Validity and reliability of the kiddie schedule for affective disorders and schizophrenia present and lifetime version DSM-5 (K-SADS-PL-5) Spanish version.

BACKGROUND: There are various language adaptations of the Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version (K-SADS-PL). In order to comply with the changes in DSM classification, the Spanish edition of the interview was in need of update and evaluation. METHODS: K-SADS-PL was adapted to correspond to DSM-5 categories. All clinicians received training, and a 90% agreement was reached. Patients and their parents or guardians were interviewed and videotaped, and the videos were exchanged between raters. Factor analysis was performed and inter-rater reliability was calculated only in the case of diagnoses in which there were more than five patients. RESULTS: A total of 74 subjects were included. The Factor Analysis yielded six factors (Depressive, Stress Hyperarousal, Disruptive Behavioral, Irritable Explosive, Obsessive Repetitive and Encopresis), representing 72% of the variance. Kappa values for inter-rater agreement were larger than 0.7 for over half of the disorders. CONCLUSIONS: The factor structure of diagnoses, made with the instrument was found to correspond to the DSM-5 disorder organization. The instrument showed good construct validity and inter-rater reliability, which makes it a useful tool for clinical research studies in children and adolescents.

Evaluation of the left ventricle longitudinal deformity using myocardial-tracking signals in severely obese adolescents.

BACKGROUND: The global prevalence of obesity in school-age children and adolescents has increased in recent decades. Obesity modifies some aspects of the cardiovascular system in order to preserve the body homoeostasis. Echocardiography to study ventricular function plays an important role in the evaluation of pathological re-modelling associated with left ventricular dysfunction. The aim of this study was to evaluate the left ventricle function and structure with conventional echocardiography and to analyse the longitudinal deformity of the left ventricle using myocardial-tracking signals in a group of severely obese adolescents. Methods and results We carried out a descriptive cross-sectional study. We describe the evaluation of the left ventricle using conventional bi-dimensional echocardiography and the myocardial-tracking signals in severely obese adolescents. There were 34 severely obese adolescents included in our study; 52% had a left ventricular ejection fraction<55%, the left ventricular end-diastolic diameter was increased in 70.5% of patients, and 32.3% had an increase in left ventricular mass. On average, 78.9% had abnormal values of left ventricle longitudinal deformations. The number of segments affected per patient was, on average, 5.8, with the anterior apical segment being the most commonly affected. There was a decrease in global longitudinal deformity in 79.4% of the cases. CONCLUSION: More than half of this group of asymptomatic severely obese adolescents showed abnormalities in left ventricular structure and function evaluated using traditional echocardiographic methods, but 100% of the cases showed abnormalities in longitudinal deformation in at least one of the 17 left ventricle segments evaluated using myocardial-tracking signals.

Isotretinoin conundrum: a randomized, openlabel, crossover study in Mexico to evaluate the bioavailability and bioequivalence of three pharmaceutical preparations of isotretinoin in healthy participants.

OBJECTIVE: The oral retinoid agent isotretinoin (13-cis-retinoic acid) is approved for the treatment of severe recalcitrant cystic acne. For registrational renewal of Oratane® in Mexico (isotretinoin; Laboratorios Dermatologicos Darier S.A. de C.V., Mexico), it was necessary to establish bioequivalence to the reference product Roaccutan® (Isotretinoin; Roche, Mannheim, Germany). Three prior studies failed to establish the bioequivalence of Oratane to Mexican-sourced Roaccutan. However, 13 studies demonstrated the bioequivalence of Oratane to Roaccutane® from multiple sources. This study compared the bioavailability of Oratane with that of Mexicansourced Roaccutan and Australian-sourced Roaccutane. METHODS: Study participants received each of the three agents in a randomized, open-label, 6-sequence, 3-way crossover study with a 2-week washout period between treatments. RESULTS: Pharmacokinetic analysis revealed that peak plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 (dosing) to infinite time (AUC0-∞) were lower for Roaccutan than for Roaccutane and Oratane (Cmax: 1,023.35, 1,223.08, and 1,224.25 ng/mL, respectively; AUC0-∞: 13,653.65, 15,681.35 and 15,733.55 ng/mL x h, respectively). The 90% CIs (test/reference) for the ratios of the geometric means indicated that Oratane was bioequivalent to Roaccutane but not to Roaccutan. In addition, Roaccutane (R2) was not bioequivalent to Roaccutan (R1; R1/R2 90% CIs: Cmax, 76.12 - 91.04; AUC0-t, 82.19 - 91.13; AUC0-∞, 82.94 - 91.57). CONCLUSION: Oratane and Australian-sourced Roaccutane could be considered bioequivalent, but neither formulation was found to be bioequivalent to Mexican-sourced Roaccutan.

