Educational interventions in pharmacovigilance to improve the knowledge, attitude and the report of adverse drug reactions in healthcare professionals: Systematic Review and Meta-analysis.

OBJECTIVES: Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance. EVIDENCE ACQUISITION: A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270. RESULTS: Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I2 = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I2 = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I2 = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I2 = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention. CONCLUSION: EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.

Medication errors in a children's inpatient antineoplastic chemotherapy facility.

BACKGROUND: Due to many antineoplastic drugs' toxicity and narrow therapeutic window, medication errors are a health concern in pediatric oncology patients. This study aimed to identify and classify medication errors in a pediatric inpatient chemotherapy facility and evaluate the outcomes of these medication errors. METHODS: We conducted an observational retrospective study over 5 months in a chemotherapy facility for pediatric patients. The evaluation consisted of the review of the available medical records. The medication errors detected were manually recorded in a medical logbook. The International Classification for Patient Safety was adjusted to our clinical setting for the analysis, the terminology, and the classification system. A descriptive analysis was performed. RESULTS: A total of 286 medical records were reviewed; one type of medication error was noted in at least 97.6%, and 962 errors were identified totally, with an overall rate of 3.36 errors per visit. Most errors occurred in the documentation stage (643; 66.8%), followed by the administration stage (227; 23.6%). Of all medication errors, 37.2% had the potential to cause injury, but only five reached the patient (0.5%), and only two (0.2%) resulted in a severe harmful incident. CONCLUSIONS: Medication errors were common, especially at the documentation stage. Better documentation strategies need to be implemented to reduce the rate of near misses and prevent potential adverse events.

INTRODUCCIÓN: Los errores de medicación son un problema de salud en niños con cáncer debido a la toxicidad y a la estrecha ventana terapéutica de muchos fármacos antineoplásicos. El objetivo de este estudio fue identificar y clasificar los errores de medicación en un centro de quimioterapia para pacientes pediátricos hospitalizados, así como evaluar los resultados de estos errores de medicación. MÉTODOS: Se llevó a cabo un estudio observacional retrospectivo realizado durante un periodo de 5 meses en un centro de quimioterapia para pacientes pediátricos. La evaluación consistió en la revisión de las historias clínicas disponibles. Los errores de medicación detectados fueron registrados manualmente en una bitácora. Para el análisis, la terminología y el sistema de clasificación, la Clasificación Internacional para la Seguridad del Paciente se ajustó a nuestro entorno clínico. Se realizó un análisis descriptivo. RESULTADOS: Se revisaron 286 historias clínicas; se observó un tipo de error de medicación al menos en el 97.6%. En total se identificaron 962 errores de medicación, con una tasa general de 3.36 errores por visita. En la etapa de documentación fue donde más errores ocurrieron (643; 66.8%), seguido de la etapa de administración (227; 23.6%). De todos los errores de medicación, el 37.2% tuvo el potencial de causar lesiones, pero solo cinco llegaron al paciente (0.5%) y solo dos (0.2%) provocaron un incidente dañino severo. CONCLUSIONES: Los errores de medicación fueron comunes, especialmente en la etapa de documentación. Es necesario implementar mejores estrategias de documentación para reducir la tasa de cuasi accidentes y prevenir posibles eventos adversos.

Medication errors in a children's inpatient antineoplastic chemotherapy facility / Errores de medicación en un centro de quimioterapia antineoplásica para pacientes pediátricos hospitalizados

Abstract Background: Due to many antineoplastic drugs' toxicity and narrow therapeutic window, medication errors are a health concern in pediatric oncology patients. This study aimed to identify and classify medication errors in a pediatric inpatient chemotherapy facility and evaluate the outcomes of these medication errors. Methods: We conducted an observational retrospective study over 5 months in a chemotherapy facility for pediatric patients. The evaluation consisted of the review of the available medical records. The medication errors detected were manually recorded in a medical logbook. The International Classification for Patient Safety was adjusted to our clinical setting for the analysis, the terminology, and the classification system. A descriptive analysis was performed. Results: A total of 286 medical records were reviewed; one type of medication error was noted in at least 97.6%, and 962 errors were identified totally, with an overall rate of 3.36 errors per visit. Most errors occurred in the documentation stage (643; 66.8%), followed by the administration stage (227; 23.6%). Of all medication errors, 37.2% had the potential to cause injury, but only five reached the patient (0.5%), and only two (0.2%) resulted in a severe harmful incident. Conclusions: Medication errors were common, especially at the documentation stage. Better documentation strategies need to be implemented to reduce the rate of near misses and prevent potential adverse events.

