Is measurement of blood pressure worthwhile in the diabetic eye clinic?

Purpose - The UK Prospective Diabetic Study has confirmed the importance of blood pressure (BP) as a major risk factor for diabetic retinopathy (DR). We wanted to investigate whether measuring the BP in the diabetic eye clinic could identify new hypertensive patients and monitor control in existing ones. Patients and methods - We compared BP in patients attending the diabetic eye clinic with home blood pressure measurement (HBPM) and ambulatory BP measurement (ABPM). In all, 106 patients attending a diabetic eye clinic were selected at random from clinic attendees. BP measurement (on an Omron 705 CP) was performed in the eye clinic and also compared to HBPM three times per day with an Omron 705 CP machine, and was compared to diabetic clinic measurements. In addition, 11 randomly chosen patients had 24 h ABPM to validate the above techniques. Results - In all, 106 patients (70 male and 36 female) were recruited for the study, of which 71 were known to be hypertensive on antihypertensive medication. Of the total, 75 patients (70.8%) had BP>140/85 in the eye clinic, of which 51 (68%) were known to be hypertensive on treatment and this was confirmed in 46 (90%) on HBPM. A total of, 24 patients (22.6%) were newly diagnosed as hypertensive in the eye clinic, which was confirmed by HBPM in 22 patients (92%). The mean BP of the measurements performed in the eye clinic was significantly higher than that carried out in the diabetic clinic (P<0.01). Tropicamide 1% and phenylephrine 2.5% eye drop instillation had no effect on BP. In 11 randomly chosen patients, 24 h ABPM validated both diabetic eye clinic and home BP measurements. Conclusion - Attendance at the diabetic eye clinic is an important chance to detect both new patients with systemic hypertension and those with inadequate BP control. Ophthalmologists should be encouraged to measure BP in their diabetic patients attending diabetic eye clinics, as it is an important risk factor for DR. On the basis of our findings, good BP control is a goal yet to be achieved in diabetic patients with retinopathy.

Hypertension and the eye

In addition to being the chief cause of death in developed countries, systemic hypertension is also a leading cause of visual impairment. The eye is an end arteriolar system and is therefore susceptible to changes in blood pressure. It is also the only place where blood vessels can be clearly viewed by noninvasive techniques. This paper reviews current research into premalignant and malignant retinal signs of systemic hypertension. Previous methods of classifying retinal hypertensive signs are identified, along with more recent image analysis techniques. The need for observing the retinal vasculature as well as measuring blood pressure for monitoring systemic hypertensive patients is discussed in relation to current research. Copyright © 2002 by Current Science Inc.

Clinical oxidative stress during leprosy multidrug therapy:impact of dapsone oxidation

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 μg/mL) and paucibacillary (0.662±0.123 μg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDTsupervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software. © 2014 Schalcher et al.

Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure

BACKGROUND: Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

METHODS AND RESULTS: Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (P<0.001) and α-smooth muscle actin (P=0.025) expression.

CONCLUSIONS: LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.

Evaluating New Matrix Pooled Testing Methods for Detecting HIV Treatment Failure with and without Covariate Information

Thesis (Master's)--University of Washington, 2016-08

A gestão da pessoa com hipertensão arterial na unidade móvel de saúde

Enquadramento: A gestão da doença, designadamente da hipertensão arterial (HTA) através do apoio à auto-gestão, aconselhamento motivacional, acesso à informação resultam em maior adesão terapêutica. Objetivos: Identificar os fatores que determinam a adesão ao tratamento na pessoa com HTA numa amostra comunitária. Metodologia: Estudo transversal, descritivo-correlacional, com amostra de 235 hipertensos (63,8% do género feminino), idade média 75 ± 8,14 anos, 62,6% casados e a maioria com o 1.º ciclo de escolaridade. Recorremos ao questionário com variáveis sociodemográficas, dietéticas, clínicas, motivacionais, relacionadas com os profissionais e serviços de saúde, Escala de Apgar Familiar, Questionário de Dependência Alcoólica, Questionário Internacional de Atividade Física, Questionário de Determinação da Saúde Nutricional, Escala de Autocuidado com a Hipertensão, Questionário de Crenças Sobre a Doença, Escala de Crenças Acerca dos Medicamentos, Escala de Satisfação dos Utentes com os Cuidados de Enfermagem na Unidade Móvel de Saúde, Questionário abreviado da Perceção do Cliente sobre o Ambiente Terapêutico, Questionário de Autorregulação, Escala de Competência Percebida e Escala de Medida de Adesão aos Tratamentos para colheita de dados. Resultados: A pressão arterial estava controlada em 34,5% da amostra, 28,2% homens e 38% mulheres. A MAT revelou um mínimo de 3,86 e um máximo de 6 com uma média de 5,66±0,49. As variáveis preditoras da adesão foram: controlo pessoal (p=0,005), identidade (p=0,000), ambiente terapêutico (p=0,001), alimentação geral (p=0,041), atividade física (p=0,007) e toma de medicamentos (p=0,000). Conclusões: Compreender os fatores envolvidos na gestão do tratamento permite perceber como podem os enfermeiros contribuir para melhorar a adesão ao regime terapêutico. Palavras-chave: Hipertensão arterial, gestão da doença crónica, adesão ao tratamento e adultos.

Studies of antihypertensive drug persistence and adherence in the Glasgow Blood Pressure Clinic

Hypertension (HTN) is a major risk factor for cardiovascular diseases including stroke, coronary heart disease (CHD), chronic renal failure, peripheral vascular disease, myocardial infarction, congestive heart failure and premature death. The prevalence of HTN in Scotland is very high and although a high proportion of the patients receive antihypertensive medications, blood pressure (BP) control is very low. Recommendations for starting a specific antihypertensive class have been debated between various guidelines over the years. Some guidelines and HTN studies have preferred to start with a combination of an antihypertensive class instead of using a single therapy, and they have found greater BP reductions with combination therapies than with monotherapy. However, it has been shown in several clinical trials that 20% to 35% of hypertensive patients could not achieve the target BP, even though they received more than three antihypertensive medications. Several factors were found to affect BP control. Adherence and persistence were considered as the factors contributing the most to uncontrolled hypertension. Other factors such as age, sex, body mass index (BMI), alcohol intake, baseline systolic BP (SBP), and the communication between physicians and patients have been shown to be associated with uncontrolled BP and resistant hypertension. Persistence, adherence and compliance are interchangeable terms and have been used in the literature to describe a patient’s behaviour with their antihypertensive drugs and prescriptions. The methods used to determine persistence and adherence, as well as the inclusion and exclusion criteria, vary between persistence and adherence studies. The prevalence of persistence and adherence have varied between these studies, and were determined to be high in some studies and low in others. The initiation of a specific antihypertensive class has frequently been associated with an increase or decrease in adherence and persistence. The tolerability and efficacy of the initial antihypertensive class have been the most common methods of explaining this association. There are also many factors that suggest a relationship with adherence and persistence. Some factors in previous studies, such as age, were frequently associated with adherence and persistence. On the other hand, relationships with certain factors have varied between the studies. The associations of age, sex, alcohol use, smoking, baseline systolic blood pressure (SBP) and diastolic BP (DBP), the presence of comorbidities, an increase in the number of pills and the relationship between patients and physicians with adherence and persistence have been the most commonly investigated factors. Most studies have defined persistence in terms of a patient still taking medication after a period of time. A medication possession ratio (MPR) ≥ 80 has been used to define compliance. Either of these terminologies, or both, have been used to estimate adherence. In this study, I used the same definition for persistence to identify patients who have continued with their initial treatment, and used persistence and MPR to define patients who adhered to their initial treatment. The aim of this study was to estimate the prevalence of persistence and adherence in Scotland. Also, factors that could have had an effect on persistence and adherence were studied. The number of antihypertensive drugs taken by patients during the study and factors that led to an increase in patients being on a combination therapy were also evaluated. The prevalence of resistance and BP control were determined by taking the BP after the last drug had been taken by persistent patients during five follow-up studies. The relationship of factors such as age, sex, BMI, alcohol use, smoking, estimated glomerular filtration rate (eGFR), and albumin levels with BP reductions for each antihypertensive class were determined. Information Services Division (ISD) data, which includes all antihypertensive drugs, were collected from pharmacies in Scotland and linked to the Glasgow Blood Pressure Clinic (GBPC) database. This database also includes demographic characteristics, BP readings and clinical results for all patients attending the GBPC. The case notes for patients who attended the GBPC were reviewed and all new antihypertensive drugs that were prescribed between visits, BP before and after taking drugs, and any changes in the hypertensive drugs were recorded. A total of 4,232 hypertensive patients were included in the first study. The first study showed that angiotensin converting enzyme inhibitor (ACEI) and beta-blockers (BB) were the most prescribed antihypertensive classes between 2004 and 2013. Calcium channel blockers (CCB), thiazide diuretics and angiotensin receptor blockers (ARB) followed ACEI and BB as the most prescribed drugs during the same period. The prescription trend of the antihypertensive class has changed over the years with an increase in prescriptions for ACEI and ARB and a decrease in prescriptions for BB and diuretics. I observed a difference in antihypertensive class prescriptions by age, sex, SBP and BMI. For example, CCB, thiazide diuretics and alpha-blockers were more likely to be prescribed to older patients, while ACEI, ARB or BB were more commonly prescribed for younger patients. In a second study, 4,232 and 3,149 hypertensive patients were included to investigate the prevalence of persistence in the Scottish population in 1- and 5-year studies, respectively. The prevalence of persistence in the 1-year study was 