Establishing the Median Infectious Dose and Characterizing the Clinical Manifestations of Mouse, Rat, Cow, and Human Corynebacterium bovis Isolates in Select Immunocompromised Mouse Strains.

Corynebacterium bovis (Cb), the cause of hyperkeratotic dermatitis in various immunocompromised mouse strains, significantly impacts research outcomes if infected mice are used. Although Cb has been isolated from a variety of species, including mice, rats, cows, and humans, little is known about the differences in the infectivity and clinical disease that are associated with specific Cb isolates. The infectious dose that colonized 50% of the exposed population (ID50 ) and any associated clinical disease was determined in athymic nude mice (Hsd:Athymic Nude-Foxn1 nu ) inoculated with Cb isolates collected from mice (n = 5), rat (n = 1), cow (n = 1), and humans (n = 2) The same parameters were also determined for 2 of the mouse isolates in 2 furred immunocompromised mouse strains (NSG [NOD. Cg-Prkdcscid Il2rgtm1Wjl /Sz] and NSG-S [NOD. Cg-Prkdcscid Il2rgtm1Wjl Tg(CMV-IL3, CSF2, KITLG)1Eav/MloySzJ]). To determine the ID 50, mice (n= 6/dose; 3 of each sex) were inoculated topically in 10-fold increments ranging from 1 to 10 8 bacteria. Mice were scored daily for 14 days for the severity of clinical signs. On days 7 and 14 after inoculation, buccal and dorsal skin swabs were evaluated by aerobic culture to determine infection status. The mouse isolates yielded lower ID50values (58 to 1000 bacteria) than did the bovine (6460 to 7498 bacteria) and rat (10,000 bacteria) isolates. Human isolates did not colonize mice or cause disease. Mouse isolates produced clinical disease of vary- ing severity in nude mice. Despite significant immunodeficiency, furred NSG and NSG-S mice required a 1000- to 3000-fold higher inoculum for colonization than did athymic nude mice. Once colonized, clinically detectable hyperkeratosis did not develop in the haired strains until 18 to 22 d after inoculation, whereas athymic nude mice that developed clinically detect- able disease showed hyperkeratosis between 6 and 14 d after inoculation. In conclusion, there are significant differences in Cb's ID 50, disease course, and severity of clinical signs between Cb isolates and among immunodeficient mouse strains.

Outreach, Screening, and Randomization of APOE ε4 Carriers into an Alzheimer's Prevention Trial: A global Perspective from the API Generation Program.

BACKGROUND: Alzheimer's disease (AD) prevention trials require a large outreach and screening funnel to identify cognitively unimpaired adults who meet the study's inclusion criteria, such as certain clinical or demographic criteria, genetic risk factors, and/or biomarker evidence of the disease. OBJECTIVES: Describe tactics and strategies to identify and enroll cognitively unimpaired adults with one (heterozygotes [HT]) or two (homozygotes [HM]) copies of the APOE ε4 allele, a genetic risk factor for dementia due to AD, into the Alzheimer's Prevention Initiative (API) Generation Program, the largest and only prevention trials for late onset AD using this enrichment technique. DESIGN AND SETTING: The Generation Program was comprised of two global, randomized, double-blind, placebo-controlled, parallel group adaptive design with variable treatment duration clinical trials. Generation Study 1 randomized participants into one of two cohorts: Cohort 1 which evaluated CAD106 vs. placebo or Cohort 2 which evaluated umibecestat vs placebo. Generation Study 2 randomized participants into two doses of umibecestat vs. placebo. The Generation Program was terminated early in 2019, while enrollment was still occurring. PARTICIPANTS: Both Generation Study 1 and Generation Study 2 enrolled cognitively unimpaired APOE ε4 HMs aged 60-75; Generation Study 2 also enrolled APOE ε4 HTs ages 60-75 with elevated brain amyloid. METHODS AND MEASUREMENTS: Describe results of the centralized and localized outreach, recruitment, screening strategies and tactics as well as characteristics of sites successful at enrolling genetically eligible participants, with a particular focus on APOE ε4 HMs given the 2-3% prevalence of this genotype. RESULTS: At the time the trial program was terminated, 35,333 individuals had consented to the optional prescreening ICF1a/ICFA and provided a sample of DNA for APOE genotyping, 1,138 APOE ε4 HMs consented to screening for Generation Study 1 (ICF1b), and 1,626 APOE ε4 carriers were randomized into either Generation Study 1 or Generation Study 2. Genetic testing registries, partnerships with genetic testing/counseling companies, and the optional prescreening ICF1a/ICFA were the most successful strategies for identifying genetically eligible participants for screening. CONCLUSIONS: It is feasible to recruit, screen and randomize cognitively unimpaired APOE ε4 carriers, particularly APOE ε4 HMs for a global AD prevention trial. The Generation Program was on track to complete enrollment by end of 2019. Factors that were key to this success included: working with sites to develop customizable outreach, recruitment, and screening programs specific to their site needs, providing forums for sites to exchange best practices, and developing partnerships between the sponsor team and trial sites.

Prediabetes is more than a pre-disease: additional evidences supporting the importance of its early diagnosis and appropriate treatment.

