Ward-based Goal-Directed Fluid Therapy (GDFT) in Acute Pancreatitis (GAP) trial: study protocol for a feasibility randomised controlled trial

IntroductionAcute pancreatitis is an inflammatory disease of the pancreas with high risk of developing multiorgan failure and death. There are no effective pharmacological interventions used in current clinical practice. Maintaining fluid and electrolyte balance is the mainstay of supportive management. Goal-directed fluid therapy (GDFT) has been shown to decrease morbidity and mortality in surgical conditions with systemic inflammatory response. There is currently no randomised controlled trial (RCT) investigating the role of GDFT based on cardiac output parameters in patients with acute pancreatitis in the ward setting. A feasibility trial was designed to determine patient and clinician support for recruitment into an RCT of ward-based GDFT in acute pancreatitis, adherence to a GDFT protocol, safety, participant withdrawal, and to determine appropriate endpoints for a subsequent larger trial to evaluate efficacy.Methods and analysisThe GDFT in Acute Pancreatitis trial is a prospective two-centre feasibility RCT. Eligible adults admitted with new onset of acute pancreatitis will be enrolled and randomised into ward-based GDFT (n=25) or standard fluid therapy (n=25) within 6 hours from the diagnosis and continuing for the following 48 hours. Cardiac output parameters will be monitored with a non-invasive device (Cheetah NICOM; Cheetah Medical). The intervention group will consist of a protocolised GDFT approach consisting of stroke volume optimisation with crystalloid fluid boluses, while the control group will receive standard care fluid therapy as advised by the clinical team. The primary endpoint is feasibility. Secondary endpoints will include safety of the intervention, complications, mortality, admission to intensive care unit, cost and quality of life.Ethics and disseminationEthics approval was granted by the London Central Research Ethics Committee (17/LO/1235, project ID: 221872). The results of this trial will be presented to international conference with interest in general surgery and acute care and published in a peer-reviewed journal.Trial registration numberISRCTN36077283.</jats:sec

Plan piloto "Horticultura responsable". Trabajo conjunto entre INTA y SENASA

Con el objetivo de incentivar a productores de hortalizas en la implementación de buenas prácticas agrícolas, se está llevando adelante un plan piloto en Baradero. La intención fue ayudarlos a posicionar sus productos de una manera más conveniente en los distintos puntos de venta utilizados (ferias, mercados, verdulerías), a través de un logo que identifica las hortalizas provenientes de las quintas donde se está ejecutando el plan. El proyecto se inició en agosto de 2015, y es fruto del trabajo conjunto entre el INTA y el SENASA. Se realizaron capacitaciones a los productores sobre manejo integrado de plagas y enfermedades, manejo del suelo, buenas prácticas agrícolas, normativa vigente en lo referente al uso de agroquímicos, plaguicidas permitidos, desinfección del suelo, seguridad e higiene, etc. Se evaluó el desempeño ambiental de los predios a través del sistema SEPIA (Sistema de Evaluación de Impacto Ambiental Ponderado), el cual permitió elaborar diagnósticos participativos y planificar procesos de mejora. Los productores realizan un registro de las labores y agroquímicos utilizados. Se realizaron monitoreos y análisis de laboratorio para residuos de plaguicidas y contaminación microbiológica por parte del SENASA. Se diseñaron piezas comunicacionales como afiches, volantes y etiquetas para cada productor, siguiendo los requisitos de la normativa. Los productores se inscribieron en el Renspa. La iniciativa contó con el apoyo del Municipio de Baradero, quién realizó difusión en los medios de comunicación y en una Jornada Municipal de Medio Ambiente realizada en mayo del 2017. Además se cuenta con el apoyo del Programa Cambio Rural ya que los productores conformaron el grupo Altiplano en Baradero y de Pro Huerta, a través de un Proyecto Especial aprobado recientemente, y gracias al cual se podrán adquirir bienes necesarios para implementar las mejoras propuestas. Los logros obtenidos son fruto del esfuerzo conjunto de proyectos de investigación y proyectos regionales, así como de distintos organismos del Estado y programas de intervención.EEA San PedroFil: Mitidieri, Mariel Silvina . Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Delprino, María Rosa. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Fortunato, Nicolás. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Fernández, A. Senasa. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Sampietro, Esteban. Senasa. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: D´Angelcola, María Elena. Instituto Nacional de Tecnología Agropecuaria (INTA). Gerencia de Control de Gestión; ArgentinaFil: Cuellas, Marisol Virginia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Área Metropolitana de Buenos Aires; ArgentinaFil: Valenzuela, Osvaldo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Bernardez, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Piris, Estela Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Barbieri, Martín Osvaldo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Brambilla, María Virginia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Del Pardo, Cecilia Karina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Ciaponi, Mirta Mabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Taquichiri, E. Actividad privada. Productor hortícola. Baradero; ArgentinaFil: Aricoma, Alfredo. Actividad privada. Productor hortícola. Baradero; ArgentinaFil: Yucra, M. Actividad privada. Productor hortícola. Baradero; ArgentinaFil: Calva, L. Actividad privada. Productor hortícola. Baradero; ArgentinaFil: Sánchez, Florencia. Ministerio de Agroindustria. Unidad de Cambio Rural II; ArgentinaFil: Heguiabeheri, Adolfo Ricardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Piola, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; ArgentinaFil: Peña, Lorena Claudina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro; Argentin

