Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Opinions, Attitudes, and Perceptions in Relation to Erectile Dysfunction and Premature Ejaculation in the Undiagnosed Spanish Male Population. Results of the PANDORA Project.

Approximately 43% of Spanish men report experiencing premature ejaculation (PE) at some point in their lives and 12.1% suffer from erectile dysfunction (ED), of whom only 16.5% have seen a doctor. Despite this, ED and PE remain undiagnosed among a supposedly healthy segment of the population. To assess the general knowledge of a representative population of healthy Spanish males of the symptoms, treatment, and expectations related to ED and PE. This was a descriptive study based on an online questionnaire in which 2,515 males aged 25-75 years with no history of ED and/or PE presented their perception of aspects related to symptoms, diagnosis, treatment, and expectations in ED and PE. The study provided an evaluation of the knowledge, attitude, and underdiagnosis of ED and/or PE in healthy males and the approach taken by urology specialists and other disciplines. The survey was completed by 2,515 healthy males, including over 80% of those who had completed secondary or higher education. 60% of the sample had never seen a urologist and 59% and 62% of the participating men responded correctly to the statements about PE and ED, respectively. Their lack of knowledge of the therapeutic alternatives was clear (74% and 76% of the panel were unaware of the existence of effective treatments for ED and PE, respectively). Despite the initiative shown by some participants in seeking information about each condition (10.3% for ED; 16.7% for PE), only 4.7% of them had been questioned about ED by a medical practitioner (1.9% for PE). The underdiagnosis rate stood at 3.5% for ED (5.6% participants >65 years) and at about 10% for PE. These results will represent a point of departure for establishing some recommendations to improve the detection and treatment of these disorders. This is the first study of its kind in Spain to analyze the underdiagnosis of ED and/or PE inferred from data reported by a population of healthy males. Screening for ED was performed with a validated questionnaire. However, the rest of the research was conducted using adaptations of validated questionnaires or a self-designed questionnaire based on and in consultation with a group of experienced andrologists. People need to have greater knowledge of both the conditions and the related false myths to make sure that they are familiar with the existence of drug treatments and socio-sanitary interventions. Primary care physicians and urologists should also be more proactive in routine visits in order to achieve better management of ED and PE. Prieto-Castro R, Puigvert-Martínez AM, Artigas-Feliu R, et al. Opinions, Attitudes, and Perceptions in Relation to Erectile Dysfunction and Premature Ejaculation in the Undiagnosed Spanish Male Population. Results of the PANDORA Project. J Sex Med 2020;17:1495-1508

Gefitinib and afatinib show potential efficacy for Fanconi anemia-related head and neck cancer

Purpose: Fanconi anemia (FA) rare disease is characterized by bone marrow failure and a high predisposition to solid tumors, especially head and neck squamous cell carcinoma (HNSCC). FA patients with HNSCC are not eligible for conventional therapies due to high toxicity in healthy cells, predominantly hematotoxicity, and the only treatment currently available is surgical resection. In this work we searched and validated two already approved drugs as new potential therapies for HNSCC in FA patients. Experimental design: We conducted a high-content screening of 3,802 drugs in a FANCA-deficient tumor cell line to identify non-genotoxic drugs with cytotoxic/cytostatic activity. The best candidates were further studied in vitro and in vivo for efficacy and safety. Results: Several FDA/EMA-approved anticancer drugs showed cancer-specific lethality or cell growth inhibition in FA HNSCC cell lines. The two best candidates gefitinib and afatinib, EGFR inhibitors approved for non-small-cell lung cancer (NSCLC), displayed non-tumor/tumor IC50 ratios of ~400 and ~100 times, respectively. Neither gefitinib nor afatinib activated the FA signaling pathway or induced chromosomal fragility in FA cell lines. Importantly, both drugs inhibited tumor growth in xenograft experiments in immunodeficient mice using two FA patient-derived HNSCCs. Finally, in vivo toxicity studies in Fanca-deficient mice showed that administration of gefitinib or afatinib was well-tolerated, displayed manageable side-effects, no toxicity to bone marrow progenitors and did not alter any hematological parameters. Conclusions: Our data present a complete preclinical analysis and promising therapeutic line of the first FDA/EMA approved anticancer drugs exerting cancer specific toxicity for HNSCC in FA patients

Bladder cancer index : Cross-cultural adaptation into Spanish and psychometric evaluation

Background: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. Methods: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. Results: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. Conclusions: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients