Impact of evidence‐based medicine on the treatment of patients with unresectable hepatocellular carcinoma

Aliment Pharmacol Ther 31 , 493–501

Summary

Background A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well‐selected patients with unresectable hepatocellular carcinoma (HCC). Aim To access whether this information has modified the use of TACE in clinical practice. Methods From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4‐year periods (1999–2002, n = 161 and 2003–2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival. Results Patients undergoing TACE increased in the 2003–2006 period (from 62% to 73%, P = 0.035), with an increase in of Child‐Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999–2002 period, there was no significant difference in survival between TACE‐treated and untreated patients, while in the 2003–2006 period, TACE‐treated patients survived longer (P < 0.0001). Conclusions Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well‐compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage.     

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea–hypopnoea index (AHI) 5–15 h^?1] and 40 controls (AHI <5 h^?1). Serum concentrations of pro‐ and anti‐inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non‐steroidal anti‐inflammatory medication, the mean level of tumour necrosis factor‐α was significantly elevated (1.54 versus 1.17 pg mL^?1, P = 0.004), whereas the level of interleukin‐1β (IL‐1β) was reduced (0.19 versus 0.23 pg mL^?1, P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti‐inflammatory cytokines, interleukin‐10 (1.28 versus 0.70 pg mL^?1, P < 0.001) and interleukin‐1 receptor antagonist (478 versus 330 pg mL^?1, P = 0.003) were elevated in the OSA group. The concentrations of C‐reactive protein increased, but IL‐1β decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro‐inflammatory, but also with the anti‐inflammatory systems.     

Impact of bone marker feedback on adherence to once monthly ibandronate for osteoporosis among Asian postmenopausal women

Aim: This study assesses the impact of serum carboxy‐terminal collagen crosslinks (CTX) bone marker feedback (BMF) on adherence to ibandronate treatment in Asian postmenopausal women with osteoporosis. Methods: This was a 12‐month (6‐monthly phased), randomized, prospective, open‐label, multi‐center study conducted in 596 (of 628 enrolled) postmenopausal women with osteoporosis (≤ 85 years old) who were naïve, lapsed, or current bisphosphonate users. Patients were randomized into two arms: serum CTX BMF at 3 months versus no‐BMF. Once‐monthly 150 mg ibandronate tablet was administered for 12 months and adherence to therapy was assessed at 6 and 12 months. In addition, patient satisfaction and safety of ibandronate treatment were also assessed. Results: Serum CTX BMF at 3 months showed no impact on adherence. The proportions of adherent patients were comparable in the BMF versus no‐BMF arms (92.6%vs. 96.0%, P = 0.16); overall, serum CTX levels were similar for adherent and non‐adherent patients. However, BMF patients felt more informed about their osteoporosis (P < 0.001) and more satisfied (P < 0.01) than no‐BMF patients. Conclusions: The Asian postmenopausal osteoporosis patients in this study had a high adherence rate to once‐monthly ibandronate therapy. Use of serum CTX BMF had no further impact on increasing adherence, but increased treatment satisfaction.     

Risk stratification and outcomes in hemodynamically stable patients with acute pulmonary embolism: a prospective, multicentre, cohort study with three months of follow-up

Summary.  Background:  The role of risk stratification in normotensive patients with acute pulmonary embolism (PE) is still unclear. Objectives:  We evaluated, in these patients, the usefulness of six prognostic markers for predicting in-hospital adverse events related to PE and 3-month mortality. Patients/Methods:  Two hundred and one consecutive patients with confirmed acute PE and normal blood pressure, who were administered conventional anticoagulation, were recruited in a multicentre prospective cohort study with 3 months of follow-up. At baseline, they received a comprehensive risk-evaluation including echocardiographic assessment of right ventricular dysfunction, determination of troponin I, brain natriuretic peptide and D-dimer, arterial blood gas analysis and a clinical score. Primary outcome of the study was PE-related in-hospital death or clinical deterioration. Secondary outcomes were in-hospital and 3-month all-cause mortality. Results:  The primary outcome occurred in one patient (0.5%), who died from PE during hospitalization. The in-hospital and 3-month all-cause mortality were 2% and 9%, respectively. None of the prognostic markers was predictive of the primary outcome. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality ( P  = 0.02, 0.01 and < 0.01, respectively). Clinical score (HR, 4.7; 95% CI, 1.9–12.0), D-dimer (4.8; 1.4–16.3), hypoxemia (5.7; 2.1–15.1) and troponin I (7.5; 2.5–22.7) were predictors of 3-month all-cause mortality on univariate analysis. On multivariate analysis clinical score and troponin I remained independently predictive. Conclusions:  We did not find prognostic markers useful as predictors of in-hospital PE-related adverse events. Clinical score, troponin I and hypoxemia predicted in-hospital all-cause mortality. Clinical score and troponin I independently predicted 3-month all-cause mortality.     

