Computational Investigation of Substituent Effects on the Alcohol + Carbonyl Channel of Peroxy Radical Self- and Cross-Reactions.

Organic peroxy radicals (RO2) are key intermediates in atmospheric chemistry and can undergo a large variety of both uni- and bimolecular reactions. One of the least understood reaction classes of RO2 are their self- and cross-reactions: RO2 + R'O2. In our previous work, we have investigated how RO2 + R'O2 reactions can lead to the formation of ROOR' accretion products through intersystem crossings and subsequent recombination of a triplet intermediate complex 3(RO···OR'). Accretion products can potentially have very low saturation vapor pressures, and may therefore participate in the formation of aerosol particles. In this work, we investigate the competing H-shift channel, which leads to the formation of more volatile carbonyl and alcohol products. This is one of the main, and sometimes the dominant, RO2 + R'O2 reaction channels for small RO2. We investigate how substituents (R and R' groups) affect the H-shift barriers and rates for a set of 3(RO···OR') complexes. The variation in barrier heights and rates is found to be surprisingly small, and most computed H-shift rates are fast: around 108-109 s-1. We find that the barrier height is affected by three competing factors: (1) the weakening of the breaking C-H bond due to interactions with adjacent functional groups; (2) the overall binding energy of the 3(RO···OR'), which tends to increase the barrier height; and (3) the thermodynamic stability of the reaction products. We also calculated intersystem crossing rate coefficients (ISC) for the same systems and found that most of them were of the same order of magnitude as the H-shift rates. This suggests that both studied channels are competitive for small and medium-sized RO2. However, for complex enough R or R' groups, the binding energy effect may render the H-shift channel uncompetitive with intersystem crossings (and thus ROOR' formation), as the rate of the latter, while variable, seems to be largely independent of system size. This may help explain the experimental observation that accretion product formation becomes highly effective for large and multifunctional RO2.

Translation, Cross-Cultural Adaptation, and Validation of the Physical Activity Scale for Individuals With Physical Disabilities for Brazilian Individuals With Parkinson's Disease.

The Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) is not available to Portuguese-Brazil. This study translates, cross-culturally adapts, and validates the PASIPD for Brazilian individuals with Parkinson's disease. The translation process followed guidelines: initial translation, synthesis, back translation, expert committee, and pretest. The validation and reliability processes were conducted with 40 individuals (15 men and 25 women) with Parkinson's disease. Concurrent validity was evaluated between PASIPD to Brazilian Portuguese, International Physical Activity Questionnaire, and Human Activity Profile. PASIPD to Brazilian Portuguese was found to be moderately correlated with International Physical Activity Questionnaire (r = .474, p < .05); however, there was no correlation with Human Activity Profile (r = .271, p < .05). We used the intrarater reliability with intraclass correlation coefficient and test-retest. Intrarater reliability was high (intraclass correlation coefficient = .80). Internal consistency was considered adequate by Cronbach's alpha (α = .70). PASIPD to Brazilian Portuguese is a valid and reliable instrument for evaluating physical activity levels in Brazilian individuals with Parkinson's disease.

Comportamento da variabilidade glicêmica em pacientes hospitalizados com Diabetes Mellitus 2 / Behavior of glycemic variability in hospitalized type 2 Diabetes Mellitus patients / Comportamiento de la variable glucémica en pacientes Hospitalizados con Diabetes Mellitus 2

Introdução: A hiperglicemia pode estar presente em até 38% dos pacientes hospitalizados.O controle glicêmico está associado a melhores desfechos clínicos. Objetivo: avaliar o comportamento da variabilidade glicêmica em pacientes hospitalizados com Diabetes Mellitus 2. Metodologia: Estudo transversal, composto por pacientes hospi-talizados com e sem diabetes, adultos e idosos, de ambos os gêneros, em terapia nutricional enteral. As glicemias foram medidas por testes de glicemia capilar e classificadas como normoglicemia, hiperglicemia e variabilidade glicêmica, avaliados a partir do desvio-padrão glicêmico e coeficiente de variação glicêmico. Foram avaliados dados bioquímicos como Proteína C-reativa. A análise de variância de duas vias (ANOVA) foi utilizada para comparar os grupos, além da correlação de Spearman. Resultados: Participaram 85 indivíduos, com diabetes mellitus 2 (20%; n= 17), e sem diabetes mellitus (80%; n = 68), sendo 34% (n = 29) adultos e 66% (n=56) idosos. Adultos e idosos com diabetes mellitus apresentaram hiperglicemia em relação aos pacientes não diabéticos (p<0,01), valores supe-riores de desvio-padrão glicêmico (p<0,01) e coeficiente de variação glicêmica em relação aos pacientes sem dia-betes (p= 0,03), no entanto, não foram classificados com variabilidade glicêmica. Os valores da Proteína C-reativa foram correlacionados com o desvio-padrão glicêmico (R= 0,29; p= 0,0065), no entanto, a quantidade de carboi-dratos infundida na dieta enteral não se correlacionou estatisticamente com as glicemias nem com a variabilidade glicêmica dos pacientes (p>0,05). Conclusão: pacientes hospitalizados com ou sem diabetes mellitus 2 não apre-sentaram variabilidade glicêmica, demonstrando um controle glicêmico na hospitalização. (AU)

