Incidence and prevalence of multiple sclerosis in Spain: a systematic review.

INTRODUCTION: Greater understanding of the prevalence and incidence of multiple sclerosis in Spain and their temporal trends is necessary to improve the allocation of healthcare resources and to study aetiological factors. METHODS: We performed a systematic search of the MedLine database and reviewed the reference lists of the articles gathered. We collected studies reporting prevalence or incidence rates of multiple sclerosis in any geographical location in Spain, with no time limits. In 70% of cases, data were extracted by 2 researchers (FGL and EAC); any discrepancies were resolved by consensus. RESULTS: We identified 51 prevalence and 33 incidence studies published between 1968 and 2018. In the adjusted analysis, the number of prevalent cases per 100 000 population increased by 26.6 (95% confidence interval [CI], 21.5-31.8) every 10 years. After adjusting for year and latitude, the number of incident cases per 100 000 population increased by 1.34 (95% CI, 0.98-1.69) every 10 years. We observed a trend toward higher prevalence and incidence rates at higher latitudes. CONCLUSIONS: The prevalence of multiple sclerosis in Spain has increased in recent decades, although case ascertainment appears to be incomplete in many studies. Incidence rates have also increased, but this may be due to recent improvements in the detection of new cases.

[Evaluation of training on the programs to optimize antimicrobial use in medical residents of the province of Las Palmas]. / Evaluación de la formación sobre el programa de optimización del uso de antimicrobianos en médicos residentes de la provincia de Las Palmas.

OBJECTIVE: Antibiotic resistance is a threat to global public health. This situation makes essential to establish programs to optimize antimicrobial use (PROA). Training needs are identified in the PROA of resident physicians and the results of the analysis of the associations between study variables and training in the rational and prudent use of antibiotics are presented in this analysis. METHODS: Cross-sectional and analytical study through a self-administered questionnaire to a group of 506 medical residents of the province of Las Palmas. The association between resident's characteristics and PROA training was calculated through logistic regression. RESULTS: The associations between response variance and speciality were observed in most of the core component analysis (opportunity p=0.003, training p=0.007, motivation p=0.055 and hand hygiene p=0.044), followed by variance according to sex (capacity p=0.028, theoretical knowledge p=0.013, hand hygiene p=0.002). Very few differences were associated with age (capacity p=0.051 and hand hygiene p=0.054) or the year of expertise (hand hygiene p=0.032). CONCLUSIONS: The main training needs of resident physicians include one health, motivation, training, hand hygiene and information. The type of speciality followed by sex are the most important determinants on antibiotic use and resistance for resident physicians.

ß-Cryptoxanthin modulates the response to phytosterols in post-menopausal women carrying NPC1L1 L272L and ABCG8 A632 V polymorphisms: an exploratory study.

Phytosterol (PS) intake may be used for hypercholesterolaemia in some groups although the presence of non-responders is well known. Carotenoids and PS/cholesterol may compete for the same transporters during absorption. As part of a randomized, double-blind, crossover, multiple-dose supplementation study with ß-cryptoxanthin (ß-Cx) and PS, single and combined, polymorphisms of ABCG8 (A632V) and NCPL1 (L272L) were determined in 19 post-menopausal women. Subjects carrying CC polymorphism for NCP1L1 (L272L) showed a net increase in total cholesterol and LDL after PS intake but, interestingly, displayed a decrease in both lipid fractions after consuming PS plus ß-Cx. For the ABCG8 (A632V) gene, CT/TT carriers consuming PS also displayed an increase in total cholesterol and LDL, but this increment was much lower after the intake of PS plus ß-Cx. Additionally, in CC carriers for ABCG8 (A632V), a greater decrease in total cholesterol and LDL was found after the intake of PS plus ß-Cx compared to that observed after PS alone. Overall, our results suggest that ß-Cx improves the response to PS in individuals carrying specific genetic polymorphisms (i.e. non-responders), opening the possibility to modulate the response to PS by food technology. (ClinicalTrials.gov NCT01074723).

Effect of ß-cryptoxanthin plus phytosterols on cardiovascular risk and bone turnover markers in post-menopausal women: a randomized crossover trial.

BACKGROUND AND AIM: Post-menopausal women are at higher risk of cardiovascular disease and bone demineralization. Phytosterols (PS) may be used for hypercholesterolemia in some groups and ß-cryptoxanthin (ß-Cx) displays a unique anabolic effect on bone. Our aim was to assess the changes in cardiovascular and bone turnover markers from the oral intake of ß-Cx and PS in post-menopausal women. METHODS AND RESULTS: A randomized, double-blind, crossover study with ß-Cx (0.75 mg/day) and PS (1.5 g/day), single and combined, was performed in 38 postmenopausal women. Diet was supplemented with 1 × 250 mL milk-based fruit drink/day for 4 weeks with a wash-out period of 4-weeks in between. Serum ß-Cx and PS were determined by UPLC and CG-FID respectively. Outcome variables included markers of bone turnover and cardiovascular risk. Biological effect was assessed by paired t test and generalized estimating equations analysis that included the previous treatment, the order of intervention and the interactions. The intake of beverages containing ß-Cx and PS brought about a significant increase in serum levels of ß-Cx, ß-sitosterol and campesterol. Intervention caused changes in almost all the markers while the order, previous treatment and the interaction did not reach statistical significance. Only the intake of the beverage containing ß-Cx plus PS brought about significant decreases in total cholesterol, c-HDL, c-LDL and bone turnover markers. CONCLUSIONS: ß-Cx improves the cholesterol-lowering effect of PS when supplied simultaneously and this combination may also be beneficial in reducing risk of osteoporosis. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov number NCT01074723.

