A phase II study of capecitabine plus oxaliplatin (XELOX): a new first-line option in metastatic colorectal cancer

Background: Capecitabine and oxaliplatin are both effective and well-tolerated monotherapies for the treatment of advanced colorectal cancer (CRC). Oxaliplatin has also been shown to be very effective when combined with 5-FU/LV in the first-line setting. Aim of the Study: Assess the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with previously untreated advanced CRC. Methods: Fifty-three patients with measurable disease received capecitabine 1,000 mg/m² twice daily on d 1–14 and oxaliplatin 130 mg/m² on d 1, every 3 wk. Of these, 52 were evaluable for safety and 49 for antitumor response. Results: There was a low rate of grade 1/2 adverse events; grade 3/4 events included leukopenia (10%), neutropenia (6%), thrombocytopenia (2%), nausea/vomiting (4%), and diarrhea (4%). The overall response rate was 39% (95% CI, 25–54%) and median time to disease progression was 7.8 mo. Conclusions: XELOX is an active and well-tolerated first-line treatment for advanced CRC. Randomized phase III studies are ongoing to compare XELOX with FOLFOX in view of the comparable efficacy and safety but superior convenience of XELOX therapy. Presented in part at the 39th American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 31–June 3, 2003.     

A comparative study of postendoscopic sphincterotomy complications with various types of electrosurgical current in patients with choledocholithiasis

BACKGROUND: Whether the type of electrosurgical current used for endoscopic sphincterotomy influences the frequency of postsphincterotomy complications is unknown. METHODS: One hundred eighty-six patients with choledocholithiasis were prospectively randomized to undergo endoscopic sphincterotomy with pure cutting current (n = 62, Group A), blended current (n = 62, Group B), or pure cutting initially followed by blended current (n = 62, Group C). Serum concentrations of amylase and lipase were evaluated in all patients 12 and 24 hours after sphincterotomy. Clinical pancreatitis was classified as mild, moderate, or severe. Postsphincterotomy bleeding was defined as a decrease in hematocrit of greater than 5%. RESULTS: Serum concentrations of amylase and lipase were greater in Groups B and C at 12 and 24 hours after the procedure, as compared with Group A. Clinical mild pancreatitis occurred in 2 patients in Group A (3.2%), 8 in Group B (12.9%), and in 8 in Group C (12.9%). The differences were statistically significant for Group A compared with either Group B or Group C (p = 0.048). Postsphincterotomy bleeding occurred in 3 patients (1.6%), one in each group. CONCLUSION: The use of pure cutting electrosurgical current during endoscopic sphincterotomy in patients with choledocholithiasis is associated with a lesser degree of pancreatic enzyme elevation and lower frequency of pancreatitis, whereas bleeding is not increased compared with blended current. Changing from pure cutting to blended current after the first 3 to 5 mm of the incision is associated with an increased rate of complications compared to the use of pure cutting current for the entire sphincterotomy.     

How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre‐test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non‐cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), LV filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F₁: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F₂: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.     

Epidemiology,pathophysiology and contemporary management of cardiogenic shock – a position statement from the Heart Failure Association of the European Society of Cardiology

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus‐driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high‐quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in‐hospital management.     

Patterns of Child and Adolescent Mental Health Care in Greece

During the last 20 years the mental health care system in Greece underwent a dramatic change; the implementation of the EEC Reg. 815/84 programme contributed to a significant shift towards the extramural care and rehabilitation of patients with long-term mental health problems. The child and adolescent mental health (CAMH) care system was transformed by this change to a lesser degree. Despite bureaucratic obstacles and other difficulties, a substantial number of CAMH outpatient services have been developed in Greece. They are concentrated mainly in the larger cities and they focus on providing assessment and to some extent therapy and counselling; prevention and promotion of CAMH are not yet perceived as priority areas. In addition, there is a lack of specialised day care services for specific populations such as young people with disorders of the autistic spectrum and intellectual disabilities. There have been some recent improvements in education and research in the field of CAMH but these sectors are in need of further investment and development. Unfortunately, the current economic crisis has affected both the development of new services and the optimal functioning of those already in operation. Nevertheless, Greece must invest in CAMH and the rights of the children and young people should be protected.     

A series of 22 patients with adult-onset Still's disease presenting with fever of unknown origin. A difficult diagnosis?