Introduction: Hyperglycemia may be present in up to 38% of hospitalized patients. Glycemic control is associated with better clinical outcomes. Objective: assess the behavior of glycemic variability in hospitalized patients with Diabetes Mellitus 2. Methodology: Cross-sectional study composed of hospitalized patients with and without diabetes, adults and elderly, of both genders, undergoing enteral nutritional therapy. Blood glucose was measured by capillary blood glucose tests and classified as normoglycemia, hyperglycemia, and glycemic variability, assessed from the glycemic standard deviation and glycemic variation coefficient. Biochemical data such as C-reactive protein were assessed. Two-way analysis of variance (ANOVA) was used to compare the groups, in addition to Spearman's correlation. Results: Eighty-five individuals with diabetes mellitus 2 (20%; n=17) and without diabetes mellitus (80%; n=68) participated in the study; 34% (n=29) were adults, and 66% (n=56) were elderly. Adults and elderly people with diabetes mellitus presented hyperglycemia concerning non-diabetic patients (p<0.01), higher values of glycemic standard deviation (p<0.01), and glycemic variation coefficient concerning patients without diabetes (p= 0.03); however, they were not classified with glycemic variability. The C-reactive protein values were correlated with the glycemic standard deviation (R= 0.29; p= 0.0065); however, the amount of carbohydrates infused in the enteral diet was not statistically correlated with glycemia or with the glycemic variability of patients (p>0.05). Conclusion: hospitalized patients with or without diabetes mellitus 2 did not show glycemic variability, demonstrating glycemic control during hospitalization. (AU)

Introducción: La hiperglucemia puede estar presente hasta en un 38% de los pacientes hospitalizados. El con-trol glucémico se asocia con mejores resultados clínicos. Objetivo: evaluar el comportamiento de la variación glucémica en pacientes con Diabetes Mellitus 2. Metodología: Estudio transversal, compuesto por pacientes hos-pitalizados con y sin diabetes, adultos y ancianos, con terapia nutricional enteral. Las glucemias fueron medidas por exámenes de glucemia capilar y clasificadas como normo glucemia, hiperglucemia y variación glucémica, evaluados a partir de la desviación estándar y coeficiente de variación glucémico. Fueron evaluados datos bioquí-micos como Proteína C-reactiva. El análisis de la variación de las dos vías (ANOVA) fue utilizada para comparar los grupos, junto a la correlación de Spearman. Resultados: Participaron 85 individuos, con diabetes mellitus 2 (20%; n+17), y sin diabetes mellitus (80%; n = 68). Adultos 34% (n=29) y ancianos 66% (n=56). Pacientes con diabetes mellitus presentaron hiperglucemia en relación a los pacientes nodiabéticos (p< 0,01), valores superiores de desviación estándar glucémico (p< 0,01) y coeficiente de variación glucémica en relación a los pacientes sin dia-betes (p= 0,03), sin embargo, no fueron clasificados con variación glucémica. Los valores de la Proteína C-reactiva fueron correlacionados con la desviación estándar glucémica (R = 0,29; P= 0,0065), la cantidad de carbohidratos administrada, no se correlacionó estadísticamente con las glucemias ni con la variación glucémica de los pacientes (p>0,05). Conclusión: pacientes hospitalizados con o sin diabetes mellitus 2 no presentaron variación glucémica, demostrando control glucémico en la hospitalización. (AU)

Organic and inorganic pollutants in Jordão and Iguaçu rivers southern Brazil impact early phases of Rhamdia quelen and represent a risk for population.

The Iguaçu River basin presents high ecological importance due to its expressive endemic ichthyofauna rate, but chemical pollution may threat this biodiversity. Jordão River is one of the main tributaries of Iguaçu River and contribute to this pollution status, since it drains large agricultural areas receiving domestic and industrial effluents before flowing into the Iguaçu River. The objective of the current study was to evaluate the toxic effects of the Iguaçu, Jordão, and the combination of their waters to the embryo-larval phase of R. quelen, investigating the consequences to the population by means of mathematical modelling. R. quelen fertilized eggs were exposed for 96 h to water samples from Iguaçu River upstream (IR), Jordão River (JR), and downstream of both rivers (MR). The analysis of micropollutants in the water showed that JR presented the most complex mixture of substances and elements, followed by IR, while MR showed the lower number of micropollutants detected. Survival rate was not a sensitive endpoint, while the deformity indices were higher in individuals exposed to water from the three studied sites. Superoxide dismutase activity was increased in MR, while non-protein thiol levels were reduced in MR and JR showing the antioxidant mechanism activation. The mathematical modelling revealed that fish exposed to JR would lead to the greater population reduction (46.19%), followed by IR (40.48%) and MR (33.33%). Although the results showed toxicity in all studied sites, the JR site is the most impacted by micropollutants but decrease its toxicity after dilution with Iguaçu River.

Increased postoperative fasting time aggravates the nutritional status in patients with gastrointestinal tract neoplasia

ABSTRACT Surgical patients with gastrointestinal cancer often suffer from malnutrition. This study aimed to evaluate the influence of fasting time on the nutritional status of patients hospitalized with preoperative and postoperative gastrointestinal tract neoplasms. Observational, longitudinal, and prospective study conducted in the surgical unit at a public-school hospital. The patients were divided into groups: upper (UGIT) and lower (LGIT) gastrointestinal tract. Follow-up started within 72 h of hospitalization with reassessment 72 h after surgery. Data collected: sex, age, type and duration of surgery, preoperative (compared with 8 h) and postoperative (compared with 24 h) fasting time, food acceptance, Subjective Global Assessment, anthropometry, and laboratory tests. Analyses: Student t, Wilcoxon, and chi-square tests. Fifty-one patients were followed up, 29 (57%) UGIT and 22 (43%) LGIT. The preoperative fasting time was 8.2±2.8 h in UGIT and 8.1±2.2 h in LGIT groups, respectively; however, postoperative fasting times in UGIT (60.4±40.7 h) and LGIT groups (57.6±38.2 h) were longer than 24 h (P<0.001). Although eutrophic in the preoperative period, in the postoperative most patients in the UGIT and LGIT groups presented, respectively, malnutrition (71%; 59%; P<0.001), severe weight loss (79%; 80%), a significant correlation between triceps skinfold and postoperative fasting time (r= -0.306; P= 0.03), and hemoglobin and albumin values (r= 0.633; P<0.001), additionally low dietary acceptance, especially in the UGIT group. Prolonging postoperative fasting time worsened the nutritional status of surgical patients, especially in the UGIT group.

RESUMEN Los pacientes quirúrgicos con cáncer gastrointestinal a menudo sufren desnutrición. El objetivo de este estudio fue evaluar la influencia del tiempo de ayuno en estado nutricional de pacientes hospitalizados con neoplasias del tracto gastrointestinal preoperatorio y posoperatorio. Estudio observacional, longitudinal y prospectivo realizado en unidad quirúrgica de un hospital escolar público. Los pacientes fueron divididos en grupos: tracto gastrointestinal superior (UGIT) y inferior (LGIT). El seguimiento se inició dentro del 72 h de la hospitalización con reevaluación 72 h después de la cirugía. Datos recolectados: sexo, edad, tipo y duración de la cirugía, tiempo de ayuno preoperatorio (comparado con 8 h) y postoperatorio (comparado con 24 h), aceptación de dieta, Evaluación Subjetiva Global, antropometría y pruebas de laboratorio. Análisis: pruebas de T, Wilcoxon y chi-cuadrado. Se siguió 51 pacientes, 29 (57%) en UGIT y 22 (43%) en LGIT. El tiempo de ayuno preoperatorio fue 8,2±2,8 h (UGIT) y 8,1±2,2 h (LGIT); sin embargo, los tiempos de ayuno posoperatorio en UGIT (60,4±40,7 h) y LGIT (57,6±38,2 h) fueron superiores a 24 h (P<0,001). Aunque eutróficos en preoperatorio, en postoperatorio la mayoría de los pacientes (UGIT y LGIT, respectivamente) presentaron desnutrición (71%; 59%; P<0,001), pérdida de peso severa (79%; 80%), correlación significativa entre pliegue cutáneo del tríceps y tiempo de ayuno posoperatorio (r= -0.306; P= 0.03), valores de hemoglobina y albúmina (r= 0,633; P<0,001), y baja aceptación de dieta, especialmente del UGIT. La prolongación del ayuno postoperatorio empeoró el estado nutricional de los pacientes quirúrgicos, especialmente del UGIT.

A study of dose indicators during intra-arterial catheter implantation for liver chemotherapy.