Safety and efficacy comparison of minocycline microgranules vs lymecycline in the treatment of mild to moderate acne: randomized, evaluator-blinded, parallel, and prospective clinical trial for 8 weeks.

BACKGROUND: Minocycline and lymecycline are used in the treatment of acne, but there is not enough evidence to support superior efficacy of one of them. METHODS: 170 participants from 14 to 34 years old with mild to moderate facial acne vulgaris were recruited. 84 had 100 mg of minocycline in a single daily dose for 8 weeks and 86 had 300 mg of lymecycline in a single daily dose for 8 weeks. Participants were evaluated at baseline, week 4 and week 8. RESULTS: 65 minocycline and 60 lymecycline patients were evaluable. The last observation carried forward for the count of non-inflammatory lesions changed from 37.5 ± 17.8 to 37.7 ± 17.8 in the minocycline group and from 36.9 ± 15.5 to 33.4 ± 19.3 in the lymecycline group (no significant changes); corresponding changes in inflammatory lesions were from 19.4 ± 12.4 to 12.2 ± 10.0 in the minocycline group and from 20.1 ± 11.3 to 12.6 ± 8.4 in lymecycline group (P< 0.05 comparing baseline vs. final in both groups). Porphyrin counts varied from 899.5 ± 613.9 to 233.5 ± 219.5 in the minocycline group and from 956.9 ± 661.8 to 411.8 ± 411.5 in the lymecycline group (P<0.05 between the groups at study end). 36 (42.9%) patients receiving minocycline suffered 55 adverse events (22 of them gastrointestinal), while 28 (33.3%) lymecycline patients had 37 adverse events (15 of them gastrointestinal). One patient in the lymecycline group withdrew the study due to gastritis, and one more patient in the same group experienced eosinophilia. CONCLUSIONS: There were no differences between the groups in non-inflammatory and inflammatory lesion counts, and in the safety profile. Treatment with minocycline induced statistically significant decrease in facial porphyrin counts compared to the group treated with lymecycline (ClinicalTrials.gov number, NCT00988026).

Effect of Obesity on Lung Function in the Pediatric and Adult Populations with Asthma: A Review.

Obesity and asthma are major global health concerns, particularly in industrialized nations. Obesity has been shown to have detrimental effects on the respiratory system and lung function owing to metabolic issues and immunological consequences. Research has indicated that obese patients with asthma (atopic or T2-high and non-atopic or T2-low) have diminished lung function in terms of functional residual capacity (FRC), residual volume (RV), expiratory reserve volume (ERV), the FEV1/FVC ratio, and FEF 25-75% due to mechanical fat loading on the diaphragm and central adiposity when compared to non-obese asthmatic patients. Therefore, it is plausible that changes in lung function are the result of a combination of mechanical (fat loading on the diaphragm, central adiposity, bronchial hyper-reactivity, and an increase in cholinergic tone), environmental (diet and exercise), and inflammatory factors (local and systemic), which can lead to the obesity-related asthma phenotype characterized by severe asthma symptoms, poor response to corticosteroid treatment, loss of lung function, and poor quality of life from an early age.

Immunostimulants for preventing respiratory tract infection in children: A systematic review and meta-analysis.

Childhood acute respiratory tract infections (ARTIs) are a significant cause of morbidity and mortality, so, immunostimulants have been used as a preventative measure. Despite this, there is no updated evidence regarding the safety and efficacy of immunostimulant drugs for this purpose. This study aimed to determine the effectiveness and safety of immunostimulants in preventing ARTIs in children based on the most recent scientific evidence. Data sources such as PubMed, Cochrane Central Register of Controlled Trials, Embase, Google Scholar, and Scopus were searched from 1965 to 10 January 2022 to identify randomized controlled trials (RCTs) comparing immunostimulants administered by any method, with placebo to prevent ARTIs on children under 18 years of age without immunodeficiencies, anatomical, genetic, or allergic conditions. In order to analyze data from the studies, we used Review Manager 5.4 (The Cochrane Collaboration, 2020), assessed the certainty of the evidence with Grading of Recommendations, Assessment, Development and Evaluations (GRADE), and assessed the quality and risk of bias of the studies using the RoB tool 1.0. Further, outcomes were combined and analyzed using meta-analysis, subgroup analysis, and sensitivity analysis. Throughout the review, we included 72 placebo-controlled clinical trials involving 12,229 children. The meta-analyses, however, included only 38 studies (52.8%) with 4643 children (38% of the total) with data on mean number of ARTIs. These studies demonstrated a reduction in the ARTIs (MD -1.12 [95%CI -1.39 to -0.85]) and ratio of means of ARTIs (0.61 [95%CI 0.54-0.69]), corresponding to a percentage reduction of 39% (95%CI, 46%-31%) with moderate-quality data. Nevertheless, since there was considerable to substantial heterogeneity and bias was unclear in all domains in 32 out of 72 trials, the quality of the evidence for efficacy was deemed low. Only 14 trials reported adverse events. The review indicates that immunostimulants reduce the incidence of ARTIs by 40% on average in susceptible children, despite low-quality evidence, heterogeneity, and the possibility of publication bias. However, further studies are needed to establish immunostimulants' safety and efficacy profiles. This review was conducted without the support of any funding and has no registered number.

Have the prevalence of eczema symptoms increased in the Mexican pediatric population? Prevalence and associated factors according to Global Asthma Network Phase I.

Background: In children, atopic dermatitis or eczema is the most common inflammatory disease of the skin. According to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase IIIB in Mexico, 5.8% of children and 4.9% of adolescents had eczema symptoms. In 2012, Global Asthma Network (GAN) was established to update the prevalence of eczema and estimate potential factors contributing to its development. Objective: To estimate the prevalence and associated factors for atopic eczema symptoms and diagnosis in children and adolescents according to GAN Phase I and compare the results with ISAAC Phase IIIB in Mexico. Methods: A cross-sectional, multicenter survey was conducted in 15 Mexican centers during the period of 2015-2017 using the GAN Phase I questionnaires in children (6-7-year-olds) and adolescents (13-14-year-olds). The prevalences obtained from the GAN Phase I study, were compared with ISAAC Phase IIIB results; a Spearman's correlation analysis was conducted between temperature, relative humidity, and altitude and eczema symptoms, and a logistic regression was performed to predict current eczema symptoms by age group. Results: A total of 35 777 children and 41 399 adolescents were included. Since ISAAC Phase IIIB, the prevalence of itchy rash in the past 12 months significantly increased in the children's group [6.6% (95% CI 5.7-7.4) vs 7.8 (95% CI 7.5-8.1), p = 0.000] and adolescents' group [5.8% (95% CI 5.0-6.7) vs 6.7% (95% CI 6.5-7.0), p = 0.000].In the adolescents' group, the prevalence of nocturnal awakenings caused by rash symptoms on more than one night per week had a negative correlation between altitude (Spearman's Rho = -0.558, p value = 0.031), and a positive correlation with the average annual temperature (Spearman's Rho = 0.604, p value = 0.017) and annual relative humidity (Spearman's Rho = 0.742, p value = 0.002). The most significant associations in children were the presence of sneezing or runny or blocked nose in the past 12 months [(OR 3.13, 95% CI 2.60-3.77), p = 0.000], the use of paracetamol in the first year of life ([OR 1.52, 95% CI 1.15-2.01), p = 0.003] and the use of antibiotics in the first year of life [(OR 1.30, 95% CI 1.08-1.55) p = 0.004]. Moreover, altitude at 100-1000 m above sea level was associated with current eczema symptoms in adolescents (p = 0.001). Conclusions: There has been a significant increase in eczema symptoms in both age groups since ISAAC Phase IIIB study. Additionally, eczema symptoms were associated with temperature, relative humidity, asthma, hay fever symptoms, the use of paracetamol and antibiotics.

Prevalence and risk factors associated with allergic rhinitis in Mexican school children: Global Asthma Network Phase I.

BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) showed a wide variability in prevalence and severity of allergic rhinitis (AR) and rhinoconjunctivitis (ARC), in addition to other atopic diseases (Asher et al, 2006).1 The Global Asthma Network (GAN) has continued to study these conditions. OBJECTIVE: To estimate the prevalence of AR and ARC in children and adolescents in Mexico and to assess their association with different risk factors. METHODS: GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016-2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by 35 780 parents of 6-7 year old primary school pupils (children) and by 41 399 adolescents, 13-14 years old. RESULTS: The current and cumulative prevalence of AR was higher in the adolescents (26.2-37.5%, respectively) in comparison to the children (17.9-24.9%, respectively), especially in female participants. This tendency was also observed in the current prevalence of ARC, where 15.1% of female adolescents reported nasal symptoms accompanied with itchy-watery eyes in the past year. The most important risk factors for AR and ARC were the presence of wheezing in the past 12 months, wheezing in the first year of life, the previous diagnosis of asthma and eczema symptoms. Furthermore, allergic symptoms had a negative tendency concerning altitude. CONCLUSION: This is the largest AR epidemiological study ever conducted in Mexico. It shows an increase in AR prevalence, as well as significant associations with modifiable risk factors, which could help to establish recommendations to reduce the burden of this condition.

Higher metabolic syndrome in obese asthmatic compared to obese nonasthmatic adolescent males.

UNLABELLED: The relationship between asthma and obesity has been documented in children and adolescents; however, few studies on metabolic syndrome and asthma have been performed. OBJECTIVE: To determine the prevalence of metabolic syndrome in adolescents among the following groups: obese with asthma (OA), obese without asthma (ONA), nonobese with asthma (NOA), and nonobese without asthma (NONA). PATIENTS AND METHODS: The authors measured anthropometric (height, weight, waist circumference, body mass index, and waist-hip ratio), clinical (Tanner stage, blood pressure, fat and muscle reserve, and exercise), and biochemical parameters (basal and load glucose, cholesterol, triglycerides, high-density lipoproteins, uric acid, and insulin) in 500 Mexican adolescents. RESULTS: A total of 111 OA, 198 ONA, 63 NOA, and 71 NONA adolescents completed the study. There were no differences in age, height, Tanner stage, high-density lipoproteins, or basal glucose among groups. Cholesterol, triglycerides, uric acid, basal insulin, and homeostasis model assessment (HOMA)-IR were significantly higher among the obese than nonobese groups but were similar between the OA and ONA groups. The prevalence of impaired fasting glucose was significantly higher among ONA versus OA males. The prevalence of metabolic syndrome (define as > or =3 abnormal cardiometabolic risk factors by de Ferranti, Cook, and International Diabetes Federation [IDF] criteria) was higher among OA teens than in the ONA group; however, this association was significant only among males. Adolescents from the ONA group were able to perform significantly more vigorous exercise than the other groups. CONCLUSION: Adolescent males who were obese and also had mild persistent asthma had a significantly higher prevalence of metabolic syndrome than obese males without asthma. However, overall, asthma seems to confer a protective effect against the prediabetes condition in males.

Factors associated with allergic rhinitis in children and adolescents from northern Mexico: International Study of Asthma and Allergies in Childhood Phase IIIB.

The epidemiology of allergic diseases has not been studied extensively in Mexico. The present study, based on the International Study of Asthma and Allergies in Childhood Phase IIIB survey, reports the prevalence of allergic rhinitis and the associated risk factors in the pediatric population in four cities in northern Mexico. Children (6-7 years old) and adolescents (13-14 years old) in public elementary and secondary schools were surveyed in 2002 and 2003. The subjects were chosen randomly from Ciudad Victoria, Mexicali, Monterrey, and Tijuana. The following categories were analyzed: occurrence of rhinitis symptoms (currently or in the last 12 months), rhinoconjunctivitis symptoms, a previous diagnosis of allergic rhinitis, and relevant environmental factors. Factors associated with rhinitis that were identified previously with the chi-squared test were analyzed using logistic regression. The number of valid questionnaires was 10,892 for schoolchildren and 12,299 for adolescents. In 6- to 7-year-old children, the following frequencies were determined: rhinitis (ever), 27.9%; current rhinitis, 24.2%; rhinoconjunctivitis, 9.2%; and diagnosis of allergic rhinitis, 5.5%. The corresponding frequencies in 13- to 14-year-old children were 33.3, 34.1, 18.4, and 3.8%. In both 6- to 7-year-old and 13- to 14-year-old children, all rhinitis items were associated with asthma symptoms, dermatitis symptoms, paracetamol consumption, and maternal smoking (odds ratio, >1; p < 0.05). The main risk factors associated with allergic rhinitis symptoms in children and adolescents from cities in northern Mexico were other allergic conditions, paracetamol consumption, and passive smoking.

The burden of asthma in an inner-city area: A historical review 10 years after Isaac.

BACKGROUND: According to the International Study of Asthma and Allergies in Childhood (ISAAC) methodology, in 2003, the prevalence of asthma symptoms in children 6-7 years old and adolescents 13-14 years old was 11.6% and 13.7%, respectively. Since then, the number of asthma cases has increased worldwide. The study was conducted in several districts in northern Mexico City to evaluate the prevalence of asthma in these age groups and examine possible risk factors. The data were compared to the 2003 results from the same area. METHODS: This was a comparative cross-sectional study following the official Global Asthma Network (GAN) methodology. The parents or guardians of participants completed a questionnaire that explored demographics, asthma symptoms, diagnoses, and possible risk factors. Central tendency measurements were determined for statistical analysis and chi-squared distribution for possible risk factors. RESULTS: A total of 2515 children aged 6-7 years and 3375 adolescents aged 13-14 years participated in the study. Compared to the ISAAC results, we found a greater prevalence of wheezing in both children (at some time in life, 19.2% vs. 27.1%; over the last year, 6.8% vs. 10.6%) and adolescents (at some time in life, 16.9% vs. 19.7%), and for children with an asthma diagnosis (4.5% vs. 5.1%). For both groups, the most common risk factor associated with wheezing was the presence of rhinitis symptoms. CONCLUSIONS: Asthma symptoms are highly prevalent in Mexico City, occurring in almost 20% of adolescents. Compared to a decade ago, there was a 7.9% increase in the prevalence of asthma symptoms in children. Almost half of the children and adolescents presenting with symptoms had experienced more than four episodes per year. However, less than 50% of children and adolescents with asthma symptoms had been diagnosed with this disorder, suggesting under-diagnosis.

