Mortality, reinfarction, left ventricular ejection fraction and costs following reperfusion therapies for acute mvocardial infarction

The comparative efficacy of thrombolytic drugs and primary angioplastyfor acute myocardial infarction have recently been studied,but long-term follow-up data have not yet been reported. Weconducted a randomized trial involving 301 patients with acutemyocardial infarction; 152 patients were randomized to primaryangioplasty and 149 to intravenous streptokinase. Left ventricularfunction was assessed with a radionuclide technique both athospital discharge and at the end of the follow-up period. Follow-updata were collected after a mean (± SD) of 31 ±9 months. Total medical costs were calculated. At the end ofthe follow-up period, 5% of the angioplasty patients had diedfrom a cardiac cause compared to 11% of the patients randomizedto intravenous streptokinase, P=0·031. Cardiac deathor a non-fatal reinfarction occurred in 7% of angioplasty patientscompared to 28% of streptokinase patients, P0·001. Therewas a sustained benefit of angioplasty compared to streptokinaseon left ventricular function. The total medical costs in thetwo groups were similar. Coronary anatomy (patency and singleor multivessel disease), infarct location and previous myocardialinfarction were important determinants of clinical outcome andcosts. After 31±9 months of follow-up, primary angioplasty comparedto intravenous streptokinase results in a lower rate of cardiacdeath and reinfarction, a better left ventricular ejection fraction,and no increase in total medical costs. (Eur Heart J 1996; 17: 382–387)     

Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occured in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group. Quantitative angiography showed a significant improvement in percentage diameter stenosis in the c7E3 group, which was not observed in all three other groups, although differences between groups were not significant. Alteplase infusion in patients with refractory unstable angina did not change the clinical course, nor the coronary morphology, c7E3 on the other hand, both improved the clinical course and the coronary lesion morphology and rheology in the same category of patients.     

Risk of fracture in patients with Guillain-Barré syndrome

Summary

The aim of this study was to evaluate fracture risk in patients with Guillain-Barré syndrome (GBS). No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture.

Introduction

Symptoms of Guillain-Barré syndrome (GBS) may vary from mild difficulty in walking to complete paralysis, which may increase the risk of fractures. Therefore, the aim of this study was to evaluate fracture risk in patients with GBS.

Methods

We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987–2012). Each patient with GBS was matched by year of birth, sex, and practice, up to six patients without a history of GBS. Outcome measure was any fracture.

Results

There were no associations between GBS and any fracture, adjusted hazard ratio (AHR) 1.01 (95 % confidence interval [CI] 0.77–1.33), or osteoporotic fracture, AHR 0.76 (95 % CI 0.50–1.17), compared with controls. Stratification to gender, age, and duration since diagnosis did not show an association either. Only for GBS patients using pain treatment, risk of fracture was doubled AHR 1.97 (95 % confidence CI 1.21–3.21) compared with controls. The risk of fracture in GBS patients exposed to pain treatment was equivalent to risk of fracture among controls exposed to pain treatment.

Conclusions

No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture, but their risk was equivalent to fracture risk among controls exposed to pain treatment.     

Mutational specificity: Spectrum of mutations in kidney,stomach, and liver from lacl transgenic mice recovered after treatment with tris(2,3-dibromopropyl)phosphate

The flame retardant tris(2,3-dibromopropyl)phosphate (TDBP), once used in cotton sleepware for children, is presently banned from commerce. It produces tumors in rodents in both a sex- and tissue-specific manner. The kidney is the main target for tumor formation in male and female rats, as well as in male mice. In contrast, tumors are formed in the liver of female animals. We have used lacl transgenic male B6C3F1 mice (Big Blue®) to examine the induction of mutation in kidney, liver, and stomach after exposure to 150 mg/kg (2 days), 300 mg/kg (4 days), and 600 mg/kg (4 days of TDBP. At the highest dose, the mutant frequency was approximately 50% above control values in the kidney (P < 0.01). A smaller increase was observed in the liver (P = 0.07), while no increase was seen in the stomach (P = 0.28). Sequence analysis of the recovered mutants showed a TDBP-specific change in mutation spectrum in kidney, which was not observed in liver and stomach. In kidney, a dose-dependent decrease in G:C → A:T transitions, including at 5′-CpG-3′ sites, was observed. This was accompanied by an increase in the loss of single G:C base pairs from approximately 3% to 15%. These results illustrate both the sensitivity and specificity of the lacl transgenic system in the analysis of tissue-specific mutation. This study also reinforces the importance of examining mutational spectra when mutant induction levels are low. © 1996 Wiley-Liss, Inc.     

Angelman syndrome in adulthood

We studied the clinical and EEG-findings in 28 adult patients (aged 20–53 years) with Angelman syndrome (AS). Twenty-three showed a maternal chromosome 15q11–13 deletion; in 5, the diagnosis was based on a combination of typical clinical findings. Compared to the clinical manifestations present in childhood, “coarsening” of facial traits (100%), thoracic scoliosis (71%), and being wheelchair-bound (39%) were found more frequently. Paroxysms of laughter were still observed in adulthood (79%), but less frequently than in childhood. Most adult patients could feed themselves, but needed help with many daily activities. The majority (82%) had epileptic seizures. Abnormal EEG-activity consisting of 2–3/s rhythmic triphasic waves of high amplitude with a maximum over the frontal regions, which has been identified in many AS children, was found in 67% of these adult patients. © 1996 Wiley-Liss, Inc.     

Viewpoints among experts and the public in the Netherlands on including a lifestyle criterion in the healthcare priority setting

ContextIt remains unclear whether there would be societal support for a lifestyle criterion for the healthcare priority setting. This study examines the viewpoints of experts in healthcare and the public regarding support for a lifestyle‐related decision criterion, relative to support for the currently applied criteria, in the healthcare priority setting in the Netherlands.MethodsWe conducted a Q methodology study in samples of experts in healthcare (n = 37) and the public (n = 44). Participants (total sample N = 81) ranked 34 statements that reflected currently applied decision criteria as well as a lifestyle criterion for setting priorities in healthcare. The ranking data were subjected to principal component analysis, followed by oblimin rotation, to identify clusters of participants with similar viewpoints.FindingsWe identified four viewpoints. Participants with Viewpoint 1 believe that treatments that have been proven to be effective should be reimbursed. Those with Viewpoint 2 believe that life is precious and every effort should be made to save a life, even when treatment still results in a very poor state of health. Those with Viewpoint 3 accept government intervention in unhealthy lifestyles and believe that individual responsibility should be taken into account in reimbursement decisions. Participants with Viewpoint 4 attribute importance to the cost‐effectiveness of treatments; however, when priorities have to be set, treatment effects are considered most important. All viewpoints were supported by a mix of public and experts, but Viewpoint 1 was mostly supported by experts and the other viewpoints were mostly supported by members of the public.ConclusionsThis study identified four distinct viewpoints on the healthcare priority setting in the Netherlands, each supported by a mix of experts and members of the public. There seems to be some, but limited, support for a lifestyle criterion—in particular, among members of the public. Experts seem to favour the decision criteria that are currently applied. The diversity in views deserves attention when policymakers want to adhere to societal preferences and increase policy acceptance.