Thrombin generation in vitro in the presence of by-passing agents in siblings with severe haemophilia A

Summary.  Previous data have shown an inter-individual difference in the thrombin generating capacity in vitro as well as phenotypic bleeding pattern among patients with severe haemophilia A (FVIII:C activity below 1%). The reason for this is not known. In addition, there are no reports on how thrombin generation may correlate between siblings. In this study, we evaluated and compared thrombin generation in vitro using plasma samples in the presence of by-passing agents (FEIBA^® and NovoSeven^®) in 21 unrelated brother pairs with and without inhibitors enrolled in the Malmö International Brother Study (MIBS). Mean maximum thrombin formation in patients with a current inhibitor titer was 182.0 ± 52.8 mmol mL⁻¹ (FEIBA^®) and 130.7 ± 54.9 mmol mL⁻¹ (rFVIIa), respectively, and somewhat higher in those without inhibitors, 222.7 ±85.5 mmol mL⁻¹ (FEIBA^®) and 142.8 ±53.6mmol mL⁻¹ (rFVIIa) ( P  = 0.16 and 0.29). The variance regarding the maximum thrombin production within a family was significantly lower compared with the thrombin production between families ( P  < 0.001 for both FEIBA^® and NovoSeven^®). Our data indicate that genetically determined factors, other than the FVIII:C activity seems to influence the phenotypic variation in thrombin formation in the presence of by-passing agents. The nature of these determinants remains to be identified.     

Prognostic value of the ankle‐brachial index in elderly patients with a stable chronic cardiovascular event

Summary. Background and Objectives: Patients with polyvascular arterial disease have a greater risk of suffering a new atherothrombotic episode than those with involvement of only one vascular territory. We have studied the predictive prognostic value of the detection of non‐diagnosed peripheral arterial disease, determined by measuring the ankle‐brachial index in a population of elderly patients with stable chronic cardiac or cerebrovascular disease. Methods: This was a multicenter, prospective cohort study with consecutive inclusion of patients between 65 and 85 years of age with a previous atherothrombotic event, but without previously established peripheral arterial disease. Results: A total of 1096 patients were evaluated during 11.7 (± 2.2) months of follow‐up. An ankle‐brachial index of < 0.9 was observed in 29.9% and > 1.4 in 6.9%. The detection of an ankle‐brachial index < 0.9 was clearly associated with the presence of a combined primary event of cardiovascular death and non‐fatal cardiovascular event [HR 1.99 (95% CI, 1.49–2.66; P < 0.001)]. There was also a significant relationship between ankle‐brachial index > 1.4 and total (P = 0.001) or cardiovascular (P = 0.020) deaths. The predictive value of both ranges of the ankle‐brachial index was maintained after adjusting for age, sex, diabetes mellitus, vascular territory, macroalbuminuria or glomerular filtration rate. Conclusions: The detection of non‐diagnosed peripheral arterial disease in patients with stable coronary or cerebrovascular events identifies a very high risk population that might benefit from more intensive treatment.     

Uncertainty,lack of control and emotional functioning in women with metastatic breast cancer: a review and secondary analysis of the literature using the critical appraisal technique

WARREN M. (2010) European Journal of Cancer Care 19 , 564–574 Uncertainty, lack of control and emotional functioning in women with metastatic breast cancer: a review and secondary analysis of the literature using the critical appraisal technique A diagnosis of metastatic (or secondary) breast cancer is frequently more distressing than the diagnosis of a primary tumour since it indicates that the cancer is no longer curable. Relatively little is known, however, about women's experiences of this condition in comparison with those diagnosed with primary breast cancer. This paper therefore reports findings from a secondary analysis of the published literature on the topic using tools from the critical appraisal skills programme to identify and analyse appropriate papers, and the constant comparative method as a means of identifying any overarching or dominant themes emerging from the literature. Uncertainty, lack of control and poor emotional functioning emerged as the main themes affecting women with metastatic breast cancer. These are discussed in relation to their antecedents in the original studies and their implications for nursing care. The themes demonstrate that living with metastatic (or secondary) breast cancer is a multifaceted experience that is influenced by a large number of factors, many of which are under‐researched in comparison with those affecting women diagnosed with primary disease. It is clear, however, that women affected by the condition need a great deal more support than they currently receive, and new services may be required to meet these needs.     

Infertility and subfecundity in population-based samples from Denmark, Germany, Italy, Poland and Spain

Background: No uniform data which give basic Information onthe societal burden of infertility and subfecundity exists inEurope. Methods: In a population-based survey the prevalenceof subfecundity was ascertained by means of a standardized interviewwith women in Denmark, Germany, Poland, Italy and Spain. Thetime of unprotected intercourse (TUI) either leading or notleading to pregnancy was applied as a uniform measure of fecundity.Population-based samples of women 25–44 years of age wererecruited. Results: Altogether 6,630 women participated in thestudy. With regard to the first pregnancy, 19% of all coupleshad a TUI of more than 12 months, which is within the rangeof most previous findings. Regarding the most recent and firstTUI in individual lives, if it had occurred within previous5 years, 23.4% overall did not conceive within 12 months (inPoland 33.3%, in north Italy and Germany 26.2%, in Denmark 23.3%,in Spain 18.6% and in south Italy 14.8%). Secondary subfecunditywas more prevalent in Poland. When stratifying for planningof a pregnancy, the differences between countries diminished,particularly for the most recent TUI. However, the pattern ofa higher prevalence of subfecundity in Poland, north Italy,Denmark and Germany and a lower prevalence (<20%) in Spainand south italy remains. Conclusions: Important differencesin the prevalence of subfecundity exist between the six Europeanregions investigated. Comparisons should first consider TUIsor planned TUIs to reduce the impact of distorting factors,which are mainly due to differing cultures of family planningin Europe.     

A Randomized Controlled Clinical Trial Comparing Ventricular Fibrillation Detection Time Between Two Transvenous Defibrillator Models

The Ventak AV is an implantable cardioverter defibrillator with dual chamber pacing capability. Features include detection and treatment of ventricular arrhythmias, detection of atrial arrhythmias, as well as dual chamber pacing. The objective of the investigation was to verify the efficacy of the Ventak AV in detecting ventricular fibrillation in the presence of dual chamber pacing. Thirty-three patients, who were to receive an implantable defibrillator were randomized (1:1) in a paired comparison study to the Ventak AV (study device) and the Ventak Mini (control) during defibrillation threshold testing. In order to create a "worst case scenario" for sensing of ventricular fibrillation, pacing was performed at high lower rate limit values (Ventak AV DDD pacing at 150/min, Ventak Mini at VVI 100/min). Ventricularfibrillation was induced and the randomized device was allowed to detect and treat the arrhythmia. This test was repeated for each patient using the alternate device in a randomized order, such that all patients were tested with both devices. The mean ventricular fibrillation detection time for the Ventak AV was 2.0+/-0.11 seconds and for the control device the detection time was 1.8+/-0.11 seconds (P = 0.26). Appropriate tachyarrhythmia therapy decision was documented in all episodes for both devices. The study patient population demonstrated equivalent ventricular fibrillation detection time between the Ventak AV and the Ventak Mini. The Ventak AV demonstrated effectiveness in detecting ventricular fibrillation in the presence of high rate dual chamber pacing.     

Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer

The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III-IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening.