Pain as a disease in the new International Classification of Diseases (ICD-11): Latin American expert consensus.

Aims: Pain diagnoses in the 10th version of the International Classification of Diseases (ICD-10) did not adequately support the current management of pain. Therefore, we aimed to review the new 11th revision (ICD-11) in order to analyze its usefulness for the management, coding, research and education of chronic pain from a Latin American perspective. Methods: The Latin American Federation of Associations for the Study of Pain convened a meeting of pain experts in Lima, Peru. Pain specialists from 14 Latin American countries attended the consensus meeting. Results: In ICD-11, chronic pain is defined as pain that persists or recurs longer than 3 months and is subdivided into seven categories: chronic primary pain and six types of chronic secondary pain. Chronic primary pain is now considered a disease in itself, and not a mere symptom of an underlying disease. Conclusion: The novel definition and classification of chronic pain in ICD-11 is helpful for better medical care, research and health statistics. ICD-11 will improve chronic pain management in Latin American countries, for both the pain specialist and the primary care physician.

Chronic pain is one of the most frequent reasons for medical consultation in Latin America. In the tenth revision of the International Classification of Diseases and Related Health Problems (ICD-10), chronic pain was not adequately defined and individual pain diagnoses were poorly defined. For the first time in Latin America, a meeting of pain experts analyzed and reviewed the 11th version of the International Classification of Diseases (ICD-11), when the Latin America Federation of Associations for the Study of Pain organized a meeting of experts from 14 Latin American countries. In ICD-11, chronic pain is recognized as a biopsychosocial phenomenon and defined as pain that continues or returns for more than 3 months. It is split into seven types: chronic primary pain and six types of chronic secondary pain. In ICD-11, chronic primary pain is now considered a disease in itself, not a mere manifestation of other disease. Our article is the first to address the problems, challenges and benefits of using ICD-11 from a Latin American perspective. It will help to facilitate and disseminate the use of this new classification of chronic pain. This will improve chronic pain treatment, statistics, research and development of better health strategies for pain management in Latin America.

Association between long term exposure to particulate matter and incident hypertension in Spain.

Exposure to air particulate matter has been linked with hypertension and blood pressure levels. The metabolic risks of air pollution could vary according to the specific characteristics of each area, and has not been sufficiently evaluated in Spain. We analyzed 1103 individuals, participants in a Spanish nationwide population based cohort study (di@bet.es), who were free of hypertension at baseline (2008-2010) and completed a follow-up exam of the cohort (2016-2017). Cohort participants were assigned air pollution concentrations for particulate matter < 10 µm (PM10) and < 2.5 µm (PM2.5) during follow-up (2008-2016) obtained through modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). Mean and SD concentrations of PM10 and PM2.5 were 20.17 ± 3.91 µg/m3 and 10.83 ± 2.08 µg/m3 respectively. During follow-up 282 cases of incident hypertension were recorded. In the fully adjusted model, compared with the lowest quartile of PM10, the multivariate weighted ORs (95% CIs) for developing hypertension with increasing PM10 exposures were 0.82 (0.59-1.14), 1.28 (0.93-1.78) and 1.45 (1.05-2.01) in quartile 2, 3 and 4 respectively (p for a trend of 0.003). The corresponding weighted ORs according to PM2.5 exposures were 0.80 (0.57-1.13), 1.11 (0.80-1.53) and 1.48 (1.09-2.00) (p for trend 0.004). For each 5-µg/m3 increment in PM10 and PM2.5 concentrations, the odds for incident hypertension increased 1.22 (1.06-1.41) p = 0.007 and 1.39 (1.07-1.81) p = 0.02 respectively. In conclusion, our study contributes to assessing the impact of particulate pollution on the incidence of hypertension in Spain, reinforcing the need for improving air quality as much as possible in order to decrease the risk of cardiometabolic disease in the population.

Iodine Deficiency and Mortality in Spanish Adults: Di@bet.es Study.

