Clinical comparison between a percutaneous hydraulic pressure delivery system and balloon tamp system using high-viscosity cement for the treatment of osteoporotic vertebral compression fractures

OBJECTIVES: Osteoporotic vertebral compression fractures (OVCFs) affect the elderly population, especially postmenopausal women. Percutaneous kyphoplasty is designed to treat painful vertebral compression fractures for which conservative therapy has been unsuccessful. High-viscosity cement can be injected by either a hydraulic pressure delivery system (HPDS) or a balloon tamp system (BTS). Therefore, the purpose of this study was to compare the safety and clinical outcomes of these two systems. METHODS: A random, multicenter, prospective study was performed. Clinical and radiological assessments were carried out, including assessments of general surgery information, visual analog scale, quality of life, cement leakage, and height and angle restoration. RESULTS: Using either the HPDS or BTS to inject high-viscosity cement effectively relieved pain and improved the patients' quality of life immediately, and these effects lasted at least two years. The HPDS using high-viscosity cement reduced cost, surgery time, and radiation exposure and showed similar clinical results to those of the BTS. In addition, the leakage rate and the incidence of adjacent vertebral fractures after the HPDS treatment were reduced compared with those after treatment using the classic vertebroplasty devices. However, the BTS had better height and angle restoration abilities. CONCLUSIONS: The percutaneous HPDS with high-viscosity cement has similar clinical outcomes to those of traditional procedures in the treatment of vertebral fractures in the elderly. The HPDS with high-viscosity cement is better than the BTS in the treatment of mild and moderate OVCFs and could be an alternative method for the treatment of severe OVCFs.

Ocular delivery of moxifloxacin-loaded liposomes / Perfil de liberação ocular de lipossomas contendo moxifloxacino

ABSTRACT Purpose: To determine the release profile of moxifloxacin encapsulated in liposomes in the aqueous humor as a controlled release system for intracameral application. Methods: Liposomes containing moxifloxacin were obtained using the lipid film hydration method and were characterized by particle size and encapsulation efficiency. Female rabbits were used for the in vivo profile release study. Liposomes containing moxifloxacin was injected into the anterior chamber of the right eye of each animal. The rabbits were divided into five groups, and a sample of aqueous humor was collected 2, 4, 8, 24, and 48 h after administration of liposomes containing moxifloxacin administration. Moxifloxacin concentrations in the aqueous humor were analyzed using high-performance liquid chromatography. Results: The average size of the liposomes containing moxifloxacin was 60.5 ± 0.72 nm with a particle size distribution of 0.307. The encapsulation efficiency of moxifloxacin in liposomes was 92.24 ± 0.24%. The results of an in vivo release study of liposomes containing moxifloxacin, showed that the maximum moxifloxacin concentration was achieved within the first 2 h after administration (5.27 ± 1.09 mg/mL) and was followed by a decrease in intracameral concentration (0.35 ± 0.05 mg/mL) until the 24 h mark. Conclusions: The in vivo experiments resulted in liposomes containing moxifloxacin that were homogenous in size and exhibited high drug encapsulation efficiency. The results indicate that liposomes containing moxifloxacin offers a satisfactory aqueous humor release profile after intracameral application.

RESUMO Objetivo: Determinar o perfil de liberação, no humor aquoso, de moxifloxacino encapsulado em lipossomas como um sistema de liberação controlada para aplicação intracameral. Métodos: Lipossomas contendo moxifloxacino foram obtidos através do método de hidratação do filme lipídico e caracterizados por tamanho da partícula e eficiência de encapsulação. Utilizaram-se coelhos fêmeas foram para o estudo do perfil de liberação in vivo. Lipossomas contendo moxifloxacino foram injetados na câmara anterior do olho direito de cada animal. Os coelhos foram divididos em cinco grupos, e uma amostra de humor aquoso foi coletada 2, 4, 8, 24 e 48 h após a administração de lipossomas contendo moxifloxacino. As concentrações de moxifloxacino no humor aquoso foram analisadas usando cromatografia líquida de alta eficiência. Resultados: O tamanho médio dos lipossomas contendo moxifloxacino foi de 60,5 ± 0,72 nm com uma distribuição de tamanho de partícula de 0,307. A eficiência de encapsulação de moxifloxacino nos lipossomas foi de 92,24 ± 0,24. Os resultados de um estudo de liberação in vivo de lipossomas contendo moxifloxacino, mostraram que a concentração máxima de moxifloxacino foi atingida dentro das primeiras 2 h após sua administração (5,27 ± 1,09 mg/mL) e foi seguida de um decréscimo na concentração intracameral (0,35 ± 0,05 mg/mL) até a marca de 24 h. Conclusão: Os experimentos in vivo resultaram em lipossomas contendo moxifloxacino que eram homogêneos em tamanho e exibiam alta eficiência de encapsulação do fármaco. Os resultados indicam que lipossomas contendo moxifloxacino oferecem um perfil de liberação de humor aquoso satisfatório após a aplicação intracameral.

