-cell lymphoma at various sites.

• Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.

     

Diabetes and new-onset atrial fibrillation in a hypertensive population

Aim The association of diabetes with new-onset atrial fibrillation (AF) remains controversial. Hypertension may partly explain the risk association ascribed to diabetes. We studied the role and characteristics of diabetes in hypertensive patients with no ischemic vascular disease.

Methods Records of 262,892 persons from the Information System for the Development of Research in Primary Care in Catalonia (Spain) were examined from July 2006 to December 2011. Included participants were?≥55-years-old and hypertensive with no ischemic heart disease, stroke, or peripheral artery disease. We used Cox proportional hazards regression to model incidences in the diabetic and non-diabetic subgroups of our population, and among diabetic patients, diabetes duration and pharmacological treatment, hemoglobin A1C, and body mass index.

Results New-onset AF incidence in diabetic patients was 13.3 per 1000 person-years (mean follow-up: 4.3 years). In non-diabetic patients, it was 10.4 per 1000 person-years (mean follow-up: 4.1 years). Diabetes hazard ratio (HR) for new-onset AF was 1.11 (95% confidence interval (CI): 1.06–1.16). Diabetic patients also diagnosed with obesity had an HR of 1.41 (95% CI: 1.22–1.64).

Conclusion Diabetes was modestly associated with new-onset AF in hypertensive patients with no ischemic vascular disease. Among diabetic patients, only obesity reached significance in its association with this arrhythmia.

• Key Messages

• Diabetes modestly associated with new-onset atrial fibrillation in hypertensive patients with no ischemic vascular disease.

• In the subgroup of patients with diabetes, only obesity reached significance in its association with atrial fibrillation.

     

Diabetic Retinopathy –Incidence And Risk Factors In A Community Setting- A Longitudinal Study

Aim: To evaluate the natural history of diabetic retinopathy (DR) in diabetic patients and to assess long term risk for other chronic diseases associated with DR.

Methods: Retrospective, community-based study. Diabetics who underwent their first fundoscopic examination during 2000–2002, and had at least one follow- up examination by the end of 2007 were included. The primary outcome was the development of DR (proliferative diabetic retinopathy (PDR), non PDR (NPDR) or macular edema.

Patients were followed for another 9 years for documentation of new diagnosis of related diseases.

Results: 516 patients' (1,032 eyes) records were included and were followed first for an average of 4.15?±?1.27 years. During follow-up, 28 (2.7%) of the total 1,032 eyes examined were diagnosed with PDR. An additional 194 (18.8%) eyes were diagnosed with new NPDR. The cumulative incidence of NPDR was 310/1,032 (30.0%). All the patients who developed PDR had prior NDPR. By the end of the 9 years extended follow up, patients with NPDR had a greater risk for developing chronic renal failure HR?=?1.71 (1.14–2.56), ischemic heart disease HR?=?1.57 (1.17–2.09), and had an increased mortality rate HR?=?1.26 (1.02–1.57)

Conclusion: DR is associated with a higher rate of diabetes complications. Patients with DR should be followed more closely.

• Key points

• During a mean follow-up of 4.5 years, the cumulative incidence of diabetic retinopathy in a community cohort was 18.8%.

• NDPR (non-proliferative diabetic retinopathy) is a predictor of PDR (proliferative diabetic retinopathy).

• In a real life setting NPDR is a marker of a poorer prognosis.

• Patients with NDPR should be monitored more closely.

     

Six-minute walking test in children

• Implications for Rehabilitation

• Six-minute walking test.

• The six-minute walking test is safe and widely performed in the world because of its easy implementation and low cost.

• Many countries have established normal values to the six-minute walking test in healthy children.

• However, the applicability of this test also gains popularity among children with other disease conditions.

     

Infliximab biosimilar CT-P13 therapy is effective and safe in maintaining remission in Crohn’s disease and ulcerative colitis – experiences from a single center

Background: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has been confirmed to be efficacious in inducing remission in inflammatory bowel diseases (IBD). The aim of this study was to evaluate the long-term efficacy and safety of CT-P13 therapy in Crohn’s disease (CD) and ulcerative colitis (UC), and to identify predictors of sustained clinical response during a 54-week CT-P13 treatment period.

Patients and methods: Patients with CD and UC, who were administered CT-P13, were prospectively enrolled. Clinical response was assessed at week 14 and week 54. Predictive factors for disease outcome at week 54 were evaluated.

