Petter Quist-Paulsen

Randomised controlled trial of smoking cessation intervention after admission for coronary heart disease

abstract Objective To determine whether a nurse led smoking cessation intervention affects smoking cessation rates in patients admitted for coronary heart disease. Design Randomised controlled trial. Setting Cardiac ward of a general hospital, Norway. Participants 240 smokers aged under 76 years admitted for myocardial infarction, unstable angina, or cardiac bypass surgery. 118 were randomly assigned to the intervention and 122 to usual care (control group). Intervention The intervention was based on a booklet and focused on fear arousal and prevention of relapses. The intervention was delivered by cardiac nurses without special training. The intervention was initiated in hospital, and the participants were contacted regularly for at least five months. Main outcome measure Smoking cessation rates at 12 months determined by self report and biochemical verification. Results 12 months after admission to hospital, 57% (n = 57/100)of patients in the intervention group and 37% (n = 44/118) in the control group had quit smoking (absolute risk reduction 20%, 95% confidence interval 6% to 33%). The number needed to treat to get one additional person who would quit was 5 (3 to 16). Assuming all dropouts relapsed at 12 months, the smoking cessation rates were 50% in the intervention group and 37% in the control group (absolute risk reduction 13%, 0% to 26%). Conclusion A smoking cessation programme delivered by cardiac nurses without special training, significantly reduced smoking rates in patients 12 months after admission to hospital for coronary heart disease.

Arterial cardiovascular risk factors and venous thrombosis: results from a population-based, prospective study (the HUNT 2)

Background An explanation for the increased risk of myocardial infarction and stroke in patients with venous thrombosis is lacking. The objective of this study was to investigate whether risk factors for arterial cardiovascular disease also increase the risk of venous thrombosis. Design and Methods Cases who had a first venous thrombosis (n=515) and matched controls (n=1,505) were identified from a population-based, nested, case-cohort study (the HUNT 2 study) comprising 71% (n=66,140) of the adult residents of Nord-Trøndelag County in Norway. Results The age- and sex-adjusted odds ratio of venous thrombosis for subjects with concentrations of C-reactive protein in the highest quintile was 1.6 (95% confidence interval: 1.2–2.2) compared to subjects with C-reactive protein in the lowest quintile. This association was strongest in subjects who experienced venous thrombosis within a year after blood sampling with a three-fold increased risk of participants in the highest versus the lowest quintile. Having first degree relatives who had a myocardial infarction before the age of 60 years was positively associated with venous thrombosis compared to not having a positive family history [odds ratio 1.3 (95% confidence interval: 1.1–1.6)]. Subjects with blood pressure in the highest quintile had half the risk of developing venous thrombosis compared to subjects whose blood pressure was in the lowest quintile. There were no associations between the risk of venous thrombosis and total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglycerides, glucose or smoking. We confirmed the positive association between obesity and venous thrombosis. Conclusions C-reactive protein and a family history of myocardial infarction were positively associated with subsequent venous thrombosis. Blood pressure was inversely correlated to venous thrombosis. These findings should be confirmed by further investigations.

Risk group assignment differs for children and adults 1–45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL‐2008 protocol

The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.

Statins and inflammation: an update

Purpose of review Randomized trials have suggested that the beneficial effects of statins could extend to mechanisms beyond cholesterol reduction. Investigations have shown that statins are associated with reduced plasma markers of inflammation, reduced T-cell and monocyte activation, and reduced blood clotting. These effects could be explained by the inhibition of L-mevalonic acid synthesis, thus affecting cell-signalling pathways. However, it has been difficult to evaluate whether the nonlipid effects of statins translate into clinically meaningful outcomes. Recent findings Inflammation, as measured by C-reactive protein (CRP), has been established as an independent cardiovascular risk factor, even in persons with low-density lipoprotein (LDL)-cholesterol. Statins have anti-inflammatory effects, and lower CRP. Reducing both LDL-cholesterol and CRP is important in order to decrease the risk of cardiovascular events. Statins significantly reduce the risk of venous thrombosis. It is probable that this effect goes beyond lipid lowering. The clinical benefit of statin therapy in infectious diseases remains to be determined by randomized controlled trials. Summary Statins have anti-inflammatory properties that are clinically important in lowering cardiovascular risk. It is probable, but not definitely proven, that some of the benefits of statins are due to their nonlipid effects.

Complying with the European Clinical Trials directive while surviving the administrative pressure – An alternative approach to toxicity registration in a cancer trial

The European Clinical Trials Directive of 2004 has increased the amount of paper work and reduced the number of initiated clinical trials. Particularly multinational trials have been delayed. To meet this challenge we developed a novel, simplified, fast and easy strategy for on-line toxicity registration for patients treated according to the Nordic/Baltic acute lymphoblastic leukaemia protocol, NOPHO ALL 2008, for children and young adults, including three randomisations. We used a risk-assessment based approach, avoiding reporting of expected adverse events and instead concentrating on 20 well-known serious, but rarer events with focus on changes in therapy introduced in the treatment protocol. This toxicity registration strategy was approved by the relevant regulatory authorities in all seven countries involved, as compliant within the EU directive of 2004. The centre compliance to registration was excellent with 98.9% of all patients being registered within 5weeks from the requested quarterly registration. Currently, four toxicities (thrombosis, fungal infections, pancreatitis and allergic reactions) have been chosen for further detailed exploration due to the cumulative fraction of patients with positive registrations exceeding 5%. This toxicity registration offers real-time toxicity profiles of the total study cohort and provides early warnings of specific toxicities that require further investigation.

