Effectiveness of antiplatelet therapy in atherosclerotic disease: comparing the ASA low-response prevalence in CVD,CAD and PAD

Although acetylsalicylic acid (ASA, aspirin) reduces the risk of ischemic events in patients with atherosclerosis, a substantial number of incidents continue to occur. As only limited data exist we evaluated the antiplatelet effectiveness of ASA in patients with different manifestations of atherosclerosis as in cerebrovascular, coronary artery and peripheral arterial disease (CVD, CAD, PAD). For the evaluation of the antiplatelet effectiveness of ASA we used whole blood aggregometry (Chrono-log Model 590). The patients in the different subgroups received ASA 100, 200 or 500 mg daily. We analysed 737 consecutive patients: 47.5 % with CVD, 33.6 % with CAD, and 18.9 % with PAD. We identified 28.0 % of the CVD, 18.1 % of the CAD and 21.6 % of the PAD patients to be ASA low-responder (ALR). Comparing subgroups treated with 100 mg ASA, 36.4 % were ALR in the CVD group as were 13.1 % of the CAD and 21.6 % of the PAD patients. Multivariate regression analysis revealed an odds ratio for being ALR of 4.50 (95 % confidence interval (CI) 1.70–11.9) when 100 mg and of 2.97 (95 % CI 1.58–5.60) when 200 mg ASA was taken compared to a dose of 500 mg. Despite the proven benefits of antiplatelet therapy in the secondary prevention of atherosclerotic disease, current antiplatelet management is suboptimal as up to 36 % of patients failed to achieve an adequate platelet inhibitory effect. Our findings may explain, at least in part, the high rates of cardiovascular events observed in the course of atherothrombotic disease and support the need to improve antiplatelet therapy.     

The increased risk of venous thromboembolism by advancing age cannot be attributed to the higher incidence of cancer in the elderly: the Tromsø study

Whether the high incidence of venous thromboembolism (VTE) in the elderly can be attributed to cancer is not well studied. We assessed the impact of cancer on risk of VTE in young, middle-aged and elderly. 26,094 subjects without a history of cancer or VTE were recruited from the Tromsø study. Incident cancer (n = 2,290) and VTE (n = 531) were recorded from baseline (1994–1995) through December 31st, 2009. Cox regression with cancer as time-varying exposure was used to calculate hazard ratios with 95 % confidence intervals (CI). Overt cancer was associated with a fivefold (95 %CI 4.3, 6.7) increased risk of VTE, with an age-dependent gradient from 26-fold (95 %CI 12.1, 56.5) increased in the young, ninefold (95 % CI 6.6, 12.7) increased in the middle-aged, and threefold (95 % CI 2.5, 4.5) increased risk in the elderly. The population attributable risks were 14, 27 and 18 %, respectively. Conclusion: The relative risk of VTE by cancer were higher in young compared to elderly subjects, but the proportion of VTEs in the population due to cancer did not differ much across age groups. Our findings indicate that the increased risk of VTE by advancing age cannot be attributed to higher incidence of cancer in the elderly.     

A classification tree for predicting recurrent falling in community-dwelling older persons

OBJECTIVES: To develop a classification tree for predicting the risk of recurrent falling in community-dwelling older persons using tree-structured survival analysis (TSSA). DESIGN: A prospective cohort study. SETTING: A community in the Netherlands. PARTICIPANTS: One thousand three hundred sixty-five community-dwelling older persons (>/=65) from the Longitudinal Aging Study Amsterdam (LASA). MEASUREMENTS: In 1995, physical, cognitive, emotional, and social aspects of functioning were assessed. Subsequently, a prospective fall follow-up, specifically on recurrent falls (two falls within 6 months) was conducted for 3 years. RESULTS: The classification tree included 11 end groups differing in risk of recurrent falling based on a minimum of two and a maximum of six predictors. The first split in the tree involved two or more falls versus fewer than two falls in the year preceding the interview. Respondents with two or more falls in the year preceding the interview (n=193) and with at least two functional limitations (n=98) had a 75% risk of becoming a recurrent faller, whereas respondents with fewer than two functional limitations were further divided into a group with regular dizziness (n=11, risk of 68%) and a group with no regular dizziness (n=84, risk of 30%). In respondents with fewer than two falls in the year preceding the interview (n=1,172), the risk of becoming a recurrent faller varied between 9% and 70%. Predictors in this branch of the tree were low performance, low handgrip strength, alcohol use, pain, high level of education, and high level of physical activity. CONCLUSION: This classification tree included 11 end groups differing in the risk of recurrent falling based on specific combinations of a maximum of six easily measurable predictors. The classification tree can identify subjects who are eligible for preventive measures in public health strategies.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Blood coagulation factors as inflammatory mediators