AIM: To identify Prediabetes (PreD) as early and serious diabetes step using clinical-biochemical characteristics in the population of the Primary Prevention Diabetes Buenos Aires (PPDBA) study. METHODS: PPDBA Study evaluated benefits of adopting healthy lifestyles to prevent T2D. It recruited people 45-75 years of age with PreD (impaired fasting glycaemia [IFG], impaired glucose tolerance [IGT] or both, American Diabetes Association criteria), using an opportunistic approach. They completed a FINDRISC questionnaire, and those with a score ≥13 points were invited to participate. When they accepted, we performed an oral glucose tolerance test (OGTT) with a complete lipid profile and HbA1c while physicians completed a clinical history. We recruited 367 persons, and depending on OGTT results, the sample was divided into normals (NGT), PreD, or with diabetes (last one was excluded in our analysis). Data were statistically analyzed using parametric and nonparametric tests and logistic regression to identify parameters associated with PreD. RESULTS: From the recruited (n = 367) 47.7% have NGT, 48.5% PreD and 3.8% unknown T2D (excluded). People with PreD were significantly older, with a higher percentage of overweight/obesity, BMI, and larger waist circumference than NGT. They also showed significantly higher fasting and 2 h post glucose load, HbA1c, and triglyceride levels. No significant differences were recorded in the blood pressure, lipid profile though both groups had abnormally high LDL-c values. They also had a larger percentage of TG/HDL-c ratios (insulin resistance indicator) (55% vs. 37.5%). Logistic regression analysis showed that PreD was significant associated with age, waist circumference, and triglyceride above target values. CONCLUSION: Our findings showed that clinical and biochemical parameters were significantly different between people with PreD and those with NGT. This evidence supports the concept that PreD is a serious dysfunction, which should be early diagnosed and treated properly to prevent its transition to T2D and its complications.

Infectivity and Shedding of Mouse Kidney Parvovirus After Oronasal Inoculation of C57BL/6, CD1, and NSG Mice.

Mouse kidney parvovirus (MKPV), the etiology of murine inclusion body nephropathy, has been identified globally in mice used for research, with an estimated prevalence of 10% in academic colonies. In immunodeficient strains, MKPV causes significant morbidity and mortality, and severe renal pathology. In contrast, in immunocompetent mice, the infection is subclinical and causes minimal pathology. We investigated viral infectivity and shedding in inbred C57BL/6NCrl (B6), outbred Crl:CD1(ICR) (CD1), and highly immunocompromised NOD. Cg - Prkdc scid Il2rg tm1Wjl/SzJ (NSG) mice. Four doses, ranging from 1.16 × 10 3 to 1.16 × 10 6 viral copies per microliter, of an MKPV inoculum were administered oronasally to 3 mice per dose per mouse type. All 3 types (B6, CD1, and NSG) had persistent infection with prolonged shedding in urine and feces. Viral copy number in the urine generally increased over time, while shedding in the feces was more variable. Among the 3 populations, CD1 mice developed viral shedding in urine earliest (4 wk after inoculation) and at higher levels (greater than 1 × 10 7 viral copies per microliter). B6 mice become viruric later (7 wk after inoculation), with lesser virus shed (1 × 10 6 viral copies per microliter or less). In CD1 and B6 mice, peak urine shedding occurred at 11 to 14 wk after inoculation, after which levels gradually declined until 35 wk after inoculation (study endpoint). In contrast, NSG mice did not become viruric until 10 wk after inoculation and continued to shed large amounts of virus (greater than 1 × 107 viral copies per microliter) in urine until the study endpoint. Two commercial immunofluorescent serologic assays failed to detect serum antibodies to MKPV nonstructural protein 1 as late as 58 wk after inoculation, whereas immunohistochemistry of infected renal tissue successfully detected anti-MKPV serum antibodies. These results increase our knowledge of the biology of MKPV and have practical application for development of effective screening programs for this pathogen.

Factores asociados con la indicación de la profilaxis pre-exposición para HIV en médicos de Argentina / Associated factors with the indication for HIV prevention of pre-exposure prophylaxis for argentinian physicians