The aim of the present study was to describe patient dose indicator levels during intra-arterial catheter (IAC) implantation for liver chemotherapy, and to determine factors affecting the dose indicators. Between January 2017 and January 2019, 61 patients with hepatic metastases from colorectal cancer were retrospectively included. Interventions were carried out in a standardised manner by three experienced radiologists on the same angiographic table without changes in protocol parameters. For each patient, clinical, radiological and dosimetry data were collected, including the air kerma area product (KAP), part of KAP due to the fluoroscopy and fluoroscopy time (FT), total kerma at the reference interventional point and peak skin dose (PSD). Local dose reference levels (RLs) were determined as the third quartile of the patient dose distributions. Univariate and multivariate analysis of factors affecting dose indicators was performed. The mean KAP was 111 Gy cm2, the mean reference point air kerma (Ka,r) was 648 mGy, the mean PSD was 613 mGy, and the mean FT was 3190 s (62% of the KAP). The mean cone beam computed tomography dose was 37.3 ± 11.8 Gy cm2, which accounted for 37% of the KAP. The RL could be proposed taking into account the third quartiles (KAP = 164.6 Gy cm2, Ka,r = 904.5 mGy, FT = 4011 s and standard deviation = 772.7 mGy). The factors affecting dose indicators were related to the patients (sex, cardiovascular risk factors, weight, body mass index), to the vascular anatomies (coeliac trunk angulation) and to the procedures (number of embolised arteries). This study allowed a better understanding of dose indicators and factors affecting these indicators during the implantation of IACs for hepatic chemotherapy, which is a long and difficult procedure. Local dose RLs were determined. Multicentre, multi-equipment studies are necessary.

Medication Non-adherence in a Prospective, Multi-center Cohort Treated with Hepatitis C Direct-Acting Antivirals.

BACKGROUND: The prevalence and risk factors for non-adherence to direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) in clinical practice settings are under-studied. OBJECTIVES: (1) To quantify DAA non-adherence in the total cohort and among subgroups with and without mental health conditions, alcohol use, and substance use, and (2) to investigate patient- and treatment-level risk factor non-adherence. DESIGN: Prospective, observational cohort study. PARTICIPANTS: A total of 1562 patients receiving DAAs between January 2016 and October 2017 at 11 US medical centers including academic and community practices. MAIN MEASURES: Self-reported medication non-adherence, defined as any missed doses in the past 7 days, surveyed early (T2: at 4 ± 2 weeks) and late in treatment (T3: 2-3 weeks prior to end of treatment). Non-adherence to post-treatment follow-up visits was defined as absence of lab results after DAA therapy completion. KEY RESULTS: Of 1447 patients, 162 (11%) reported non-adherence at T2 or T3. Medical records indicated 262 (17%) of the 1562 participants had not returned for post-treatment visits. At baseline, 37% of patients reported mental health conditions, 15% reported alcohol use, and 23% reported using substances in the previous year. Baseline characteristics associated with DAA non-adherence included alcohol use (OR 1.96), younger age (< 35 years vs. > 55 years: OR 3.40), non-white race (OR > 2.26), and DAA treatment cohort, but not substance use or mental health condition. Non-adherence to follow-up exhibited association with younger age and a higher baseline overall symptom burden. Among 1287 patients with evaluable sustained virologic response (SVR) data, 53 patients (4%) did not achieve SVR. The bivariate correlation between adherence and SVR was negligible (r = 0.01). CONCLUSIONS: DAA non-adherence was low and SVR rates were high. Mental health conditions, substance use, and alcohol use should not disqualify patients from DAA therapy. Patients with alcohol use disorder before DAA therapy initiation may benefit from targeted on-treatment support.

Urban, individuals of color are impacted by fentanyl-contaminated heroin.

The present phase of the overdose epidemic is characterized by fentanyl-contaminated heroin, particularly in the eastern United States (U.S.). However, there is little research examining how changes in drug potency are affecting urban, racial minority individuals who have been affected by both the "old" epidemic of the 1940s through 1980s, as well as the "new" present day epidemic. A focus on the drug using experiences of racial minorities is needed to avoid perpetuating discriminatory responses to drug use in communities of color, which have characterized past U.S. policies. This qualitative study was conducted from March through June 2018 to examine recent experiences of urban, individuals of color who inject drugs to assess the impact of the current overdose epidemic on this understudied population. Interviews were conducted with 25 people who reported current injection drug use. The interviews were transcribed and analyzed using a general inductive approach to identify major themes. Fifteen of 25 participants reported experiencing a non-fatal overdose in the past two years; eight suspected their overdose was fentanyl-related. Likewise, 15 had ever witnessed someone else overdose at least once. Overdoses that required multiple doses of naloxone were also reported. Participants employed several methods to attempt to detect the presence of fentanyl in their drugs, with varying degrees of success. Carrying naloxone and utilizing trusted drug sellers (often those who also use) were strategies used to minimize risk of overdose. Contaminated heroin and increased risk for overdose was often encountered when trusted sources were unavailable. This population is suffering from high rates of recent overdose. Removal of trusted drug sources from a community may inadvertently increase overdose risk. Ensuring access to harm reduction resources (naloxone, drug testing strips) will remain important for addressing ever-increasing rates of overdose among all populations affected.

