Per Näsman

Effect of Intravenous Nimodipine on Blood Pressure and Outcome After Acute Stroke

BACKGROUND AND PURPOSE The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.

Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study

This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9–11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n=67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (P<0.05) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase ⩾2 g/dl was significantly higher in the iron group (93%) than in the no-iron group (53%) (per-protocol population; P=0.001). Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference. The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy (P=0.029) and after 15 weeks approximately 10 000 IU (>25%) lower in the iron group, as was the total epoetin dose (P=0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.

Periodontitis Increases the Risk of a First Myocardial Infarction: A Report From the PAROKRANK Study

Background— The relationship between periodontitis (PD) and cardiovascular disease is debated. PD is common in patients with cardiovascular disease. It has been postulated that PD could be causally related to the risk for cardiovascular disease, a hypothesis tested in the Periodontitis and Its Relation to Coronary Artery Disease (PAROKRANK) study. Methods and Results— Eight hundred five patients (<75 years of age) with a first myocardial infarction (MI) and 805 age- (mean 62±8), sex- (male 81%), and area-matched controls without MI underwent standardized dental examination including panoramic x-ray. The periodontal status was defined as healthy (≥80% remaining bone) or as mild-moderate (from 79% to 66%) or severe PD (<66%). Great efforts were made to collect information on possibly related confounders (≈100 variables). Statistical comparisons included the Student pairwise t test and the McNemar test in 2×2 contingency tables. Contingency tables exceeding 2×2 with ranked alternatives were tested by Wilcoxon signed rank test. Odds ratios (95% confidence intervals) were calculated by conditional logistic regression. PD was more common (43%) in patients than in controls (33%; P<0.001). There was an increased risk for MI among those with PD (odds ratio, 1.49; 95% confidence interval, 1.21–1.83), which remained significant (odds ratio, 1.28; 95% confidence interval, 1.03–1.60) after adjusting for variables that differed between patients and controls (smoking habits, diabetes mellitus, years of education, and marital status). Conclusions— In this large case–control study of PD, verified by radiographic bone loss and with a careful consideration of potential confounders, the risk of a first MI was significantly increased in patients with PD even after adjustment for confounding factors. These findings strengthen the possibility of an independent relationship between PD and MI.Background— The relationship between periodontitis (PD) and cardiovascular disease is debated. PD is common in patients with cardiovascular disease. It has been postulated that PD could be causally related to the risk for cardiovascular disease, a hypothesis tested in the Periodontitis and Its Relation to Coronary Artery Disease (PAROKRANK) study. Methods and Results— Eight hundred five patients (<75 years of age) with a first myocardial infarction (MI) and 805 age- (mean 62±8), sex- (male 81%), and area-matched controls without MI underwent standardized dental examination including panoramic x-ray. The periodontal status was defined as healthy (≥80% remaining bone) or as mild-moderate (from 79% to 66%) or severe PD (<66%). Great efforts were made to collect information on possibly related confounders (≈100 variables). Statistical comparisons included the Student pairwise t test and the McNemar test in 2×2 contingency tables. Contingency tables exceeding 2×2 with ranked alternatives were tested by Wilcoxon signed rank test. Odds ratios (95% confidence intervals) were calculated by conditional logistic regression. PD was more common (43%) in patients than in controls (33%; P <0.001). There was an increased risk for MI among those with PD (odds ratio, 1.49; 95% confidence interval, 1.21–1.83), which remained significant (odds ratio, 1.28; 95% confidence interval, 1.03–1.60) after adjusting for variables that differed between patients and controls (smoking habits, diabetes mellitus, years of education, and marital status). Conclusions— In this large case–control study of PD, verified by radiographic bone loss and with a careful consideration of potential confounders, the risk of a first MI was significantly increased in patients with PD even after adjustment for confounding factors. These findings strengthen the possibility of an independent relationship between PD and MI. # CLINICAL PERSPECTIVE {#article-title-44}

Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.

PURPOSE The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated. PATIENTS AND METHODS One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument. RESULTS At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (>10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P < .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements. CONCLUSION Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.

Does early EBV infection protect against IgE sensitization

Background There is indirect evidence that an increased infectious burden is associated with a decreased prevalence of IgE-mediated allergy during childhood. Objective To determine whether there is a relation between the serostatus of 13 different viruses and parentally reported infections and IgE sensitization in 2-year-old children. To investigate whether there is an interaction between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to IgE sensitization. Methods A total of 246 infants were followed prospectively to 2 years of age with clinical examinations, skin prick test, and specific IgE analyses and through analysis of seropositivity against adenovirus, influenza, parainfluenza, respiratory syncytial virus, CMV, EBV, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Results There was some evidence that IgE sensitization (24%) tended to be more common among children who were seropositive against few compared with children who were seropositive against many viruses, but this was not statistically significant, and there was no consistent trend across the groups. IgE sensitization was statistically significantly less prevalent at 2 years of age among infants who were seropositive against EBV but not other viruses (adjusted odds ratio, 0.34; 95% CI, 0.14-0.86). The interaction of seropositivity against both CMV and EBV antibodies indicated a further reduction in the risk for IgE sensitization (adjusted odds ratio for interaction, 0.10; 95% CI, 0.01-0.92), indicating effect modification associated with seropositivity against CMV. Conclusion Our results indicate that acquisition of EBV infection during the first 2 years of life is associated with a reduced risk of IgE sensitization, and this effect is enhanced by CMV coinfection.

