Cost-utility analysis of methylphenidate treatment for children and adolescents with ADHD in Brazil

Objective: To perform a cost-utility analysis on the treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate immediate-release (MPH-IR) in children and adolescents from Brazil. Method: A Markov model was constructed to compare MPH-IR vs. no treatment. A 24-week naturalistic study was conducted to collect transition probabilities and utility data. Effectiveness was expressed as quality-adjusted life-years (QALY), and costs reported in 2014 international dollars (I$). The perspective was the Brazilian Unified Health System as payer, and the time horizon was 6 years. Results: Of 171 patients, 73 provided information at baseline, and 56 at week 24. Considering the MPH-IR monthly cost of I$ 38, the incremental cost-effectiveness ratio (ICER) of treatment was I$ 9,103/QALY for children and I$ 11,883/QALY for adolescents. In two-way sensitivity analysis, considering one Gross National Product per capita (I$ 11,530) as willingness-to-pay, a cost of no-treatment lower than I$ 45/month would render MPH-IR a cost-saving strategy. Discussion: MPH-IR treatment of children and adolescents is cost-effective for ADHD patients from the Brazilian public health system perspective. Both patients and the healthcare system might benefit from such a strategy. Trial registration number: NCT01705613.

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.

Safety and tolerability of controlled-release oxycodone on postoperative pain in patients submitted to the oncologic head and neck surgery / Segurança e tolerabilidade da oxicodona de liberação controlada em dores pós-operatórias em pacientes submetidos à operações oncológicas de cabeça e pescoço

Objective: To evaluate the safety and tolerability of controlled-release oxycodone in the treatment of postoperative pain of head and neck oncologic resections. Methods: We conducted a prospective, observational and open study, with 83 patients with moderate to severe pain after head and neck oncological operations. All patients received general anesthesia with propofol, fentanyl and sevoflurane. Postoperatively, should they have moderate or severe pain, we began controlled-release oxycodone 20 mg 12/12 b.i.d on the first day and 10 mg b.i.d. on the second. We assessed the frequency and intensity of adverse effects, the intensity of postoperative pain by a verbal numeric scale and the use of rescue analgesia from 12 hours after administration of the drug and between 7 and 13 days after the last oxycodone dose. Results: The most common adverse events were nausea, vomiting, dizziness, pruritus, insomnia, constipation and urinary retention, most mild. No serious adverse events occurred. In less than 12 hours after the use of oxycodone, there was a significant decrease in the intensity of postoperative pain, which remained until the end of the study. The rescue medication was requested at a higher frequency when the opioid dose was reduced, or after its suspension. Conclusion: Controlled release oxycodone showed to be safe and well tolerated and caused a significant decrease in post-operative pain. .

Objetivo: avaliar a segurança e a tolerabilidade da oxicodona de liberação controlada no tratamento da dor pós-operatória de ressecções oncológicas de cabeça e pescoço. Métodos: estudo prospectivo, observacional e aberto. Foram estudados 83 pacientes com dor de moderada a intensa após operações oncológicas de cabeça e pescoço. Todos receberam anestesia geral com propofol, fentanil e sevoflurano. No pós-operatório, quando apresentaram dor moderada ou intensa, foi iniciada oxicodona de liberação controlada, 20mg de 12/12 horas no primeiro dia e 10mg de 12/12 horas no segundo dia. A frequência e a intensidade de efeitos adversos, a intensidade da dor pós-operatória pela escala verbal numérica e o uso de medicação analgésica de resgate foram avaliadas de 12/12 horas após a administração do medicamento e entre 7 e 13 dias após a última dose de oxicodona. Resultados: os efeitos adversos mais frequentes foram: náusea, vômito, tontura, prurido,insônia, constipação e retenção urinária, sendo a maioria, de leve intensidade. Não ocorreram eventos adversos graves. Em menos de 12 horas após o emprego da oxicodona, ocorreu diminuição significativa da intensidade da dor pós-operatória, que permaneceu até o final do estudo. A medicação de resgate foi solicitada em uma frequência maior quando a dose do opioide foi reduzida,ou após sua suspensão. Conclusão: aoxicodona de liberação controlada demonstrou ser segura e bem tolerada e promoveu diminuição significativa da dor pós-operatória. .