72.9%, while it was only 62.8% in the 5-year study. Those patients taking ARB and ACEI showed high rates of persistence and those taking diuretics and alpha blockers had low rates of persistence. The association of persistence with clinical characteristics was also investigated. Younger patients were more likely to totally stop their treatment before restarting their treatment with other antihypertensive drugs. Furthermore, patients who had high SBP tended to be non-persistent. In a third study, 3,085 and 1,979 patients who persisted with their treatment were included. In the first part of the study, MPR was calculated, and patients with an MPR ≥ 80 were considered as adherent. Adherence rates were 29.9% and 23.4% in the 1- and 5-year studies, respectively. Patients who initiated the study with ACEI were more likely to adhere to their treatments. However, patients who initiated the study with thiazide diuretics were less likely to adhere to their treatments. Sex, age and BMI were different between the adherence and non-adherence groups. Age was an independent factor affecting adherence rates during both the 1- and 5-year studies with older patients being more likely to be adherent. In the second part of the study, pharmacy databases were checked with patients' case notes to compare antihypertensive drugs that were collected from the pharmacy with the antihypertensive prescription given during the patient’s clinical visit. While 78.6% of the antihypertensive drugs were collected between clinical visits, 21.4% were not collected. Patients who had more days to see the doctor in the subsequent visit were more likely to not collect their prescriptions. In a fourth study, 3,085 and 1,979 persistent patients were included to calculate the number of antihypertensive classes that were added to the initial drug during the 1-year and 5-year studies, respectively. Patients who continued with treatment as a monotherapy and who needed a combination therapy were investigated during the 1- and 5-year studies. In all, 55.8% used antihypertensive drugs as a monotherapy and 44.2% used them as a combination therapy during the 1-year study. While 28.2% of patients continued with treatment without the required additional therapy, 71.8% of the patients needed additional therapy. In all, 20.8% and 46.5% of patients required three different antihypertensive classes or more during the 1-year and 5-year studies, respectively. Patients who started with ACEI, ARB and BB were more likely to continue as monotherapy and less likely to need two more antihypertensive drugs compared with those who started with alpha-blockers, non-thiazide diuretics and CCB. Older ages, high BMI levels, high SBP and high alcohol intake were independent factors that led to an increase in the probability of patients taking combination therapies. In the first part of the final study, BPs were recorded after the last drug had been taken during the 5 year study. There were 815 persistent patients who were assigned for this purpose. Of these, 39% had taken one, two or three antihypertensive classes and had controlled BP (controlled hypertension [HTN]), 29% of them took one or two antihypertensive classes and had uncontrolled BP (uncontrolled HTN), and 32% of the patients took three antihypertensive classes or more and had uncontrolled BP (resistant HTN). The initiation of an antihypertensive drug and the factors affecting BP pressure were compared between the resistant and controlled HTN groups. Patients who initiated the study with ACEI were less likely to be resistant compared with those who started with alpha blockers and non-thiazide diuretics. Older patients, and high BMI tended to result in resistant HTN. In the second part of study, BP responses for patients who initiated the study with ACEI, ARB, BB, CCB and thiazide diuretics were compared. After adjusting for risk factors, patients who initiated the study with ACEI and ARB were more respondent than those who took CCB and thiazide diuretics. In the last part of this study, the association between BP reductions and factors affecting BP were tested for each antihypertensive drug. Older patients responded better to alpha blockers. Younger patients responded better to ACEI and ARB. An increase in BMI led to a decreased reduction in patients on ACEI and diuretics (thiazide and non-thiazide). An increase in albumin levels and a decrease in eGFR led to decreases in BP reductions in patients on thiazide diuretics. An increase in eGFR decreased the BP response with ACEI. In conclusion, although a high percentage of hypertensive patients in Scotland persisted with their initial drug prescription, low adherence rates were found with these patients. Approximately half of these patients required three different antihypertensive classes during the 5 years, and 32% of them had resistant HTN. Although this study was observational in nature, the large sample size in this study represented a real HTN population, and the large pharmacy data represented a real antihypertensive population, which were collected through the support of prescription data from the GBPC database. My findings suggest that ACEI, ARB and BB are less likely to require additional therapy. However, ACEI and ARB were better tolerated than BB in that they were more likely to be persistent than BB. In addition, users of ACEI, and ARB have good BP response and low resistant HTN. Linkage patients who participated in these studies with their morbidity and mortality will provide valuable information concerning the effect of adherence on morbidity and mortality and the potential benefits of using ACEI or ARB over other drugs.