La profilaxis pre-exposición (PrEP) es una medida eficaz para la prevención de la transmisión del VIH. Con la implementación de la misma, algunos estudios señalan una reducción en la transmisión superior al 90%, cuando la adherencia es alta. Sin embargo, el uso de Emtricitabina/ Tenofovir alafenamida (FTC/TDF) en la Argentina aún no esta aprobado por las autoridades regulatorias. En profesionales de Argentina el conocimiento, aval y factores asociados con la prescripción de la PrEP no ha sido evaluada. Este es un estudio de corte transversal mediante una encuesta on line realizada en Agosto de 2017. La misma fue distrubuida entre profesionales de Argentina y valoró diferentes aspectos de la PrEP (conocimiento, aval e indicación de la misma). Los resultados obtenidos se expresaron en frecuencias y porcentajes. Para las asociaciones entre variables categóricas se realizó un análisis univariado (test de chi2 ) y de regresión logística binaria. Se consideró como significativo, un valor de p < 0.05. La encuesta fue realizada por 238 profesionales pertenecientes a 81 centros asistenciales. Los escenarios clínicos donde se observó mayor predisposición a la indicación de PrEP fueron: parejas discordantes (77%), trabajadores/as sexuales (61%), pacientes transgénero (32%), adictos a drogas intravenosas (31%), hombres que mantienen sexo con otros hombres (HSH) (23%). Los factores asociados con la prescripción de PrEP fueron: cargo asistencial de jefe de servicio (p<0.05), médicos especialistas en enfermedades infecciosas (p<0.05), atención de más de 200 pacientes seropositivos para el virus de la inmunodeficiencia humana (VIH) por año (p<0.009), prescripción previa de profilaxis post-exposición (p<0.008). Los autores concluyen señalando que, a pesar de no estar aprobado por los entes regulatorios, la PrEP ha sido prescripta off label por profesionales de Argentina. Entre ellos, aquellos que adoptaron la prescripción fueron los que mostraron mayor experiencia en la atención de pacientes VIH positivos, jefes/as de servicio y especialistas en infectología. Estos resultados podrían ser utilizados en un futuro para impulsar nuevas herramientas de prevención en la transmisión de VIH

Pre-exposure prophylaxis (PrEP) is an effective measure to prevent HIV transmission. If the adherence is high, transmission rates are reduced by more than 90%. In Argentina, FTC-TDF is not yet approved for PrEP by the local regulatory agency.  PrEP  awareness,  PrEP  adoption, and factors associated with adoption among argentine physicians had not been studied to date. We designed a cross-sectional online survey conducted in August 2017 among argentine physicians and valored differents items about PrEP, (knowledge, attitudes, and beliefs associated with adoption). Univariate analysis was performed; the associations between categorical variables were analyzed by means of the chi2  test. The level of significance was considered with p <0.05. A total of 238 surveys were received from 81 centers in Argentina. Clinical scenarios associated with the highest prescription were: serodiscordant couples 77%, sex workers 61%, transgender patients 32%, people who inject drugs 31%, and men who have sex with men (MSM) 23%. Factors associated with PrEP prescription between physicians were been chief of staff (p<0.05), been an infectious diseases specialist (p<0.05), assist more than 200 HIV seropositive patients per year (p<0.009) and having prescribed postexposure prophylaxis (PEP) (p<0.008). The authors concluded that in spite of not yet approved by the local regulatory agency, PrEP is been prescribed off- label by argentine physicians. Adopters were more likely to have experience providing HIV care, been chief of staff and ID specialist. These results could be used to plan future HIV prevention strategies in Argentina.

Actividad física y factores de riesgo cardiovascular: evidencia de su interrelación a nivel nacional / Physical activity and cardiovascular risk factors: evidence of their interrelation nationwide

RESUMEN Antecedentes: En nuestro país la prevalencia de diabetes tipo 2 (DT2) y de factores de riesgo cardiovascular (FRCV) aumenta continuamente. Aunque el fenómeno se acompaña de adopción de estilos de vida no saludable que facilitan dicho crecimiento, es escasa la implementación de estrategias que puedan modificar la situación. Objetivo: Revisar la evidencia disponible sobre la magnitud del problema de la diabetes y los FRCV en nuestro país, su posible relación con la práctica de actividad física y potencial mecanismo de acción. Metodología: Evaluación de datos de la tercera Encuesta Nacional de Factores de Riesgo (ENFR) e información referida a factores que contribuyen al crecimiento de la prevalencia de DT2. Igualmente estrategias exitosas utilizadas a nivel mundial para su prevención. Resultados: El índice de masa corporal registrado en la población estudiada muestra un aumento del porcentaje de personas con sobrepeso/obesidad inverso a la práctica de actividad física. Igualmente los resultados de las pruebas de tolerancia a la glucosa oral muestran que sus alteraciones (prediabetes/diabetes) son menores entre quienes realizaban actividad física. El porcentaje de personas con valores de presión arterial dentro del rango normal al igual que de colesterol circulante (según valores meta de guías internacionales), es también significativamente menor entre quienes practicaban actividad física. Conclusión: La evidencia presentada demuestra objetivamente la necesidad/ventajas de implementar un programa de prevención primaria de diabetes a gran escala a nivel nacional para disminuir su crecimiento y la pertinencia de incluir la práctica de actividad física como estrategia de prevención tal como propone el PPDBA.

ABSTRACT Background: In our country, the prevalence of type 2 diabetes (DT2) and cardiovascular risk factors (CVRF) increases continuously. Although the phenomenon is accompanied by the adoption of unhealthy lifestyles that facilitate such growth, there is little implementation of strategies that can modify the situation. Objective: To review the available evidence on the magnitude of the problem of diabetes and CVRF in our country, its possible relationship with the practice of physical activity and potential mechanism of action. Methodology: Evaluation of data from the Third National Survey of Risk Factors (ENFR) and information referred to factors that promote the prevalence growth of T2D. Additionally, successful strategies have been used worldwide for its prevention. Results: The body mass index registered in the studied population shows an increase in the percentage of people with overweight/obesity inverse to the practice of physical activity. Likewise, the results of the oral glucose tolerance tests show that their alterations (prediabetes/ diabetes) are lower among those who performed physical activity. The percentage of people with blood pressure values within the normal range as well as circulating cholesterol (according to target values of international guidelines), is also significantly lower among those who practiced physical activity. Conclusion: The presented evidence objectively demonstrates the need/advantages of implementing a large-scale diabetes primary prevention program at the national level to.