Adherencia terapéutica y flexibilidad en el uso de las insulinas basales

Desde 1921, los beneficios alcanzados por las investigaciones sobre insulinoterapia han sido constantes. Sin embargo, el temor a las hipoglucemias y la rigidez horaria para administrar la insulina aún interfieren sobre la adherencia al tratamiento, que es esencial para lograr un buen control de la glucemia y minimizar las complicaciones en los pacientes con diabetes. En este contexto, se analiza la posibilidad de utilizar un análogo de insulina ultra-lento (degludec) que posee un perfil farmacocinético prolongado y predecible por más de 24 horas. En ensayos clínicos demostró que, al administrarlo en un esquema de dosis flexible mantiene un buen control de la glucemia, sin que aumente el riesgo de hipoglucemias. Si bien en la práctica clínica es aconsejable seguir un plan establecido, la posibilidad de flexibilizar el horario en la aplicación diaria del análogo ultra-lento en caso de ser necesario, podría mejorar la adherencia en pacientes con una vida social y laboral activa y poco previsible.

Since 1921, the benefits achieved by insulin therapy research have been constant. However, the fear of a hypoglycemia incidence and rigid time schedules of insulin therapy still interfere with treatment adherence, which is essential to achieve optimal glycemic control and minimize complications in diabetic patients. The possibility of using an ultra long-acting insulin analogue (degludec), which has an extensive and predictable pharmacokinetic profile over 24 hours, is analyzed in this context. Clinical trials have shown that this ultra long-acting insulin analogue administered in a flexible dosage treatment, reached a good glycaemic control with no increase on hypoglycemia risk. Although to follow a predefined plan in clinical practice is recommended, the possibility of flexibility in day to day dosage timing of this specific insulin analogue on requirement, could improve adherence in patients with a non-predictable and active social life and workday.

Studies on development of controlled delivery of combination drug(s) to periodontal pocket.

Aim: The aim of this study to develop the controlled delivery of combination drug(s) to periodontal pocket. Materials and Methods: In the present investigation mucoadhesive gel formulations were prepared using carboxy methylcellulose (CMC), methylcellulose (MC), hydroxyethylcellulose (HEC), polyvinylpirrolidone (PVP), polycarbophil (PC), and poloxamer. Each formulation was characterized in terms of polarizing light microscopy, gelation, gel melting, hardness, compressibility, adhesiveness, cohesiveness, syringeability, adhesion to a mucin disk, rheological studies, drug release, and antibacterial activities. Addition of CMC and PVP to the gel favored hexagonal phase formation. The gelation temperature was decreased linearly with an increasing concentration of drug(s), whereas, the melting temperature increased with the concentration of drug(s). Increasing the concentrations of each polymeric component significantly increased formulation hardness, compressibility, adhesiveness, mucoadhesion, and syringeability, yet a decreased cohesiveness. Increased time of contact between the formulation and mucin significantly increased the required force of detachment. Drug release from all formulations was non-diffusion controlled and significantly decreased as the concentration of the polymer was increased, due to the concomitant increased viscosity of the formulations and the swelling kinetics of PC, following contact with the dissolution fluid. Result: Antibacterial studies revealed that a gel with 30% HEC had a growth inhibition zone on agar with all three strains. Conclusion: Formulations containing HEC exhibited superior physical characteristics for improved drug delivery to the periodontal pocket and are now the subject of long-term clinical investigations.

Sistemas biodegradáveis contendo acetato de prednisolona para administração orbitária / Biodegradable systems containing prednisolone acetate for orbital administration

OBJETIVO: O presente estudo objetivou o desenvolvimento e a avaliação de um sistema biodegradável de liberação de fármacos com característica de liberação prolongada, destinado à administração orbitária de acetato de prednisolona (AP). MÉTODOS: O sistema desenvolvido, na forma de microesferas (MEs) de poli-e-caprolactona (PCL) contendo o AP, foi obtido pelo método de evaporação de solvente. As MEs foram caracterizadas por microscopia eletrônica de varredura (MEV), calorimetria diferencial exploratória (DSC), avaliação do teor de encapsulação e pelo perfil de liberação in vitro. O perfil de liberação in vivo foi avaliado em coelhos após administração peribulbar de uma suspensão aquosa das MEs. A biocompatibilidade local do sistema foi verificada por meio de análise histopatológica da região de implantação. RESULTADOS: Após obtenção das MEs, a análise morfológica por MEV mostrou a viabilidade do método de obtenção do sistema. O teor de AP encapsulado foi de 43 ± 7 por cento e pode ser considerado bastante satisfatório. A caracterização do sistema por DSC, além de confirmar a sua estabilidade, não indicou a existência de interação entre o fármaco e o polímero. O estudo de liberação in vitro indicou que o sistema apresenta perfil de liberação prolongada. O estudo in vivo confirmou o perfil de liberação prolongado do AP a partir das MEs, sugerindo, também, a viabilidade do sistema devido à ausência de toxicidade local. CONCLUSÃO: O conjunto dos resultados obtidos neste trabalho é relevante e credencia o sistema desenvolvido como uma possível alternativa ao tratamento de orbitopatias inflamatórias.

