Bilateral Optic Neuritis due to Isoniazid (INH).

Optic nerve involvement is a rare side effect of isoniazid (INH) and has not been described in children. We describe this adverse reaction in a 10-year-old boy, who was treated for tuberculous meningitis. The patient showed almost complete resolution following withdrawal of INH and administration of pyridoxine and steroids.

Off-label drug use in a pediatric intensive care unit.

Objective. To determine the extent and nature of off-label drug use in children admitted to a Pediatric Intensive Care Unit (PICU) Methods. This prospective exploratory study was conducted in a tertiary care hospital in a metropolitan city in India after obtaining clearance from the institutional ethics committee. Subjects admitted in PICU from February-August 2006 were enrolled in the study. In addition to the demographic data and diagnosis, details of drugs prescribed (name, dose and route and frequency of administration) were obtained from hospital records. British National Formulary 2005 was used to determine if the prescriptions were off-label and if so, they were categorized as off-label for age, indication, dosage or frequency and route of administration. Descriptive statistics was used to determine the proportion of off-label drug use. Fischer’s exact test was used to determine if there was significant difference (P<0.05) in off-label use between patients with multiple system affection and those with single system affection and between those requiring artificial ventilatory support and those not requiring it. Results. Three hundred subjects received 2237 analyzable prescriptions. Of these 1579 (70.58%) prescriptions were offlabel in nature. Off-label drug use was prevalent in all age-groups and in all systemic afflictions. The proportion of off-label drug use was not influenced by severity of illness, as judged by involvement of multiple systems or need for ventilatory support. The list of off-label drugs used included old as well as new molecules. Most commonly used drugs in PICU were also the most common off-label drugs. Conclusion. Off-label drug use is highly prevalent in PICU settings.

Informed consent documents submitted for initial review: What do they state about compensation for injured research participants.

Background : Research carries a small but definite risk of injury to participants. However, there is no unanimity amongst the stakeholders regarding the nature and extent of compensation to be provided to an injured participant. Aims : To determine the extent to which issues related to the provision of free treatment and compensation for research-related injury are addressed in the protocols submitted to Ethics Committees (ECs). Setting and Design : Retrospective review of protocols submitted to two ECs in India. Material and Methods : Initial protocols submitted to two ECs during the calendar years 2007 and 2008 were reviewed. Statements related to treatment and compensations for study-related injury were studied for adequacy regarding provisions for free emergency treatment, and free treatment and compensation for research-related injury. Presence of special conditions, exclusions, and caveats, if any, were noted. Statistical Analysis Used : The proportion of protocols providing free treatment and compensation for research-related injury was presented as a percentage. Results : The Informed Consent Documents (ICD) of 138 protocols were accessed. These included 115 (83.33%) industry-sponsored, 20 (14.49%) government-sponsored and three (2.17%) investigator-initiated projects. Forty-six (33.33%) intended to provide free treatment for a trial-related injury. Forty-two (30.43%) projects did not have any policy about providing treatment for a trial-related injury, whereas several others included statements that intended to provide treatment, but with certain restrictions. Thirty-three (23.91%) ICDs had statements indicating that there was no provision for compensation and 65(47.10%) ICDs stated nothing on the issue. Conclusion : ICDs submitted for initial review are not in conformity with the provisions for treatment of and compensation for research-related injuries enunciated in national guidelines and draft guidelines.

Can indian classical instrumental music reduce pain felt during venepuncture.

Objective. To determine comparative efficacy of local anesthetic cream, Indian classical instrumental music and placebo, in reducing pain due to venepuncture in children. Methods. Children aged 5-12yr requiring venepuncture were enrolled in a prospective randomized clinical trial conducted at a tertiary care center. They were randomly assigned to 3 groups: local anesthetic (LA), music or placebo (control) group. Eutactic mixture of local anesthetic agents (EMLA) and Indian classical instrumental music (raaga-Todi) were used in the first 2 groups, respectively. Pain was assessed independently by parent, patient, investigator and an independent observer at the time of insertion of the cannula (0 min) and at 1- and 5 min after the insertion using a Visual Analog Scale (VAS). Kruskal- Wallis and Mann-Whitney U tests were used to assess the difference amongst the VAS scores. Results. Fifty subjects were enrolled in each group. Significantly higher VAS scores were noted in control (placebo) group by all the categories of observers (parent, patient, investigator, independent observer) at all time points. The VAS scores obtained in LA group were lowest at all time points. However, the difference between VAS scores in LA group were significantly lower than those in music group only at some time-points and with some categories of observers (parent: 1min; investigator: 0-, 1-, 5 min and independent observer: 5 min). Conclusion. Pain experienced during venepuncture can be significantly reduced by using EMLA or Indian classical instrumental music. The difference between VAS scores with LA and music is not always significant. Hence, the choice between EMLA and music could be dictated by logistical factors.

Off-label drug use in children.

OBJECTIVE: To determine the extent and nature of off-label drug use in children admitted to a pediatric general ward in a tertiary health care centre METHODS: Consecutive patients aged 1 mo-12 years admitted to the general wards in a tertiary care center in Mumbai over a two-month period were prospectively enrolled in the study. British National Formulary [BNF] version 2005 was used to ascertain if the drug use was "off-label". The off-label use was categorized as: administration of a greater/lesser dose, administration at a higher/lower frequency than indicated, administration for indications not described, administration of a drug not licensed for use in that age group and/ or use of alternative routes of administration. Descriptive statistics was used for calculating the off-label drug use. RESULTS: Two thousand prescriptions received by 600 subjects (M:F= 1.47:1) were analyzed. One thousand and forty-five (50.62%) prescriptions were off-label. The off-label drug use rate was 1.74+/-1.56 per patient. The maximum rate of off-label drugs was in infants (2.33/patient). 'alteration in dosage' was by far the commonest reason for off-label use; followed by 'age' and 'indication'. Furosemide (i. v.), diazepam (i.v), cefotaxime (i.v), ethambutol (tab) and prednisolone (tab) were the five commonest off-label drugs used in the study population. CONCLUSIONS: Off-label drug use was highly prevalent in general pediatric ward of a tertiary care hospital in India.

Necrotizing adenoviral pneumonia: manifestation of nosocomial infection in pediatric intensive care unit.

A 5-year-old child admitted in the pediatric intensive care unit developed fever and crepitations in the chest on 6(th) day of admission. She succumbed to her illness depite administration of adequate supportive and ventilatory care and anti-microbial therapy. At autopsy, she was diagnosed to have chronic ligneous type of tuberculous meningitis and necrotizing adnoviral pneumonia. There are hardly any reports of nosocomial adenoviral pneumonia from Indian centers. The case serves to remind intensivists to consider this diagnosis so that appropriate therapeutic adjustments and measures to prevent the spread of infection to other critically ill subjects are initiated.

Clinical research in India: great expectations?

India is considered as a preferred site for conducting global clinical trials. Existence of a large treatment-naïve population, availability of English-speaking, skilled doctors, plenty of clinical material, and cost-savings are obvious advantages for carrying out clinical research in India. However, challenges exist at various levels. Lack of formal training in bioethics and research methodology, heavy burden of clinical duties and sub-optimal administrative support restrict investigators. Absence of oversight of functioning of ethics committees (ECs) and lack of mechanisms for ensuring quality of ethics review heighten societal concerns about safety of participants. Conducting research on issues not relevant to local needs and failure to ensure post-trial access further enhance society's cynicism. These issues need to be tackled through capacity building, training of investigators and EC members, strengthening of EC functioning and encouraging greater community participation.