The HRT misuse and osteoporosis epidemic: a possible future scenario

Recent controversies with hormone replacement therapy (HRT) have caused much concern in women and their health-care providers. As a result, the number of HRT users in the USA has fallen dramatically. Consequently, the potential HRT-induced reduction in fracture risk is lost so that, in the next few years, we can expect an excess of 43,008 fractures per year in women aged 65 - 69 years. In addition, the recent evidence on the merits of early initiation of HRT on cardiovascular disease risk and neurocognitive function and the effect of type and combination of hormones on breast cancer risk now require an urgent review by the regulatory authorities of their recommendations about HRT

Effects of low-dose continuous combined conjugated estrogens and medroxyprogesterone acetate on menopausal symptoms, body weight, bone density, and metabolism in postmenopausal women.

OBJECTIVE: The purpose of this study was to determine the effects of a low dose of conjugated equine estrogens and medroxyprogesterone acetate plus calcium supplementation on bone density, metabolism, body weight, and symptoms in young postmenopausal women. STUDY DESIGN: Sixty postmenopausal women, aged 45 to 56 years, were randomized in an open-label, 2-year trial that compared treatment with low-dose continuous combined hormone replacement therapy that contained 0.3 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate plus 1000 mg of calcium per day or treatment with 1000 mg of calcium per day alone. Menopausal symptoms were evaluated for the first 12 weeks of the study; bleeding profiles, bone mineral density, bone turnover, and body weight were assessed for 24 months. RESULTS: After 24 months, we evaluated 15 subjects in the control group (with a 50% drop-out rate) and 23 patients (with a 23% drop-out rate) in the low-dose continuous combined hormone replacement therapy group. Low-dose continuous combined hormone replacement therapy was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile and minimal side effects. In comparison with basal values, bone mineral density significantly (P <.05) increased by 2.72% +/- 0.3% in the low-dose continuous combined hormone replacement therapy group and decreased by 7.9% +/- 0.8% (P <.05) in the control group after 24 months, with parallel changes in bone metabolism marker action. In the control group, body mass index significantly (P <.05) increased from baseline value with a weight gain of 3%; in the low-dose continuous combined hormone replacement therapy group, the body mass index did not change after 24 months of treatment, and the 1.3% gain in body weight was not significant. CONCLUSION: Low-dose continuous combined hormone replacement therapy can alleviate subjective symptoms and minimize body transformations that are associated with early menopause and provide an effective protection against the activation of bone turnover and osteoporosis

Aerodiol: the efficacy and tolerability of intranasal estrogen administration. An overview