PURPOSE: The present study aimed to evaluate an injectable extended-release formulation of prednisolone acetate (PA) for orbital administration. METHODS: Microspheres (MEs) of poly-e-caprolactone (PCL) containing PA were developed by the method of solvent evaporation. The MEs obtained were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), encapsulation efficiency and in vitro release profile. The in vivo release profile was evaluated in rabbits after periocular injection of an aqueous suspension of MEs. The local biocompatibility of the system was verified by histopathologic analysis of the deployment region. RESULTS: After MEs preparation, morphological analysis by SEM showed the feasibility of the employed method. The content of PA encapsulated was 43 ± 7 percent and can be considered as satisfactory. The system characterization by DSC technique, in addition to confirm the system stability, did not indicate the existence of interaction between the drug and the polymer. The in vitro release study showed the prolonged-release features of the developed system. Preliminary in vivo study showed the absence of local toxicity and confirmed the prolonged release profile of PA from MEs, suggesting the viability of the developed system for the treatment of orbital inflammatory diseases. CONCLUSION: The results obtained in this work are relevant and accredit the system developed as a possible alternative to the treatment of inflammatory orbitopathy.

Supraphysiological cyclic dosing of sustained release T3 in order to reset low basal body temperature

The use of sustained release tri-iodothyronine (SR-T3) in clinical practice, has gained popularity in the complementary and alternative medical community in the treatment of chronic fatigue with a protocol (WT3) pioneered by Dr. Denis Wilson. The WT3 protocol involves the use of SR-T3 taken orally by the patient every 12 hours according to a cyclic dose schedule determined by patient response. The patient is then weaned once a body temperature of 98.6 degrees F has been maintained for 3 consecutive weeks. The symptoms associated with this protocol have been given the name Wilson's Temperature Syndrome (WTS). There have been clinical studies using T3 in patients who are euthyroid based on normal TSH values. However, this treatment has created a controversy in the conventional medical community, especially with the American Thyroid Association, because it is not based on a measured deficiency of thyroid hormone. However, just as estrogen and progesterone are prescribed to regulate menstrual cycles in patients who have normal serum hormone levels, the WT3 therapy can be used to regulate metabolism despite normal serum thyroid hormone levels. SR-T3 prescription is based exclusively on low body temperature and presentation of symptoms. Decreased T3 function exerts widespread effects throughout the body. It can decrease serotonin and growth hormone levels and increase the number of adrenal hormone receptor sites. These effects may explain some of the symptoms observed in WTS. The dysregulation of neuroendocrine function may begin to explain such symptoms as alpha intrusion into slow wave sleep, decrease in blood flow to the brain, alterations in carbohydrate metabolism, fatigue, myalgia and arthralgia, depression and cognitive dysfunction. Despite all thermoregulatory control mechanisms of the body and the complex metabolic processes involved, WT3 therapy seems a valuable tool to re-establish normal body functions. We report the results of 11 patients who underwent the WT3 protocol for the treatment of CFS. All the patients improved in the five symptoms measured. All patients increased their basal temperature. The recovery time varied from 3 weeks to 12 months.

[Novel transdermal drug delivery systems]

Delivery of drugs into systemic circulation via skin has generated lots of interest during the last decade. Transdermal drug delivery systems offer many advantages over the conventional forms or sustained release delivery systems. When technically feasible, topical delivery of drug products for both local and systemic indications offer many advantages over oral or parenteral routes, such as the need for fewer administration, constant blood level, elimination of the potential for both under and overdosing, and avoidance of first-pass metabolism. Skin structure shows that it is relatively impermeable to exogenous substances and drugs. Understanding this structure will help us to improve drug delivery using prodrugs, chemical enhancers, iontophoresis, electroporation and ultrasound waves. This review will overview the structure and function of skin, the skin routes, the interactions between skin and drug delivery systems and advantageous and disadvantageous of skin as a route for drug delivery. Thus the properties and interactions of three entities-the skin, the drug and the drug delivery excipients-is going to be considered

Effect of anti-Helicobacter pylori therapy on outcome of iron-deficiency anemia: a randomized, controlled study.