[Efficacy and safety of fingolimod in routine clinical practice in patients with relapsing-remitting multiple sclerosis in Spain: an intermediate analysis of the MS NEXT study]. / Efectividad y seguridad del fingolimod en la practica clinica habitual en pacientes con esclerosis multiple remitente recurrente en España: analisis intermedio del estudio MS NEXT.

INTRODUCTION: Fingolimod is a disease modifying therapies, which has showed clinical efficacy and an acceptable safety profile in clinical trials with relapsing-remitting multiple sclerosis (RRMS) patients. AIM: To assess fingolimod effectiveness and safety in patients with RRMS in clinical practice. PATIENTS AND METHODS: We present an interim analysis (July 2015) of MS NEXT, an observational, retrospective and multicenter study. 442 patients were included (mean age: 41 ± 9 years; median baseline EDSS: 3.0; 70% female; 284 previously treated with first-line disease modifying therapies, 139 with natalizumab and 19 without a previous treatment; mean fingolimod treatment duration: 25 ± 9 months) treated with fingolimod from November 2011 and with at least 12 months follow-up. 56 neurology-unit Spanish hospitals enrolled patients. Basal clinical and demographic data were recorded. Relapses, EDSS scores and radiological activity were recorded at baseline and annually. Adverse events were also recorded during the follow-up period. RESULTS: After two years of follow-up: annual relapse rates decreased by 76%, the proportion of relapse-free patients was 67%, of disability progression-free patients confirmed at 3 months was 91%, of relapse and disability progression-free patients was 63%, of radiological activity-free patients was 50%, and the proportion of relapse, disability progression and radiological activity-free patients was 35%. Only 3.9% of patients discontinued fingolimod permanently during the first year of treatment. CONCLUSIONS: In this interim analysis, most of patients treated with fingolimod in clinical practice had a controlled clinical disease activity, stable disability progression and high persistency.

TITLE: Efectividad y seguridad del fingolimod en la practica clinica habitual en pacientes con esclerosis multiple remitente recurrente en España: analisis intermedio del estudio MS NEXT.Introduccion. El fingolimod es un tratamiento modificador de la enfermedad que ha demostrado eficacia y seguridad en ensayos clinicos en pacientes con esclerosis multiple remitente recurrente (EMRR). Objetivo. Evaluar la efectividad y la seguridad del fingolimod en pacientes con EMRR en la practica clinica. Pacientes y metodos. Se presentan los resultados del analisis intermedio (julio de 2015) del MS NEXT, un estudio observacional, multicentrico y retrospectivo. Se incluyo a 442 pacientes (edad media: 41 ± 9 años; escala expandida del estado de discapacidad basal, mediana: 3; 70% mujeres; 284 previamente tratados con tratamientos modificadores de la enfermedad de primera linea, 139 con natalizumab y 19 naive; media de tratamiento con fingolimod: 25 ± 9 meses) tratados con fingolimod a partir de noviembre de 2011 y con al menos 12 meses de seguimiento. Participaron 56 hospitales españoles. Se recogieron datos demograficos y clinicos (basal y anualmente, numero de brotes, puntuacion en la escala expandida del estado de discapacidad y actividad radiologica). Tambien se registraron los efectos adversos durante el seguimiento. Resultados. Tras dos años de tratamiento, la tasa anualizada de brotes se redujo un 76%; el 67% de los pacientes estaba libre de brotes; el 91%, libre de progresion de la discapacidad confirmada a los tres meses; el 63%, libre de brotes y progresion de discapacidad; el 50%, libre de actividad radiologica, y el 35%, libre de brotes, progresion de discapacidad y actividad radiologica. Un 3,9% abandono el fingolimod permanentemente. Conclusiones. En este analisis intermedio, la mayoria de los pacientes tratados con fingolimod en la practica clinica presenta una actividad clinica controlada y una elevada persistencia al tratamiento.

Factores determinantes del inicio de tratamiento con levodopa/carbidopa/entacapona en pacientes españoles con enfermedad de Parkinson / Factors determining when to start levodopa/carbidopa/entacapone treatment in Spanish patients with Parkinson's disea