Global Asthma Network Phase I study in Mexico: prevalence of asthma symptoms, risk factors and altitude associations-a cross-sectional study.

BACKGROUND: Global Asthma Network (GAN) was established in 2012 as a development to the International Study of Asthma and Allergies in Childhood to improve asthma care globally. OBJECTIVE: To survey asthma, allergic rhinitis and atopic dermatitis in primary and secondary school children and to investigate and evaluate its prevalence, severity, management and risk factors in Mexico. METHODS: GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016-2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by parents of 6-7-year-old primary school pupils (school children) and by 13-14-year-old adolescents. RESULTS: A total of 35 780 school children and 41 399 adolescents participated. Wheezing ever prevalence was 26.2% (95% CI 25.8% to 26.7%) in school children and 23.9% (95% CI 23.4% to 24.3%) in adolescents. The corresponding frequencies for current wheeze were 10.2% (95% CI 9.9% to 10.5%) and 11.6% (95% CI 11.2% to 11.9%). In school children, the risk factors for current wheeze were rhinitis (OR 4.484; 95% CI 3.915% to 5.134%) and rash symptoms (OR 1.735; 95% CI 1.461% to 2.059%). For adolescents, rhinitis symptoms (OR 3.492; 95% CI 3.188% to 3.825%) and allergic rhinitis diagnosis (OR 2.144; 95% CI 1.787% to 2.572%) were the most significant. For both groups, there was a negative relation with centres' sea level altitude higher than 1500 m above mean sea level (p<0.005). CONCLUSIONS: The most important risk factors for asthma symptoms in both age groups were the presence of rhinitis and rash symptoms or diagnosis. On the other hand, sea level altitude higher than 1500 metres was a protective factor.

Cost-effectiveness analysis of OM-85 vs placebo in the prevention of acute respiratory tract infections (ARTIs) in children that attend day-care centers.

BACKGROUND: Children that attend day-care centers frequently contract acute respiratory tract infections (ARTIs). ARTIs represent a burden for both children and parents. Systematic reviews on the use of immunostimulants for the prevention of juvenile recurrent ARTIs have provided moderate evidence of efficacy and safety. The aim of the study was to establish whether the immunostimulant, OM-85, was cost-effective in preventing ARTIs in children 2-6 years old that attended day-care centers or preschools in Mexico. We performed a systematic review to evaluate the efficacy of OM-85. For costs, we assumed an institutional perspective, which included the costs of care and supplies over a study period of six months, during the autumn-winter seasons. We created decision trees and constructed a model to identify pharmacoeconomic parameters. We generated 1000 estimations with the bootstrap method to calculate descriptive statistics of pharmacoeconomic parameters. We evaluated cost-effectiveness compared to treatment without immunostimulants. RESULTS: The mean (SD) incidences of ARTIs were 5.59 ± 0.29 without immunostimulants and 2.97 ± 0.32 with OM-85, during the study period. The mean (25th, 75th percentile) direct costs of ARTIs were 57.04 (37.11, 76.39) US$ (US dollars) without immunostimulants and 48.53 (37.35, 58.93) US$ with OM-85, with a mean increment of - 8.51(- 17.08, 0.75) US$, and a mean cost-effectiveness of - 17.94 (- 36.48, 1.66) US$. The direct costs plus the cost of one parent missing work to care for the child with ARTI were 125.76 (102.83, 150.16) US$, without immunostimulant and 85.21 (72.15, 98.81) US$, with OM-85. The increment was - 40.55 (- 68.29, - 13.95) US$, and the cost-effectiveness was - 86.89 (- 142.37, - 29.34) US$.Part of the cost reduction was ascribed to the reduced use of medications, particularly antibiotics. CONCLUSIONS: Our results were consistent with previous clinical studies conducted in closed institutions in Mexico. OM-85 reduced the number of ARTIs and the frequency of antibiotics use. We concluded that OM-85 was cost-effective for preventing ARTIs in children that attended day-care centers, particularly when parental absenteeism was covered by the institutions.

Obesity and metabolic risks in children.