BACKGROUND: Helicobacter pylori infection may play a role in iron-deficiency anemia. METHODS: In 52 patients with iron-deficiency anemia, H. pylori status was determined using rapid urease test and histology. H. pylori -positive patients were randomly assigned to receive anti- H. pylori treatment either immediately (Group I) or after a delay of one month (Group II); in addition, all patients received oral ferrous sulfate for three months. Patients testing negative for H. pylori (Group III) received only oral ferrous sulfate. Hematological parameters were tested every month. RESULTS: Of 52 patients, 32 (61.5%) had H. pylori infection. At the end of one month, median increase in hemoglobin level was lower in Group II than in Groups I and III (1.1 g/dL vs. 3.6 g/dL and 1.9 g/dL, respectively; p=0.025), as were that in serum iron (19 mcg/dL vs. 55.5 mcg/dL and 41 mcg/dL; p=0.019). During the second month, after H. pylori infection in Group II had been treated, median increase in hemoglobin in this group was comparable to those in Groups I and III (3.7 g/dL vs. 2.5 g/dL and 2.5 g/dL. CONCLUSION: In patients with iron-deficiency anemia, presence of H. pylori infection is associated with a poorer response to oral iron therapy, which improves with treatment for H. pylori infection.

Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty.

OBJECTIVE: To evaluate the efficacy of long acting GnRH analogue in improving the auxological outcome of patients with central isosexual precocious puberty (CIPP) and to determine the factors influencing the response. METHODS: Thirty-five patients (30 girls, 5 boys) with CIPP were treated with a long acting GnRH analogue, triptorelin. Final height outcomes and factors affecting treatment were analyzed. RESULTS: Treatment was started at the chronological age (CA) of 6.5 1.8 years in girls and 4.4 1.5 years in boys and continued for a period of 3.7 1.8 years in girls and 6 1.8 years in boys. Follow-up period after discontinuation of treatment was 2.2 0.5 years in girls and 2.6 0.3 years in boys. Treatment led to regression of precocious puberty and reversal of secondary sexual characteristics. There was decline in growth rate reflected by a fall in heightSD of 0.8 0.8 in girls and 2.3 0.9 in boys (p = 0.014), an even greater retardation in bone age (BA) advancement with a decrease in BA-CA of 1.7 1 years in girls and 2.7 1 years in boys and a fall in heightSDBA of 1.5 1.1 in girls and 2.1 1.6 in boys. Final height (149.8 6.9 cm in girls and 161.9 3.9 cm in boys) exceeded projected height at the onset of treatment (143.4 8.3 cm in girls and 154.3 2.7 cm in boys) by 6.4 2.4 cm in girls and 7.6 1.5 cm in boys ( p < 0.001 in both the groups). Factors influencing height gain included age at start of therapy (r = 0.715), BA-CA at the time of initiation of treatment (r = 0.734), heightSDBA at the onset of treatment ( r = 0.566) and the duration of treatment (r = 0.711). Girls treated at an age of less than 6 years (n = 9) had a greater height gain (8.7 1.6 cm versus 5.3 1.9 cm, p < 0.001) and achieved similar final height (148.7 8 cm versus 150.2 6.6 cm) in those treated after this age (n = 21). No side effects of GnRH therapy were observed in the study. CONCLUSION: Long acting GnRH therapy is effective in improving the auxological outcome of patients with CIPP. Maximum benefit is observed in girls with greater bone age advancement treated at a younger age and for a longer duration of treatment. These girls had lower bone age advance at discontinuation of treatment.

Efecto clínico de una formulación de teofilina de liberación sostenida en pacientes asmáticos moderados o severos con intercrisis / Clinic effect of a theophylline of sustained action in asthmatic patients with moderate o severe asthma

Se evaluó el efecto clínico de la formulación de teofilina de acción sostenida (Aristegui 300 mg, cápsulas) a la dosis de 9 mg/kg de peso/día (cada 12 horas) en la consulta de asma bronquial del Hospital Docente Provincial Clínico Quirúrgico de Santa Clara, en el periodo comprendido de febrero a septiembre de 1997. El tiempo de tratamiento fue de un mes y se realizaron cinco consultas. La muestra estuvo constituida por 30 pacientes asmáticos, moderados o severos. Se analizaron las variables: asistencia a cuerpo de guardia, uso de salbutamol en aerosol y se realizaron mediciones objetivas de la función pulmonar a todos los pacientes en las diferentes consultas. Con la utilización de la formulación disminuyeron significativamente el flujo espiratorio pico, el volumen espiratorio forzado en un segundo y el flujo medio espiratorio máximo y existió baja incidencia de efectos adversos.