Introducción: La enfermedad de Parkinson (EP) cuenta con un tratamiento sintomático amplio. No existe información fidedigna sobre los factores que influyen en la elección del tratamiento. Objetivo: Identificar los factores que determinan el inicio del tratamiento con levodopa/carbidopa/entacapona (LCE) en pacientes con EP. Pacientes y métodos: Estudio observacional, transversal retrospectivo y multicéntrico en pacientes con EP idiopática en tratamiento con LCE. Se recogieron datos sobre factores potencialmente implicados, como determinantes del inicio del tratamiento con LCE en la práctica clínica habitual. Resultados: Se estudió a 1.050 pacientes (edad media 71,3 ± 8,7 años; 58,2%, hombres), con 13,8 ± 12,9 meses de evolución hasta el diagnóstico y 74,5 ± 53,6 meses hasta el momento del inicio del tratamiento con LCE. Los síntomas iniciales incluyeron: temblor (70,6%), reducción de destreza (43,2%) y lentitud de movimientos (41,5%). El estadio de Hoehn y Yahr mayoritario al inicio de LCE fue 2 (57,5%), mientras que la escala de Schwab y England presentó una puntuación media de 73,4%. Ochocientos veintidós pacientes (78,3%) recibieron otros fármacos antes de LCE (tiempo medio entre inicio de tratamiento e inicio con LCE: 40,5 ± 47,2 meses). Los factores clínicos determinantes para iniciar el tratamiento con LCE fueron la presencia de bradicinesia (84,7%), rigidez diurna (72,2%), empeoramiento general (72,2%), dificultad marcha (66,4%), temblor (62,7%), rigidez nocturna (56,1%) e inestabilidad postural (53%). El único factor psicosocial determinante identificado fue la dificultad para realizar las actividades habituales de la vida diaria (84,3%). Conclusiones: En la EP, el inicio del tratamiento con LCE viene determinado fundamentalmente por los déficits motores y la discapacidad asociada

Introduction: Several therapeutic options are available for the symptomatic treatment of Parkinson's disease (PD). There is no reliable information about which factors are involved in the choice of treatment. Objective: To identify factors contributing to the decision to start treatment with devodopa/carbidopa/entacapone (LCE) in patients with PD. Patients and methods: We completed a descriptive cross-sectional retrospective multicentre study of patients with idiopathic PD receiving LCE. Clinical data were collected with special attention to factors that could potentially determine when to initiate treatment with LCE in normal clinical practice. Results: We studied 1050 patients with a mean age of 71.3 ± 8.7 years (58.2% men). Average time from the onset of symptoms to diagnosis was 13.8 ± 12.9 months, with a latency time of 74.5 ± 53.6 months before starting LCE treatment. The most common initial symptoms were tremor (70.6%), reduced dexterity (43.2%) and slowness of movement (41.5%). At the start of LCE treatment, most patients were in Hoehn and Yahr stage 2 (57.5%), with an average rating of 73.4% on the Schwab and England scale. Eight hundred twenty-two patients (78.3%) received treatment with other drugs before starting LCE (mean time between starting any PD treatment and starting LCE was 40.5 ± 47.2 months). Clinical factors with a moderate, marked, or crucial effect on the decision to start LCE treatment were bradykinesia (84.7%), daytime rigidity (72.2%), general decline (72.2%), difficulty walking (66.4%), tremor (62.7%), nocturnal rigidity (56.1%), and postural instability (53%). Difficulty performing activities of daily living was the only psychosocial factor identified as having an influence on the decision (84.3%). Conclusions: The decision to start patients with idiopathic PD on LCE treatment is mainly determined by motor deficits and disabilities associated with disease progression

Experiencia de uso y satisfacción con rivastigmina transdérmica en cuidadores de pacientes con enfermedad de Alzheimer de leve a moderada previamente tratados con rivastigmina oral a dosis altas / From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease

Introducción: Rivastigmina, tratamiento para la enfermedad de Alzheimer (EA) levemoderada, es el primer inhibidor de la colinesterasa administrable por vía transdérmica. Se describen la experiencia de uso y la satisfacción de los cuidadores informales con los parches de rivastigmina, así como el cambio clínico percibido en los pacientes con su empleo. Métodos: Estudio observacional, transversal y multicéntrico, con 239 investigadores y 1851 cuidadores informales de pacientes con EA leve-moderada, tratados con rivastigmina transdérmica durante ≥ 6 meses, y que previamente recibían dosis altas de rivastigmina por vía oral. Resultados: La edad media de los cuidadores fue 59,8 ± 14,4 años (70,9% mujeres). El 79,8% compartía domicilio con el paciente, dedicando 10,0 ± 7,1 h/día a su cuidado. Para la mayoría de los cuidadores las instrucciones del parche fueron comprensibles (97,1%) y la aplicación fácil o muy fácil (92,1%). La principal dificultad mencionada fueron problemas de adhesión (26,8%). En general, los abandonos del tratamiento se produjeron por reacciones cutáneas. El 76,5% de los cuidadores estuvieron satisfechos o muy satisfechos con el parche y el 77,4% consideró que interfería poco o nada en las actividades diarias propias. El 94,3% prefirió la vía transdérmica respecto a la vía oral. La Impresión Clínica Global de Cambio fue mejor en algún grado para el 61,3% de los cuidadores y para el 53% de los investigadores. Se notificaron pocos olvidos de la medicación. Conclusiones: La mayoría de los cuidadores de pacientes con EA leve-moderada prefirieron la vía transdérmica de rivastigmina a la vía oral, notificando satisfacción global, facilidad de uso e impacto reducido en sus actividades diarias propias con la ruta transdérmica, así como mejora de los pacientes respecto al tratamiento anterior