Resumen Introducción: Los errores de medicación son un problema de salud en niños con cáncer debido a la toxicidad y a la estrecha ventana terapéutica de muchos fármacos antineoplásicos. El objetivo de este estudio fue identificar y clasificar los errores de medicación en un centro de quimioterapia para pacientes pediátricos hospitalizados, así como evaluar los resultados de estos errores de medicación. Métodos: Se llevó a cabo un estudio observacional retrospectivo realizado durante un periodo de 5 meses en un centro de quimioterapia para pacientes pediátricos. La evaluación consistió en la revisión de las historias clínicas disponibles. Los errores de medicación detectados fueron registrados manualmente en una bitácora. Para el análisis, la terminología y el sistema de clasificación, la Clasificación Internacional para la Seguridad del Paciente se ajustó a nuestro entorno clínico. Se realizó un análisis descriptivo. Resultados: Se revisaron 286 historias clínicas; se observó un tipo de error de medicación al menos en el 97.6%. En total se identificaron 962 errores de medicación, con una tasa general de 3.36 errores por visita. En la etapa de documentación fue donde más errores ocurrieron (643; 66.8%), seguido de la etapa de administración (227; 23.6%). De todos los errores de medicación, el 37.2% tuvo el potencial de causar lesiones, pero solo cinco llegaron al paciente (0.5%) y solo dos (0.2%) provocaron un incidente dañino severo. Conclusiones: Los errores de medicación fueron comunes, especialmente en la etapa de documentación. Es necesario implementar mejores estrategias de documentación para reducir la tasa de cuasi accidentes y prevenir posibles eventos adversos.

Midazolam reduction with pre-operative melatonin in abdominal hysterectomy: double-blind randomized clinical trial.

INTRODUCTION: Midazolam is a benzodiazepine used for sedation, however, can cause respiratory depression and increases morbidity in patients. Melatonin is an effective alternative to manage anxiety in the perioperative period and could help to reduce the use of benzodiazepines during surgery. The aim of this clinical trial was to determine the efficacy of pre-operative sedation with a single-dose melatonin to reduce intraoperative use of midazolam in women under total abdominal hysterectomy (TAH). MATERIALS AND METHODS: This is a double-blind randomized clinical trial conducted in women over 25 years, scheduled for TAH, with American Society of Anesthesiologists Grade I or II. Each patient was randomly assigned to receive 5 mg of melatonin prolonged-release oral capsules or placebo. Midazolam use for anesthetic management was the decision of the treating anesthesiologist and sedation status was determined using the observer's assessment of alertness/sedation scale. RESULTS: In patients receiving melatonin, the use of midazolam during surgery was less than in patients receiving placebo. In addition, melatonin produces sedation 30 min after administration, the sedative effect was maintained at 60- and 90-min. Furthermore, hospital stay was shorter in patients who received melatonin (p = 0.006). CONCLUSION: Melatonin is effective for reduces intraoperative midazolam consumption and hospital stay in women undergoing TAH.