Results: 57 CD and 57 UC patients were included; 55 CD and 49 UC patients completed the induction therapy and 50 CD and 46 UC patients completed the 54-week treatment period. Clinical remission was achieved in 65.5% of CD and 75.5% of UC patients at week 14. Rate of continuous clinical response was 51% in both CD and UC at week 54. None of the examined parameters were predictive to the clinical outcome neither in CD, nor in UC.

Conclusion: This study confirmed the long-term efficacy and safety of CT-P13 therapy in IBD. Response rates at week 54 were similar in CD and UC.     

Association of shift-work,daytime napping,and nighttime sleep with cancer incidence and cancer-caused mortality in Dongfeng-tongji cohort study

Background: Few studies investigated the combined effects of night-shift work, daytime napping, and nighttime sleep on cancer incidence and mortality.

Methods: A total of 25,377 participants were included in this study. Information on sleep habits, cancer incidences, and mortalities were collected. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals (HRs, 95%CIs).

Results: Male subjects experienced ≥20 years of night-shift work, or without daytime napping had an increased risk of cancer, when compared with males who did not have night-shift work or napped for 1–30?min [HR (95%CI)?=?1.27 (1.01–1.59) and 2.03 (1.01–4.13), respectively]. Nighttime sleep for ≥10?h was associated with a separate 40% and 59% increased risk of cancer [HR (95%CI)?=?1.40 (1.04–1.88)] and cancer-caused mortality [HR (95%CI)?=?1.59 (1.01–2.49)] than sleep for 7–8?h/night. Combined effects of three sleep habits were further identified. Male participants with at least two above risk sleep habits had a 43% increased risk of cancer [HR (95%CI)?=?1.43 (1.07–2.01)] and a 2.07-fold increased cancer-caused mortality [HR (95%CI)?=?2.07 (1.25–3.29)] than those who did not have any above risk sleep habits. However, no significant associations were observed among women.

Conclusions: Long night-shift work history, without daytime napping, and long nighttime sleep duration were independently and jointly associated with higher cancer incidence among males.

• KEY MESSAGES

• Night-shift work of ≥20 years, without napping, and nighttime sleep of ≥10?h were associated with increased cancer incidence.

• Nighttime sleep ≥10?h was associated with a 2.07-fold increased cancer-caused mortality among males.

• Combined effects of night-shift work ≥20 years, without napping, and nighttime sleep ≥10?h on increasing cancer incidence were existed among males.

     

Efficacy of rasagiline for the treatment of Parkinson’s disease: an updated meta-analysis

Objective: Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson’s disease (PD), both as monotherapy and combination therapy.

Methods: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson’s disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included. Outcomes were unified Parkinson’s disease rating scale (UPDRS) and the three subscales.

Results: Ten studies fulfilled the inclusion criteria and 2709 patients were evaluated. The overall analysis revealed a significant improvement in change of total UPDRS scores in 1?mg/day and 2?mg/day rasagiline groups compared to placebo. Significant improvement in Part I (Mentation) of UPDRS scores was observed in 1?mg/day, but not in 2?mg/day rasagiline treatment group. Part II (ADL) and Part III (Motor) subscales significantly improved with both doses of rasagiline. Both monotherapy and combination therapy significantly improved total UPDRS scores.

Conclusions: Our results confirm the efficacy of rasagiline in PD. Further studies are required to establish the optimal dose of rasagiline, as well as to determine its effectiveness in different combination therapy protocols.

• KEY MESSAGES

• Rasagiline treatment was associated with significant improvement of UPDRS scores and the scores of the subscales.

• Both monotherapy and combination therapy significantly improved total UPDRS scores.

• Effect of rasagiline on total UPDRS scores was not dose-dependent.

     

Urological symptoms among 23,240 men in the general danish population – concerns about symptoms,their persistence and influence on primary care contacts

Objective: To analyse possible associations between men’s likelihood of contacting a general practitioner (GP) for urological symptoms and the persistence of the symptoms, the influence on daily activities and the level of concern about the symptoms.

Design: Web-based nationwide cross-sectional questionnaire study.

Setting: The general population in Denmark.

Subjects: 48,910 randomly selected men aged 20+ years.

Main outcome measures: Urological symptom prevalence and odds ratios for GP contact with urological symptoms in regard to concern for the symptom, influence on daily activities and the persistence of the symptom.

