Non-Invasive Strategies for Nose-to-Brain Drug Delivery.

Intranasal drug administration is a promising method for delivering drugs directly to the brain. Animal studies have described pathways and potential brain targets, but nose-to-brain delivery and treatment efficacy in humans remains debated. We describe the proposed pathways and barriers for nose-to-brain drug delivery in humans, drug properties that influence central nervous system delivery, clinically tested methods to enhance absorption, and the devices used in clinical trials. This review compiles the available evidence for nose-to-brain drug delivery in humans and summarizes the factors involved in nose-to-brain drug delivery.

Percepción de la competencia comunicativa médica durante la entrevista clínica en un hospital docente peruano: validación y aplicación de un instrumento evaluativo / Perception of medical communication skills during the clinical interview in a Peruvian teaching hospital: validation and application of an assessment tool

OBJETIVO Determinar la percepción de los pacientes sobre la destreza en la comunicación de los médicos que atienden en consultorio externo de un hospital docente de Lima, Perú, según el instrumento Communication Assessment Tool. MÉTODOS La población de estudio fue el colectivo de pacientes atendidos en los consultorios externos del Hospital Cayetano Heredia. El cuestionario Communication Assessment Tool consta de 15 preguntas, se utilizó una versión validada al castellano. La percepción de la destreza en comunicación se determinó como la sumatoria de los puntajes del total de las premisas, entre la cantidad de las premisas. Se definió como mala (1), justa (2), buena (3), muy buena (4) y excelente (5). RESULTADOS El porcentaje de pacientes que calificaron la competencia comunicativa como "mala" (puntaje Communication Assessment Tool promedio) fue de 6,8%, "justa" 27,2%, "buena" 23,9%, "muy buena" 30,1% y "excelente" 12,1%. Se hallaron diferencias estadísticamente significativas respecto a los rangos de edad y entre los distintos grados de instrucción. El grupo de pacientes entre 18 y 29 años otorgó puntajes más altos en el Communication Assessment Tool (rango = 2,2 a 4,87; p = 0,001). Además, cuando el nivel educativo del encuestado fue superior tendió a colocar puntajes más altos (rango = 3,67 a 4,73; p = 0,001). CONCLUSIONES Se determinó que 66,2% de los pacientes tuvo una percepción positiva, sólo 12,11% lo calificó como "excelente", un valor muy por debajo a lo reportado en la literatura. Los que brindaron mejor calificación fueron los pacientes jóvenes y con mayor grado de instrucción.

OBJECTIVE To determine the perception of patients regarding physicians' communication skills at the outpatient clinic of a teaching hospital in Lima-Peru, using the Communication Assessment Tool (CAT). METHODS The study population was the group of patients treated in the outpatient clinics of the Cayetano Heredia Hospital. The CAT questionnaire contains 15 questions, and a version validated for Spanish was used. The perception of communication skills was defined as the sum of the scores of all the items, over the number of items, defined as: poor (1), fair (2), good (3), very good, (4), and excellent (5). RESULTS The percentage of patients who rated communication skills as "poor" (average CAT Score) was 6.8%, "fair" 27.2%, "good" 23.9%, "very good" 30.1 and "excellent" 12.1%. Statistically significant differences were found when comparing the age ranges and among the different levels of education. The group of patients between 18 and 29 years old gave higher scores in the instrument (range 2.2 to 4.87, p = 0.001). Furthermore, when the educational level of the respondent was high, the participants tended to rate physicians with higher scores (range 3.67 to 4.73, p = 0.001). CONCLUSION We found that 66.2% of patients had a positive perception of the physicians' communication skills; only 12.1% rated it as "excellent," a value well below what is reported in the literature. Those who gave the best rating were younger patients with the highest level of education.

Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

AIM: Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA1c . This study explores the relationship between HbA1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. METHODS: Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA1c and FPG was assessed using a Kappa index. RESULTS: At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. CONCLUSION: The relationship between HbA1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA1c to diagnose diabetes mellitus in this setting.

Rural-to-urban migration and risk of hypertension: longitudinal results of the PERU MIGRANT study.