INTRODUCCIÓN: El midazolam es una benzodiazepina utilizada para la sedación, sin embargo, puede causar depresión respiratoria y aumentar la morbilidad en los pacientes. La melatonina es una alternativa eficaz para controlar la ansiedad en el período perioperatorio y podría ayudar a reducir el uso de benzodiazepinas durante la cirugía. El objetivo de este ensayo clínico fue determinar la eficacia de la sedación preoperatoria con una dosis única de melatonina para reducir el uso intraoperatorio de midazolam en mujeres sometidas a histerectomía abdominal total (HTA). MATERIAL Y MÉTODOS: Se trata de un ensayo clínico aleatorizado doble ciego realizado en mujeres mayores de 25 años, programadas para TAH, con American Society of Anesthesiologists Grado I o II. Cada paciente fue asignado al azar para recibir 5 mg de cápsulas orales de liberación prolongada de melatonina o placebo. El uso de midazolam para el manejo anestésico fue decisión del anestesiólogo tratante y el estado de sedación se determinó mediante la escala OAA/S. RESULTADOS: En las pacientes que recibieron melatonina, el uso de midazolam durante la cirugía fue menor que en las pacientes que recibieron placebo. Además, la melatonina produce sedación 30 min después de la administración, el efecto sedante se mantuvo a los 60 y 90 min. Además, la estancia hospitalaria fue más corta en los pacientes que recibieron melatonina (p = 0.006). CONCLUSIÓN: La melatonina es eficaz para reducir el consumo de midazolam intraoperatorio y la estancia hospitalaria en mujeres sometidas a HTA.

Effect of Tibolone on Bone Mineral Density in Postmenopausal Women: Systematic Review and Meta-Analysis.

Low bone mineral density (BMD) on postmenopausal women causes bone fragility and fracture risk. Tibolone seems to prevent bone loss. Therefore, this systematic review with meta-analysis synthesizes the tibolone effect on BMD percent change in lumbar spine (LS), femoral neck (FN), and total hip (TH) in postmenopausal women. Controlled trials that provided tibolone evidence on the efficacy of tibolone in preventing loss of BMD were included. Regarding the included studies, a pooled mean difference (MD) with 95% confidence intervals (95%CI) was estimated to determine the BMD percentage change. Eleven studies were identified and eight were included in the quantitative analysis. Tibolone at a dose of 2.5 mg increased BMD compared with non-active controls at 24 months in LS (MD 4.87%, 95%CI: 4.16-5.57, and MD 7.35%, 95%CI: 2.68-12.01); and FN (MD 4.85%, 95%CI: 1.55-8.15, and 4.21%, 95%CI: 2.99-5.42), with Hologic and Lunar scanners, respectively. No difference was observed when tibolone 2.5 mg dose was compared with estrogen therapy (ET) at 24 months, LS (MD -0.58%, 95%CI: -3.77-2.60), FN (MD -0.29%, 95%CI: -1.37-0.79), and TH (MD -0.12%, 95%CI: -2.28-2.53). Therefore, tibolone increases BMD in LS and FN compared to non-active controls, and there was no showed difference with ET.

Effect of Tai Chi on Markers of Oxidative Stress: Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to synthesize the evidence of the effect of practicing Tai Chi on oxidative stress markers (OxSM). METHODS: This systematic review and meta-analysis was conducting using the MEDLINE, Cochrane Library, ScienceDirect, Scopus, Epistemonikos, Lilacs, and Ovid databases to identify randomized (RCT) and non-randomized (NRCT) clinical trials that evaluated the Tai Chi effect on OxSM compared to sedentary behavior, walking or yoga. Pooled mean differences (MDs) with 95% confidence intervals (95%CI) were estimated using the inverse variance method to determine the effect of Tai Chi on OxSM. PROSPERO register: CRD42019138362. RESULTS: Five RCT and five NRCT were included. Compared to sedentary behavior, regular Tai Chi practice increases the levels of the enzymes superoxide dismutase (MD = 34.97 U/mL, (95%CI, 9.45 to 60.48), 344 participants) and catalase (MD = 15.63 U/mL, (95%CI, 4.05 to 27.22), 110 participants), as well as reducing the levels of lipoperoxides (MD = -0.02 µmol/L, (95%CI, -0.04 to -0.00), 234 participants). For comparisons with walking or yoga, only one study per activity was identified comparing the effect on OxSM. CONCLUSIONS: Regular Tai Chi practice increases the levels of superoxide dismutase and catalase, as well as reducing the levels of lipoperoxides. More studies are necessary to determine the effect of Tai Chi on OxSM when compared to other physical activities.

