Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: the NEXT-in-CML study.

In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.

Family caregiver mistreatment of the elderly: prevalence of risk and associated factors.

BACKGROUND: The detection of elder mistreatment is emerging as a public health priority; however, abusive behaviors exercised by caregivers are little known and rarely detected among primary health care professionals. This study aims to estimate the prevalence of risk of abuse against community-residing elderly with moderate to severe dependency whose caregivers are relatives. In addition, we aim to describe the association between such a risk and socio-demographic variables, cognitive and dependency state of the victim, and the scale of the caregiver's anxiety, depression, and burden. METHODS: Cross-sectional study developed in 72 Primary Health Care teams from Barcelona, Spain. Participants were caregivers and their dependent care recipients (N = 829). Home interviews included the Caregiver Abuse Screen (CASE); self-reported abuse from care recipient; activities of daily living and cognitive state of the care recipient; anxiety and depression in caregivers and Caregiver Burden Scale. The relationship prior to the dependency, positive aspects of caregiving, and social support for the caregiver were also assessed. Multivariate analysis was performed using logistic regression with risk of abuse as dependent variable. RESULTS: Caregivers were mainly women (82.8%) with a mean age of 63.3 years. Caregivers and care recipients lived in the same household in 87.4% of cases, and 86.6% had enjoyed a good previous relationship. Care recipients were women (65.6%), with a mean age of 84.2 years, and 64.2% had moderate to severe cognitive impairment. CASE demonstrated a prevalence of 33.4% (95% CI: 30.3-36.7) of abuse risk by the caregiver. Logistic regression showed as statistically significant: caregiver burden (OR = 2.75; 95% CI: 1.74-4.33), caregiver anxiety (OR = 2.06; 95% CI: 1.40-3.02), caregiver perception of aggressive behavior in the care recipient (OR = 7.24; 95% CI: 4.99-10.51), and a bad previous relationship (OR = 4.66; 95% CI: 1.25-17.4). CONCLUSIONS: Prevalence of risk of abuse is high among family caregivers. Our study has found risk factors in family caregivers that are preventable to an extent, namely: anxiety and feelings of burden. It is essential to become aware of these risk factors and their causes to intervene and help primary as well secondary prevention.

Life cycle assessment of solar photo-Fenton and solar photoelectro-Fenton processes used for the degradation of aqueous α-methylphenylglycine.

A comparative Life Cycle Assessment (LCA) of solar photo-Fenton and solar photoelectro-Fenton, two solar-driven advanced oxidation processes (AOPs) devoted to the removal of non-biodegradable pollutants in water, is performed. The study is based on the removal, at laboratory scale, of the amino acid α-methylphenylglycine, a good example of soluble and non-biodegradable target pollutant. The system under study includes chemicals, electricity, transport of all raw materials to the plant site, and the generation of emissions, but it does not take into account the impact of the infrastructure needed to build a hypothetical solar plant. Nine environmental impact categories are included in the LCA: global warming potential, ozone depletion potential, aquatic eutrophication potential, acidification potential, human toxicity potential, photochemical ozone formation potential, fresh water aquatic ecotoxicity potential, marine aquatic ecotoxicity potential, and terrestrial ecotoxicity potential and abiotic resource depletion potential. Although previous experimental results show that both AOPs are able to efficiently degrade the pollutant, the LCA indicates that solar-driven photo-Fenton is the most environmentally friendly alternative, mainly because the use of electricity in solar photoelectro-Fenton experiments involves high environmental impacts.

[Health system interventions assessment in Spain: an approach through the analysis of the time trends and the geographical variability of avoidable mortality between 1986 -2001]. / Medida del resultado de las intervenciones sanitarias en España: una aproximación mediante el análisis temporal y espacial de la mortalidad evitable entre 1986-2001.

BACKGROUND: Many studies have proposed Avoidable Mortality (ME) to monitor the performance of health services although its usefulness is limited by the multiplicity of the avoidable mortality lists being used. Time trends from 1986-2001 and the geographical distribution of avoidable mortality by provinces, are presented for Spain. METHODS: An Avoidable Mortality consensus list is being used. It includes avoidable mortality through the intervention of health services (ISAS in Spanish) and through health policy interventions (IPSI in Spanish). Time trends are analyzed adjusting Poisson or Joinpoint regression models and the annual percentages of change (APC) are estimated. Changes in geographical distribution between the first half of the analysed period and the second are tested by means of standard mortality ratios (SMR) and comparative mortality rates (CMR) for each province. RESULTS: Between 1986 and 2001 avoidable mortality decreased (APC: -1.68; CI: -1.99 and -1.38) slightly more than non-avoidable mortality (APC: -1.28; CI: -1.40 and -1.17). Higher reduction was observed for ISAS mortality (APC: -2.77; CI: -2.89 and -2.65) and an irregular trend for IPSI (between 1986-1990 increase APC: 4.86; CI: 3.32 and 6.41, between 1990-95 stabilization APC: -0.03; CI: -2.32 and 2.31 and finally 1995-2001 decrease APC: -3.57; CI: -4.72 and -2.40). CONCLUSIONS: Avoidable mortality decreased more than non avoidable mortality and important geographical variability can be observed among provinces which should be monitored in order to identify the health services weaknesses. The higher ISAS mortality was observed in southern provinces and the higher IPSI mortality in some areas on the coast. The pattern is somewhat similar for both analyzed periods.