Adult-onset Still's disease (AOSD) remains a perplexing, difficult to diagnose clinical entity, with clinical characteristics that are often broad and encountered in numerous other clinical entities. This vague clinical presentation is depicted in the commonly used diagnostic criteria, as the ones by Yamaguchi and Fautrel. The authors sought to investigate how diagnostic criteria apply in a series of 22 new cases of AOSD patients presenting with fever of unknown origin (FUO) and diagnosed at the Internal Medicine Department of Hatzikosta General Hospital of Ioannina, Greece. The aims of the study were: (1) to study the incidence of AOSD and (2) to retrospectively apply different classifications to the data of these patients in search of a more efficient way of diagnosing these patients in the future. The annual incidence of AOSD was estimated at two new cases per 10⁵. The clinical manifestations of the patients are discussed, with an emphasis on specific manifestations being considered as criteria by Yamaguchi and Fautrel classifications. Four patients exhibited markedly increased serum d-dimers, a finding of which the potential pathophysiologic implications are discussed. Serum ferritin levels have additive values, both for diagnostic and cost-reduction purposes in cases presenting as FUO; serum ferritin values are not included in any diagnostic set of criteria at present. The finding of high levels of d-dimers in AOSD needs further studies.     

Automated Office Blood Pressure is Associated with Urine Albumin Excretion in Hypertensive Subjects

BackgroundWe aimed to investigate the association between automated office blood pressure (AOBP) readings and urine albumin excretion (UAE), and to assess if this association is as close as that between 24-h ambulatory blood pressure (ABP) and UAE. A strong association would suggest that AOBP may serve as an indicator of early renal impairment.MethodsIn a sample of 162 hypertensives, we compared AOBP with ABP measurements and their associations with UAE in two consecutive 24-h urine collections measured by an immunoturbidimetric assay. Microalbuminuria was defined as UAE of 30-300 mg/24 h.ResultsThe age of the subjects was 53 ± 13 (mean ± s.d.) years. Twenty-two were microalbuminuric. In those, AOBP and 24-h ABP were higher than in the normoalbuminuric subjects: 152 ± 19 and 147 ± 20 vs. 138 ± 15 and 130 ± 11 mm Hg for systolic blood pressure (SBP), and 97 ± 15 and 92 ± 14 vs. 86 ± 10 and 82 ± 8 mm Hg for diastolic blood pressure (DBP) (P < 0.001). Correlations between AOBP and 24-h ABP with log-transformed urine albumin were 0.30 (P < 0.001) and 0.43 (P < 0.001) for SBP and 0.27 (P < 0.001) and 0.33 (P < 0.001) for DBP. Adjusting for age, sex, body mass index, and estimated glomerular filtration rate, both AOBP and 24-h ABP were independently associated with urine albumin (P < 0.001 for both associations). Receiver operating characteristics curve analysis showed a similar predictive ability for microalbuminuria for AOBP and for 24-h ABP (area under the curve: 0.819 (P < 0.001) for SBP, 0.836 (P < 0.001) for DBP vs. 0.830 (P < 0.001) for SBP and 0.845 (P < 0.001) for DBP).ConclusionsIn this study, microalbuminuria correlated similarly with high-quality AOBP and ABP readings, further supporting the use of AOBP in the clinical setting.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.76.     

A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90?days: analysis from the EVEREST trial

Hospitalization for worsening chronic heart failure results in high post-discharge mortality, morbidity, and cost. However, thorough characterization, soon after discharge of patients with early post-discharge events has not been previously performed. The objectives of this study were to describe the baseline, in-hospital, and post-discharge clinical, laboratory, and neurohormonal profiles of patients hospitalized for worsening heart failure with reduced ejection fraction (EF) who die or are re-admitted for cardiovascular (CV) causes within 90 days of initial hospitalization. Retrospective analysis of 4,133 patients hospitalized for worsening heart failure with EF ≤40% in the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which randomized patients to tolvaptan or placebo, both in addition to standard therapy. Clinical and laboratory parameters were obtained within 48?h of admission, during hospitalization, and post-discharge weeks 1, 4, 8, and every 8?weeks thereafter for a median of 9.9?months. Patients with events within 90?days were compared with those with later/no events. All-cause mortality (ACM) and CV re-hospitalization were independently adjudicated. Within 90?days of admission, 395 patients (9.6%) died and 801 patients (19.4%) were re-hospitalized for CV causes. Significant baseline and longitudinal differences were seen between groups with early versus later (>90?days) or no events at 12?months post-randomization. Post-discharge outcomes were similar in the tolvaptan and placebo groups. Patients with early post-discharge events experienced clinically significant worsening in signs and symptoms, laboratory values, and neurohormonal parameters soon after discharge. Identifying these abnormalities may facilitate efforts to reduce post-discharge mortality and re-hospitalization.