Efficacy and safety of oral magnesium supplementation in reducing febrile neutropenia episodes in children with solid tumors treated with cisplatin-based chemotherapy: randomized clinical trial.

PURPOSE: Hypomagnesemia has been associated with febrile neutropenia (FN) in pediatric patients receiving cisplatin-based chemotherapy (CDDPBC). The primary aim was to determine whether oral magnesium supplementation reduces FN episodes in pediatric patients with solid tumors treated with CDDPBC. METHOD: This randomized clinical trial, with open-label, single-center, parallel group and superiority design was conducted in Hospital Infantil de Mexico Federico Gomez at Mexico City. Children ≥ 9 years with solid tumors that were to receive a CDDPBC cycle were invited to participate. Each chemotherapy cycle with CDDPBC was randomly assigned to receive oral magnesium supplementation (250 mg/day) or not receive magnesium supplementation (control group). Efficacy was determined by relative risks (RR) with 95% confidence intervals (95% CI) as well as with numbers needed to treat (NNT). Active surveillance was conducted to assess safety in both groups. Analyses were carried out by intention to treat. ClinicalTrials.gov number NCT03449693. RESULTS: One hundred and one chemotherapy cycles with CDDPBC were analyzed (50 in the magnesium supplement arm and 51 in control group). Baseline clinical characteristics were similar comparing both groups. Oral magnesium supplementation reduces FN episodes compared to control group [RR 0.53, (95% CI 0.32-0.89), NNT = 4]. In the supplemented group, patients had fewer episodes of septic shock secondary to FN [RR 0.43, (95% CI 0.02-0.94), NNT = 6] and FN appeared on average 5 days later (p = 0.031). Hypomagnesemia episodes and adverse events were similar across both groups. CONCLUSION: Oral supplementation with magnesium reduces FN episodes neutropenia in pediatric patients with solid tumors treated with CDDPBC.

Association of rs2000999 in the haptoglobin gene with total cholesterol, HDL-C, and LDL-C levels in Mexican type 2 diabetes patients.

Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.

Outpatient treatment for people with cancer who develop a low-risk febrile neutropaenic event.