Establishing a children’s orthopaedic hospital for Malawi: A review after 10 years

Background BEIT CURE International Hospital (BCIH) opened in 2002 providing orthopaedic surgical services to children in Malawi. This study reviews the hospital’s progress 10 years after establishment of operational services. In addition we assess the impact of the hospital’s Malawi national clubfoot programme (MNCP) and influence on orthopaedic training. Methods All operative paediatric procedures performed by BCIH services in the 10th operative year were included. Data on clubfoot clinic locations and number of patients treated were obtained from the MNCP. BCIH records were reviewed to identify the number of healthcare professionals who have received training at the BCIH. Results 609 new patients were operated on in the 10th year of hospital service. Patients were treated from all regions; however 60% came from Southern regions compared with the 48% in the 5th year. Clubfoot, burn contracture and angular lower limb deformities were the three most common pathologies treated surgically. In total BCIH managed 9,842 patients surgically over a 10-year period. BCIH helped to establish and co-ordinate the MNCP since 2007. At present the program has a total of 29 clinics, which have treated 5748 patients. Furthermore, BCIH has overseen the full or partial training of 5 orthopaedic surgeons and 82 orthopaedic clinical officers in Malawi. Conclusion The BCIH has improved the care of paediatric patients in a country that prior to its establishment had no dedicated paediatric orthopaedic service, treating almost 10,000 patients surgically and 6,000 patients in the MNCP. This service has remained consistent over a 10-year period despite times of global austerity. Whilst the type of training placement offered at BCIH has changed in the last 10 years, the priority placed on training has remained paramount. The strategic impact of long-term training commitments are now being realised, in particular by the addition of Orthopaedic surgeons serving the nation.

Frecuencia de hipertensión arterial en los adultos mayores de las parroquias urbanas de Cuenca-Ecuador, 2015

Introducción: A nivel mundial la población de adultos mayores se incrementa, Ecuador no se queda fuera de esta transición demográfica y así aumentan también todas las enfermedades asociadas con la edad, principalmente la hipertensión arterial. Objetivo: Determinar la frecuencia de hipertensión arterial en adultos mayores de las parroquias urbanas de la ciudad de Cuenca, 2015. Metodología: Se realizó un estudio descriptivo en una muestra de 378 adultos mayores. Fueron hipertensos aquellos pacientes que tengan dos tomas de presión arterial separadas como mínimo una semana en las cuales la presión arterial sistólica sea >o= a 140 mmHg y presión arterial diastólica >o= a 90 mmHg. Se clasificó según parámetros sociodemográficos, antecedentes familiares, estado nutricional y actividad física. El muestreo fue de las zonas censales de cada parroquia, se usó un muestreo aleatorio simple. Los datos fueron analizados en el programa SPSS versión 15.0, utilizando distribución de frecuencias, medidas de tendencia central: media y medidas de dispersión: desvió estándar. Resultados: la frecuencia de hipertensión arterial fue 52,5%. El 65,1% de hipertensos fueron mujeres y el 34.9% hombres. El 57,6% de hipertensos fueron estuvieron entre los 65 y 74 años. El 41,2% tenía instrucción primaria completa. El 76,4% no tenía una ocupación laboral. El 51,2% no tenía antecedentes familiares de HTA. El 40% realizaba actividad física moderada. El 41,9% presentó obesidad. Conclusión: la frecuencia de hipertensión arterial en los adultos mayores de las parroquias urbanas de la ciudad de Cuenca fue del 52,5%

Valor pronóstico del incremento de la tensión arterial sistólica con el ejercicio en pacientes hipertensos con enfermedad coronaria conocida o sospechada.