Cost effectiveness of a smoking cessation program in patients admitted for coronary heart disease.

Background Smoking cessation is probably the most important action to reduce mortality after a coronary event. Smoking cessation programs are not widely implemented in patients with coronary heart disease, however, possibly because they are thought not to be worth their costs. Our objectives were to estimate the cost effectiveness of a smoking cessation program, and to compare it with other treatment modalities in cardiovascular medicine. Methods A cost-effectiveness analysis was performed on the basis of a recently conducted randomized smoking cessation intervention trial in patients admitted for coronary heart disease. The cost per life year gained by the smoking cessation program was derived from the resources necessary to implement the program, the number needed to treat to get one additional quitter from the program, and the years of life gained if quitting smoking. The cost effectiveness was estimated in a low-risk group (i.e. patients with stable coronary heart disease) and a high-risk group (i.e. patients after myocardial infarction or unstable angina), using survival data from previously published investigations, and with life-time extrapolation of the survival curves by survival function modeling. Results In a lifetime perspective, the incremental cost per year of life gained by the smoking cessation program was ∊280 and ∊110 in the low and high-risk group, respectively (2000 prices). These costs compare favorably to other treatment modalities in patients with coronary heart disease, being approximately 1/25 the cost of both statins in the low-risk group and angiotensin-converting enzyme inhibitors in the high-risk group. In a sensitivity analysis, the costs remained low in a wide range of assumptions. Conclusions A nurse-led smoking cessation program with several months of intervention is very cost-effective compared with other treatment modalities in patients with coronary heart disease.

Predictors of smoking cessation in patients admitted for acute coronary heart disease.

Background Smoking cessation is probably the most important single action after a coronary event. In order to increase the effectiveness of smoking cessation programs, it is important to have knowledge of the predictors of smoking cessation. Further, it is unknown whether smoking cessation programs have impact on these predictors. Methods Data were obtained from a randomized controlled trial of smoking cessation intervention in 240 smokers aged less than 76 years admitted for myocardial infarction, unstable angina, or cardiac bypass surgery. Baseline characteristics were prospectively recorded. Smoking cessation was determined by self report and biochemical verification at 12 months follow-up. Results In multivariate logistic regression analysis, a high level of nicotine addiction, low level of self-confidence in quitting and having previous coronary heart disease were significant negative predictors of smoking cessation at 12 months follow-up. Having previous coronary heart disease and a diagnosis other than acute myocardial infarction as a reason for admission were important negative predictors of abstinence in the usual care group, in contrast to the intervention group, although this did not reach a level of significance in the subgroup interaction analyses. A high level of nicotine addiction was a strong negative predictor in both groups. Conclusion A high level of nicotine addiction is an important negative predictor of smoking cessation, even within an individualized smoking cessation program. Smoking cessation intervention seems to be especially effective in patients with previous coronary heart disease and in patients with unstable angina or coronary artery bypass surgery, compared to usual care.

Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry

Hereditary thrombotic thrombocytopenic purpura, Upshaw-Schulman syndrome, ADAMTS13 Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is a rare recessively inherited disease. Underlying is a severe constitutional deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, due to compound heterozygous or homozygous mutations in the ADAMTS13 gene. The clinical picture is variable and more and more patients with an adult-onset are diagnosed. In the majority of countries the only available treatment is plasma, which when administered regularly can efficiently prevent acute disease bouts. The decision to initiate regular prophylaxis is often not easy, as evidence based guidelines and long term outcome data are lacking. Through the hereditary TTP registry (www.ttpregistry.net, ClinicalTrials.gov identifier: NCT01257269), which was initiated in 2006 and is open to all patients diagnosed with Upshaw-Schulman syndrome and their family members, we aim to gain further information and insights into this rare disease, which eventually will help to improve clinical management of affected patients.

Does smoking cessation improve Quality of Life in patients with coronary heart disease

Objective. To evaluate whether smoking cessation after a coronary event improves quality of life, and to assess whether quality of life is a predictor of smoking cessation. Design. Health-related quality of life at baseline and at 12 months follow up were measured in a randomised smoking cessation trial of 240 smokers aged under 76 years admitted for myocardial infarction, unstable angina or coronary bypass surgery. At 12 months follow up 101 had managed to give up smoking (quitters), and 117 were smokers (sustained smokers). Results. The quitters and sustained smokers had similar improvements in all quality of life domains from baseline to 12 months follow up. Further, after adjustment for differences in baseline characteristics, the quality of life was not significantly different in the quitters compared to the sustained smokers neither at baseline nor at 12 months follow up. Conclusions. Smoking cessation did not improve quality of life compared to sustained smoking after a coronary event in a 12 month follow up. Quality of life was not a significant predictor of smoking cessation.

High prevalence of hereditary thrombotic thrombocytopenic purpura in Central Norway: from clinical observation to evidence.

Essentials The population prevalence of hereditary thrombotic thrombocytopenic purpura (TTP) is unknown. We studied the prevalence of hereditary TTP and population frequencies of two ADAMTS‐13 mutations. A high frequency of hereditary TTP related to ADAMTS‐13 mutation c.4143_4144dupA was found. Vicinity of ABO blood group and ADAMTS‐13 loci may facilitate screening of ADAMTS‐13 mutations.