Dacomitinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: To assess the cost-effectiveness of first-line treatment with dacomitinib compared with gefitinib in patients newly diagnosed with advanced NSCLC EGFR-positive in the context of Spain. Materials & methods: A partitioned survival model was developed including costs, utilities and disutilities to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with dacomitinib versus gefitinib. Results: Dacomitinib presented higher QALYs (0.51) compared with gefitinib (0.45). Dacomitinib costs were €33,061 in comparison with €26,692 for gefitinib arm. An incremental cost-effectiveness ratio of €111,048 was obtained for dacomitinib. Conclusion: Dacomitinib was more effective in terms of QALYs gained than gefitinib. However, to obtain a cost-effectiveness alternative, a discount greater than 25% in dacomitinib acquisition cost is required.

Sustainable Production of Hydrogen by Steam Reforming of Ethanol Using Cobalt Supported on Nanoporous Zeolitic Material.

Cobalt catalysts supported on Y zeolite and mesoporized Y zeolite (Y-mod) have been studied in steam reforming of ethanol (SRE). Specifically, the effect of the mesoporosity and the acidity of the y zeolite as a support has been explored. Mesoporous were generated on Y zeolite by treatment with NH4F and the acidity was neutralized by Na incorporation. Four cobalt catalysts supported on Y zeolite have been prepared, two using Y zeolite without mesoporous (Co/Y, Co/Y-Na), and two using Y zeolite with mesoporous (Co/Y-mod and Co/Y-mod-Na). All catalysts showed a high activity, with ethanol conversion values close to 100%. The main differences were found in the distribution of the reaction products. Co/Y and Co/Y-mod catalysts showed high selectivity to ethylene and low hydrogen production, which was explained by their high acidity. On the contrary, neutralization of the acid sites could explain the higher hydrogen selectivity and the lower ethylene yields exhibited by the Co/Y-Na and Co/Y-mod-Na. In addition, the physicochemical characterization of these catalysts by XRD, BET surface area, temperature-programmed reduction (TPR), and TEM allowed to connect the presence of mesoporous with the formation of metallic cobalt particles with small size, high dispersion, and with high interaction with the zeolitic support, explaining the high reforming activity exhibited by the co/y-mod-Na sample as well as its higher hydrogen selectivity. It has been also observed that the formation of coke is affected by the presence of mesoporous and acidity. Both properties seem to have an opposite effect on the reforming catalyst, decreasing and increasing the coke deposition, respectively.

Test de PCR a SARS-CoV-2 persistentemente positivo. No siempre la detección del virus es COVID-19 / PCR test for SARS-CoV-2 persistently positive. Virus detection is not always COVID-19

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Osimertinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: Osimertinib improves progression-free survival in first-line EGFR mutation-positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR-TKIs (0.42). Osimertinib costs were €83,258.99, in comparison with €29,209.45 for the standard EGFR-TKIs. An incremental cost-effectiveness ratio of €273,895.36/QALY was obtained for osimertinib. Conclusion: Osimertinib was more effective in terms of QALYs gained than comparators (erlotinib-gefitinib). However, to obtain a cost-effectiveness alternative, a discount greater than 60% in osimertinib acquisition cost is required.

Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 Phase II Multicenter Trial.

BACKGROUND: The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma. METHODS: We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR). RESULTS: On an intent-to-treat analysis, the ORR was 78% (n = 36; 95% confidence interval [CI]: 63%-89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9-33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75% (95% CI: 60%-85%), and the 2-year local relapse rate was 2% (95% CI: 0%-11%). CONCLUSION: In this selected population, initial chemotherapy results in promising activity, but the observed toxicity does not support further investigation of this specific regimen. Nevertheless, these early results warrant further testing of this strategy in an enriched population and in randomized trials.

Rethinking classification of prematurity: a new clinical algorithm that improves etiologic assignment of preterm births.

