Application of a cost-effective methodology for the refurbishment of DOCOMOMO buildings. A case study in Northern Spain.

The energy rehabilitation of listed buildings guaranteeing heritage values but allowing a use that contributes to their conservation, supposes a challenge with the need of a holistic approach. Buildings of the Modern Movement, many of which are registered as DOCOMOMO (DOcumentation and COnservation of buildings, sites and neighbourhoods of the MOdern Movement), are a particular case since many of them are not yet listed or are under unclear requirements. This paper explores the inclusion of a cost-effective methodology as part of the decision-making in the energy rehabilitation of these DOCOMOMO buildings, applying it to the case study of an office building located in the north of Spain. Different scenarios were studied balancing cost-effectiveness, energy efficiency and rehabilitation requirements. In this case study, the analysis may allow policymakers to have supportive arguments to subsidize certain elements (as e.g., steel frames), or allow the use of alternative options with similar aesthetic characteristics, but at a much lower cost. This second option will constitute the unique cost-effective scenario, with energy savings of between 25.36 % and 38.8 %. The inclusion of a cost-effective methodology as part of the mechanics for decision-making in the energy refurbishment of DOCOMOMO buildings permits the optimisation of the intervention guaranteeing their use and the conservation of heritage values.

Effect of Encapsulated Purple Garlic Oil on Microvascular Function and the Components of Metabolic Syndrome: A Randomized Placebo-Controlled Study-The ENDOTALLIUM Study.

Endothelial dysfunction (ED) is associated with progressive changes contributing to clinical complications related to macro- and microvascular diseases. Garlic (Allium sativum L.) and its organosulfur components have been related to beneficial cardiovascular effects and could improve endothelial function. The ENDOTALLIUM Study aimed to evaluate the effect of the regular consumption of encapsulated purple garlic oil on microvascular function, endothelial-related biomarkers, and the components of metabolic syndrome (MetS) in untreated subjects with cardiometabolic alterations. Fifty-two individuals with at least one MetS component were randomized (1:1) in a single-center, single-blind, placebo-controlled, parallel-group study. The participants received encapsulated purple garlic oil (n = 27) or placebo (n = 25) for five weeks. Skin microvascular peak flow during post-occlusive reactive hyperemia significantly increased in the purple garlic oil group compared to the placebo group (between-group difference [95%CI]: 15.4 [1.5 to 29.4] PU; p = 0.031). Likewise, hs-CRP levels decreased in the purple garlic group compared to the control group (-1.3 [-2.5 to -0.0] mg/L; p = 0.049). Furthermore, we observed a significant reduction in the mean number of MetS components in the purple garlic group after five weeks (1.7 ± 0.9 vs. 1.3 ± 1.1, p = 0.021). In summary, regular consumption of encapsulated purple garlic oil significantly improved microvascular function, subclinical inflammatory status, and the overall MetS profile in a population with cardiometabolic alterations.

Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry.

PURPOSE: The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. METHODS: HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1-3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). RESULTS: A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003-10 (210), and GEICAM-2006-10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. CONCLUSIONS: This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted. TRIAL REGISTRATION: ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127.

Survival impact of primary tumor resection in de novo metastatic breast cancer patients (GEICAM/El Alamo Registry).

The debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach's outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990-2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study's criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results.

Impact of an osteoporosis specialized unit on bone health in breast cancer survivals treated with aromatase inhibitors.

OBJECTIVE: Considering the increased fracture risk in early breast cancer patients treated with aromatase inhibitors (AI), we assessed the impact of a preventive intervention conducted by a specialized osteoporosis unit on bone health at AI treatment start. MATERIAL AND METHODS: Retrospective cohort of postmenopausal women who started treatment with AI after breast cancer surgical/chemotherapy treatment and were referred to the osteoporosis unit for a comprehensive assessment of bone health. Bone densitometry and fracture screening by plain X-ray were performed at the baseline visit and once a year for 5 years. RESULTS: The final record included 130 patients. At AI treatment start, 49% had at least one high-risk factor for fractures, 55% had osteopenia, and 39% osteoporosis. Based on the baseline assessment, 79% of patients initiated treatment with bisphosphonates, 88% with calcium, and 79% with vitamin D. After a median of 65 (50-77) months, 4% developed osteopenia or osteoporosis, and 14% improved their densitometric diagnosis. Fifteen fractures were recorded in 11 (8.5%) patients, all of them receiving preventive treatment (10 with bisphosphonates). During the follow-up period, patients with one or more high-risk factors for fracture showed a greater frequency of fractures (15% vs. 3%) and experienced the first fracture earlier than those without high-risk factors (mean of 99 and 102 months, respectively; P=0.023). CONCLUSIONS: The preventive intervention of a specialized unit at the start of AI treatment in breast cancer survivors allows the identification of patients with high fracture risk and may contribute to preventing bone events in these patients.