A prototype single-port device for pressurized intraperitoneal aerosol chemotherapy. Technical feasibility and local drug distribution

Abstract Purpose: To evaluate the technical feasibility and homogeneity of drug distribution of pressurized intraperitoneal aerosol chemotherapy (PIPAC) based on a novel process of intraperitoneal drug application (multidirectional aerosolization). Methods: This was an in vivo experimental study in pigs. A single-port device was manufactured at the smallest diameter possible for multidirectional aerosolization of the chemotherapeutic drug under positive intraperitoneal pressure. Four domestic pigs were used in the study, one control animal that received multidirectional microjets of 9 mL/sec for 30 min and three animals that received multidirectional aerosolization (pig 02: 9 mL/sec for 30 min; pigs 03 and 04: 3 mL/sec for 15 min). Aerosolized silver nitrate solution was applied for anatomopathological evaluation of intraperitoneal drug distribution. Results: Injection time was able to maintain the pneumoperitoneum pressure below 20 mmHg. The rate of moderate silver nitrate staining was 45.4% for pig 01, 36.3% for pig 02, 36.3% for pig 03, and 72.7% for pig 04. Conclusions: Intra-abdominal drug distribution had a broad pattern, especially in animals exposed to the drug for 30 min. Our sample of only four animals was not large enough to demonstrate an association between aerosolization and a higher silver nitrate concentration in the stained abdominal regions.

Contact lenses as drug controlled release systems: a narrative review / As lentes de contacto como sistema de libertação controlada de fármacos: uma revisão narrativa

ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs) have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS). Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.

RESUMO A forma mais frequente de aplicação terapêutica em oftalmologia consiste na instilação de gotas oculares, mas dadas as limitações anatómicas e fisiológicas do olho, é necessária dosagem frequente com possível repercussão na adesão do paciente à terapêutica. Nas últimas décadas, as lentes de contacto (CLs) têm surgido como um potencial sistema de libertação controlada de fármacos na superfície ocular (DCRS) para correção do erro refrativo. Está em curso uma extensa investigação para entender a melhor forma de modificar as CLs, de modo a aumentar o tempo de residência e a biodisponibilidade do medicamento na superfície ocular dentro de níveis terapêuticos. Ao corrigirem a ametropia, estes dispositivos poderão simultaneamente desempenhar um papel na gestão de perturbações oftalmológicas, tais como a síndrome do olho seco, glaucoma, alergia ocular e infecção corneana, que podem comprometer o porte seguro e confortável das CLs. Nesta revisão narrativa, os autores explicam como as estruturas da superfície ocular determinam a difusão de fármacos no olho e sintetizam as estratégias para aumentar a permanência e biodisponibilidade dos mesmos. Em seguida, apresentam os resultados e as aplicações clínicas das CLs embebidas em fármacos, como DCRS, através da incorporação de barreiras de difusão, de monómeros funcionais, da liberação controlada por iões, da impressão molecular, de nanopartículas e pelo processo camada sobre camada. Os autores concluem avaliando o impacto destes novos sistemas de entrega de agentes farmacológicos ao melhorar o seu transporte no tecido alvo, reduzindo a sua absorção sistémica e os seus efeitos colaterais indesejáveis, e discutem perspectivas futuras.