Pursuing use of optimal formulations for paediatric HIV epidemic control - a look at the use of LPV/r oral pellets and oral granules.

INTRODUCTION: Despite a significant reduction in mother-to-child transmission of HIV, an estimated 180,000 children were infected with HIV in 2017, and only 52% of children under 15 years of age living with HIV (CLHIV) are on life-saving antiretroviral therapy (ART). Without effective treatment, half of CLHIV die before the age of two years and only one in five survives to five years of age. DISCUSSION: Over the past four years, the United States Food and Drug Administration tentatively approved new formulations of lopinavir/ritonavir (LPV/r) in the form of oral pellets and oral granules. However, the slow uptake of the aforementioned formulations in the low- and middle-income countries with the highest paediatric HIV burden is largely due to three challenges: limited manufacturing capacity; current unit cost of the pellets and granules; and slow uptake of these new formulations by policy makers and health care workers. CONCLUSIONS: Solutions to overcome these barriers include ensuring availability of an adequate supply of LPV/r oral pellets and oral granules, considering all programmatic and clinical factors when selecting paediatric ART formulations, and leveraging current resources to decrease paediatric HIV morbidity and mortality.

Association of anemia and malnutrition in hospitalized patients with exclusive enteral nutrition.

INTRODUCTION: enteral nutrition therapy maintains and/or regains the nutritional status of the common patient in hospital settings, where anemia and malnutrition are food related and are very common diseases. OBJECTIVE: to determine and associate the presence of anemia and malnutrition in hospitalized patients with exclusive enteral nutrition. METHODS: a prospective, cross-sectional study with patients receiving exclusive enteral nutrition up to 72 hours after hospitalization. A nutritional evaluation was performed, consisting of anthropometric data, such as weight, circumferences, and skinfolds; dietary evaluation (data were collected through an electronic medical record) and biochemistry data (hemogram, albumin, C-reactive protein, capillary glucose monitoring). RESULTS: the population consists of 77 individuals. As the patients presented greater severity of anemia, corrected arm muscle area, calf circumference and serum albumin levels were reduced while C-reactive protein increased significantly (p < 0.05). In relation to the low weight classification according to the body mass index (BMI), it was observed that the anthropometric parameters such as corrected arm muscle area (R = 0.74, p < 0.001), adductor pollicis muscle thickness (R = 0.23, p = 0.046) and calf circumference (R = 0.81, p < 0.001) decreased as did biochemical parameters albumin (R = 0.26; p = 0.048) and capillary blood glucose (R = 0.34, p = 0.018). CONCLUSION: anemia has an important relation with anthropometric markers that evaluate the depletion of lean mass; the BMI has a strong association with all the anthropometric parameters evaluated, as well as the albumin and capillary blood glucose, except with the values of hemoglobin.

Association of anemia and malnutrition in hospitalized patients with exclusive enteral nutrition / Asociación entre anemia y malnutrición en pacientes hospitalizados con nutrición enteral exclusiva

Introduction: enteral nutrition therapy maintains and/or regains the nutritional status of the common patient in hospital settings, where anemia and malnutrition are food related and are very common diseases. Objective: to determine and associate the presence of anemia and malnutrition in hospitalized patients with exclusive enteral nutrition. Methods: a prospective, cross-sectional study with patients receiving exclusive enteral nutrition up to 72 hours after hospitalization. A nutritional evaluation was performed, consisting of anthropometric data, such as weight, circumferences, and skinfolds; dietary evaluation (data were collected through an electronic medical record) and biochemistry data (hemogram, albumin, C-reactive protein, capillary glucose monitoring).Results: the population consists of 77 individuals. As the patients presented greater severity of anemia, corrected arm muscle area, calf circumference and serum albumin levels were reduced while C-reactive protein increased significantly (p < 0.05). In relation to the low weight classification according to the body mass index (BMI), it was observed that the anthropometric parameters such as corrected arm muscle area (R = 0.74, p < 0.001), adductor pollicis muscle thickness (R = 0.23, p = 0.046) and calf circumference (R = 0.81, p < 0.001) decreased as did biochemical parameters albumin (R = 0.26; p = 0.048) and capillary blood glucose (R = 0.34, p = 0.018).Conclusion: anemia has an important relation with anthropometric markers that evaluate the depletion of lean mass; the BMI has a strong association with all the anthropometric parameters evaluated, as well as the albumin and capillary blood glucose, except with the values of hemoglobin