La asociación entre un incremento exagerado de la presión arterial sistólica con el ejercicio (IEPASE) y la probabilidad de eventos cardiovasculares es controvertida. Nuestro propósito fue determinar la posible asociación de un IEPASE con la supervivencia y con el riesgo de eventos cardíacos graves en pacientes hipertensos con enfermedad coronaria conocida o sospechada. Se trata de un estudio retrospectivo y observacional sobre una muestra de 5.226 pacientes con historia de hipertensión arterial y enfermedad coronaria conocida o sospechada referidos a ecocardiografía de ejercicio. El IEPASE se definió como un incremento de la presión arterial sistólica con el ejercicio igual o superior al percentil 95 de esta población (80 mmHg). Los objetivos fueron mortalidad total, mortalidad de origen cardíaco e infarto de miocardio (IM). En un seguimiento medio de 4,7 años, se registraron 978 muertes (371 de origen cardíaco) y 798 IM. Las tasas anuales de mortalidad, mortalidad de origen cardíaco e IM fueron del 2,73; 0,83 y 2,63% en pacientes con IEPASE y de 4,4; 1,58 y 3,98%, respectivamente en aquellos sin IEPASE (p < 0,001; p = 0,012 y p = 0,014, respectivamente). Tras un ajuste multivariado, el IEPASE resultó predictor de mortalidad por cualquier causa (HR: 0,70; IC 95%: 0,52-0,95; p = 0,023) e IM (HR: 0,69; IC 95%: 0,50-0,95; p = 0,022), pero la asociación con mortalidad cardiaca no alcanzó significación estadística (HR: 0,72; IC 95%: 0,43-1,20; p = 0,2). El IEPASE se asoció con mayor probabilidad de supervivencia y menor riesgo de IM en pacientes hipertensos con enfermedad coronaria conocida o sospechada.

Evidencia sobre la eficacia de cannabinoides en el dolor neuropático oncológico

Contexto: La eficacia de los cannabinoides en el dolor neuropático es desconocida. El control del dolor es determinante en los pacientes ya que genera un impacto negativo en la calidad de vida de los pacientes. Objetivo: El presente trabajo pretende demostrar la evidencia sobre la eficacia de los medicamentos cannabinoides en el control del dolor neuropático oncológico, mediante la evaluación de la literatura disponible. Metodología: Se realizó una revisión sistemática de literatura incluyendo estudios experimentales, observacionales y revisiones sistemáticas en un periodo de 15 años. Se incluyeron todos los estudios desde el años 2000 con evidencia IB según la escala de evidencia de Oxford. Resultados: Cuatro estudios cumplieron criterios para su inclusión, sin embargo la evidencia es baja y no permite recomendar o descartar los cannabinoides como terapia coadyuvante en control del dolor neuropático oncológico. La combinación de THC/CDB (Sativex®) parece ser un medicamento seguro pues no se reportaron muertes asociadas a su uso, sin embargo la presentación de eventos adversos a nivel gastrointestinal y neurológico podría aumentar el riesgo de interacciones medicamentosas y tener un impacto negativo en la calidad de vida de los pacientes oncológicos. Conclusiones: No hay suficiente literatura y la evidencia no es suficiente para recomendar o descartar el uso de los cannabinoides en dolor neuropático oncológico. Futuros estudios deben realizarse para analizar el beneficio de estos medicamentos. Aunque ética y socialmente hay resistencia para el uso de los cannabinoides, actualmente hay una gran discusión política en el mundo y en Colombia para su aceptación como terapia en el control del dolor.

Revisión de la literatura científica sobre publicidad de medicamentos de venta libre y comportamiento del consumidor

El consumo de medicamentos es un asunto que actualmente se ha convertido en una preocupación a nivel global, ya que no todos los medicamentos están sujetos a prescripción médica, y esto implica que su consumo dependa de otras fuentes de información, como la publicidad masiva o el consejo de personas legas, entre otros. Esta revisión se basó en la publicidad y el impacto que tiene esta frente al consumidor. La presente revisión se dividió en dos categorías dado la relevancia del tema, en la primera se encuentra las características de los medicamentos de venta libre donde se evidenció cómo funciona el sector de la industria farmacéutica, las características de los medicamentos en general y los riesgos del abuso de este comportamiento. Así mismo, en la segunda categoria se habló sobre la publicidad y mercadeo de ventas libres donde se evidenció el alto impacto que tiene la publicidad en el consumidor, las restricciones que hay en el contexto nacional e internacional.