Incidence of chemotherapy-induced nausea and vomiting with moderately emetogenic chemotherapy: ADVICE (Actual Data of Vomiting Incidence by Chemotherapy Evaluation) study.

PURPOSE: This study aims to determine the incidence of nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC), under medical practice conditions and the accuracy with which physicians perceive CINV. METHODS: Chemotherapy-naive patients receiving MEC between April 2012 and May 2013 were included. Patients completed a diary of the intensity of nausea and number of vomiting episodes. Complete response and complete protection were assessed as secondary endpoints. RESULTS: Of 261 patients included, 240 were evaluated. Median age was 64 years, 44.2 % were female and 11.2 % were aged less than 50 years; 95.3 % of patients received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist + corticosteroid as antiemetic treatment. Vomiting within 5 days of chemotherapy administration occurred in 20.8 %, nausea in 42 % and significant nausea in 23.8 % of patients. An increase in the percentage of patients with significant nausea (from 9.4 to 21.7 %) and vomiting (from 9.2 to 16.5 %) was observed from the acute to the delayed phase. Complete response was 84.2 % in the acute phase, 77 % in the late phase and 68.9 % in overall period. Complete protection was 79.5 % in the acute phase, 68.8 % in the late phase and 62.4 % throughout the study period. Physicians estimated prophylaxis would be effective for 75 % of patients receiving MEC, compared with 54.1 % obtained from patients' diary. CONCLUSION: Despite receiving prophylactic treatment, 31 % of patients did not achieve a complete response and 38 % complete protection. In general, nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis.

Analysis of the changes induced by bevacizumab using a high temporal resolution DCE-MRI as prognostic factors for response to further neoadjuvant chemotherapy.

BACKGROUND: Antiangiogenic drugs are being used in the treatment of locally advanced breast cancer. The effect of these drugs can be monitorized using high temporal resolution dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). PURPOSE: To evaluate changes in tumor microvasculature induced by bevacizumab and the usefulness of these changes predicting response to further neoadjuvant therapy. MATERIAL AND METHODS: Seventy patients with locally advanced breast cancers were treated with one cycle of bevacizumab followed by neoadjuvant therapy, combining bevacizumab and cytotoxic chemotherapy. Two DCE-MRI were performed before and after bevacizumab. Changes in tumoral volume, pharmacodynamic curves, and pharmacokinetic variables (K(trans), Kep, Ve, AUC90) in a ROI (ROI 1) encompassing the entire tumor and in another ROI (ROI 2) in the area of higher values of K(trans) were analyzed. Correlations with pathological response were made: parametrical and non-parametrical statistical analysis and ROC curves were used; a P < 0.05 was considered significant. RESULTS: Significant changes in tumoral volume (-4%), pharmacodynamic curves, and pharmacokinetic variables in ROI 1 K(trans) (-45%), Kep (-38%), Ve (-11%), and AUC90 (-44%) and ROI 2 K(trans) (-43%), Kep (-39%), Ve (-5%), and AUC90 (-45%) were observed after bevacizumab (P < 0.05). The effect of bevacizumab was not different between responders and non-responders (P > 0.05), and these changes could not predict response to further neoadjuvant therapy. CONCLUSION: Bevacizumab induces remarkable tumoral volume, pharmacodynamics, and pharmacokinetic changes. However, these changes could not be used as early predictors for response to further neoadjuvant therapy.

Bone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: results from a 2-year multicentre observational study (ZOMAR study).

BACKGROUND: We evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied. METHODS: In a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4mg every 28days) from the baseline visit. RESULTS: 234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3months (P<0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214-20.839; P=0.0259]) and at 3months (3.41 [95% CI: 1.367-8.498; P=0.0085]). HRs >2 were found for increased baseline and 3-month levels of NTX and CTC (P<0.05). Only increased baseline BSAP levels were associated with DP (HR=2.25 [95% CI: 1.391-3.626; P=0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3months of NTX and BSAP were significantly associated with mortality (HRs=3.59 [95% CI: 1.375-9.382; P=0.0091] and 3.25 [95% CI: 1.293-8.189; P=0.0120], respectively). CTC and BSAP were correlated during all study timepoints (P<0.05). CONCLUSIONS: Baseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value.