Results: Some 23,240 men responded to the questionnaire, yielding a response rate of 49.8%. The prevalence of at least one urological symptom was 59.9%. Among men experiencing at least one urological symptom almost one-fourth reported contact to general practice regarding the symptom. Approximately half of the symptoms reported to be extremely concerning were discussed with a GP.

Conclusion: Increased symptom concern, influence on daily activities and long-term persistence increased the likelihood of contacting a GP with urological symptoms. This research points out that guidelines for PSA testing might be challenged by the high prevalence of urological symptoms.

• Key points

• ?The decision process of whether to contact the general practitioner (GP) is influenced by different factors, but contradictory results has been found in triggers and barriers for help-seeking with urological symptoms.

• ??Increased symptom concern, influence on daily activities and long-term persistence consistently increased the likelihood of contacting a general practitioner with urological symptoms in men.

• ??Only 50% of the symptoms reported to be extremely concerning were however discussed with the GP.

• ??Guidelines for PSA testing might be challenged by the high prevalence of urological symptoms.

     

Mortality in patients with atrial fibrillation and common co-morbidities – a cohort study in primary care

Objective: To study the association between cardiovascular co-morbidities and mortality risk in primary care patients with atrial fibrillation.

Methods: The study population included all adults (n?=?12,283)?≥?45 years diagnosed with AF at 75 primary care centres in Sweden between 2001 and 2007. The outcome was mortality (until 2010) and data were explored for co-morbidities using Cox regression with hazard ratios (HRs). Analyses were performed stratified by sex and by age-group (45–64, 65–74 and ≥75 years of age) with adjustment for age, socio-economic factors and relevant co-morbidities.

Results: During a mean of 5.8 years (standard deviation 2.4) of follow-up, 3954 (32%) patients died (1971 (35%) women, and 1983 (30%) men). High HRs were found for congestive heart disease (CHF) and cerebrovascular diseases for all age-groups among men and women (except for the 45–64 year old women); for coronary heart disease among the oldest men; for diabetes among the 65–74 year old men and the 45–64 year old women. Low HRs were found for hypertension among women ≥75 years of age.

Conclusions: In this clinical setting, CHF and cerebrovascular diseases were consistently associated with mortality in all age-groups. The possible protective effect by hypertension among elderly women should be interpreted with caution.

• KEY MESSAGES

• We found congestive heart failure and cerebrovascular diseases to be consistently associated with mortality in both women and men.

• We found hypertension to be associated with lower mortality risk among women ≥75 years of age, although this finding must be interpreted with caution.

• Depression was found to be associated with increased mortality risk among men and women aged 65–74 years of age.

     

Variations in older people’s use of general practitioner consultations and the relationship with mortality rate in Vantaa,Finland in 2003–2014

Abstract

Objective: It is generally expected that the growth of the older population will lead to an increase in the use of health care services. The aim was to examine the changes in the number of visits made to general practitioners (GP) by the older age groups, and whether such changes were associated with changes in mortality rates.

Design and setting: A register-based observational study in a Finnish city where a significant increase in the older population took place from 2003 to 2014. The number of GP visits made by the older population was calculated, the visits per person per year in two-year series, together with respective mortality rates.

Subjects: The study population consisted of inhabitants aged 65?years and older (65+) in Vantaa that visited a GP in primary health care.

Main outcome measures: The number of GP visits per person per year in the whole older population during the study years.

Results: In 2009–2010, there was a sudden drop in GP visits per person in the younger (65–74?years) age groups examined. In the population aged 85+, use of GP visits remained at a fairly constant level. The mortality rate decreased until the year 2008. After that, the positive trend ended and the mortality rate plateaued.

Conclusions: Simultaneously with the decline in GP visits per person in the older population, the mortality rate leveled off from its positive trend in 2009–2010. Factors identified being associated with the number of GP consultations were organizational changes in primary health care, economic recession causing retrenchment, and even vaccinations during the swine flu epidemic.

• Key points

• Along with an increasingly ageing population, concern over the supply of publicly funded health care has become more pronounced.

• The amount of GP visits of 65+ decreased in primary health care, especially in the youngest groups.

• However, in the oldest age groups (85+), the use of GPs remained unchanged regardless of changes in service supply.

• As the rate of GP visits among the population of 65+ declined, the positive trend in the mortality rate ceased.