BACKGROUND: People with febrile neutropaenia are usually treated in a hospital setting. Recently, treatment with oral antibiotics has been proven to be as effective as intravenous therapy. However, the efficacy and safety of outpatient treatment have not been fully evaluated. OBJECTIVES: To compare the efficacy (treatment failure and mortality) and safety (adverse events of antimicrobials) of outpatient treatment compared with inpatient treatment in people with cancer who have low-risk febrile neutropaenia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11) in the Cochrane Library, MEDLINE via Ovid (from 1948 to November week 4, 2018), Embase via Ovid (from 1980 to 2018, week 48) and trial registries (National Cancer Institute, MetaRegister of Controlled Trials, Medical Research Council Clinical Trial Directory). We handsearched all references of included studies and major reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing outpatient with inpatient treatment for people with cancer who develop febrile neutropaenia. The outpatient group included those who started treatment as an inpatient and completed the antibiotic course at home (sequential) as well as those who started treatment at home. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, methodological quality, and extracted data. Primary outcome measures were: treatment failure and mortality; secondary outcome measures considered were: duration of fever, adverse drug reactions to antimicrobial treatment, duration of neutropaenia, duration of hospitalisation, duration of antimicrobial treatment, and quality of life (QoL). We estimated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data; we calculated weighted mean differences for continuous data. Random-effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: We included ten RCTs, six in adults (628 participants) and four in children (366 participants). We found no clear evidence of a difference in treatment failure between the outpatient and inpatient groups, either in adults (RR 1.23, 95% CI 0.82 to 1.85, I2 0%; six studies; moderate-certainty evidence) or children (RR 1.04, 95% CI 0.55 to 1.99, I2 0%; four studies; moderate-certainty evidence). For mortality, we also found no clear evidence of a difference either in studies in adults (RR 1.04, 95% CI 0.29 to 3.71; six studies; 628 participants; moderate-certainty evidence) or in children (RR 0.63, 95% CI 0.15 to 2.70; three studies; 329 participants; moderate-certainty evidence).According to the type of intervention (early discharge or exclusively outpatient), meta-analysis of treatment failure in four RCTs in adults with early discharge (RR 1.48, 95% CI 0.74 to 2.95; P = 0.26, I2 0%; 364 participants; moderate-certainty evidence) was similar to the results of the exclusively outpatient meta-analysis (RR 1.15, 95% CI 0.62 to 2.13; P = 0.65, I2 19%; two studies; 264 participants; moderate-certainty evidence).Regarding the secondary outcome measures, we found no clear evidence of a difference between outpatient and inpatient groups in duration of fever (adults: mean difference (MD) 0.2, 95% CI -0.36 to 0.76, 1 study, 169 participants; low-certainty evidence) (children: MD -0.6, 95% CI -0.84 to 0.71, 3 studies, 305 participants; low-certainty evidence) and in duration of neutropaenia (adults: MD 0.1, 95% CI -0.59 to 0.79, 1 study, 169 participants; low-certainty evidence) (children: MD -0.65, 95% CI -0.1.86 to 0.55, 2 studies, 268 participants; moderate-certainty evidence). With regard to adverse drug reactions, although there was greater frequency in the outpatient group, we found no clear evidence of a difference when compared to the inpatient group, either in adult participants (RR 8.39, 95% CI 0.38 to 187.15; three studies; 375 participants; low-certainty evidence) or children (RR 1.90, 95% CI 0.61 to 5.98; two studies; 156 participants; low-certainty evidence).Four studies compared the hospitalisation time and found that the mean number of days of hospital stay was lower in the outpatient treated group by 1.64 days in adults (MD -1.64, 95% CI -2.22 to -1.06; 3 studies, 251 participants; low-certainty evidence) and by 3.9 days in children (MD -3.90, 95% CI -5.37 to -2.43; 1 study, 119 participants; low-certainty evidence). In the 3 RCTs of children in which days of antimicrobial treatment were analysed, we found no difference between outpatient and inpatient groups (MD -0.07, 95% CI -1.26 to 1.12; 305 participants; low-certainty evidence).We identified two studies that measured QoL: one in adults and one in children. QoL was slightly better in the outpatient group than in the inpatient group in both studies, but there was no consistency in the domains included. AUTHORS' CONCLUSIONS: Outpatient treatment for low-risk febrile neutropaenia in people with cancer probably makes little or no difference to treatment failure and mortality compared with the standard hospital (inpatient) treatment and may reduce time that patients need to be treated in hospital.

The rs1256031 of estrogen receptor ß gene is associated with type 2 diabetes.

AIM: To determine the association between the rs1256031 polymorphism and risk of developing type 2 diabetes. MATERIALS AND METHODS: Cases and controls study. 597 individuals with type 2 diabetes and 605 without it participated. Genotyping of the rs1256031 polymorphism of the ERß gene was performed by real-time PCR using TaqMan assay. For the multivariate analysis, a multiple logistic regression was performed that included the main confounding variables. RESULTS AND CONCLUSION: A multiple logistic regression analysis was performed, adjusting for age, WHR, BMI and gender. The dominant model showed a protective effect compared to the TT genotype (OR = 0.596, IC95% [0.458-0.776]). DISCUSSION: The proportions of native American, European and African ancestry were characterized and no difference was found in the study groups. The protective effect obtained in the dominant model could to be due a regulatory function in the transcription or the processing of the primary transcript. Our result are the first to report an association between the polymorphism rs1256031 and the reduction of the risk of T2D in the Mexican population. The rs1256031 polymorphism show reduced risk of developing T2D and is potential markers for predicting T2D.

A strategy for the clinical remission of acute lymphoblastic leukemia elicited by treatment of ß-thalassemia major: A case report.