[Avoidable mortality. Changes in the new century?]. / La mortalidad evitable. Cambios en el nuevo siglo?

OBJECTIVES: To analyze time trends and the geographical distribution of avoidable mortality in the autonomous community of Valencia and its health departments by sex in the periods 1990-1994, 1995-1999, and 2000-2004. MATERIAL AND METHOD: Twenty-one causes of avoidable mortality were analyzed. The deaths analyzed corresponded to residents in the autonomous community of Valencia between 1990 and 2004. Age-standardized mortality rates were calculated using the direct method. To study time trends in the geographical area of interest for each period and sex, comparative mortality ratios were calculated. To analyze geographical distribution, standardized mortality rates were calculated by the indirect method. RESULTS: The total number of avoidable deaths was 38,061 (7.1% of overall deaths). Men accounted for 76.2% and women for 23.8%. By groups, 82.4% were preventable and 17.6% were treatable. Preventable deaths represented 86.5% of deaths in men and 69.4% of those in women. Avoidable mortality in Valencia significantly decreased in both sexes, this decrease being more marked in the group of treatable deaths and in men. Mortality from lung cancer in women significantly increased. Between 2000 and 2004, none of the health departments showed a significant excess of treatable mortality. CONCLUSIONS: In the autonomous community of Valencia, there was a greater decrease in avoidable mortality than in general mortality. The increase in lung cancer in women was notable.

Description, etiology, and prevention of an outbreak of diffuse lamellar keratitis after LASIK.

PURPOSE: To describe an outbreak of diffuse lamellar keratitis (DLK) and provide a hypothesis about the etiology. METHODS: A retrospective analysis was carried out on 328 eyes of 220 patients who underwent LASIK over 9 months. The occurrence of DLK using two different methods of cleaning and sterilizing surgical instruments and an autoclave reservoir were analyzed. Microbial analyses were carried out by two laboratories on samples obtained from the original autoclave reservoir and tubing. A chi-square test was used to compare qualitative values. The Student t test was used to compare numerical values. RESULTS: Forty-six (24.5%) of 188 cases of DLK were diagnosed. Sphingomona paucimobilis and Burkholderia pickettii were isolated in the reservoir of the steam sterilizer. Electron microscopy revealed gram-negative microbes on the tubing walls. After changing the reservoir of the steam sterilizer and implementing a new cleaning and sterilization protocol based on air-drying the instruments and draining and drying the reservoir of the sterilizer, the occurrence of DLK stopped. No statistically significant correlation was noted between the occurrence of DLK and gender, age, or volume of tissue removed. CONCLUSIONS: Data obtained during this DLK outbreak support the theory that a bacterial endotoxin, which can survive short-cycle steam sterilization, could be responsible for an outbreak of DLK. We recommend cleaning and sterilization protocols based on air-drying surgical instruments and leaving the reservoirs completely dry at the end of each surgical day.

[Mortality surveillance in cities: results in Valencia and Alicante, [Spain]]. / Análisis de la mortalidad en ciudades: resultados en Valencia y Alicante.

OBJECTIVES: To describe mortality patterns, in general and by selected specific causes in Valencia and Alicante, to establish internal inequalities by districts, and to evaluate changes in the magnitude of these inequalities over time. METHODS: Deaths among residents of Valencia and Alicante in the periods 1990-1992 and 1996-1998 were assigned to residential municipal districts. Comparisons between the periods studied and between cities were carried out using the relative risk derived from a Poisson regression model. A comparative mortality figure was calculated using the 17 largest groups of the 9th International Classification of Diseases. Rates adjusted by the direct method, standardized mortality ratio, potential years of life lost (PYLL) ratio and life expectancy at birth were calculated by districts in each study period. RESULTS: The risks of death from all causes decreased between the first and second periods in both men and women in both cities. Life expectancy significantly increased in both cities for men and in Valencia for women. The city of Valencia had the greatest risk of death in both periods. Some causes of death increased (groups 5 and 6, mental and nervous system disorders and sensory organ diseases). By districts, there was greater variability in Valencia than in Alicante, especially in districts 1 and 11 in Valencia, which showed a high risk of death. CONCLUSIONS: The process of internal mortality surveillance by districts is reproducible. In the city of Valencia there were inequalities in mortality that were maintained over time. The city of Alicante showed less internal variability in its mortality indicators.