Introduction: Rivastigmine, a treatment for mild to moderate Alzheimer disease (AD), is the first cholinesterase inhibitor to be available in the transdermal format. We aim to describe user experience and satisfaction with the rivastigmine patch, as well as any clinical changes perceived in patients. Methods: Observational, cross-sectional, multicentre study with 239 investigators and 1851 informal caregivers of patients with mild to moderate AD. Patients were treated with transdermal rivastigmine patches for ≥ 6 months and had previously received high doses of oral rivastigmine. Results: Mean caregiver age was 59.8 ± 14.4 years and 70.9% were women. They spent 10.0 ± 7.1 hours per day providing care and 79.8% lived with the patient. Patch instructions were described as easy to follow by 97.1% of the caregivers and 92.1% of them rated patch application as easy or very easy. The most commonly cited disadvantage was adhesion problems (26.8%). Discontinuation of treatment was due to cutaneous reactions in most cases. Overall, 76.5% of the caregivers were satisfied or very satisfied with transdermal treatment and 77.4% considered that its interference with daily activities was minimal or null. The patch was preferred to oral treatment by 94.3% of caregivers. Clinical Global Impression of Change ratings improved according to 61.3% of the caregivers and 53% of the investigators. Few caregivers reported medication forgetfulness. Conclusions: Most caregivers of patients with mild to moderate AD preferred the transdermal format of rivastigmine to the oral format. Caregivers also reported overall satisfaction, ease of use, and reduced impact on daily activities for transdermal rivastigmine format, in addition to patient improvement compared to their condition under the previous treatment

Factors determining when to start levodopa/carbidopa/entacapone treatment in Spanish patients with Parkinson's disease.

INTRODUCTION: Several therapeutic options are available for the symptomatic treatment of Parkinson's disease (PD).There is no reliable information about which factors are involved in the choice of treatment. OBJECTIVE: To identify factors contributing to the decision to start treatment with levodopa/carbidopa/entacapone (LCE) in patients with PD. PATIENTS AND METHODS: We completed a descriptive cross-sectional retrospective multicentre study of patients with idiopathic PD receiving LCE. Clinical data were collected with special attention to factors that could potentially determine when to initiate treatment with LCE in normal clinical practice. RESULTS: We studied 1050 patients with a mean age of 71.3±8.7 years (58.2% men). Average time from onset of symptoms to diagnosis was 13.8±12.9 months, with a latency time of 74.5±53.6 months before starting LCE treatment. The most common initial symptoms were tremor (70.6%), reduced dexterity (43.2%) and slowness of movement (41.5%). At the start of LCE treatment, most patients were in Hoehn and Yahr stage 2 (57.5%), with an average rating of 73.4% on the Schwab & England scale. Eight hundred twenty two patients (78.3%) received treatment with other drugs before starting LCE (mean time between starting any PD treatment and starting LCE was 40.5±47.2 months). Clinical factors with a moderate, marked, or crucial effect on the decision to start LCE treatment were bradykinesia (84.7%), daytime rigidity (72.2%), general decline (72.2%), difficulty walking (66.4%), tremor (62.7%), nocturnal rigidity (56.1%), and postural instability (53%). Difficulty performing activities of daily living was the only psychosocial factor identified as having an influence on the decision (84.3%). CONCLUSIONS: The decision to start patients with idiopathic PD on LCE treatment is mainly determined by motor deficits and disabilities associated with disease progression.

From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease.

INTRODUCTION: Rivastigmine, a treatment for mild to moderate Alzheimer disease (AD), is the first cholinesterase inhibitor to be available in the transdermal format. We aim to describe user experience and satisfaction with the rivastigmine patch, as well as any clinical changes perceived in patients. METHODS: Observational, cross-sectional, multicentre study with 239 investigators and 1851 informal caregivers of patients with mild to moderate AD. Patients were treated with transdermal rivastigmine patches for ≥ 6 months and had previously received high doses of oral rivastigmine. RESULTS: Mean caregiver age was 59.8±14.4 years and 70.9% were women. They spent 10.0±7.1hours per day providing care and 79.8% lived with the patient. Patch instructions were described as easy to follow by 97.1% of the caregivers and 92.1% of them rated patch application as easy or very easy. The most commonly cited disadvantage was adhesion problems (26.8%). Discontinuation of treatment was due to cutaneous reactions in most cases. Overall, 76.5% of the caregivers were satisfied or very satisfied with transdermal treatment and 77.4% considered that its interference with daily activities was minimal or null. The patch was preferred to oral treatment by 94.3% of caregivers. Clinical Global Impression of Change ratings improved according to 61.3% of the caregivers and 53% of the investigators. Few caregivers reported medication forgetfulness. CONCLUSIONS: Most caregivers of patients with mild to moderate AD preferred the transdermal format of rivastigmine to the oral format. Caregivers also reported overall satisfaction, ease of use, and reduced impact on daily activities for transdermal rivastigmine format, in addition to patient improvement compared to their condition under the previous treatment.