Urbanization can be detrimental to health in populations due to changes in dietary and physical activity patterns. The aim of this study was to determine the effect of migration on the incidence of hypertension. Participants of the PERU MIGRANT study, that is, rural, urban and rural-to-urban migrants, were re-evaluated after 5 years after baseline assessment. The outcome was incidence of hypertension; and the exposures were study group and other well-known risk factors. Incidence rates, relative risks (RRs) and population attributable fractions (PAFs) were calculated. At baseline, 201 (20.4%), 589 (59.5%) and 199 (20.1%) participants were rural, rural-to-urban migrant and urban subjects, respectively. Overall mean age was 47.9 (s.d.±12.0) years, and 522 (52.9%) were female. Hypertension prevalence at baseline was 16.0% (95% confidence interval (CI) 13.7-18.3), being more common in urban group; whereas pre-hypertension was more prevalent in rural participants (P<0.001). Follow-up rate at 5 years was 94%, 895 participants were re-assessed and 33 (3.3%) deaths were recorded. Overall incidence of hypertension was 1.73 (95%CI 1.36-2.20) per 100 person-years. In multivariable model and compared with the urban group, rural group had a greater risk of developing hypertension (RR 3.58; 95%CI 1.42-9.06). PAFs showed high waist circumference as the leading risk factor for the hypertension development in rural (19.1%), migrant (27.9%) and urban (45.8%) participants. Subjects from rural areas are at higher risk of developing hypertension relative to rural-urban migrant or urban groups. Central obesity was the leading risk factor for hypertension incidence in the three population groups.

Manual MGIT™ system for the detection of Mycobacterium tuberculosis: insights from a high TB burden setting.

OBJECTIVE: To evaluate the diagnostic performance of manual MGIT™ (MMGIT) compared to the gold standard, Löwenstein-Jensen (LJ), in the diagnosis of pulmonary tuberculosis (TB) in a high-burden setting. METHODS: Individuals with suspected TB enrolled in parallel diagnostic trials during 2007-2011 were included. Two samples were obtained from each patient and inoculated into MMGIT and LJ medium. Diagnostic tests were performed, and the incremental yield of a second test and time to detection (TTD) were calculated. Analyses were performed per patient and per sample. Gold standard was based on LJ culture. RESULTS: In the per patient and per sample analysis, we evaluated 1436 patients and 4142 samples. The sensitivity and specificity for smear and MMGIT per sample were respectively 89.9%/92.2% and 97.1%/98.9%. Contamination was observed in 1.4% of samples on MMGIT. The mean TTD (days) was 11.8 for MMGIT and 22.9 for LJ. The sensitivity and specificity for smear and MMGIT per patient were respectively 89.9% and 92.2% and 97.1% and 98.3%. A second MMGIT culture had an incremental yield of 1.6%. CONCLUSIONS: MMGIT has high sensitivity and specificity, regardless of smear result, with a 50% reduction in TTD compared to LJ. These features make MMGIT an acceptable TB diagnostic method for use in resource-limited settings.

Obesity risk in rural, urban and rural-to-urban migrants: prospective results of the PERU MIGRANT study.

BACKGROUND: Although migration and urbanization have been linked with higher obesity rates, especially in low-resource settings, prospective information about the magnitude of these effects is lacking. We estimated the risk of obesity and central obesity among rural subjects, rural-to-urban migrants and urban subjects. METHODS: Prospective data from the PERU MIGRANT Study were analyzed. Baseline data were collected in 2007-2008 and participants re-contacted in 2012-2013. At follow-up, outcomes were obesity and central obesity measured by body mass index and waist circumference. At baseline, the primary exposure was demographic group: rural, rural-to-urban migrant and urban. Other exposures included an assets index and educational attainment. Cumulative incidence, incidence ratio (IR) and 95% confidence intervals (95% CI) for obesity and central obesity were estimated with Poisson regression models. RESULTS: At baseline, mean age (±s.d.) was 47.9 (±12.0) years, and 53.0% were females. Rural subjects comprised 20.2% of the total sample, whereas 59.7% were rural-to-urban migrants and 20.1% were urban dwellers. A total of 3598 and 2174 person-years were analyzed for obesity and central obesity outcomes, respectively. At baseline, the prevalence of obesity and central obesity was 20.0 and 52.5%. In multivariable models, migrant and urban groups had an 8- to 9.5-fold higher IR of obesity compared with the rural group (IR migrants=8.19, 95% CI=2.72-24.67; IR urban=9.51, 95% CI=2.74-33.01). For central obesity, there was a higher IR only among the migrant group (IR=1.95; 95% CI=1.22-3.13). Assets index was associated with a higher IR of central obesity (IR top versus bottom tertile 1.45, 95% CI=1.03-2.06). CONCLUSIONS: Peruvian urban individuals and rural-to-urban migrants show a higher incidence of obesity compared with their rural counterparts. Given the ongoing urbanization occurring in middle-income countries, the rapid development of increased obesity risk by rural-to-urban migrants suggests that measures to reduce obesity should be a priority for this group.