Acute lymphoblastic leukemia (ALL) has been suggested as a long-term complication in patients with ß-thalassemia major (ß-TM). A 12-months-old male patient was diagnosed with ß-TM. The patient required a blood transfusion weekly for 2 years. At the age of 4 years, a splenectomy was performed due to massive splenomegaly and frequent transfusion requirements. The histopathological analysis of the spleen revealed extensive hemosiderosis. ALL-L1 with the T immunophenotype and without central nervous system (CNS) involvement was diagnosed when the patient was 5 years old, and treated with anti-leukemic combination chemotherapy and CNS radiotherapy. The patient completed 24 months of treatment and has been in complete remission for 7 years, without long-term adverse events.

Risk Factors for Febrile Neutropenia in Children With Solid Tumors Treated With Cisplatin-based Chemotherapy.

Febrile neutropenia (FN) is a common and potentially fatal adverse drug reaction of cisplatin-based chemotherapy (CDDPBC) in pediatric patients. Hence, the aim of this study was to determine the incidence and independent risk factors for FN in pediatric patients with solid tumors treated with CDPPBC. Cohort integration was performed in the first cycle of chemotherapy with CDDPBC and patients were followed up to 6 months after the last cycle. FN was defined according to the Common Terminology Criteria for Adverse Events. Relative risks were calculated with confidence intervals at 95% (95% CI) to determine FN risk factors. Multiple logistic regression was performed to identify independent risk factors. One hundred and thirty-nine pediatric patients (median age 7.4 y, range 0.08 to 17 y) were included in the study. FN incidence was 62.5%. Independent risk factors for FN were chemotherapy regimens including anthracyclines (odds ratio [OR]=19.44 [95% CI, 5.40-70.02), hypomagnesaemia (OR=8.20 [95% CI, 1.81-37.14]), and radiotherapy (OR=6.67 [95% CI, 1.24-35.94]). It is therefore concluded that anthracyclines-containing regimens, hypomagnesaemia, and radiotherapy are independent risk factors for FN in patients receiving CDDPBC.

Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors: A Retrospective Cohort Study.

Cisplatin, a major antineoplastic drug used in the treatment of solid tumors, is a known nephrotoxin. This retrospective cohort study evaluated the prevalence and severity of cisplatin nephrotoxicity in 54 children and its impact on height and weight.We recorded the weight, height, serum creatinine, and electrolytes in each cisplatin cycle and after 12 months of treatment. Nephrotoxicity was graded as follows: normal renal function (Grade 0); asymptomatic electrolyte disorders, including an increase in serum creatinine, up to 1.5 times baseline value (Grade 1); need for electrolyte supplementation <3 months and/or increase in serum creatinine 1.5 to 1.9 times from baseline (Grade 2); increase in serum creatinine 2 to 2.9 times from baseline or need for electrolyte supplementation for more than 3 months after treatment completion (Grade 3); and increase in serum creatinine ≥3 times from baseline or renal replacement therapy (Grade 4).Nephrotoxicity was observed in 41 subjects (75.9%). Grade 1 nephrotoxicity was observed in 18 patients (33.3%), Grade 2 in 5 patients (9.2%), and Grade 3 in 18 patients (33.3%). None had Grade 4 nephrotoxicity. Nephrotoxicity patients were younger and received higher cisplatin dose, they also had impairment in longitudinal growth manifested as statistically significant worsening on the height Z Score at 12 months after treatment. We used a multiple logistic regression model using the delta of height Z Score (baseline-12 months) as dependent variable in order to adjust for the main confounder variables such as: germ cell tumor, cisplatin total dose, serum magnesium levels at 12 months, gender, and nephrotoxicity grade. Patients with nephrotoxicity Grade 1 where at higher risk of not growing (OR 5.1, 95% CI 1.07-24.3, P=0.04). The cisplatin total dose had a significant negative relationship with magnesium levels at 12 months (Spearman r=-0.527, P=<0.001).

[Apa1 VDR polymorphism and osteoporosis risk in postmenopausal Mexican women]. / Papel del polimorfismo Apa1 del gen VDR en el riesgo de osteoporosis en mujeres mexicanas posmenopáusicas.