Buenos resultados tras tratamiento con láser CO2 de leiomioma en el pezón / Successful Treatment of Leiomyoma of the Nipple With Carbon Dioxide Laser

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Estudio transversal comparativo de las fórmulas CKD-EPI y MDRD-4 a partir de la historia clínica informatizada de Atención Primaria de Barcelona / A comparative, cross-sectional study of the CKD-EPI and MDRD-4 equations from the Primary Care computerized clinical history of Barcelona

Antecedentes: La prevalencia de enfermedad renal crónica (ERC) en España supera el 7%. Su diagnóstico precoz puede ayudar a frenar la evolución. En Atención Primaria (AP) se calcula el filtrado glomerular estimado (FGe) mediante fórmulas basadas en la creatinina plasmática(CrP).Objetivos: Comparar los FG e según las fórmulas MDRD-4 y CKD-EPI a partir de la historia clínica informatizada (HCI) y la clasificación de ERC en una población de AP. Material y métodos: Estudio transversal. Se incluyó a pacientes de 20-99 años, asignados a centros de AP de Barcelona, con CrP entre julio de 2008 y junio de 2010. Se obtuvieron losdatos de la HCI. Se calculó el FGe mediante CKD-EPI y MDRD-4.Resultados: Se estudió a un total de 447.140 personas: 58,7% mujeres, 56,6 (DE 18,8) años. El 32,5% con diagnóstico de hipertensión arterial, 11% con diabetes mellitus y 9,3% con enfermedad cardiovascular asociada. La CrP media fue 0,89 (0,28) mg/dL, FGe por MDRD-4 de 80,59(21,04) mL/min/1,73 m2y por CKD-EPI de 85,03 (21,13) mL/min/1,73 m2. La CKD-EPI, respecto a MDRD-4, clasificó el 2,3% de los pacientes en estadios menos avanzados de ERC, el 96,8% en el mismo y el 0,9% en más avanzados. El índice kappa fue de 0,87. En números absolutos clasificó en estadios 3b-4-5 (posible derivación a nefrología) a 958 pacientes más, con 691 personas >69 años en estadio 3b.Conclusiones: Utilizar una u otra fórmula puede variar el FGe. La CKD-EPI tiende a clasificar enestadios más avanzados en > 69 años. El uso de cada fórmula puede hacer cambiar el número y tipo de derivaciones a nefrología

Background: The prevalence of chronic kidney disease (CKD) in Spain is higher than 7%. Its early diagnóstico can help to delay its progression. Glomerular filtration rate (GFR) based on serum creatinine (SC) is calculated in primary care (PC) to identify CKD. Objectives: To compare GFR by MDRD-4 and CKD-EPI equations obtained from clinical records(CR) and to compare the classification of CKD in a primary care population. Material and methods: A cross-sectional study was performed, including patients 20-99 years old, assigned to primary care centers of Barcelona, with a SC recorded between July 2008 and June 2010. Data were obtained from the CRs. GFR was calculated from MDRD-4 and CKD-EPI equations. Results: A total of 447,140 persons were studied (58.7% females, 56.6 [SD 18.8] years old).Of these 32.5% were diagnosed of hypertension, 11.0% diabetes and 9.3% had some associated cardiovascular disease. SC 0.89 (0.28) mg/dL (78.7 [SD 24.8] mol/L), GFR being 80.59(21.04) mL/min/1.73 m2by MDRD-4, and 85.03 (21.13) mL/min/1.73 m2by CKD-EPI. CKD-EPI compared to MDRD-4 classified 2.3% of patients in less advanced stages of CKD, 96.8% in the same stage and 0.9% in more advanced stages. Kappa coefficient: 0.87. In absolute numbers, CKD-EPI classified in 3b-4-5 stages (candidates for referral to nephrology) 958 patients more,691 of them being patients > 69 years old and stage 3b.Conclusions: Using one equation or another could vary the estimation of GFR. CKD-EPI tends to classify patients older than 69 into more advanced stages. Each equation can change the number and type of referral to nephrology (AU)

Carga asociada a la administración de rivastigmina transdérmica y a su presentación oral en cuidadores de pacientes con enfermedad de Alzheimer / Burden associated with the administration of transdermal rivastigmine versus its oral version in caregivers of Alzheimer’s disease patients

Introducción: La enfermedad de Alzheimer (EA) es la demencia más común en la vejez, y conlleva un elevado estrés y una importante carga familiar. Objetivo: Evaluar las diferencias en satisfacción y carga asociada a la administración de rivastigmina por vía transdérmica y oral en cuidadores de pacientes con EA. Material y métodos: Estudio observacional, transversal y multicéntrico que incluyó a cuidadores de pacientes con EA de leve a moderadamente grave tratados con rivastigmina. Se evaluó la molestia asociada a la administración, la carga soportada y la satisfacción con el tratamiento. Resultados: Se incluyeron 497 cuidadores/grupo. La edad media de los cuidadores fue de 58,1 ± 14,2 años, y cerca del 75% eran mujeres. La mayoría de cuidadores eran parientes cercanos. La dificultad para tragar la medicación supuso molestias medias o elevadas al 38,2% de los cuidadores del grupo oral, mientras que la dificultad para colocar el parche lo fue para el 4,6%. El tratamiento transdérmico alcanza molestias medias de 6,7 puntos y el oral de 10,1 (p <0,0001); la sobrecarga no mostró diferencias significativas (21,4 ± 7,2 frente a 21,5 ± 6,9, respectivamente). Respecto a la facilidad de uso, el 88,3% consideró fácil o muy fácil el parche, y el 71,2% la cápsula. La afectación de la vida del cuidador fue nula o muy ocasional en el 66,4% con tratamiento transdérmico, frente al 51,1% con tratamiento oral. El 75,1% se mostraron satisfechos con el tratamiento transdérmico, frente al 55,9% con el oral (p <0,0001). Conclusiones: Los cuidadores de pacientes con EA mostraron una mayor satisfacción con el tratamiento de rivastigmina transdérmica y menores molestias asociadas (AU)