BACKGROUND: We undertook this study to establish the prevalence of overweight, obesity, abdominal obesity, high blood pressure, and high glucose and triglyceride levels in school-age children from Mexico City, as well as to determine how overweight and obesity are related to the other risk factors. METHODS: The study was a cross-sectional survey comprised of 1819 children (6-13 years of age) attending six elementary schools. Gender, age, weight, height, waist circumference, blood pressure, and levels of triglycerides and glucose were registered. Percentiles were calculated according to American standards for BMI, height, waist circumference, and blood pressure. RESULTS: Compared to American references, mean percentiles for waist circumference and BMI were >50, and mean height percentiles were <50. Prevalence of overweight was 22.3 and 23.6% for boys and girls, respectively; obesity, 28 and 21.2%; abdominal obesity, 22.1 and 11.7%; high triglyceride levels, 11.3 and 15.4%; high blood pressure, 4.8 and 5.8%, respectively. Overweight, obesity, and abdominal obesity are associated with higher blood pressure and triglyceride levels (odds ratio>1.0, p<0.05). Percentiles for BMI, waist circumference, systolic blood pressure, and diastolic blood pressure also had significant correlations (r>0.2, p<0.001). CONCLUSIONS: This population of Mexican school-age children was shorter and heavier than their American standards. The prevalence of metabolic risks was similar to those reported in American adolescents in NHANES surveys.

Insights on the mechanism of action of immunostimulants in relation to their pharmacological potency. The effects of imidazoquinolines on TLR8.

Imidazoquinolines are powerful immunostimulants (IMMS) that function through Toll-like receptors, particularly TLR7 and TLR8. In addition to enhancing the immune response, IMMS also function as antineoplastic drugs and vaccine adjuvants. These small compounds display almost the same molecular structure, except in some cases in which atom in position 1 varies and changes the imidazole characteristics. A variable acyclic side chain is also always attached at atom in position 2, while another chain may be attached at atom in position 1. These structural differences alter immune responses, such as the production of interferon regulatory factor and nuclear factor-κB (IRF-NFκB). In this work, quantum mechanics theory and computational chemistry methods were applied to study the physicochemical properties of the crystal binding site of TLR8 complexed with the following six IMMS molecules: Hybrid-2, XG1-236, DS802, CL075, CL097 and R848 (resiquimod). The PDB IDs of the crystals were: 4R6A, 4QC0, 4QBZ, 3W3K, 3W3J, and 3W3N respectively. Thus, were calculated, the total energy, solvation energy, interaction energy (instead of free energy) of the system and interaction energy of the polar region of the IMMS. Additionally, the dipole moment, electrostatic potential, polar surface, atomic charges, hydrogen bonds, and polar and hydrophobic interactions, among others, were assessed. Together, these properties revealed important differences among the six TLR8-immunostimulant complexes, reflected as different interaction energies and therefore different electrostatic environments and binding energies. Remarkably, the interaction energy of a defined polar region composed of the highly polarized N3, N5 atoms and the N11 amino group, acted as a polar pharmacophore that correlates directly with the reported immunopharmacological potency of the six complexed molecules. Based on these results, it was concluded that accurate physicochemical analysis of the crystal binding site could reveal the binding energy (measured as interaction energy) and associated molecular mechanism of action between IMMS and TLR8. These findings may facilitate the development and design of improved small molecules with IMMS properties that are targeted to the TLR system and have enhanced pharmacological effectiveness and reduced toxicity.

