Multivariate guard-bands and total risk assessment on multiparameter evaluations with correlated and uncorrelated measured values

Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k'). The multivariate coverage factor (k') was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.

Alopecia following oral acyclovir for the treatment of Herpes simplex keratitis

The authors report acyclovir-induced alopecia in a patient treated for herpetic keratouveitis. A 32-years-old female was diagnosed with herpetic keratouveitis. She was placed on prednisolone acetate [l%] suspension four times a day, atropine sulfate [1%] thrice a day and oral acyclovir 400 mg twice-daily Three weeks following oral acylovir, keratouveitis improved, but she developed alopecia without any drug eruptions. Oral acyclovir was discontinued. Three months later, alopecia completely resolved. Alopecia may be considered a possible complication following oral acyclovir

Encefalitis por virus varicela zoster: a propósito de un caso / Encephalitis by varicella zoster virus: a propos of a case

Se trata de una paciente blanca, femenina, de 79 años, que en el curso de un herpes zoster oftálmico comienza con manifestaciones clínicas neurológicas, que se interpretaron inicialmente como reacciones adversas al tratamiento oral con aciclovir; siendo el sistema nervioso central la localización extracutánea más frecuente de este herpes virus; y la forma más común de afectación neurológica en esta infección es una encefalitis, se pensó en esta entidad a pesar de su atipicidad no reportada en la bibliografía consultada, lo que motivó a realizar una revisión exhaustiva de este tema. La paciente evolucionó satisfactoriamente con desaparición de los síntomas y signos clínicos.

It deals with a 79-years-old, white, female patient, beginning with neurological clinical manifestations in the course of ophthalmologic zoster herpes. Initially they were interpreted as adverse reactions of the acyclovir treatment. Being the central nervous centre the most frequent extra-cutaneous location of this herpes virus, and encephalitis the most common neurologic affection in this infection, we thought about this entity despite of its atypicity, which was not found in the consulted bibliography. It motivated us to make an exhaustive review of this theme. The evolution of the patient was positive, disappearing the clinic signs and symptoms.

Insuficiência renal aguda associada ao uso de aciclovir endovenoso / Acute renal failure related to intravenous acyclovir

OBJETIVO: Avaliar a incidência e evolução da IRA em pacientes que utilizaram aciclovir por via intravenosa. MÉTODOS: Foram revisados, durante um período de sete meses consecutivos, os prontuários médicos de pacientes acima de 13 anos de idade que usaram aciclovir endovenoso (EV) por cinco dias ou mais. A IRA foi considerada quando a creatinina sérica, previamente normal, aumentava acima de 2 mg/dl. Foi analisado o tipo de tratamento instituído nos casos de IRA e sua evolução. RESULTADOS: Oitenta e cinco pacientes receberam aciclovir por via endovenosa durante o período estudado. Foram incluídos no estudo 41 pacientes. A IRA desenvolveu-se em 8 dos 41 pacientes estudados (19,5 por cento). O tempo médio para o início do aumento dos níveis séricos da creatinina, após o início do uso da droga, foi de 4,2 dias, com o pico dos níveis da creatinina sérica aparecendo entre 3 a 14 dias (média 7,1 dias). A recuperação da função renal, avaliada pela queda dos níveis da creatinina, variou de 1 a 7 dias ( média de 3,6 dias). A resolução da IRA ocorreu após medidas gerais de hidratação, aumento do tempo de infusão e ajuste da dose do aciclovir. CONCLUSÃO: O aciclovir provocou IRA em 19,5 por cento dos pacientes, que evoluíram bem em todos os casos observados, com retorno da função renal pré-tratamento após medidas de hidratação, reajuste da dose e aumento do tempo de infusão. Não houve necessidade de hemodiálise em nenhum paciente. A droga apresenta segurança de uso, desde que cuidados sejam implementados durante sua administração.

Ibn'Sina rounds

We continue these excerpts from the case records of Dr Abubakr, current resident to that august, testy and infinitely wise consultant physician, Dr Ibn 'Sina The Ibn'Sina Rounds are presentations of actual clinical situations with a moral and teaching value

Herpes simplex cutáneo-mucoso y virus de inmunodeficiencia humana (HIV) / Herpes simplex cutaneous-mucous and human immunodeficiency virus (HIV)

El virus herpes simplex (HSV) constituye una de las enfermedades que más comunmente afectan a los humanos y el déficit inmunológico producido por el virus de inmunodeficiencia humana (HIV), predispone claramente a su reactivación. A medida que cae el recuento de CD4 pueden desarrollarse lesiones herpéticas mucocutáneas severas y notarse hallazgos de características inusuales. El HSV es la infección viral que produce lesiones cutáneas en pacientes HIV(+) con mayor frecuencia. Además, el HSV puede ser un cofactor en la adquisición de la infección por HIV. El aciclovir es el agente antiviral de elección para el tratamiento del HSV en pacientes inmunodeprimidos. El foscarnet es muy efectivo cuando la infección es resistente al aciclovir