Ultra-hypofractionated stereotactic radiotherapy for prostate cancer in 5 fractions: current evidences and our clinical experience

AIMS: The present is a retrospective evaluation of acute genito-urinary (GU) and gastro-intestinal (GI) toxicity, in addition to biochemical recurrence rate in 57 prostate cancer patients treated at our Institution with ultra-hypofractionated RT (UHRT) schedule. METHODS: From January 2021 to December 2022 we have treated 57 patients with prostate cancer, using an UHRT scheme of 5-fractions every other day for a total dose delivered of 36.25 Gy, according to the PACE-B trial treatment schedule. Good urinary function, assessed by International Prostate Symptom Score (IPSS), were required. The simulation CT scans were acquired in supine position and fused with MRI for CTVs definition for every patient. Each treatment was performed by Accuray's TomoTherapy with daily IGRT. The evaluation of the set-up was very restrictive before daily treatment delivery. RESULTS: According to RTOG toxicity scale, the acute GU toxicity at 3 months from RT, GU toxicity was G0 for 30 patients (52.6%), G1 for 26 (45.6%) and G2 for one only (1.75%); rectal toxicity was G0 for 56 patients (98.25%) and G1 for one only (1.75%). The median follow-up (FU) was 9 months (2-24 months). In the following FU months, we observed progressively lower urinary and rectal toxicity, except for one patient who showed G2 GU toxicity at 12 months. All but one patient had a progressive PSA value decrease. CONCLUSIONS: In our experience, UHRT appears to be safe and well tolerated even without the use of rectal spacer devices. A longer FU is necessary to evaluate late toxicity and disease control rate.

Cardiac Magnetic Resonance Assessment Of Interstitial Myocardial Fibrosis And Cardiomyocyte Hypertrophy In Hypertensive Mice Treated With Spironolactone.

Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Mice were randomized to l-nitro-ω-methyl ester (l-NAME, 3 mg/mL in water; n=22), or l-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l-NAME (l-NAME+S) showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 ± 0.09 for l-NAME versus 0.25 ± 0.03 for l-NAME+S, P<0.001; τic: 0.42 ± 0.11 for l-NAME groups versus 0.12 ± 0.05 for l-NAME+S group). Mice treated with a combination of l-NAME and spironolactone were similar to placebo-treated controls at 7 weeks. Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression.

Patients with non-insulin depending diabetes mellitus and metabolic syndrome are suboptimal treated in swiss primary care.

The prevalence of complicated hypertension is increasing in America and Europe. This survey was undertaken to assess the status quo of primary care management of hypertension in patients with the high-risk comorbid diseases metabolic syndrome (MetS) and/or type 2 diabetes mellitus (non-insulin depending diabetes mellitus (NIDDM)). Data of anti-hypertensive treatment of 4594 Swiss patients were collected over 1 week. We identified patients with exclusively NIDDM (N = 95), MetS (N = 168), and both (N = 768). Target blood pressure (TBP) attainment, frequency of prescribed substance-classes, and correlations to comorbidities/end-organ damages were assessed. In addition, we analyzed the prescription of unfavorable beta-blockers (BB) and high-dose diuretics (Ds). In NIDDM, Ds (61%), angiotensin receptor blockers (ARBs) (40%), and angiotensin converting enzyme inhibitors (ACEIs) (31%) were mostly prescribed, while in MetS, drugs prevalence was Ds (68%), ARBs (48%), and BB (41%). Polypharmacy in patients with MetS correlated with body mass index; older patients (>65 years) were more likely to receive dual-free combinations. TBP was attained in 25.2% of NIDDM and in 28.7% of MetS patients. In general, low-dose Ds use was more prevalent in NIDDM and MetS, however, overall, Ds were used excessively (NIDDM: 61%, MetS: 68%), especially in single-pill combination. Patients with MetS were more likely to receive ARBs, ACEIs, CCBs, and low-dose Ds than BBs and/or high-dose Ds. Physicians recognize DM and MetS as high-risk patients, but select inappropriate drugs. Because the majority of patients may have both, MetS and NIDDM, there is an unmet need to define TBP for this specific population considering the increased risk in comparison to patients with MetS or NIDDM alone.