In vitro and in vivo evaluation of nano-based films for buccal delivery of zolpidem

Abstract Insomnia is becoming increasingly prevalent in the world general population. Therapies used by patients include over-the-counter therapies, herbal and dietary supplements, and pharmacological or nonpharmacological treatments. Among these, zolpidem is a pharmacological treatment popularly used for insomnia. Zolpidem is well tolerated and especially efficacious for initiation of sleep, and therefore is effective for the treatment of sleep-onset insomnia. The purpose of the present study was to design and evaluate zolpidem nanoparticle-impregnated buccal films to prolong the duration of its action. Zolpidem nanospheres were prepared by double emulsion solvent evaporation and then loaded into buccoadhesive films (Z1-Z4) comprised of different concentrations of HPMC K100, Eudragit® RL 100, and carbopol 974P. The prepared films were characterized for physicomechanical properties, mucoadhesion, percent hydration, in vitro drug release, ex vivo permeation, and in vivo studies. In vitro drug release was found to depend upon film composition. Ex vivo studies showed that film Z4 had the highest flux. In vivo studies revealed that administration of zolpidem nanosphere-impregnated film enhanced absorption of the drug (p < 0.0001), with a higher peak plasma concentration (52.54 ± 8.22 ng/mL) and area under the curve from time 0 to α (236.00 ± 39.51 ng.h/mL) than oral administration. The increase in time taken to reach the maximum drug concentration (1.5 h) further signifies the potential of these films to provide prolonged drug release. Given these promising results, we concluded that these buccal films could be an alternative route for effective zolpidem delivery.

Hospitalización por episodios de cianosis en recién nacidos de edad gestacional igual o mayor a 34 semanas / Hospital Admissions due to cyanosis episodes in newborns with gestational age of 34 weeks or more

Objetivo: Caracterizar la hospitalización por episodios de cianosis en recién nacidos (RN) > 34 semanas. Pacientes y método: Estudio retrospectivo que incluyó la totalidad de los RN hospitalizados por episodios de cianosis entre enero de 2007 y diciembre de 2012. En ellos se aplicaron 2 protocolos de estudio que consideraban exámenes de primera y segunda línea; estos últimos ante la recurrencia de eventos. El protocolo de primera línea consideró exámenes bioquímicos generales, radiografía de tórax y ecocardiografía en casos seleccionados, en tanto que el protocolo de segunda línea incluyó electroencefalograma, electrocardiograma, resonancia magnética nuclear encefálica, screening metabólico ampliado, ácido pirúvico, ácido láctico y en caso de convulsiones, citoquímico y cultivo de líquido cefalorraquídeo y reacción en cadena de la polimerasa para herpes. Resultados: Noventa y ocho de un total de 3.454 (2,8%) RN hospitalizados ingresaron por episodio de cianosis. La edad gestacional (EG) fue 37,8 + 1,36 semanas; peso al nacimiento: 3145 + 477 g. Edad materna: 32 + 4,8 años. El 19,4% de las madres tenía antecedentes mórbidos: diabetes gestacional (8,1%), síndrome hipertensivo del embarazo (5,1%), colestasia intrahepática (3,1%) y retardo del crecimiento (3,1%). Género: 48,8% masculino, parto por cesárea: 68,4%. Edad al ingreso: 1,9 + 1,4 días; duración de la hospitalización: 4,2 + 4,2 días. En todos los pacientes se practicaron exámenes de primera línea y en el 39,8% exámenes de segunda línea. En el 21,4% de los RN se identificó una causa, siendo el síndrome convulsivo el más frecuente (33%). Los RN con diagnóstico asociado presentaron 3,8 + 2,7 episodios de cianosis versus 1,5 + 2,4 en el grupo sin diagnóstico (NS). El 15,4% se fueron de alta con monitor; no hubo reingresos. Conclusión: La incidencia de hospitalización neonatal por episodios de cianosis fue de 6 por 1.000 RN vivos. Solo en cerca de un 20% de ellos es posible identificar una causa, siendo la más frecuente el síndrome convulsivo.

