Management of children with high‐risk Hodgkin lymphoma

Most children and adolescents with newly diagnosed high‐risk Hodgkin lymphoma (HL) will achieve remission and cure with conventional chemotherapy with or without radiation therapy. However, these therapies can lead to long‐term side effects. Therapy is titrated on the basis of risk group stratification using clinical prognostic factors and, in most cases, then refined through assessment of interim or end of chemotherapy response, primarily using functional imaging with fluorodeoxyglucose positron emission tomography. No study has clearly demonstrated the factors that are sufficient in identifying the patients at highest risk for relapse that may benefit from therapy intensification. This review summarizes recent clinical trials in paediatric high‐risk HL, along with key findings from studies in adults with high‐risk HL that are applicable to the paediatric population. New directions in prognostic classification and targeted therapies are reviewed. Considerations for clinical practice at the current time outside the clinical trial setting are provided.     

Five‐year clinical outcomes of sirolimus‐eluting versus paclitaxel‐eluting stents in high‐risk patients

Objectives and Background : First generation drug‐eluting stents have shown differential efficacy in high‐risk patient subsets at one year. It is unclear whether these differences endure over the medium‐ to long‐term. We compared the five‐year clinical efficacy and safety of sirolimus‐eluting stents (SES) and paclitaxel‐eluting stents (PES) in a population of high‐risk patients. Methods : The patient cohorts of the ISAR‐DESIRE, ISAR‐DIABETES, and ISAR‐SMART‐3 randomized trials were followed up for five years and data were pooled. The primary efficacy endpoint of the analysis was the need for target lesion revascularization (TLR) during a five‐year follow‐up period. The primary safety endpoint was the combination of death or myocardial infarction (MI) after five years. Results : A total of 810 patients (405 patients in the SES group and 405 patients in the PES group) was included. Over five years TLR was reduced by 39% with SES compared with PES stent (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.44–0.85; P = 0.004). No difference was observed according to death or MI rates between the two groups (HR 1.10; 95% CI 0.80–1.50; P = 0.57). Definite stent thrombosis occurred in 0.2% (n = 1) in the SES group and in 1.6% (n = 6) in the PES group (HR 0.16; 95% CI 0.02–1.34; P = 0.12). Conclusions : In high‐risk patient subsets the lower rate of 12‐month TLR observed with SES in comparison PES is maintained out to five years. In terms of safety, although there was no difference in the overall incidence of death or MI, there was a trend towards more frequent stent thromboses with PES. © 2011 Wiley‐Liss, Inc.     

Fracture risk with intermittent high‐dose oral glucocorticoid therapy

Objective

To evaluate the risk of fracture in patients receiving intermittent therapy with high‐dose oral glucocorticoids (GCs).

Methods

The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of “current” and “no exposure.” The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation.

Results

Patients who intermittently received high‐dose GCs (daily dose ≥15 mg) and had no or little previous exposure to GCs (cumulative exposure ≤1 gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this risk increased substantially with increasing cumulative exposure. Among patients who received a daily dose ≥30 mg and whose cumulative exposure was >5 gm, the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval [95% CI] 2.54–5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49–6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29–25.08).

Conclusion

Intermittent use of high‐dose oral GCs (daily dose ≥15 mg and cumulative exposure ≤1 gm) may result in a small increased risk of osteoporotic fracture. Conversely, patients who receive several courses of high‐dose GCs (daily dose ≥15 mg and cumulative exposure >1 gm) have a substantially increased risk of fracture.

     

Prevalent high‐risk respiratory hygiene practices in urban and rural Bangladesh

Objectives To identify existing respiratory hygiene risk practices, and guide the development of interventions for improving respiratory hygiene. Methods We selected a convenience sample of 80 households and 20 schools in two densely populated communities in Bangladesh, one urban and one rural. We observed and recorded respiratory hygiene events with potential to spread viruses such as coughing, sneezing, spitting and nasal cleaning using a standardized assessment tool. Results In 907 (81%) of 1122 observed events, households’ participants coughed or sneezed into the air (i.e. uncovered), 119 (11%) into their hands and 83 (7%) into their clothing. Twenty‐two per cent of women covered their coughs and sneezes compared to 13% of men (OR 2.6, 95% CI 1.6–4.3). Twenty‐seven per cent of persons living in households with a reported monthly income of >72.6 US$ covered their coughs or sneezes compared to 13% of persons living in households with lower income (OR 3.2, 95% CI 1.6–6.2). In 956 (85%) of 1126 events, school participants coughed or sneezed into the air and 142 (13%) into their hands. Twenty‐seven per cent of coughs/sneezes in rural schools were covered compared to 10% of coughs/sneezes in urban schools (OR 2.3, 95% CI 1.5–3.6). Hand washing was never observed after participants coughed or sneezed into their hands. Conclusion There is an urgent need to develop culturally appropriate, cost‐effective and scalable interventions to improve respiratory hygiene practices and to assess their effectiveness in reducing respiratory pathogen transmission.     