Introducción: la terapia de nutrición enteral mantiene y/o recupera el estado nutricional del paciente en cuidados hospitalarios, donde la anemia y la desnutrición están relacionadas con los alimentos y son enfermedades muy comunes. Objetivo: determinar y asociar la presencia de anemia y malnutrición en pacientes hospitalizados con nutrición enteral exclusiva. Métodos: estudio transversal prospectivo con pacientes que recibieron nutrición enteral exclusiva hasta 72 horas tras la hospitalización. Se realizó una evaluación nutricional por medio de datos antropométricos tales como peso, circunferencias y pliegues cutáneos, evaluación dietética (datos recogidos a través de un expediente médico electrónico) y datos bioquímicos (hemograma, albúmina, proteína C reactiva, monitorización capilar de glucosa). Resultados: la muestra está compuesta de 77 personas. En los pacientes que presentaban una anemia de mayor gravedad, el área del músculo del brazo corregida, la circunferencia de la pantorrilla y los niveles de albúmina sérica se redujeron, mientras que la proteína C-reactiva aumentó significativamente (p < 0,05). Con relación a la clasificación de bajo peso según el IMC, se observó que los parámetros antropométricos, como el área del músculo del brazo corregida (R = 0,74, p < 0,001), el espesor del músculo aductor del pulgar (R = 0,23, p = 0,046) y la circunferencia de la pantorrilla (R = 0,81, p < 0,001) disminuyeron, al igual que los parámetros bioquímicos de albúmina (R = 0,26, p = 0,048) y glucosa en sangre capilar (R = 0,34, p = 0,018). Conclusión: la anemia tiene una relación importante con marcadores antropométricos que evalúan el agotamiento de la masa magra; el IMC tiene una fuerte asociación con todos los parámetros antropométricos evaluados, así como con la albúmina y la glucosa en sangre capilar, excepto con los valores de hemoglobina

Co-calibration of two self-reported measures of adherence to antiretroviral therapy.

Adherence to antiretroviral therapy (ART) is an important determinant of clinical success assessed in many HIV studies. Harmonizing adherence data from studies that use different measures is difficult without a co-calibration equation to convert between validated instruments. Our purpose was to co-calibrate two commonly used adherence measures: the AIDS Clinical Trials Group (ACTG) questionnaire and the Visual Analog Scale (VAS). We used robust linear regression to develop a co-calibration equation in a clinical care cohort. The outcome was the 30-day VAS percentage of ART taken and the predictors were ACTG questions. We evaluated the equation's goodness of fit in five STTR (Seek, Test, Treat, Retain) consortium studies where individuals completed both measures: 2 criminal justice; 2 international; and 1 other high-risk vulnerable population. We developed a three-phase decision rule to convert ACTG to VAS in 1045 participants. First, when the last missed dose on the ACTG was reported as >30 days ago, the VAS was set to 100% (N = 582). Second, if "doses missed" was zero for all items, VAS was 100% (N = 104). Third, among remaining participants (N = 359), VAS was estimated as 96.8% minus 2.9% times the number of missed doses ("doses per day" was non-significant). Correlation between predicted and reported VAS was r = 0.80 in the criminal justice group (N = 446), r = 0.46 in the international group (N = 311), r = 0.32 in the other vulnerable population (N = 63), and r = 0.66 overall. When outliers due to inversion of the VAS scale were excluded (n = 25), these correlations were 0.88, 0.78, 0.80, and 0.86, respectively. We concluded that a simple decision rule and equation allowed us to co-calibrate between two widely used adherence measures thus combining data from studies with different instruments. This study highlighted issues with VAS inversions and its limitations as a single item. Combining studies using different instrument facilitates larger pooled datasets to address key research questions.

The association between poor antiretroviral adherence and unsafe sex: differences by gender and sexual orientation and implications for scale-up of treatment as prevention.