     

Atopic dermatitis,asthma and allergic rhinitis in general practice and the open population: a systematic review

Objective: To examine whether significant differences exist between the self-reported prevalence of atopic disorders in the open population compared with physician diagnosed prevalence of atopic disorders in general practice. Methods: Medline (OvidSP), PubMed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed for articles providing data on the prevalence of asthma, allergic rhinitis and eczema in a GP setting. Studies were only included when they had a cross-sectional or cohort design and included more than 100 children (aged 0-18 years) in a general practice setting. All ISAAC studies (i.e. the open population) that geographically matched a study selected from the first search, were also included. A quality assessment was conducted. The primary outcome measures were prevalence of eczema, asthma and allergic rhinitis in children aged 0-18 years. Results: The overall quality of the included studies was good. The annual and lifetime prevalences of the atopic disorders varied greatly in both general practice and the open population. On average, the prevalence of atopic disorders was higher in the open population. Conclusion: There are significant differences between the self-reported prevalence of atopic disorders in the open population compared with physician diagnosed prevalence of atopic disorders in general practice. Data obtained in the open population cannot simply be extrapolated to the general practice setting. This should be taken into account when considering a research topic or requirements for policy development. GPs should be aware of the possible misclassification of allergic disorders in their practice.

• Key Points

• Epidemiological data on atopic disorders in children can be obtained from various sources, each having its own advantages and limitations.

• On average, the prevalence of atopic disorders is higher in the open population.

• GPs should take into account the possible misclassification of atopic disorders in their practice population.

• Policymakers should be aware that data obtained in the open population cannot simply be extrapolated to the general practice setting.

     

Exercise cardiac power and the risk of coronary heart disease and cardiovascular mortality in men

Purpose: The aim of this study was to examine the relationship of exercise cardiac power (ECP), defined as a ratio of directly measured maximal oxygen uptake with peak systolic blood pressure during exercise, with the risk of mortality from coronary heart diseases (CHD) and cardiovascular diseases (CVD).

Design: Population-based cohort study with an average follow-up of 25 years from eastern Finland. About 2358 men at baseline participated in exercise stress test and 182 CHD and 302 CVD deaths occurred.

Results: Men with low ECP (16.4?mL/mmHg, highest quartile) after adjusting for age and examination year. Low ECP was associated with a 2.8-fold risk of CHD and 2.4-fold for CVD mortality after additional adjustment for conventional risk factors. After further adjustment for leisure time physical activity, the results hardly changed (HR 2.5, 95% CI 1.71–3.67, p?Conclusion: ECP provides non-invasive and easily available measure for the prediction of CHD and CVD mortality. One of the most potential explanation for the association between ECP and the risk of CHD and CVD mortality is an elevated afterload and peripheral resistance indicated by hypertension.

• Key messages

• Index of exercise cardiac power defined as the ratio of directly measured maximal oxygen uptake (VO_2max) with peak systolic blood pressure gives prognostic information in coronary heart disease (CHD) and CVD mortality risk stratification.

• ECP provides non-invasive and easily available measure for the prediction of CHD and CVD mortality.

• One of the most potential explanation for the association between ECP and the risk of CHD and CVD mortality is an elevated afterload and peripheral resistance indicated by hypertension.

     

“The complaining women”: health professionals’ perceptions on patients with fibromyalgia in Spain

Purpose: The aim of this study is twofold: (1) to explore health service providers’ perceptions regarding fibromyalgia patients in Spain and (2) to analyze possible consequences of these perceptions in terms of how health service providers construct the disease and treat their patients.

Design: Qualitative study.

Subjects/Patients: Twelve health service providers (eight men, four women) involved in the care of fibromyalgia patients. Providers were from different disciplines and included general practitioners, rheumatologists, occupational doctors, psychologists, psychiatrists, physiotherapists and behavioral specialists from Spain.

Method: We performed individual semistructured interviews, which were recorded and transcribed to conduct a qualitative content analysis supported by Atlas.ti-7.

Results: We identified three categories from the interviews: (1) the fibromyalgia patient prototype: the complaining woman, (2) fibromyalgia is considered a women’s health issue, but male patients are a privileged minority, and (3) health professionals’ attitudes toward fibromyalgia patients: are they really suffering or pretending?

Conclusion: The uncertainty surrounding fibromyalgia together with the fact that those affected are primarily women, seem to influence professional practice in terms of lack of recognition of Fibromyalgia as a severe disease. Increased training of all health professionals is essential to improving the support and attention given to patients suffering from fibromyalgia.