AIM: To analyze the association between Apa1 VDR polymorphism and osteoporosis in Mexican mestizo postmenopausal women. METHODS: A cross-sectional study was conducted in 534 postmenopausal mestizo women from Mexico City to determine the association of the Apa1 Vitamin D Receptor gene polymorphism (rs7975232) with osteoporosis and osteoporosis plus fracture. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Genotyping was performed using real-time PCR with an allelic discrimination assay. RESULTS: The Apa1 allele frequencies were no different between groups. No association was found between Apa1 genotypes and osteoporosis (AA, OR: 1.08; 95% CI: 0.62-1.87; AC, OR: 0.70; 95% CI: 0.45-1.07). Similar results were obtained for osteoporosis plus fracture (AA, OR: 0.93; 95% CI: 0.50-1.71; AC, OR: 0.70; 95% CI 0.45-1.07). After adjusting for age, the result remained. CONCLUSION: These findings are in agreement with previous studies reporting no association of Apa1 VDR polymorphism with osteoporosis.

[Clinical research XXIII. From clinical judgment to meta-analyses]. / Investigación clínica XXIII. Del juicio clínico a los metaanálisis.

Systematic reviews (SR) are studies made in order to ask clinical questions based on original articles. Meta-analysis (MTA) is the mathematical analysis of SR. These analyses are divided in two groups, those which evaluate the measured results of quantitative variables (for example, the body mass index -BMI-) and those which evaluate qualitative variables (for example, if a patient is alive or dead, or if he is healing or not). Quantitative variables generally use the mean difference analysis and qualitative variables can be performed using several calculations: odds ratio (OR), relative risk (RR), absolute risk reduction (ARR) and hazard ratio (HR). These analyses are represented through forest plots which allow the evaluation of each individual study, as well as the heterogeneity between studies and the overall effect of the intervention. These analyses are mainly based on Student's t test and chi-squared. To take appropriate decisions based on the MTA, it is important to understand the characteristics of statistical methods in order to avoid misinterpretations.

Las revisiones sistemáticas (RS) son estudios que intentan contestar una pregunta clínica por medio del uso de artículos originales. Los metaanálisis (MTA) son el análisis matemático de las revisiones sistemáticas. Estos análisis se dividen en dos grandes grupos: aquellos que evalúan los resultados medidos como variables cuantitativas (por ejemplo, el índice de masa corporal ­IMC­) y aquellos que evalúan variables cualitativas (por ejemplo, si un paciente está vivo o muerto, o si ha mejorado o no de su enfermedad). Los primeros utilizan en general la diferencia de medias. Para los segundos se puede utilizar el cálculo de razón de momios (RM) u odds ratio (OR), riesgo relativo (RR), reducción absoluta del riesgo (RAR), hazard ratio (HR), etcétera. Estos análisis se grafican por medio de forest plots que permiten tanto la evaluación individual de los estudios como la del resultado final, así como la heterogenidad de estas comparaciones. Asimismo, estos análisis se basan en análisis estadísticos básicos como la t de Student y la chi cuadrada. Para la toma de decisiones basadas en las RS y en los MTA, es importante evaluar cuidadosamente los posibles sesgos y los apartados estadísticos con el fin evitar malas interpretaciones.

Hearing loss in Mexican children treated with cisplatin.

OBJECTIVE: Cisplatin is widely used to treat a variety of pediatric solid tumors. One of the most severe and debilitating adverse drug reactions experienced by patients who receive cisplatin therapy is permanent bilateral hearing loss. The aim of this study was to evaluate the incidence and risk factors for cisplatin-induced hearing loss in Mexican pediatric patients. METHODS: Detailed medical and drug histories, including use of cisplatin as well as other drugs known to cause hearing loss, were collected from patient medical records. Results of audiology tests on pediatric patients with solid tumors were collected at baseline, during treatment and at the end of cisplatin chemotherapy. Hearing loss was classified according to the Common Terminology Criteria for Adverse Events. Bivariate and multivariate analyses were performed using survival curves. RESULTS: Fifty-nine pediatric patients, median age 11 years (range, 3-17 years) were included in the study. The incidence of cisplatin-induced hearing loss was 56%. Individual risk factors including age (< 5 years), male sex, and concomitant medications were not associated with an increased risk of cisplatin-induced hearing loss. Patients with a diagnosis of osteosarcoma and a cumulative cisplatin dose greater than 400 mg/m(2) were at higher risk of hearing loss compared with all other tumor and cumulative dose combinations (HR = 2.47 [95% CI, 1.043-5.831]). CONCLUSIONS: Cumulative dose and tumor type are associated with an increased risk of cisplatin-induced hearing loss. Further research is required to characterize fully the interindividual variation in hearing loss in Mexican patients.