BACKGROUND: There is a need for a better etiologic classification of preterm births and for tools to help to determine the possible etiologies of these births. OBJECTIVE: Having previously developed the Barcelona Etiology of Prematurity (BEP) algorithm, based on a new classification for preterm births, we sought to validate this algorithm in clinical studies whereby doctors retrospectively assigned the etiology of preterm birth according to principal cause and associated causes. METHOD: In phase 1 of the study, 91 preterm neonates consecutively admitted to a tertiary hospital were etiologically classified by doctors using the BEP algorithm. In phase 2, another 29 cases, representing the full spectrum of standard clinical scenarios, were classified by 20 doctors randomly divided into two groups of 10: one group used the algorithm and the other did not. RESULTS: In phase 1, the doctors were able to assign the etiology of all 91 clinical cases using the BEP algorithm, showing a 95.6% level of agreement with the etiologies set by the authors. In phase 2, for the 572 total evaluations, the group that used the BEP algorithm had significantly fewer errors in assigning the principal cause of prematurity than the group that did not use the algorithm (4.51 vs. 16.20%, respectively; p < 0.0001), and also demonstrated a higher level of correlation in assigning the associated causes. CONCLUSIONS: The proposed classification may be used to retrospectively categorize the etiology of preterm births, and the BEP algorithm facilitates this task enabling greater accuracy and precision in clinical data.

Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study.

PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.

Effectiveness of physical activity advice and prescription by physicians in routine primary care: a cluster randomized trial.

BACKGROUND: Physical activity promotion is a priority, but contribution of physicians' interventions is unclear. The effectiveness of the PEPAF ("Experimental Program for Physical Activity Promotion"), which was implemented exclusively by physicians in routine primary care from October 2003 to December 2004, was assessed. METHODS: Fifty-six Spanish family physicians were randomized to either the intervention (n = 29) or standard care (n = 27) arm of the trial. The physicians recruited 4317 physically inactive patients (2248 for intervention and 2069 for control protocols) from a systematic sample after assessing their physical activity in routine practice. Intervention physicians provided advice to all patients and a physical activity prescription to the subgroup attending an additional appointment (30%). The main outcome measure was the change in physical activity measured by blinded nurses using the 7-Day Physical Activity Recall. Secondary outcomes included cardiorespiratory fitness and health-related quality of life. RESULTS: At 6 months, intervention patients increased physical activity more than controls (adjusted difference, 18 min/wk [95% confidence interval, 6-31 min/wk]; metabolic equivalent tasks x hours per week, 1.3 [95% CI, 0.4-2.2]). The proportion of the population achieving minimal physical activity recommendations was 3.9% higher in the intervention group (1.2%-6.9%; number needed to treat, 26). No differences were found in secondary outcomes. The effect of intervention was positively modified in subjects older than 50 years (P < or = .01) and in the prescription subgroup (P < .001). CONCLUSIONS: Family physicians were effective for increasing physical activity of primary care patients. Overall clinical effect was small but relevant for population public health. Within the intervention program, clinically relevant effects were seen in patients receiving a physical activity prescription. Trial Registration clinicaltrials.gov Identifier: NCT00131079.

Targeting physical activity promotion in general practice: characteristics of inactive patients and willingness to change.

BACKGROUND: Counselling in routine general practice to promote physical activity (PA) is advocated, but inadequate evidence is available to support this intervention, and its sustainable implementation over time is difficult. OBJECTIVES: To describe the characteristics of physically inactive adults visiting GPs and the factors associated with their willingness to change PA. METHODS: A cross-sectional analysis of 4317 Spanish people aged 20-80 years, selected by systematic sampling among those attending 56 public primary health care practices identified as inactive by their GPs in 2003. PA (7-day PAR), PA stage of change, health-related quality of life (SF-36), cardiovascular risk factors, and social and demographic characteristics were measured. Multivariate mixed effects ordinal logistic models were adjusted to identify factors associated with motivational readiness to change. RESULTS: At least 70% (95% CI: 67.6% to 72.8%) of patients assessed by GPs did not achieve minimal PA recommendations. In addition, 85% (95% CI: 83% to 86.3%) had at least an additional cardiovascular risk factor. Only 30% (95% CI: 25.8% to 33.5%) were prepared for or attempting a change. A younger age; retirement or work at home; higher education and social class levels; obesity; and hypertension were associated with a higher motivational readiness to change (p < 0.05). CONCLUSION: The overburden that would result from counselling such a high proportion of inactive primary care patients justifies a targeted strategy for PA promotion in family practice. Selection of a target population based on readiness to change, the combination of risk factors and socio-demographic characteristics of patients is suggested in order to prioritise promotion efforts.

Peritonitis biliar tras la retirada del tubo en T / Biliary peritonitis following T tube removal

La proteccion de una sutura biliar con tubo en T (kehr), es una practica habitual en cirugia digestiva. Normalmente es un drenaje que no presenta complicaciones. El proposito de esta comunicacion es presentar dos casos de peritonitis biliar tras retirada electiva de un tubo de kehr. Esta es una rara y grave complicacion que requiere un diagnostico precoz y correccion quirurgica inmediata