Use of sibutramine in obese mexican adolescents: a 6-month, randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: The prevalence of overweight and obesity in children and adolescents is increasing in both the United States and Mexico. OBJECTIVE: The goal of this article was to assess the efficacy and safety of sibutramine in obese Mexican adolescents. METHODS: This was a 6-month, randomized, double-blind, placebo-controlled, prospective clinical trial of sibutramine QD. Male and female patients aged 14 to 18 years with sex-specific body mass index (BMI) for age and sex >85th percentile were eligible. The primary end points for the trial were the baseline versus end point absolute values for body weight, BMI, and percentage of the initial BMI (%BMI); secondary end points were waist circumference and percentage of the initial waist circumference (%waist). These were measured at days -15, 0, 30, 60, 90, 120, 150, and 180 of the study. Quality of life was assessed at the study start and end using the 36-Item Short-Form Health Survey (SF-36) questionnaire. Blood pressure and heart rate were assessed, and adverse events (AEs) were recorded. Both groups received individually tailored diet and exercise programs. RESULTS: Forty-six patients (age range, 14-18 years) with a BMI >95th percentile for age were included (sibutramine group, n = 23 [14 females, 9 males]; placebo group, n = 23 [12 females, 11 males]). Twenty-one patients in the sibutramine group and 19 patients in the placebo group completed the 6-month trial. Using the intent-to-treat data, weight (mean [SD]) in the sibutramine group changed from 92.5 (14.6) kg to 85.7 (14.4) kg, for a net weight loss of 7.3 kg (95% CI 4.6-9.9), a waist circumference loss of 8.0 cm (95% CI, 4.7-11.3), and a % BMI loss of 9.2% (95% CI, 6.9-11.6). In the placebo group, weight changed from 98.9 (22.7) kg to 94.6 (22.5) kg, a weight loss of 4.3 kg (95% CI, 1.7-6.9), a waist circumference loss of 3.8 cm (95% CI, 0.7-7.0), and a %BMI loss of 5.2% (95% CI, 2.4-7.9) (P < 0.05 for all intragroup comparisons; P > 0.05 for the intergroup comparisons). Mean (SD) scores on the SF-36 scale in the sibutramine group changed from 78.0 (13.3) at baseline to 84.8 (7.4) at study end (P < 0.05); the respective values in the placebo group were 82.8 (10.3) and 87.3 (7.6) (P < 0.05). At base-line, systolic blood pressure (SBP) was 116.7 (5.9) mm Hg in the sibutramine group and 118.3 (7.6) mm Hg in the placebo group; at end point, the respective SBPs were 112.4 (9.6) mm Hg and 112.6 (6.5) mm Hg. At baseline, diastolic blood pressure (DBP) was 78.9 (4.5) mm Hg in the sibutramine group and 79.5 (5.2) mm Hg in the placebo group; at end point, the respective DBPs were 73.5 (6.3) mm Hg and 76.6 (6.2) mm Hg. At baseline, heart rate was 76.3 (6.4) beats/min in the sibutramine group and 81.1 (9.5) beats/min in the placebo group; at end point, the respective findings were 79.8 (8.8) beats/min and 77.6 (8.6) beats/min (P > 0.05 for all preceding intergroup comparisons). One patient in the sibutramine group had increased blood pressure (at month 3) and 3 had increased heart rate (at months 1, 2, and 4); 2 patients receiving placebo had increased blood pressure (month 3) and 2 had increased heart rate (at months 1 and 3). These changes disappeared in 1 week and did not require treatment or trial suspension. Additionally, in the sibutramine group, 3 patients experienced 4 mild AEs: headache, dry mouth, headache with nausea, and headache with weakness and paleness (P > 0.05). In the placebo group, 3 patients experienced 4 mild AEs: 2 cases of headache, as well as 1 case of headache with somnolence and 1 case of headache with dry mouth (P > 0.05). CONCLUSION: Sibutramine 10 mg QD in addition to diet and exercise was effective and generally well tolerated in this population of obese Mexican adolescents.

Use of sibutramine in obese Hispanic adolescents.

A study on the treatment of obese adolescents with the use of sibutramine in private practice is presented. Patients consisted of 24 boys and 43 girls with obesity (body mass index [BMI]>85th percentile sex-specific BMI for age and sex) ranging from 12 to 18 years of age. Patients were given sibutramine 10 mg per day for 6 months. With the last observation carried forward adjustment, after 6 months of treatment, patients' average weight changed from 91.6+/-19.7 kg to 81.9+/-19.0 kg (P<.001), that is, 89.5+/-7.3% of initial weight. The most frequently reported adverse events included increased blood pressure and pulse rate (n=7), constipation (n=8), dry mouth (n=4), and constipation and dry mouth (n=3). Sibutramine may be considered effective for the treatment of obese adolescents, with a level of safety similar to that observed in adult patients.

Use of sibutramine in overweight adult hispanic patients with type 2 diabetes mellitus: a 12-month, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: The management of type 2 diabetes mellitus is complicated by the presence of risk factors related to overweight and obesity, particularly visceral adiposity. However, weight loss and weight maintenance are difficult for patients with diabetes, and the benefits of dietary modifications are typically modest. Sibutramine is a serotonin- and norepinephrine-reuptake inhibitor that reduces food intake by inducing early satiety and attenuates the decrease in basal energy expenditure associated with weight loss. Previous trials of sibutramine in overweight and obese patients with type 2 diabetes have shown significant weight loss accompanied by better glycemic control. OBJECTIVE: The goal of this study was to assess the effect on body weight and glycemic control of sibutramine in combination with glibenclamide in obese Hispanic patients with type 2 diabetes. METHODS: This was a 12-month, randomized, double-blind, placebo-controlled clinical trial conducted at the Endocrinology Service, General Hospital of Mexico, Mexico City. Included were overweight or obese (body mass index [BMI] >27 kg/M2) patients with type 2 diabetes between the ages of 24 and 65 years who had been receiving glibenclamide monotherapy for at least 2 weeks and whose glucose concentrations were stable. Patients were randomized to receive sibutramine 10 mg or placebo once daily. The primary efficacy measures were change in body weight, waist circumference, and glycosylated hemoglobin (HbA1c). Anthropometrics and fasting glucose concentrations were measured monthly. HbA1c was determined at baseline and at 6 and 12 months. Laboratory parameters were measured at baseline and at the end of the study. RESULTS: Forty-four patients were randomized to receive sibutramine (28 women, 16 men; mean [SD] age, 47.6 [9.0] years), and 42 were randomized to receive placebo (31 women, 11 men; mean age, 45.8 [8.1] years). Twenty-four patients in the sibutramine group and 23 in the placebo group completed the trial. In the sibutramine group, body weight was reduced from a mean (SD) of 73.9 (10.3) kg at baseline to 69.8 (10.6) kg at month 12; BMI decreased from 29.9 (2.6) to 28.2 (2.9) kg/M2; waist circumference was reduced from 94.9 (8.4) to 90.8 (8.4) cm; the plasma fasting glucose concentration decreased from 140.4 (29.4) to 114.2 (32.0) mg/dL; and the HbA1c value was reduced from 8.9% (1.2) to 8.3% (1.2) (all, P < 0.001). In the placebo group, the corresponding changes were from 74.5 (10.3) kg at baseline to 73.1 (11.2) kg at month 12; from 30.1 (2.5) to 29.5 (2.9) kg/M2; from 94.4 (7.3) to 93.1 (8.3) cm (P < 0.05); from 140.7 (25.2) to 123.9 (38.3) mg/dL (P < 0.05); and from 9.0% (1.2) to 9.1% (1.3). In the sibutramine group, weight loss continued for up to 12 months. CONCLUSION: In this population of obese Hispanic patients with type 2 diabetes, sibutramine combined with glibenclamide therapy achieved weight loss for up to 12 months and was associated with better glycemic control than placebo.