• Implications for rehabilitation

• Fibromyalgia

• ??In order to improve fibromyalgia patients´ attention, health providers should learn how to assist patients without prejudices.

• ??Training programs for health providers should include sensitization about the severity of fibromyalgia.

• ??Health providers should be aware of the existence of stereotypes about women suffering from fibromyalgia.

• ??Fibromyalgia protocols should give skills to health providers to avoid offering a gender-biased attention to patients.

     

Erroneous computer-based interpretations of atrial fibrillation and atrial flutter in a Swedish primary health care setting

Abstract

Objective: To describe the incidence of incorrect computerized ECG interpretations of atrial fibrillation or atrial flutter in a Swedish primary care population, the rate of correction of computer misinterpretations, and the consequences of misdiagnosis.

Design: Retrospective expert re-analysis of ECGs with a computer-suggested diagnosis of atrial fibrillation or atrial flutter.

Setting: Primary health care in Region Kronoberg, Sweden.

Subjects: All adult patients who had an ECG recorded between January 2016 and June 2016 with a computer statement including the words ‘atrial fibrillation’ or ‘atrial flutter’.

Main outcome measures: Number of incorrect computer interpretations of atrial fibrillation or atrial flutter; rate of correction by the interpreting primary care physician; consequences of misdiagnosis of atrial fibrillation or atrial flutter.

Results: Among 988 ECGs with a computer diagnosis of atrial fibrillation or atrial flutter, 89 (9.0%) were incorrect, among which 36 were not corrected by the interpreting physician. In 12 cases, misdiagnosed atrial fibrillation/flutter led to inappropriate treatment with anticoagulant therapy. A larger proportion of atrial flutters, 27 out of 80 (34%), than atrial fibrillations, 62 out of 908 (7%), were incorrectly diagnosed by the computer.

Conclusions: Among ECGs with a computer-based diagnosis of atrial fibrillation or atrial flutter, the diagnosis was incorrect in almost 10%. In almost half of the cases, the misdiagnosis was not corrected by the overreading primary-care physician. Twelve patients received inappropriate anticoagulant treatment as a result of misdiagnosis.

• Key points

• Data regarding the incidence of misdiagnosed atrial fibrillation or atrial flutter in primary care are lacking. In a Swedish primary care setting, computer-based ECG interpretations of atrial fibrillation or atrial flutter were incorrect in 89 of 988 (9.0%) consecutive cases.

• Incorrect computer diagnoses of atrial fibrillation or atrial flutter were not corrected by the primary-care physician in 47% of cases.

• In 12 of the cases with an incorrect computer rhythm diagnosis, misdiagnosed atrial fibrillation or flutter led to inappropriate treatment with anticoagulant therapy.

     

Association of daylight saving time transitions with incidence and in-hospital mortality of myocardial infarction in Finland

Introduction Circadian rhythm disturbance increases cardiovascular risk but the effects of daylight saving time (DST) transitions on the risk of myocardial infarction (MI) are unclear.

Methods We studied association of DST transitions in 2001–2009 with incidence and in-hospital mortality of MI admissions nationwide in Finland. Incidence rations (IR) of observed incidences on seven days following DST transition were compared to expected incidences.

Results Incidence of MI increased on Wednesday (IR 1.16; CI 1.01–1.34) after spring transition (6298 patients’ cohort). After autumn transition (8161 patients’ cohort), MI incidence decreased on Monday (IR 0.85; CI 0.74–0.97) but increased on Thursday (IR 1.15; CI 1.02–1.30). The overall incidence of MI during the week after each DST transition did not differ from control weeks. Patient age or gender, type of MI or in-hospital mortality were not associated with transitions. Renal insufficiency was more common among MI patients after spring transition (OR 1.81; CI 1.06–3.09; p?p?=?0.007), but more common after autumn transition (OR 1.21; 1.00–1.46; p?Conclusions DST transitions are followed by changes in the temporal pattern but not the overall rate of MI incidence. Comorbidities may modulate the effects DST transitions.

• KEY MESSAGES

• Both spring and autumn daylight saving time transitions changed the temporal occurrence pattern but not the overall incidence of myocardial infarction occurrence on the week following the clock shift.

• The age or gender distribution of patients, ratio of different types of myocardial infarctions or in-hospital mortality were not affected by clock shifts.

• The effect of daylight saving time transitions on MI incidence may be modified by the presence of diabetes.