Favourable long term prognosis in stable angina pectoris: an extended follow up of the angina prognosis study in Stockholm (APSIS)

Objective: To evaluate the long term prognosis of patients with stable angina pectoris. Design: Registry based follow up (median 9.1 years) of patients participating in the APSIS (angina prognosis study in Stockholm), which was a double blind, single centre trial of antianginal drug treatment. Patients: 809 patients (31% women) with stable angina pectoris < 70 (mean (SD) 59 (7) years at inclusion) and an age and sex matched reference population from the same catchment area. Interventions: Double blind treatment with metoprolol or verapamil during 3.4 years (median), followed by referral for usual care with open treatment. Main outcome measures: Cardiovascular (CV) death and non-fatal myocardial infarction (MI) in the APSIS cohort and total mortality in comparison with reference subjects. Results: 123 patients died (41 MI, 36 other CV causes) and 72 had non-fatal MI. Mortality (19% v 6%, p<0.001) and fatal MI (6.6% v 1.6%, p < 0.001) were increased among male compared with female patients. Diabetes, previous MI, hypertension, and male sex independently predicted CV mortality (p < 0.001). Diabetes greatly increased the risk in a small subgroup of female patients. Male patients had higher mortality than men in the reference population during the first three years (cumulative absolute difference 3.8%) but apparently not thereafter. Female patients had similar mortality to women in the reference population throughout the 9.1 years of observation. Conclusions: Female patients with stable angina had similar mortality to matched female reference subjects but male patients had an increased risk. Diabetes, previous MI, hypertension, and male sex were strong risk factors for CV death or MI.

Regular hypnotic drug treatment in a sample of 32,679 Swedes: associations with somatic and mental health, inpatient psychiatric diagnoses and suicide, derived with automated record-linkage.

&NA; We studied Swedish survey responders who reported regular treatment with hypnotic drugs, to find associations to perceived health problems, inpatient psychiatric diagnoses, and subsequent suicide. Among 32,679 sampled Swedes, 26,952 (83%) participated, 500 of which (2%) reported regular hypnotic drug treatment. The rate of treatment was higher in women, and increased by age in both sexes. The major findings were high odds of concurrent psychoactive drug treatments, nervous symptoms and insomnia, as well as high rates of circulatory and musculoskeletal conditions in both sexes, with indicators of disability and sleep‐disturbing symptoms. During a 15‐year period, 35% of the men and 21% of the women who reported regular hypnotic drug treatment had also been admitted to inpatient psychiatric care. Substance abuse was diagnosed in 20% of the men and 4.3% of the women reporting hypnotic drug treatment. In multiple logistic regression models, the highest odds for regular hypnotic drug treatment were incurred by recent/current insomnia, nervous symptoms, and other psychoactive drug treatment. We conclude that therapy was principally given according to some current peer guidelines. Yet, further research is needed into the risk/benefit ratio of sustained hypnotic drug therapy in patients with qualifying somatic and psychiatric disorders to obtain a more uniformly based consensus.

Clinical significance of mucosal inflammation of the vermiform appendix.

In 942 emergency appendectomies, the clinical data of 77 patients with inflammatory changes confined to the mucosa of the vermiform appendix were compared with data from 622 patients with diffuse acute appendicitis and 243 patients without evidence of inflammation in the appendix. In all cases, routine histologic sections of the specimens were reviewed. Of the 77 patients with mucosal appendices! inflammation, SO were female and 50% were under 17 years of age. In several clinical aspects, such as incidence of nausea, vomiting, migration of pain, and localized muscular rigidity, there existed significant differences between patients with mucosal inflammation and patients with diffuse appendicitis. Conversely, no statistically significant differences were found between patients with mucosal inflammation and patients without evident ap-pendiceal inflammation. These results in addition to the frequent finding of historically indistinguishable changes in appendices removed incidentally suggest that the condition is not responsible for the actual complaint.

Is the prognosis in patients with diabetes and heart failure a matter of unsatisfactory management? : An observational study from the Swedish Heart Failure Registry

To analyse the long‐term outcome, risk factor panorama, and treatment pattern in patients with heart failure (HF) with and without type 2 diabetes (T2DM) from a daily healthcare perspective.

Improved survival in myeloma patients: starting to close in on the gap between elderly patients and a matched normal population

The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender‐ and age‐matched cohort Swedish population (n = 9 340 682). Median overall survival for non‐high‐dose treated patients was 2·8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4·9 years) compared to conventional treatment (2·3 years). Among non‐high‐dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high‐dose treated patients was 6·9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non‐high‐dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.