The effects of depot leuprorelin on IVF.

The trial studied the effects of depot leuprorelin on the IVF cycle and was done on nine couples. A single intramuscular injection of depot leuprorelin was given to the woman a couple days before ovulation. Seven days after ovulation, the serum progesterone level was measured and showed the same normal level as the natural ovulatory cycle. The progesterone levels varied from 12.59 to 96.0 ng/ml. On day three of the menstruation, the hormonal profiles showed a complete pituitary and ovarian suppression. FSH, LH and estrogen levels were less than 4.1 mIU/ml, 2.8 mIU/ml and 9.4 pg/ml respectively. The hMG stimulation took 11 days on average (9-15 days). A hundred and two oocytes were retrieved and among these there were 86 mature oocytes (84.3%). All oocytes were inseminated despite prematurity and resulted in 82.35 per cent fertilization. Normal fertilization occurred in 77.45 per cent (79/102). Good embryos developed in 58.23 per cent (46/79). No more than three embryos were transferred. Four women conceived, among them there was a set of twins. The implantation rate was 44.44 per cent (4/9). One abortion was found in the early first trimester. The take home baby rate was 33.33 per cent (3/9).

A comparative evaluation of pharmacokinetics of conventional and slow-release carbamazepine formulation in newly treated patients of epilepsy: a random evaluation.

Study was conducted to compare the pharmacokinetic profile of conventional and slow-release carbamazepine formulations in Indian epileptic patients. Twenty consecutive untreated patients of partial seizures were randomly assigned to receive either conventional carbamazepine (200 mg thrice a day) or slow-release carbamazepine formulation (200 mg thrice a day), 10 patients in each group. The serum carbamazepine concentrations were measured on 10th day and 20th day of treatment. The blood samples were collected before the morning dose. In the conventional treatment group five patients experienced side effects as compared to two in the slow-release group. On 10th day mean serum carbamazepine levels were significantly higher in conventional group (8.27 +/- 1.39 micrograms/ml) in comparison to slow release group (4.28 +/- 3.89 micrograms/ml). The difference was statistically significant (p < 0.05). On 20th day carbamazepine levels fell significantly in conventional group only (8.27 +/- 1.39 micrograms/ml to 5.76 +/- 2.32 micrograms/ml, p < 0.05). At this stage the difference in mean carbamazepine levels of two groups became insignificant (p < 0.05). In conclusion, controlled release formulations provide more steady serum concentrations of carbamazepine along with better tolerability.

Experiencia en el empleo de dosis alternas de neurolépticos de depósito en el tratamiento de las psicosis crónicas / Experience in using alternate doses of depositing neuroleptics in the treatment of chronic psychoses

Se revisan los antecedentes clínios de 38 pacientes, usuarios de neurolépticos de depósito de larga data, controlados en la Unidad de Psicofármacos del Servicio de Psiquiatría de Valdivia. Pacientes mayoritariamente esquizofrénicos, de sexo femenino, con 43,3 años de edad promedio. un 63,2 por ciento presentaba quejas y efectos secundarios ligados al tratamiento. Los pacientes reciben alternada y sucesivamente dos diferentes dosis del Neuroléptico de Depósito sin modificar la periodicidad en uso; una de las dosis será la empleada con anterioridad (dosis original), la otra será mayor o menor que la dosis original. El propósito en la gran mayoría fue minimizar los efectos secundarios y obtener un mejor ajuste farmacológico individual del paciente. La revisión consideró los pacientes con a lo menos 6 meses de exposición al régimen de dosis alternas; al evaluar los resultados los pacientes se dividieron en 4 grupos: la dosis de mantención se fijó en una dosis inferior a la original (34,5 por ciento), permanecen con dosis alternas (36,8 por ciento), en ambos grupos los pacientes se han mantenido estables. En el 13,2 por ciento se debió regresar a la dosis original y el 15,5 por ciento recibía una dosis mayor que la original