Non-adherence to safer sex and non-adherence to ART can each have adverse health consequences for HIV-infected individuals and their sex partners, but little is known about the association of these behaviors with each other. This "dual risk" has potential negative public health consequences since non-adherence can lead to the development of resistant virus that can then be transmitted to sex partners. Among participants in the Multi-site Adherence Collaboration in HIV we examined, at study baseline, the association between the frequency of unprotected sex (assessed by self-report) and ART adherence (assessed by Medication Event Monitoring System, Aardex) among the sexually active participants in the five studies (N = 459) that collected sexual risk behavior. The bivariate association between sexual risk behaviors and ART adherence was assessed by Pearson correlations; subsequently regression analyses were used to evaluate the role of demographic characteristics, depression and substance use in explaining the "dual risk" outcome (sexual risk and non-adherence). Among participants who had been sexually active, more unprotected anal/vaginal sex was weakly associated with poorer ART adherence (r = -0.12, p = 0.01 for the overall sample). Further analysis showed this association was driven by the heterosexual men in the sample (r = -0.29, p < 0.001), and was significant only for this group, and not for gay/bisexual men or for women (heterosexual and homosexual). Neither substance use nor depression accounted for the association between sexual risk and ART adherence. HIV-infected heterosexual men who are having difficulty adhering to ART are also more likely to engage in risky sexual behaviors and therefore may benefit from counseling about these risk behaviors. We must identify procedures to screen for these risk behaviors and develop interventions, appropriately tailored to specific populations and identified risk factors, that can be integrated into routine clinical care for people living with HIV. This will become increasingly important in the context of wider access to treatment globally, including new recommendations for ART initiation earlier in a patients' disease course (e.g., "Test and Treat" paradigms).

A pilot study of health beliefs and attitudes concerning measures of antiretroviral adherence among prisoners receiving directly observed antiretroviral therapy.

High level adherence to antiretroviral therapy (ART) is required to achieve and maintain suppression of HIV replication. Although directly observed therapy (DOT) has been suggested as an intervention to improve adherence, there is a paucity of data describing the attitudes and beliefs regarding DOT for ART among HIV-infected individuals. This study was designed to evaluate the acceptability and psychometric properties of a survey instrument for use in assessing barriers and facilitators of adherence to ART DOT in prison. From July 1, 1999 to April 1, 2000, we piloted an interviewer-administered questionnaire to assess health beliefs and attitudes regarding HIV treatment among 65 HIV-infected prison inmates receiving one or more of their antiretrovirals via directly observed therapy (DOT). The first 24 participants were administered the questionnaire to determine the feasibility of surveying prisoners in a correctional setting. There were no adherence data collected on these participants. The remaining 41 participants had their adherence measured in addition to receiving the questionnaire. Thirty-one were included in the final analysis because 10 did not complete the study. Multiple antiretroviral adherence measures (electronic device medication monitoring [eDEM] caps, medication administration records [MARs], and pill counts) were assessed among a subset of the participants (n = 31) and correlated to the instrument response items. The median internal consistency reliability coefficient for the multi-item scales was 0.79. The strongest correlation between inmates' beliefs and their adherence was between "positive beliefs about protease inhibitors" and the MAR adherence measure (r = 0.72; p < 0.001). This study provides preliminary support for the psychometric properties of the survey in this correctional setting.

Motivational interviewing to support antiretroviral therapy adherence: the role of quality counseling.

OBJECTIVE: Although research linking motivational interviewing (MI) to behavior change exists, few studies report on MI's quality or explore how it may influence effectiveness. We studied MI quality and adherence to antiretroviral therapy (ART) in the context of a randomized, controlled trial. METHODS: We used a structured instrument to code MI sessions and then correlated ART adherence (measured by electronic bottle cap monitor and pill count data at study exit) with specific counseling behaviors and the proportion of interactions that achieved quality benchmarks. RESULTS: The sample (n = 47) was predominantly male (79%), minority (90%), had a mean age of 40, and averaged 79% adherence at exit. On three of five benchmarks, most MI sessions achieved the targeted quality level: 100% achieved them for MI-consistent statements; 85% for complex reflections; 63% for reflections to questions ratio; 44% for global therapist rating; 19% for using open-ended questions. ART adherence was positively associated with the ratio of reflections to questions (r = .39, p = .02), affirming statements (r = .38, p = .02), and negatively associated with closed-ended questions (r = -.33, p = .04). DISCUSSION: Good quality MI can be conducted within the structure of a controlled trial but was generally not associated with ART adherence. CONCLUSION: Documenting treatment fidelity is critical to judging the efficacy of MI-based interventions. PRACTICE IMPLICATIONS: Regular feedback and close monitoring are needed to maintain MI quality.

STa and cGMP stimulate CFTR translocation to the surface of villus enterocytes in rat jejunum and is regulated by protein kinase G.