Hypercalcemia, hypervitaminosis A and 3-epi-25-OH-D3 levels after consumption of an "over the counter" vitamin D remedy. a case report.

Intoxication from vitamin D supplements has been rarely reported but, nowadays, it occurs more frequently. 3-epi-25-OH-D(3) is highly prevalent in adults and it is considered of biological relevance. We report a case of vitamin D toxicity with hypercalcemia, acute renal failure and hypervitaminosis A after consuming an over-the-counter vitamin D supplement. Our data suggest that the contribution of 3-epi-25-OH-D(3) is not altered during vitamin D toxicity, although the serum levels of 25-OH-D(3) and 3-epi-25-OH-D(3) may display a different rate of clearance. The patient also displayed hypervitaminosis A unrelated to diet, possibly caused by renal failure related to the hypercalcemia induced by vitamin D toxicity. Because of the increasing use of over-the-counter vitamin D supplements and the potential iatrogenic hypercalcemia related to hypervitaminosis A, the present case highlights the importance of evaluating both the use of (non-) prescribed medication and vitamin A status during vitamin D toxicity.

No hay indicios de diferencias entre no diabéticos y diabéticos en el efecto de la corrección de la anemia en la enfermedad renal crónica / No disponible

No disponible

Training programme in techniques of self-control and communication skills to improve nurses' relationships with relatives of seriously ill patients: a randomized controlled study.

The interpersonal relationships with relatives of seriously ill patients may cause anxiety on the part of nurses and the need for adequate communication and self-control skills. To assess the efficacy of training nurses in self-control techniques and communication skills when they interact with relatives of seriously ill patients we planned a randomized, controlled trial in two parallel groups: an experimental group, with immediate training, and a control group, with training delayed for 6 months. We recruited 61 nurses from the nursing staff of a university hospital of 500 beds. The intervention consisted of training in relaxation, cognitive restructuring and some communication skills. The outcome variables were communication skills measured under simulated conditions using an observation instrument of our own, administered by observers masked with respect to the study groups, and the levels of state-anxiety measured with the self-assessment questionnaire the State-Trait Anxiety Inventory, under imaginary conditions. The two groups initially had similar scores in the scales of communication skills, and state and trait-anxiety. After intervention, compared with the control group, the experimental group showed significant improvements in the skills of listening, emphasizing, interrupting and coping with emotions (P < 0.05). State-anxiety levels did not show any changes. In conclusion, the joint training in self-control and communication improves some communication skills in nurses when they interact with relatives of seriously ill patients under simulated conditions.

The intricate relationship between evidence and clinical practice in kidney transplantation.

Clinical practice is supposed to be evidence-based but it always conveys underlying values, judgements, moral principles or axioms. We explore the evidence-based nature of clinical practice in the fast-changing field of kidney transplantation and its relationship with values in five different interventions: those well supported on evidence, focussed on the use of immunosuppressant drugs like cyclosporine, mycophenolate mofetil and tacrolimus, and the elective withdrawal of cyclosporine or steroids; disputable interventions where evidence, focussed on anti-lymphocyte antibodies, is strong but not strong enough to be applied on the majority of occasions; interventions not supported by randomised controlled trials with focus on primary treatment of vascular graft rejection and rescue treatment for acute graft rejection; interventions not widely applied despite strong evidence from sources other than randomised controlled trials, with focus on HLA-matched kidney transplants in cadaver donor and living donor transplants; and finally, a variety of interventions when evidence is lacking. Being aware of the factors influencing every clinical decision we can make the strength of evidence and the nature of the values underlying them explicit and we will find it easier to improve the process of transferring evidence into practice and openly face and acknowledge the values involved.

Comparison of the long-term mortality in Hodgkin's disease patients with that of the general population.

BACKGROUND: Although Hodgkin's disease can be treated successfully, its long-term survival rate has yet to be definitely established. We compared the long-term mortality rate of patients diagnosed as having Hodgkin's disease with that of the general population. PATIENTS AND METHODS: We studied a retrospective cohort of 477 patients who received pathology-confirmed diagnoses of Hodgkin's disease between 1967 and 1993 and were treated with combined chemotherapy or radiotherapy with follow-up from the day of diagnosis. Standardised mortality ratios were computed with reference rates taken from the Spanish population. RESULTS: The follow-up was complete for 427 (89.5%) of the patients. The median follow-up time was 8 years, 133 patients (28%) died and the median survival time was 21 years. The overall survival rates were 80% at 5 years, 70% at 10 years, and 64% at 15 years after diagnosis. The standardised mortality ratios were 10.8 (95% confidence interval: 9.0-12.8, P < 0.0001) overall, 5.5 in patients in favourable stages (IA, IIA), and 15.2 in those with unfavourable stages (IB, IIB, III, IV). There was a decreasing trend in mortality by calendar period (standardised mortality ratios for 1967-1975, 1976-1974 and 1985-1993: 16.8, 10.3 and 5.1, respectively). Higher mortality was observed in all periods of follow-up after diagnosis, even after 20 years. CONCLUSIONS: Despite the improvements in treatment, mortality in Hodgkin's disease remains higher than in the general population in all disease stages, even 20 years after diagnosis.