Objectives: A retrospective study was performed between January 2007 and December 2012 to assess the admission rates of newborns due to episodes of cyanosis Patients and method: Retrospective study that included all the newborns hospitalized with episodes of cyanosis between January 2007 and December 2012. In them were employed two study protocols that considered first and second line tests, the latter in view of recurrence of events. The first line protocol considered general biochemical tests, chest x-ray and echocardiography in selected cases, while the second line protocol included electroencephalogram, electrocardiogram, nuclear magnetic resonance of the brain, expanded metabolic screening, pyruvic acid, lactic acid, and in case of seizures, cytochemical, and culture of cerebrospinal fluid (CSF) and PCR (polymerase chain reaction) for herpes. Results: A total of 98 (2.8%) out of 3,454 newborns were admitted due to episodes of cyanosis. Gestational age: 37.8 + 1.4 weeks, birth weight: 3,145 + 477 g. Maternal age: 32 + 4.8 years. Disease was present in 19.4% of mothers; gestational diabetes (8.1%), pregnancy induced hypertension (5.1%), intrahepatic cholestasis (3.1%), and intrauterine growth retardation (3.1%). Gender: 48.8% male, 51.2% female (NS). Birth: caesarean section, 68.4%, and vaginal delivery, 31.6%. Age on admission 1.9 + 1.4 days. Hospital stay: 4.2 + 4.2 days. First line tests were performed in 100% of patients with 39.8% fulfilling the criteria for second line study. A condition was detected in 21.4%, with convulsive syndrome was the most frequent (33%). Newborns with an identified condition had 3.8 + 2.7episodes versus 1.5 + 2,4 in those without diagnosis (NS). A home oxygen monitor was given to 15.4%. There were no re-admissions. Conclusions: Most newborns admitted due to cyanosis are discharged with a condition of unknown origin. In this study, convulsive syndrome was the most frequent cause.

Variación secular de los nacimientos, peso y longitud al nacer: perspectiva local / Secular variation of births, weight and length at birth: Local perspective

Objetivo: Analizar la evolución de los nacimientos y medidas antropométricas al nacer entre 1974-2011 en el Hospital de Limache, Región de Valparaíso, Chile. Pacientes y métodos: Se construyeron series de tiempo de nacimientos, peso y longitud al nacer, peso y talla baja al nacer. Se modelaron las tendencias con regresiones multivariadas usándose splines para representar los cambios de tendencia por década. Resultados: La serie comprende 17.574 nacimientos. Hubo un aumento de los nacimientos/año en los 70 (30/año) y disminución de 17 y 22 nacimientos/año en los 80 y 90 (p < 0,001); después, sin tendencia significativa. Los recién nacidos entre 2000-2011 registran 266 g más que los de la década de los 70 (p < 0,001), alcanzando actualmente en promedio 3.530 g. El bajo peso al nacer disminuyó de 8% en los 70 a 1,1% después de 2000. La longitud al nacer incrementó 1 cm en 37 años, con disminución de la talla baja de 7,6% a 2,1% en el periodo estudiado. Conclusión: Los nacimientos en el Hospital de Limache disminuyeron y las medidas antropométricas al nacer mejoraron; sin embargo, hay que considerar los posibles sesgos que distorsionan estas estimaciones.

Objective: To analyse the outcomes of births and anthropometric measurements at birth of children born between 1974 and 2011 at Limache Hospital (Valparaíso, Chile). Patients and method: Times series were constructed of births, weight and length at birth, and low weight and length at birth. The trend was modelled with linear and logistical regressions using splines to represent breaks in the trend by decade. Results: The series includes 17,574 births. There was an increase in births per year in the 1970s (30/year) and declines in them to 17 and 22 births/year in the 1980s and 1990s, respectively (P < .001), with no significant trend thereafter. Newborns from 2000 to 2011 weighed 266 grams more than those in the 1970s (P < .001), and have now reached a mean weight of 3,530 g. Low birthweight fell from 8% in the 1970s to 1.1% after 2000. Birth length increased by 1 cm in the 37 years studied, with a reduction of low birth length from 7.6% to 2.1% during the period. Conclusion: Live births in the Limache Hospital declined, and anthropometric measurements at birth improved in the years analysed. This information is useful in developing interventions, taking into account the possible selection biases that could distort these estimates and their interpretation.