After the first observations about blood coagulation by Hippocrates, it took until the early 1900s before the classic theory of blood coagulation was presented. As more and more other coagulation factors were discovered, the four-factor coagulation scheme became more complex, but better understood, leading to the current coagulation cascade. As during the last decade it turned out that coagulation factors might do more than just promoting (or inhibiting) blood coagulation, new scientific avenues were pursued focusing on coagulation-independent properties of individual coagulation factors. This led to the current understanding that coagulation factors, like tissue factor (TF), FVII, FX, and thrombin, are important players in inflammation, vascular development, angiogenesis, and tumorigenesis. However, the molecular mechanism by which coagulation factors exert their pleiotropic effects in pathophysiology remains one of the major challenges in the field. This overview presents current insight in how the main coagulation factors might induce inflammation.     

Self-rated health among older adults: a cross-national comparison

Self-rated health (SRH) may have different implications in various social and cultural settings. However, few studies are available concerning SRH among older persons across countries. The aim of this study was to analyse whether there are cross-national differences in the association between status characteristics, several diseases common among older persons, activities of daily living (ADL), and SRH. The study base was the Comparison of Longitudinal European Studies on Aging (CLESA), which includes data from six population-based studies on aging conducted in Finland, Israel, Italy, The Netherlands, Spain and Sweden. The study population comprised 5,629 persons, with participants from all countries except Italy. Logistic regression analyses were used to assess the relationship between status characteristics, health conditions, ADL and SRH. To examine whether the association among status characteristics, health conditions, ADL and outcome differed across the CLESA countries, interaction terms defined as variable*country were considered separately for each variable. Regression analyses revealed that sex, education, lifetime occupation, heart disease and respiratory disease were differently distributed across countries. Among homogeneous factors, marital status (OR=1.21), hypertension (OR=1.41), stroke (OR=1.67), diabetes (OR=2.15), cancer (OR=1.47), musculoskeletal diseases (OR=2.44), and ADL (OR=2.72) turned out to be significantly associated with fair or poor SRH. The results indicate that there are differences in self-ratings of health across countries. These differences cannot be explained entirely by status characteristics, self-reported diseases or functional ability. However, an important finding was that in all countries most of the indicators of medical and functional health were homogeneously associated with SRH.     

Human adult bone marrow mesenchymal stem cells repair experimental conduction block in rat cardiomyocyte cultures.

OBJECTIVES: We evaluated whether human adult bone marrow-derived mesenchymal stem cells (hMSCs) could repair an experimentally induced conduction block in cardiomyocyte cultures. BACKGROUND: Autologous stem cell therapy is a novel treatment option for patients with heart disease. However, detailed electrophysiological characterization of hMSCs is still lacking. METHODS: Neonatal rat cardiomyocytes were seeded on multi-electrode arrays. After 48 h, abrasion of a 200- to 450-microm-wide channel caused conduction block. Next, we applied adult hMSCs (hMSC group, n = 8), human skeletal myoblasts (myoblast group, n = 7), rat cardiac fibroblasts (fibroblast group, n = 7), or no cells (control group, n = 7) in a channel-crossing pattern. Cross-channel electrical conduction was analyzed after 24 and 48 h. Intracellular action potentials of hMSCs and cardiomyocytes were recorded. Immunostaining for connexins and intercellular dye transfer (calcein) assessed the presence of functional gap junctions. RESULTS: After creation of conduction block, two asynchronously beating fields of cardiomyocytes were present. Application of hMSCs restored synchronization between the two fields in five of eight cultures after 24 h. Conduction velocity across hMSCs (0.9 +/- 0.4 cm/s) was approximately 11-fold slower than across cardiomyocytes (10.4 +/- 5.8 cm/s). No resynchronization occurred in the myoblast, fibroblast, or control group. Intracellular action potential recordings indicated that conduction across the channel presumably occurred by electrotonic impulse propagation. Connexin-43 was present along regions of hMSC-to-cardiomyocyte contact, but not along regions of cardiomyocyte-to-myoblast or cardiomyocyte-to-fibroblast contact. Calcein transfer from cardiomyocytes to hMSCs was observed within 24 h after co-culture initiation. CONCLUSIONS: Human mesenchymal stem cells are able to repair conduction block in cardiomyocyte cultures, probably through connexin-mediated coupling.