Clinical evaluation of the efficacy and safety of calcium dobesilate in patients with chronic venous insufficiency of the lower limbs.

Several venotonic drugs have been used in the treatment of chronic venous insufficiency (CVI) of the lower limbs, most of them from natural sources. Calcium dobesilate, from synthetic origin, has been shown to improve clinical symptoms of these venous conditions. Three hundred fifty-two patients with CVI in grades I and II of Widmer's classification were included from an open population between January 1999 and June 2000; patients received calcium dobesilate 500 mg every 8 hours for 9 weeks. A basal recording and recordings every 3 weeks were made of heaviness, pain, cramps, and paresthesias of the lower limbs with a severity scale, and edema was assessed by measurement of the circumference of ankles and calves. Two hundred eighty-six patients (81.3%) were women and 66 (18.7%) were men with a mean age of 45.7 +/-14.1 years; 200 patients (56.8%) were grade I and 150 (42.6%) were grade II of Widmer's classification, and two patients had no classification, with a mean duration of symptoms of 6.5 +/-7.4 years. All of the symptoms had a significant reduction from the first to the final visit of treatment; 70% of the patients complained of moderate to severe heaviness of the lower limbs at the beginning of the study, whereas 10% of the patients presented this symptom at the end of treatment. Likewise, 75%, 37%, and 41% of the patients, respectively, complained of moderate to severe pain, cramps, and paresthesias of the lower limbs at the beginning of the study, with a reduction in this prevalence to 6%, 2%, and 4%, respectively, at the end of treatment (p<0.001, Wilcoxon test). In regard to edema of ankles and calves, a significant reduction in circumferences was registered in both sites at the end of treatment; for instance, the mean circumference of the right ankle was reduced from 23.78 +/-0.27 to 22.71 +/-0.31 cm while the right calf had a reduction from 35.08 +/-0.41 to 33.83 +/-0.5 cm (p<0.001, paired t test). Side effects were registered in 17.9% of the patients. This trial shows that calcium dobesilate had significant efficacy in the improvement of all the symptoms in patients with CVI, achieving this effect with an acceptable safety profile.

Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension.

This 6-month randomized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension. Following a 2-week washout to confirm the diagnosis of hypertension, antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day. A body mass index in excess of 27 kg/m2 was required for entry. At study end, weight had changed from 75.4+/-9.6 to 70.0+/-9.5 kg in the sibutramine group and from 77.9+/-9.0 to 74.5+/-9.4 kg in the placebo group. In the sibutramine group, systolic blood pressure was 127.8+/-5.8 mm Hg after stabilization and 125.2+/-8.5 mm Hg after completion of the trial; respective values for diastolic blood pressure were 82.4+/-3.7 and 81.5+/-4.6 mm Hg. With placebo, blood pressure dropped from 129.0+/-7.1/80.9+/-4.9 mm Hg to 122.8+/-9.7/80.3+/-5.4 mm Hg at the same timepoints. In the sibutramine group, 14 patients reported 21 adverse events, most frequently headache (n=5), constipation (n=4), and dry mouth (n=4). In the placebo group, 13 patients had 20 adverse events. Sibutramine is safe and effective in overweight Hispanic patients with hypertension, but monitoring of blood pressure and titration of antihypertensive medication are necessary.