Rabdomiólisis grave secundaria a deshidratación hipernatrémica / Severe rhabdomyolysis secondary to severe hypernatraemic dehydration

Introducción: La rabdomiólisis es una enfermedad poco frecuente en pediatría. El objetivo es presentar un paciente en el que se desarrolló secundario a una deshidratación hipernatrémica grave tras una diarrea aguda. Caso clínico: Lactante de 11 meses que consultó por fiebre, vómitos, diarrea y anuria. Presentó convulsión tónico-clónica autolimitada. Ingresó en mal estado general, severamente deshidratado, con escasa reactividad. En las pruebas complementarias destacó acidosis metabólica grave, hipernatremia e insuficiencia renal prerrenal. Al tercer día apreció leve hipotonía axial y elevación de creatín fosfokinasa 75.076 UI/l, interpretado como rabdomiólisis. Se inició hiperhidratación y alcalinización sistémica, con buena respuesta clínica y bioquímica, siendo dado de alta sin secuelas motoras. Conclusiones: La hipernatremia grave está descrita como causa rara de rabdomiólisis e insuficiencia renal. En pacientes críticos es importante un alto índice de sospecha de rabdomiólisis y determinación seriada de la creatín fosfokinasa para su detección y tratamiento precoz.

Introduction: Rhabdomyolysis is a rare paediatric condition. The case is presented of a patient in whom this developed secondary to severe hypernatraemic dehydration following acute diarrhoea. Case report: Infant 11 months of age who presented with vomiting, fever, diarrhoea and anuria for 15 hours. Parents reported adequate preparation of artificial formula and oral rehydration solution. He was admitted with malaise, severe dehydration signs and symptoms, cyanosis, and low reactivity. The laboratory tests highlighted severe metabolic acidosis, hypernatraemia and pre-renal kidney failure (Sodium [Na] plasma 181 mEq/L, urine density> 1030). He was managed in Intensive Care Unit with gradual clinical and renal function improvement. On the third day, slight axial hypotonia and elevated cell lysis enzymes (creatine phosphokinase 75,076 IU/L) were observed, interpreted as rhabdomyolysis. He was treated with intravenous rehydration up to 1.5 times the basal requirements, and he showed a good clinical and biochemical response, being discharged 12 days after admission without motor sequelae. Conclusions: Severe hypernatraemia is described as a rare cause of rhabdomyolysis and renal failure. In critically ill patients, it is important to have a high index of suspicion for rhabdomyolysis and performing serial determinations of creatine phosphokinase for early detection and treatment.

Thyroid function, autoimmunity and nodules in hematological malignancies

Objective Hematological malignancies encompass a large spectrum of disease entities whose treatment by chemo/radiotherapy could lead to thyroid complications. To the best of our knowledge, no study has simultaneously addressed thyroid function, autoimmunity and nodularity. Therefore, we decided to conduct one.Materials and methods We evaluated 82 Caucasian patients (36 women and 46 men), who were treated at our Oncology division for hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphatic leukemia, non-Hodgkin lymphoma and polycythemia vera) and compared them with a control group of 104 patients. Patients who had received or were receiving external head/neck radiotherapy were excluded. All oncological patients and control individuals underwent thyroid ultrasonography and thyroid function and autoimmunity tests.Results A lower prevalence of enlarged thyroid and nodules were found in patients with respect to controls. The rate of thyroid nodules was the highest in multiple myeloma and polycythemia vera, and the lowest in chronic lymphatic leukemia. Non-Hodgkin lymphoma patients had the smallest thyroid nodules while men with multiple myeloma the biggest ones. No patient had hypothyroidism, while 5.6% of patients had subclinical hyperthyroidism. In contrast, within the control group the rates of hypothyroidism and hyperthyroidism, overt and subclinical, were 3.8%, 20.2%, 0% and 0% respectively. Moreover, the overall rate of thyroid autoantibody positiveness in patients was significantly lower than controls.Conclusion In our experience, we found a significantly lower prevalence of thyroid abnormalities in hematologic patients who underwent chemotherapy, but not radiotherapy, with respect to controls. Arch Endocrinol Metab. 2015;59(3):236-44.