Introduction: Alzheimer’s disease (AD) is the most common form of dementia in elderly people, being widely known the stress and burden associated with the care and drug administration. Purpose: To assess differences between caregiver satisfaction and burdens associated with transdermal and oral rivastigmine for the care of patients with AD. Patients and methods: Non interventional, cross-sectional and multicenter study that included caregivers of patients with mild to moderately severe AD treated with rivastigmine. We evaluated discomfort associated with administration route, satisfaction with the treatment and caregiver burden. Results: 497 caregivers were recruited per group. Mean age was 58.1 ± 14.2 and 75% were women. Most caregivers were close relatives. Difficulty swallowing pills involves average or high complaints in 38.2% of oral group caregivers, whereas the difficulty to place the patch represents only a complaint in 4.6% of transdermal group caregivers. The transdermal treatment reaches average discomfort scores of 6.7 points while the oral treatment reaches 10.1 (p <0.0001). The burden scale was not signifi cantly different between groups (21.4 ± 7.2 patches vs 21.5 ± 6.9 oral). 88.3% and 71.2% considered easy or very easy to place the patch or administered the pill, respectively. The involvement of the caregiver’s life was nil or very occasional in 66.4% of patch caregivers vs 51.1% of oral ones. Significant differences in satisfaction were observed: 75.1% satisfied or very satisfied with transdermal vs 55.9% with oral treatment (p <0.0001). Conclusions: Caregivers of AD patients were more satisfied with transdermal rivastigmine treatment which is also linked with less associated discomfort (AU)

Fenómeno de Koebner tras escleroterapia de varices / Koebner phenomenon after sclerotherapy of varicose veins in the lower limbs

El fenómeno de Koebner fue descrito en 1877 por Heinrich Koebner como la aparición de lesiones típicas de una determinada dermatosis en áreas de piel sana desencadenadas tras diferentes traumatismos. Presentamos el caso de una mujer de 33 años valorada en nuestra consulta por aparición de lesiones psoriasiformes tras el tratamiento mediante escleroterapia con polidocanol de pequeñas varículas en las extremidades inferiores (AU)

Koebner phenomenon was first described in 1877 as the appearance of psoriatic lesions in the uninvolved skin of psoriatic patients as a consequence of trauma. We report a 33-year-old woman referred to our department for evaluation of multiple psoriasiform skin lesions appearing after sclerotherapy for varicose veins of the legs (AU)

Usefulness of TrichoScan professional in the evaluation of hair loss in females. Report of 180 cases.

BACKGROUND: TrichoScan Professional is a computerized program used for digital measurement of hair growth and hair loss. The aim of our study was to undertake an evaluation with TrichoScan Professional of female patients consulting at our hospitals for hair loss. The purpose of our study was to determine whether TrichoScan was able to identify differences in hair parameters that would correlate with the pattern of alopecia or according to the age of the patients evaluated. MATERIAL AND METHODS: One hundred-eighty women that consulted consecutively for loss of hair were included. Patients were aged between 8 and 85 years (mean age 36 years). Data including age, the number of hairs, hair density per square centimetre, anagen and telogen percentage and percentage of terminal and miniaturized hair were analysed. RESULTS: Results observed with TrichoScan were as below: number of hairs (mean 154.9; range 34-316). Hair density per square centimetre (mean 239; range 52-486). Hair in anagen phase (mean 62.4%; range 9-93%). Hair in telogen phase (mean 37.4%; range 7-91%). Terminal hair (mean 95.2%; range 82-100%). Vellus hair (mean 4.7%; range 0-17%). Pearson's correlation test was used to measure the strength of the association of age with the rest of parameters. The statistical analysis showed a significant correlation between age and both the number of hairs and the hair density per square centimetre. However, no significant correlation between age and rest of the parameters was observed. CONCLUSIONS: TrichoScan Professional may help to quantify hair density and in our sample, this was the only parameter showing a significant decrease according to age in various types of alopecia affecting the females.

Adalimumab-induced lupus erythematosus.

Adalimumab, an anti-tumour necrosis factor agent, especially used in the treatment of rheumatoid arthritis, has a good safety profile. One of the most common side-effects of adalimumab is the development of autoantibodies. Despite the induction of autoantibodies, the clinical presentation of immune-mediated complications upon adalimumab therapy, including a lupus-like syndrome, is very rare. We have recently evaluated a new case of adalimumab-induced lupus erythematosus.