The cystic fibrosis transmembrane conductance regulator (CFTR) is critical to cAMP- and cGMP-activated intestinal anion secretion and the pathogenesis of secretory diarrhea. Enterotoxins released by Vibrio cholerae (cholera toxin) and Escherichia coli (heat stable enterotoxin, or STa) activate intracellular cAMP and cGMP and signal CFTR on the apical plasma membrane of small intestinal enterocytes to elicit chloride and fluid secretion. cAMP activates PKA, whereas cGMP signals a cGMP-dependent protein kinase (cGKII) to phosphorylate CFTR in the intestine. In the jejunum, cAMP also regulates CFTR and fluid secretion by insertion of CFTR from subapical vesicles to the surface of enterocytes. It is unknown whether cGMP signaling or phosphorylation regulates the insertion of CFTR associated vesicles from the cytoplasm to the surface of enterocytes. We used STa, cell-permeant cGMP, and cAMP agonists in conjunction with PKG and PKA inhibitors, respectively, in rat jejunum to examine whether 1) cGMP and cGK II regulate the translocation of CFTR to the apical membrane and its relevance to fluid secretion, and 2) PKA regulates cAMP-dependent translocation of CFTR because this intestinal segment is a primary target for toxigenic diarrhea. STa and cGMP induced a greater than fourfold increase in surface CFTR in enterocytes in association with fluid secretion that was inhibited by PKG inhibitors. cAMP agonists induced a translocation of CFTR to the cell surface of enterocytes that was prevented by PKA inhibitors. We conclude that cAMP and cGMP-dependent phosphorylation regulates fluid secretion and CFTR trafficking to the surface of enterocytes in rat jejunum.

Physician facilitation of patient involvement in care: correspondence between patient and observer reports.

The authors surveyed 128 patients with type 2 diabetes mellitus (1) to evaluate the congruence between patients' and observers' perceptions of physicians' facilitation of patients' involvement in care and (2) to identify which physician behaviors were most closely related to patients' perceptions that their doctors encouraged them to be involved in their care. The patients reported the degree to which they perceived that their physicians encouraged their involvement in the medical care process. Raters blind to the study hypotheses coded audiotapes of the physician-patient interactions. Pearson's r and simultaneous multiple regression used to address the study questions indicated a small to moderate, but statistically significant, association between patients' perceptions and observers' reports concerning the physicians' levels of facilitation. Open-ended questions, responding to patient questions, and offering fewer alternatives were all associated with the patients' positive reports of physician facilitation.

Behavioural stress blunts the creatinine clearance increase induced by a protein load in healthy subjects.

BACKGROUND: The aim of this study was to investigate how behavioural states related to different levels of stress affected the increments of glomerular filtration rate induced by an acute protein load. METHODS: Thirteen healthy subjects were enrolled. Each subject was studied from 9:00 h to 15:00 h on two consecutive days. In random order, after a protein meal (1.2 g/kg b.w. of protein), each subject was required to remain in a relaxing, sitting position (resting period, R), or to solve graphical and mathematical problems (behavioural stress period, S). Mean blood pressure (MBP) and heart rate (HR) were monitored by an ambulatory blood pressure device. Urine samples collected in each period were used to measure glomerular filtration rate (GFR, creatinine clearance) and urinary sodium excretion (UNa+V). RESULTS: Significant decreases in MBP and HR were observed during the resting period after the protein load, which significantly increased GFR. There was also a large increase of UNa+V. During S, the GFR changes were no longer seen whereas the increse of UNa+V was maintained. HR and MBP did not change compared to the prestimulus period. CONCLUSIONS: We conclude that in healthy subjects behavioural stress can blunt the increase in GFR that follows a protein load, presumably by neuro-humoral activated mechanisms. In our experimental conditions, behavioural stress did not affect UNa+V.

Emergência hipertensiva / Hypertensive emergencies

A emergência hipertensiva é uma condiçäo de risco iminente de vida caracterizada por elevaçäo súbita da pressäo arterial e comprometimento de órgäo-alvo. O cérebro, coraçäo, rins, retina e aorta säo alvos frequentes. Säo importantes a presteza diagnóstica e o tratamento precoce. Dá-se escolha aos anti-hipertensivos parenterais de açäo rápida e de curta duraçäo, evitando-se, porém, quedas pressóricas que comprometam a perfusäo de órgäos ou sistemas. O objetivo desta revisäo é mostrar como se diagnostica e se trata precocemente a emergência hipertensiva.

Cyclophosphamide hemorrhagic cystitis requiring urinary diversion.

Hemorrhagic cystitis secondary to cyclophosphamide is a well recognized and unique urologic complication of this widely used agent. Cessation of the drug and supportive care are usually sufficient for management but refractory cases are difficult to treat and potentially life-threatening. A review of the pathology and treatment of this disorder is presented with specific reference to a patient requiring urinary diversion.