The PREHAMI (PREsillion™ in high‐risk acute myocardial infarction) registry

Objectives : To evaluate the efficacy of the new Cobalt–Chromium (Co‐Cr) Presillion? stent for the treatment of high‐risk acute myocardial infarction (MI) patients. Background : Percutaneous coronary intervention (PCI) with stent represents the gold standard treatment for acute MI. Methods and Results : We enrolled patients with high‐risk acute MI (either ST‐segment elevation MI or non‐ST‐segment elevation MI) treated with PCI using a new Co‐Cr bare metal stent with closed cells design and limited balloon compliance. We considered high‐risk features as one of the following: age ≥70 years, ejection fraction ≤35%, glomerular filtration rate ≤60 mL/min, diabetes mellitus, rescue PCI, or chronic atrial fibrillation or other conditions requiring long‐term oral anticoagulation therapy. Primary outcome of the study was rate of major adverse cardiac events (MACE) defined as all‐cause death, new MI, and target‐vessel revascularization. A total of 129 consecutive patients were enrolled (69 ± 11 years, 74% men): 71 (55%) patients with ST‐segment elevation MI and 58 (45%) patients with non‐ST‐segment elevation MI. A total of 153 vessels (169 lesions and 179 stents) were treated. The device success rate was high (98.8%). In‐hospital MACE rate was 5.4% mainly because of death associated with the acute MI. At 1‐year follow‐up, the MACE rate was 17.3%, with 11% all‐cause death (7.9% of cardiac origin), 0.6% of stent thrombosis, and 4.6% target‐vessel revascularization. Conclusions : The use of the Co‐Cr Presillion stent in patients with high‐risk acute MI treated invasively seems to be safe and efficacious with optimal deliverability and good long‐term outcomes and represents a good option in the treatment of these patients. © 2011 Wiley‐Liss, Inc.     

Serum apolipoprotein C‐III in high‐density lipoprotein: a key diabetogenic risk factor in Turks

Aims We studied determinants of serum apolipoprotein C‐III (apoC‐III) and whether levels of apoC‐III or its fractions predict metabolic syndrome (MetS), Type 2 diabetes and coronary heart disease (CHD). Methods The predictive value of apoC‐III, measured by immunoturbimetric immunoassay in 802 tracked individuals of a Turkish general population in determining cardiometabolic risk was assessed over 4.4 ± 1.2 years’ follow‐up. Patients with MetS, Type 2 diabetes and CHD at baseline were excluded. Results Total apoC‐III, as well as both fractions, was significantly, linearly and inversely related to smoking status, positively to alcohol usage and to levels of complement C3. Mid and high tertiles of total or non‐high density lipoprotein (HDL) apoC‐III predicted significantly and independently incident MetS; they predicted CHD with risk ratios of 1.6 [95% confidence intervals (CI) 1.02–2.5], for 1 sd increment, after adjustments that included HDL cholesterol and body mass index (BMI). The highest tertile of HDL apoC‐III was a major independent predictor of new‐onset diabetes with a 2.5‐fold risk ratio for 1 sd increment (95% CI 1.5–4.0) in combined sexes, after adjustment for waist circumference, HDL cholesterol and other confounders and was a better predictor than waist girth. Conclusions Serum total apoC‐III or its fractions are linearly and inversely associated with smoking, positively with alcohol usage and serum complement C3. The presumably dysfunctional HDL apoC‐III is a stronger predictor of Type 2 diabetes than waist girth in Turks. Non‐HDL apoC‐III predicts strongly the development of MetS as well as incident CHD, independent of HDL cholesterol, BMI and non‐lipid factors. The atherogenicity of apoC‐III and dysfunctionality of HDL apoC‐III carry huge public health implications in Turks.