Differences in hospital- and ventilator-associated pneumonia due to Staphylococcus aureus (methicillin-susceptible and methicillin-resistant) between Europe and Latin America: a comparison of the EUVAP and LATINVAP study cohorts.

PURPOSE: A comparison is made of epidemiological variables (demographic and clinical characteristics) and outcomes in patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) in the Latin American VAP (LATINVAP) vs. the European Union VAP (EUVAP) cohorts of patients admitted to intensive care units (ICUs). METHODS: The EUVAP project was a prospective, multicenter observational study reporting 827 patients with HAP/VAP in 27 ICUs from 9 European countries. The LATINVAP project was a multicenter prospective observational study, with an identical design, performed in 17 ICUs from 4 Latin American countries involving 99 patients who developed HAP/VAP. Episodes of VAP/HAP caused by S. aureus, MSSA, and MRSA were compared in both cohorts. RESULTS: Forty-five patients had S. aureus HAP/VAP in the EUVAP cohort vs. 11 patients in the LATINVAP cohort. More patients had MRSA in the LATINVAP study than in the EUVAP (45% vs. 33%). ICU mortality among patients with MSSA HAP/VAP in EUVAP was 10% vs. 50% for LATINVAP (OR=9.75, p=0.01). Fifteen patients in the EUVAP cohort developed MRSA HAP/VAP as opposed to 5 in LATINVAP. In the EUVAP study there was an ICU mortality rate of 33.3%. In the LATINVAP cohort, the ICU mortality rate was 60% (OR for death=3.0; 95%CI 0.24-44.7). CONCLUSION: MRSA pneumonia was associated with poorer outcomes in comparison with MSSA. Our study suggests significant variability among European and Latin American ICU practices that may influence clinical outcomes. Furthermore, patients with pneumonia in Latin America have different outcomes.

Magnesium sulfate as a vehicle for nebulized salbutamol in acute asthma.

PURPOSE: Magnesium sulfate is thought to be an effective bronchodilator when administered intravenously to patients with acute severe asthma, and it can be safely administered via inhalation to patients with stable asthma. Our goal was to determine if isotonic magnesium sulfate could be used as a vehicle for nebulized salbutamol for patients with acute asthma. METHODS: We enrolled 35 patients with acute asthma in a randomized, double-blind, controlled trial. After measurement of peak expiratory flow, patients received 2.5 mg salbutamol plus either 3 mL normal saline solution (n = 16) or isotonic magnesium sulfate (n = 19) through a jet nebulizer. Peak flow was reassessed 10 and 20 minutes after treatment. RESULTS: Peak flow at baseline was similar in the two groups. Ten minutes after baseline, the mean (+/- SD) percentage increase in peak flow was greater in the magnesium sulfate-salbutamol group (61% +/- 45%) than in the normal saline-salbutamol group (31% +/- 28%; difference = 30%; 95% confidence interval [CI] for the difference: 3% to 56%; P = 0.03). At 20 minutes, the percentage increase in peak flow was 57% greater in the magnesium sulfate group (95% CI: 4% to 110%, P = 0.04). There was a significant inverse correlation between baseline peak flow (percent of predicted) and the percentage increase in peak flow at 20 minutes in the magnesium sulfate group (r = -0.82, P <0.0001), but not in the saline group (r = -0.12, P = 0.67). CONCLUSION: In patients with acute asthma, isotonic magnesium sulfate, as a vehicle for nebulized salbutamol, increased the peak flow response to treatment in comparison with salbutamol plus normal saline.