[Clinical research XVII. χ(2) test, from the expected to the observed]. / Investigación clínica XVII. Prueba χ(2), de lo esperado a lo observado.

When you want to show if there is a statistical association or differences between categorical variables, it is recommended to use the χ(2) test. This nonparametric test is one of the most used in clinical research; it contrasts nominal or ordinal qualitative variables that are observed in clinical practice. This test calculates the p value that determines whether differences between groups are real or due to chance. The χ(2) test is the basis of other tests to analyze qualitative ordinal variables as χ(2) for linear trend, which compares three groups with two outcomes or McNemar test, which contrasts two related samples (a before and afterward comparison) or Mantel-Haenszel χ(2), which controls for potential confounding variables. When using small samples, where the expected results are less than 5, Fisher's exact test should be used. These tests are the most widely used in the medical literature; however, they do not give us the magnitude or the direction of the event and a proper interpretation that requires clinical judgment is needed.

Cuando se busca demostrar que existe relación o diferencias estadísticamente significativas, entre las variables categóricas se utiliza la prueba de χ2. Esta prueba no paramétrica es una de las más usadas en la investigación clínica, ya que contrasta variables cualitativas nominales u ordinales observadas en la práctica clínica. Con esta prueba se calcula el valor de p para decidir si las diferencias entre los grupos son reales o se deben al azar. Esta prueba genéricamente recibe el nombre de χ2 o chi cuadrada (dependiendo de las preferencias idiomáticas) y es la base de otras pruebas con las que se analizan las variables cualitativas ordinales: la χ2 de tendencia lineal, con la que se comparan tres grupos que pueden tener dos desenlaces; la prueba de McNemar, que sirve para contrastar dos muestras relacionadas (antes y después de una maniobra); o la χ2 de Mantel-Haenszel, que controla el efecto de variables potencialmente confusoras. Para muestras pequeñas, en las que el resultado esperado es menor de 5, se debe utilizar la prueba exacta de Fisher. Como se puede ver, este grupo de pruebas es el de mayor uso en los artículos médicos, sin embargo, no dan cuenta de la magnitud ni de la dirección del evento, por lo que su adecuada interpretación requiere del juicio clínico.

Allele frequency distribution of CYP2C9 2 and CYP2C9 3 polymorphisms in six Mexican populations.

Allele frequency differences of functional CYP2C9 polymorphisms are responsible for some of the variation in drug response observed in human populations. The most relevant CYP2C9 functional variants are CYP2C9*2 (rs1799853) and CYP2C9 3 (rs1057910). These polymorphisms show variation in allele frequencies among different population groups. The present study aimed to analyze these polymorphisms in 947 Mexican-Mestizo from Mexico City and 483 individuals from five indigenous Mexican populations: Nahua, Teenek, Tarahumara, Purepecha and Huichol. The CYP2C9*2 allele frequencies in the Mestizo, Nahua and Teenek populations were 0.051, 0.007 and 0.005, respectively. As for CYP2C9 3, the allelic frequencies in the Mestizo, Nahua and Teenek populations were 0.04, 0.005 and 0.005, respectively. The CYP2C9 2 and CYP2C9 3 alleles were not observed in the Tarahumara, Purepecha and Huichol populations. These findings are in agreement with previous studies reporting very low allele frequencies for these polymorphisms in American Indigenous populations.