A novel biweekly multidrug regimen of gemcitabine, oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) in pretreated patients with advanced colorectal carcinoma

Previous results suggest that GEM affects 5-fluorouracil (5-FU) metabolism and pharmacokinetics in cancer patients, while combined with oxaliplatin, levo-folinic acid, and 5-FU (GOLF regimen), at doses achievable in cancer patients, determines high cytotoxic and proapoptotic antitumour activity in colon cancer cells in vitro. On these bases we designed a phase I–II clinical trial testing the GOLF regimen in patients with metastatic colorectal carcinoma, who had received at least a prior line of chemotherapy. In total, 29 patients (20 males and nine females) enrolled in the study received every 2 weeks, gemcitabine (patients #1–3 received 600 mgm2; patients # 4–6 received 850 mgm2; while patients # 7–29 received 1000 mgm2) on the day 1, levo-folinic acid (100 mgm2) on the days 1 and 2; 5-fluorouracil (400 mgm2) in bolus injection, followed by a 22-h continuous infusion (800 mgm2) on the days 1 and 2, and oxaliplatin (85 mgm2), 6 h after the 5-FU bolus on day 2. The most frequent side effect was grade I–II haematological toxicity. In total, 28 patients were evaluable for response: three achieved a complete response, nine a partial response, 10 had a stable disease, and six progressed. The average time to progression and overall survival of the patients was, respectively, 7.26 and 22 months. Our GOLF combination is well tolerated and seems promising for the treatment of advanced colorectal cancer

Bloating is associated with worse quality of life, treatment satisfaction, and treatment responsiveness among patients with constipation-predominant irritable bowel syndrome and functional constipation

Background: The management of bloating is unclear and its relationship with patients' well-being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient-reported outcomes. Methods: Thirty-nine centers for functional gastrointestinal disorders joined the laxative inadequate relief survey. We enrolled 2203 consecutive outpatients with functional constipation (FC) or constipation-predominant irritable bowel syndrome (IBS-C) in two cross-sectional waves. Both wave 1 and 2 included the SF-12, the patient assessment of constipation-symptoms (PAC-SYM), and the treatment satisfaction questionnaire for medication (TSQM-2). Wave 2 only included a global rating of change (GRC) scale to assess patients' assessment of efficacy concerning treatment switches occurred in the 3 months prior to the interview. Bloating in the abdomen was defined on the basis of PAC-SYM item 3. Key Results: The average age was 50.1 years (SD, 16.7) and 82.1% of patients were women. The prevalence of bloating was 91.6% (n = 1970). Bloating was associated with SF-12 Physical Composite Score (p < 0.01), SF-12 Mental Composite Score (p < 0.01), GRC (p < 0.01), Satisfaction with treatment effectiveness (p < 0.01), convenience of administration (p < 0.01), and side effects (p < 0.01) after adjustment for possible confounders. Conclusions & Inferences: Our data suggest that patients regard bloating as a key element in assessing clinical changes and treatments' efficacy as this symptom exerts a strong influence on patient-reported outcomes independent of possible confounders and other symptoms of constipation. Our data provide the rationale to investigate the efficacy and tolerability of new treatments specifically addressing this important, yet disregarded, patients' complain

Confirmatory factor analysis of the Patient Assessment of Constipation-Symptoms (PAC-SYM) among patients with chronic constipation

PAC-SYM is widely adopted to asses constipation severity. However, it has been validated in a small sample, few items have been included based on expert opinion and not on empirical grounds, and its factor structure has never been replicated. We aimed at evaluating the psychometric properties of PAC-SYM in patients with chronic constipation

High Intensity Kaon Experiments (HIKE) at the CERN SPS Proposal for Phases 1 and 2

A timely and long-term programme of kaon decay measurements at an unprecedented level of precision is presented, leveraging the capabilities of the CERN Super Proton Synchrotron (SPS). The proposed HIKE programme is firmly anchored on the experience built up studying kaon decays at the SPS over the past four decades, and includes rare processes, CP violation, dark sectors, symmetry tests and other tests of the Standard Model. The programme is based on a staged approach involving experiments with charged and neutral kaon beams, as well as operation in beam-dump mode. The various phases will rely on a common infrastructure and set of detectors

High Intensity Kaon Experiments (HIKE) at the CERN SPS Proposal for Phases 1 and 2

International audienceA timely and long-term programme of kaon decay measurements at an unprecedented level of precision is presented, leveraging the capabilities of the CERN Super Proton Synchrotron (SPS). The proposed HIKE programme is firmly anchored on the experience built up studying kaon decays at the SPS over the past four decades, and includes rare processes, CP violation, dark sectors, symmetry tests and other tests of the Standard Model. The programme is based on a staged approach involving experiments with charged and neutral kaon beams, as well as operation in beam-dump mode. The various phases will rely on a common infrastructure and set of detectors