Estrogen supplementation, given mainly by oral or transdermal route has been shown to decrease climacteric symptoms, bone turnover, prevent postmenopausal bone loss, and significantly reduce fracture risk in both early and late postmenopausal women. Estrogens exert their principal biological effects through the actions on 2 different intracellular estrogen receptor (ER) proteins, ERa and ERb. These receptors, are completely distinct in their action. However, regardless the type of receptor involved, the response induced through the action of ER induction can be dependent also on the total dose exposure rather than estradiol concentrations at subsaturating levels. The nasal route is an effective and well-established route of drug delivery. Nasal administration produces a pulsed profile of plasma estradiol, with plasma levels rising rapidly and returning to pre-administration levels within 12 h (fall to 10% of their peak level within approximately 2 h). As a consequence, daily intranasal administration results in a pulse-like estrogen profile, rather than the relatively sustained serum levels attained with both oral and transdermal administration. In addition, exposure obtained with a single dose is compared with the exposure obtained with the same total dose given as 2 divided doses administered 12 h apart. It's known that different route of administration exert different biological and clinical RESULTS: In the years, several clinical studies have demonstrated the efficacy and safety of intranasal estradiol in the treatment of climacteric symptoms, compared with other routes of estrogen administration. Interestingly, intranasal therapy also showed a lower tendency to stimulate endometrial proliferation than the oral route, with a high incidence of atrophic endometrium maintained during the long-term study. The reduced level of stimulation of the reproductive organs produced by Aerodiol compared with oral estradiol therapy of equivalent efficacy on climacteric symptoms may be related to the pulsed kinetic profile of estradiol exposure that occurs with the intranasal route. Improvement of climacteric symptoms observed with nasal estradiol administration is comparable to that seen with transdermal or oral estrogens. A similar reduction in Kupperman Index or in the number of hot flushes was reported over a 6-month period with results similar to those of several studies performed with transdermal patches delivering estradiol or with conjugated equine estrogen. Different routes of administration may exert different results in terms of compliance, biological and clinical effects even if long term clinical trials are needed for demonstrating it. The pulsed kinetics of Aerodiol may exert less side effects in terms of coagulation cascade activation and a favourable lipid profile with less mammary tissue stimulation. These aspects became of paramount importance since the recent publication of 2 trials, Women Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS), regardless their important population selection bias and uncertain results, left important consequences in terms of HRT indication and use for both women and clinicians. In conclusion, Aerodiol introduces the new concept of pulsed estrogen therapy. Pulsed estrogen therapy is safe, well accepted and highly efficient in alleviating postmenopausal symptoms and prevent postmenopausal bone loss. Aerodiol therapy demonstrated also a lower stimulation of reproductive tissues (endometrium, breast) compared with the equivalent oral therapy, with important repercussion for future HRT strategies

Effects of oral contraceptives on bone mineral density

Osteoporosis is a major health problem that leads to a high incidence of spine, radial, and hip fractures. It is now well recognized that a chronically hypoestrogenic state increases bone turnover that, in turn, causes a critical decrease in bone mineral density (BMD), an important determinant of fracture risk. During the premenopausal period, hypogonadism can have deleterious effects on skeletal health by reducing peak bone mass or inducing precocious bone loss. In young women, hypothalamic amenorrhea, caused by gonadotropin-releasing hormone pulsatility dysregulation, is often associated with bone loss. Although the relationship between hypothalamic amenorrhea and bone density is not completely understood, the most plausible intervention for this disorder at the moment seems to be the use of hormone replacement. Oral contraceptives are associated with an improvement in BMD if assumed upon the onset of anovulatory cycles and, therefore, estrogen deficiency, but confer no benefit in healthy women with normal ovarian function. In perimenopausal oligomenorrheic women, the use of oral contraceptives seems to have bone-sparing effects. In conclusion, the protective role of oral contraceptives on bone density is biologically plausible, since this treatment represents a replacement therapy with continuous exposure to exogenous estrogens

Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists.

In a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A) leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas spine bone density and total body bone density significantly (P < 0.001 and P < 0.05, respectively) decreased after 3 and 6 months of GnRH-A administration. Conversely, in the ipriflavone-treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medically induced hypogonadism