Background: Longitudinal data assessing the impact of iodine deficiency (ID) on mortality are scarce. We aimed to study the association between the state of iodine nutrition and the risk of total and cause-specific mortality in a representative sample of the Spanish adult population. Methods: We performed a longitudinal observational study to estimate mortality risk according to urinary iodine (UI) concentrations using a sample of 4370 subjects >18 years representative of the Spanish adult population participating in the nationwide study Di@bet.es (2008-2010). We used Cox regression to assess the association between UI at the start of the study (<50, 50-99, 100-199, 200-299, and ≥300 µg/L) and mortality during follow-up (National death registry-end of follow-up December 2016) in raw models, and adjusted for possible confounding variables: age, sex, educational level, hypertension, diabetes, obesity, chronic kidney disease, smoking, hypercholesterolemia, thyroid dysfunction, diagnosis of cardiovascular disease or cancer, area of residence, physical activity, adherence to Mediterranean diet, dairy and iodinated salt intake. Results: A total of 254 deaths were recorded during an average follow-up period of 7.3 years. The causes of death were cardiovascular 71 (28%); cancer 85 (33.5%); and other causes 98 (38.5%). Compared with the reference category with adequate iodine nutrition (UI 100-300 µg/L), the hazard ratios (HRs) of all-cause mortality in the category with UI ≥300 µg/L were 1.04 (95% confidence interval [CI 0.54-1.98]); however, in the categories with 50-99 UI and <50 µg/L, the HRs were 1.29 [CI 0.97-1.70] and 1.71 [1.18-2.48], respectively (p for trend 0.004). Multivariate adjustment did not significantly modify the results. Conclusions: Our data indicate an excess mortality in individuals with moderate-severe ID adjusted for other possible confounding factors.

Activation of 5-HT1A and 5-HT7 receptors enhanced a positively reinforced long-term memory.

Memory is one of the most important capabilities of our mind since it determines our individuality. Memory formation involves different stages: acquisition, consolidation and retrieval. There are many studies about early stages, however little is known about memory retrieval. Retrieval is the use of learned information and represents a big problem in patients with memory deficits where the main issue is that they can learn but cannot remember. Previous findings have demonstrated that 5-hydroxytryptamine (5-HT) is a neurotransmitter involved in memory process. Hence, here we are exploring the role of 5-HT in memory retrieval by using its metabolic precursor l-tryptophan and several ligands at 5-HT1A and 5-HT7 receptors. Experimental protocol consisted of evaluating conditioned responses (%CR) after one week of interruption following autoshaping sessions for memory formation; a decrease of %CR was interpreted as memory decay. Systemic administration of: (1) l-tryptophan (50 and 100 mg/kg), (2) 5-HT1A receptor agonist 8-OH-DPAT (0.031 and 0.062 mg/kg), (3) the selective antagonist 5-HT1A receptor WAY 100635 (0.3 and 0.6 mg/kg), (4) the 5-HT7 receptor agonist, LP 211, in a dose-dependent manner (1, 2.5, 5.0 and 10.0 mg/kg) enhanced memory retrieval. Further, the 5-HT7 receptor antagonist, SB 269970 (10.0 mg/kg), had no effect. Finally, SB 269970 (10.0 mg/kg) significantly blocked memory retrieval enhancement produced by 10.0 mg/kg LP 211, but not that induced by 2.5 mg/kg LP 211.These results, taken together, suggest that activation of 5-HT1A and 5-HT7 receptors enhanced memory retrieval and these receptors may be therapeutic targets to improve long-term memory retrieval.

Incidence and regression of metabolic syndrome in a representative sample of the Spanish population: results of the cohort di@bet.es study.

