Long‐term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle‐aged Ts65Dn mice,a model of Down syndrome

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age‐related cholinergic degeneration, and increased brain expression of β‐amyloid precursor protein (AβPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long‐term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AβPP and β‐amyloid levels of TS mice. Melatonin was administered for 5 months to 5‐ to 6‐month‐old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)‐positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AβPP or β‐amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age‐related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age‐related progression of cognitive deterioration found in DS.     

Differences in the causes of death of HIV-positive patients in a cohort study by data sources and coding algorithms

OBJECTIVES:: To compare causes of death (CoDs) from two independent sources: National Basic Death File (NBDF) and deaths reported to the Spanish HIV Research cohort [Cohort de adultos con infección por VIH de la Red de Investigación en SIDA CoRIS)] and compare the two coding algorithms: International Classification of Diseases, 10th revision (ICD-10) and revised version of Coding Causes of Death in HIV (revised CoDe). METHODS:: Between 2004 and 2008, CoDs were obtained from the cohort records (free text, multiple causes) and also from NBDF (ICD-10). CoDs from CoRIS were coded according to ICD-10 and revised CoDe by a panel. Deaths were compared by 13 disease groups: HIV/AIDS, liver diseases, malignancies, infections, cardiovascular, blood disorders, pulmonary, central nervous system, drug use, external, suicide, other causes and ill defined. RESULTS:: There were 160 deaths. Concordance for the 13 groups was observed in 111 (69%) cases for the two sources and in 115 (72%) cases for the two coding algorithms. According to revised CoDe, the commonest CoDs were HIV/AIDS (53%), non-AIDS malignancies (11%) and liver related (9%), these percentages were similar, 57, 10 and 8%, respectively, for NBDF (coded as ICD-10). When using ICD-10 to code deaths in CoRIS, wherein HIV infection was known in everyone, the proportion of non-AIDS malignancies was 13%, liver-related accounted for 3%, while HIV/AIDS reached 70% due to liver-related, infections and ill-defined causes being coded as HIV/AIDS. CONCLUSION:: There is substantial variation in CoDs in HIV-infected persons according to sources and algorithms. ICD-10 in patients known to be HIV-positive overestimates HIV/AIDS-related deaths at the expense of underestimating liver-related diseases, infections and ill defined causes. CoDe seems as the best option for cohort studies.     

Determinants of efficiency in reducing child mortality in developing countries. The role of inequality and government effectiveness

The main aim of this article was to analyze the relationship of income inequality and government effectiveness with differences in efficiency in the use of health inputs to improve the under-five survival rate (U5SR) in developing countries. Robust Data Envelopment Analysis (DEA) and regression analysis were conducted using data for 47 developing countries for the periods 2000–2004, 2005–2009, and 2010–2012. The estimations show that countries with a more equal income distribution and better government effectiveness (i.e. a more competent bureaucracy and good quality public service delivery) may need fewer health inputs to achieve a specific level of the U5SR than other countries with higher inequality and worse government effectiveness.     

Systematic review of efficacy and safety of pemetrexed in non-small-cell-lung cancer

Introduction Lung cancer accounts for 20 % of cancer deaths in Spain. The most frequent subtype (87 %) is non-small cell lung cancer (NSCLC). Pemetrexed is a recently marketed drug added to NSCLC therapeutic arsenal. It seems to have become one of the most used options for the treatment of this condition over the last 3 years. Aim of the review To evaluate the efficacy and safety of pemetrexed in NSCLC, in the different therapy lines. Method A systematic search of published literature was conducted using the main databases (MEDLINE, EMBASE, the Cochrane Library and the Center for Reviews and Dissemination) and subsequently a search of referenced literature was performed. We included clinical trials, meta-analyses and systematic reviews. The evaluation of the quality of the articles was performed by pairs using specific assessment scales, Critical Appraisal Skills Program (CASP) adapted for CASP Spain. Then we extracted data on efficacy and safety according to the treatment line assessed. Results We identified 277 references. Finally, nine clinical trials and a meta-analysis complied with inclusion criteria. In first-line induction, treatment with pemetrexed associated with a platinum was similar in terms of efficacy to other alternative chemotherapy regimens, except in patients with non-squamous histology, in whom survival was higher in the experimental group. In maintenance treatment, greater efficacy was seen with pemetrexed in patients with non-squamous histology. In second-line treatment, there were no significant differences in terms of efficacy and safety for pemetrexed treatment versus other chemotherapy options. The most frequent adverse reactions were: hematological, gastrointestinal and neurological. All were significantly less frequent with pemetrexed versus other alternative therapies, except for liver toxicity. Conclusions Due to the high degree of uncertainty as to its efficacy in certain subgroups of patients, including conflicting data; to its recent incorporation, and therefore lack of safety data in the medium and long term, and the high budgetary impact of its incorporation into health systems, it seems reasonable to optimize its use, identifying those patients who may benefit most.     

Effects of health care decentralization in Spain from a citizens’ perspective

The aim of this article is to analyze the impact of the decentralization of the public national health system in Spain on citizens’ satisfaction with different dimensions of primary and hospital care. Using micro-data from the Health Barometer 1996–2009 and taking advantage of the exogeneity of the different pace of decentralization across Spain using a difference-in-differences strategy, we find that, in general, decentralization has not improved citizens’ satisfaction with different features of the health services. In our base model, we find that there are even some small negative effects on a subset of variables. Sensitivity analysis confirms that there is no empirical evidence for supporting that decentralization has had a positive impact on citizens’ satisfaction with health care. We outline several possible reasons for this.     

Fijación lumbar posterior empleando el sistema de imagen quirúrgica O-arm: experiencia inicial

ObjectThe use of transpedicular screw fixation has been widely accepted for the treatment of degenerative and traumatic pathology of the lumbar spine. Complications of spinal instrumentation can be serious. Screw misplacement can result in unintended durotomy, nerve root and/or cauda equina injury. In comparison to fluoroscopy-assisted screw placement, computer-assisted image guidance has been shown to achieve overall higher rates of accuracy. The O-arm is able to obtain computed tomography (CT)-type images with multiplanar reconstruction. In this study we evaluated a cohort of patients who underwent posterior lumbar fusion with pedicle screws utilizing the O-arm imaging system.MethodsA retrospective review of 40 consecutive patients who underwent posterior lumbar fusion surgery with O-arm utilization, was performed. The study population included 14 males and 26 females. Age range was 39-85 years with an average of 63.8 years. Twenty one patients had degenerative lumbar stenosis (52.5%) and 19 had spondylolisthesis (47.5%). Intraoperative CT-images were obtained. The mean time for surgery and screw placement was assessed.ResultsA total of 252 pedicle screws were sited using O-arm navigation system, with a mean of 6.3 screws per patient (range 4-10). On the basis of intraoperative CT, 3 screws were redirected, representing a 98.81% accuracy rate.The mean duration of surgery was 157.2 (90-240) minutes and the mean time for screw placement was 7.13 (3.08-15) minutes per screw.Three patients (7.5%) developed superficial wound infections which were treated conservatively. No patients required a return to the operating room because of screw malposition.ConclusionThe use of intraoperative O-arm imaging system with computer-assisted navigation significantly increases the surgical accuracy and safety of pedicle screw placement in lumbar fusion surgery.