[The evaluation of the quality of clinical trials: the rationale, usefulness and drawbacks]. / Evaluación de la calidad de los ensayos clínicos: justificación, utilidad e inconvenientes.

The quality of a randomised controlled trial should be understood as its internal validity, that is, the extent in which the study conclusions show correctly what actually happened in the design and conduct phases. This validity may be compromised by multiple biases coming from the allocation of subjects to study groups, treatment administration, observation of outcome variables, patient follow-up and statistical analysis. The presence of bias is assessed through three kinds of measurements: individual components, checklists and numerical scales. In systematic reviews some kind of quality assessment is necessary, which evaluates the quality of individual trials by means of several methods: a) a threshold that sets the minimal level of quality required; b) the relationship between quality and variability in trial results; c) sensitivity analysis, and d) quality scores as weights of trials. However, there exists considerable discrepancy among the published scales whereas their usefulness to assess the quality of trials to be included in the systematic review is a matter of controversy. We hope that the Consolidated Standards of Reporting Trials (CONSORT) initiative to standardize the report of randomized controlled trials and other proposals will contribute to obtain a more realistic view for each trial and to improve their internal validity.

A randomized trial comparing cyclosporine and steroids with cyclosporine, azathioprine, and steroids in cadaveric renal transplantation.

BACKGROUND: In renal transplantation, triple-drug therapy (low-dose cyclosporine [CsA] combined with azathioprine plus steroids) has been replacing double-drug therapy (CsA plus steroids) in clinical practice without much evidence in favor of either therapy. Previous trials comparing the two immunosuppressive regimens gave conflicting results. We attempted to determine whether triple therapy is at least equivalent to double therapy. METHODS: A randomized trial was performed in 250 adult cadaveric renal transplant recipients, comparing double therapy (CsA [10 mg/kg/day] plus prednisone) with triple therapy (CsA [6 mg/kg/day] plus azathioprine plus prednisone). The median follow-up time was 930 days. RESULTS: The incidence of acute rejection episodes refractory to treatment was 11% in double therapy and 4% in triple therapy (relative risk reduction: 64%; 95% confidence interval: 5-100%; P=0.035). Patients in the double therapy group required more intensive antirejection treatment, and their pathologic lesions were more severe. The proportion of patients with acute rejection was similar (double therapy: 45% vs. triple therapy: 40%) as was the incidence of chronic renal dysfunction (double therapy: 17% vs. triple therapy: 15.5%), the 4-year graft survival (double therapy: 71% vs. triple therapy: 83%, P=0.089), and patient survival (double therapy: 94% vs. triple therapy: 93%). In 29 patients (23%), 35 episodes of azathioprine-induced leukopenia were recorded, and in 9 of them azathioprine had to be discontinued. The incidence of other adverse events did not differ between the groups. CONCLUSIONS: Triple therapy caused fewer episodes of refractory acute rejection episodes and was as efficacious and safe as double therapy.

[Impact of legal regulations on the quality of clinical trials carried out in Spain]. / Impacto de la normativa legal en la calidad de los ensayos clínicos realizados en España.

BACKGROUND: In Spain since 1982 laws require that clinical trials involving drugs be approved before implementation. We studied the impact of regulations on the quality of published trials. METHODS: Four sets of trials were chosen: trials implemented after 1982 and registered as approved; trials implemented after 1982 but not registered; trials implemented before 1982; and trials conducted outside Spain. Trials were identified via MEDLINE, EMBASE, and Indice Médico Español. Sets were compared with regard to indicators of quality, as obtained from the information in the published reports. The comparison was based on a total of 273 Spanish trials published between 1988 and 1990, 85 approved and 188 unregistered; 97 old trials, published between 1980 and 1982; and 152 non-Spanish trials published between 1988 and 1990. RESULTS: Approved trials, compared to their unregistered and old counterparts, were more often informed randomised, more of their published reports included lists of reasons for exclusions and information on consent and achieved higher scores of a quality index. Approved trials, compared to non-Spanish trials, had lower proportion of sample size justification, greater discrepancies between randomised and analyzed cases and a trend to lower quality scores. Multiple logistic regression analysis of quality scores showed that approved trials had higher scores than unregistered trials when single-centre trials (odds ratio for reaching scores in the upper quartile: 2.90; 95% confidence interval: 1.27 - 6.64) and similar when multicentre trials. CONCLUSIONS: Approved trials achieved better indicators of quality than unregistered trials but did not achieve the standards of quality prevailing in the international community.