INTRODUCTION: Metabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Identification of occurrence and regression trends of MetS could permit elaboration of preventive strategies with new targets. The objective of this study was to analyze the occurrence and regression rates of MetS and its associated factors in the representative cohort of Spain of the di@bet.es study. RESEARCH DESIGN AND METHODS: The di@bet.es study is a prospective cohort where 5072 people representative of the Spanish population over 18 years of age were randomly selected between 2009 and 2010. Follow-up was a median of 7.5 (IQR 7.2-7.9) years, with 2408 (47%) participating subjects. A total of 1881 (78%) subjects had all the pertinent data available and were included in this study. RESULTS: Of the 1146 subjects without baseline criteria for MetS, 294 (25.7%) developed MetS during follow-up, while of the 735 patients with prior MetS, 148 (20.1%) presented regression. Adjusted MetS incidence per 1000 person-years was 38 (95% CI 32 to 44), while regression incidence was 36 (95% CI 31 to 41). Regression rate was independently higher than incidence rate in the following: women, subjects aged 18-45, university-degree holders, patients without central obesity, without hypertension, as well as those with body mass index of <25 kg/m2. Lower progression and higher regression rates were observed with an adapted 14-point Mediterranean Diet adherence screener questionnaire score of >11 in both groups and with >500 and>2000 MET-min/week of physical activity, respectively. CONCLUSIONS: This study provides MetS incidence and regression rates, and identifies the target population for intervention strategies in Spain and possibly in other countries.

Ambient temperature and prevalence of diabetes and insulin resistance in the Spanish population: Di@bet.es study.

Objective The activity of brown adipose tissue is sensitive to changes in ambient temperature. A lower exposure to cold could result in an increased risk of developing diabetes at population level, although this factor has not yet been sufficiently studied. Design We studied 5072 subjects, participants in a national, cross-sectional population-based study representative of the Spanish adult population (Di@bet.es study). All subjects underwent a clinical, demographic and lifestyle survey, a physical examination and blood sampling (75 g oral glucose tolerance test). Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). The mean annual temperature (°C) in each individual municipality was collected from the Spanish National Meteorology Agency. Results Linear regression analysis showed a significant positive association between mean annual temperature and fasting plasma glucose (ß: 0.087, P < 0.001), 2 h plasma glucose (ß: 0.049, P = 0.008) and HOMA-IR (ß: 0.046, P = 0.008) in multivariate adjusted models. Logistic regression analyses controlled by multiple socio-demographic variables, lifestyle, adiposity (BMI) and geographical elevation showed increasing odds ratios for prediabetes (WHO 1999), ORs 1, 1.26 (0.95-1.66), 1.08 (0.81-1.44) and 1.37 (1.01-1.85) P for trend = 0.086, diabetes (WHO 1999) ORs 1, 1.05 (0.79-1.39), 1.20 (0.91-1.59) and 1.39 (1.02-1.90) P = 0.037, and insulin resistance (HOMA-IR ≥75th percentile of the non-diabetic population): ORs 1, 1.03 (0.82-1.30), 1.22 (0.96-1.55), 1.26 (0.98-1.63) (P for trend = 0.046) as the mean annual temperature (into quartiles) rose. Conclusions Our study reports an association between ambient temperature and the prevalence of dysglycemia and insulin resistance in Spanish adults, consistent with the hypothesis that a lower exposure to cold could be associated with a higher risk of metabolic derangements.

Environmental enrichment reverses memory impairment induced by toluene in mice.

Toluene is the main component of a variety of inhalants that are used for intoxication purposes. Alterations in memory have been reported in inhalant users; however, it is unclear whether these impairments could be reversed, and the mechanisms involved in the putative recovery. Therefore, the main purpose of this study was to model the deleterious effects of toluene on memory in mice and to evaluate the effect of environmental enrichment on that response. In the second part of the study, the concentrations of glutamate and GABA, following chronic toluene exposure and after environmental enrichment treatment, were evaluated. Adolescent mice were exposed to either a single or repeated schedule of toluene administration and their responses to object recognition were analyzed. An independent group of mice was repeatedly exposed to toluene and then housed either under environmental enrichment or standard conditions for four weeks. At the end of the housing period, the rodents' performance in object recognition test, as well as the concentrations of neurotransmitters, were analyzed. The results showed that toluene caused memory impairment in mice that received a single or repeated solvent exposure. Remarkably, environmental enrichment could reverse memory deficits induced by repeated administration of toluene. Cessation of toluene exposure in mice in standard housing did not produce that response. The glutamate and GABA tissue contents were not involved in the effects of toluene or environmental enrichment of memory.