Physician Health in the Times of COVID-19.

BACKGROUND AND OBJECTIVES: A virtual registry study evaluating real world evidence on physicians' use of prophylactic regimens for protection against SARS-CoV-2. This paper summarizes the interim results. METHODS: Asymptomatic physicians at risk of acquiring SARS-CoV-2 responded to online questions at baseline and 7 weeks post-baseline. Baseline data included demographics, prophylaxis regimen (including "no prophylaxis") and start date. Participants who provided complete week-7 data (information on type of health facility [COVID/Non-COVID], number of presumed/confirmed cases exposed to, PPE use, SARS-CoV-2 testing and symptoms, regimen adherence and intercurrent illness) comprised the Completer population. Limited data (regimen adherence, SARS-CoV-2 testing) was collected for participants who failed to provide complete week7 data. Those providing limited/complete information comprised the Evaluable population. RESULTS: Of 369 enrolled participants, 182 (mean age 42±11.05 years) comprised the Evaluable population. They showed a male preponderance (67.6%). Practitioners from Maharashtra (59.9%) and specialties of Pediatrics, Internal Medicine, Anesthesiology and Critical Care (63.2%) accounted for the majority. ICMR's HCQ prophylaxis regimen was initiated by 125 (68.7%) participants with 31 (17%) initiating 'No prophylaxis'. The highest adherence was for the ICMRregimen (87.2%). In the Completer population comprising 150 participants, 87 were exposed to presumed (81) and/or confirmed cases (60). Most exposures to confirmed cases (49, 81.7%) were high-risk. PPE use was generally high (75-100%). Most participants (94.7%) did not report an AE. The proportions with an AE was similar with ICMR regimen (5.9%) and no prophylaxis (6.5%). INTERPRETATION AND CONCLUSIONS: Physicians in India preferred ICMR's HCQ regimen. The regimen appears to be safe and associated with a high level of adherence.

Congenital Hypothyroidism: An Unusual Combination of Biochemical Abnormalities.

A forty-five-day-old female infant presented with prolonged jaundice with clinical features suggestive of congenital hypothyroidism (CHT). On investigations, the infant was noted to have indirect hyperbilirubinemia (13.8 mg/dl) with increased levels of AST (298 IU/dl) and ALT (174 IU/dl) in the serum. The child had low levels of free T3 (<1 pg/ml) and free T4 (0.4 ng/dl) secondary to thyroid agenesis detected on radionuclide scan and ultrasonography of the neck and raised levels of TSH (>500 microIU/ml) in the serum. The combination of indirect hyperbilirubinemia and raised levels of hepatic transaminases has not been reported in babies with CHT. Following institution of oral thyroxin therapy, the serum bilirubin levels ameliorated (2.9 mg/dl) considerably by 15 days of therapy and the serum levels of AST (40 IU/dl) and ALT (20 IU/dl) got normalized. The case demonstrates that raised levels of hepatic transaminases can occur in infants with CHT and these can resolve just with thyroxin therapy, obviating the need for extensive investigative laboratory work-up.

Sildenafil in pediatric pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.

Awareness about and views of parents on the off-label drug use in children.

BACKGROUND: Off-label use of drugs is widely prevalent in children mainly due to a limited data generated in children during drug development process. Parents play a critical role in giving consent for their child to participate in clinical trials. Very few studies have assessed the opinion of the parents regarding such use and permitting their child to participate in clinical trials. OBJECTIVE: In view of lack of information about the awareness among parents regarding both off-label drug use in children as well as about allowing their child to participate in clinical research especially from a developing country, this study was conducted. METHODS: Adults accompanying patients in a tertiary care hospital were administered a validated, structured questionnaire following written informed consent. The questionnaire consisted of 18 items broadly divided into 5 themes - parental views on safety and labelled use of drugs in children, awareness of off-label drug use in children, communication from healthcare worker about it, parental views on off-label drug use in children and willingness to allow their child to participate in a clinical trial. Chi-square or Fisher's exact probability test and McNemar's test were used for analysis. RESULTS: Initially, a majority of the participants felt that the drugs used in children in hospital (89.5%) and prescribed by a family physician (80.3%) were either safe or extremely safe while after the concept of off-label drug use is explained, a significant reduction in the proportion (59.3% in hospital and 59.8% by family physician) of parents felt the same. Only 30% parents were aware of off-label drug use in children. Ninety-three percent of the parents wanted to be informed whenever a doctor prescribes a drug in an off-label manner and a similar percentage felt the off-label drug use would increase the side-effects. Seventy three percent parents felt the off-label drug use is illegal and 57% would ask for change to a labelled drug in case of such prescription in their children. A majority of the parents would allow their child to participate in case of a life-threatening condition (59.8%) or in case of a chronic illness (51.3%) but significantly less when their child is healthy. CONCLUSION: The present study has found a low level of awareness regarding the concept of off-label drug use in children amongst the public. Our study also shows that parents expect that the doctor explains the fact to them, although they appear to vest a large amount of trust in the doctor's judgement in doing the best for their sick child. Parents were more willing to allow their child's participation in clinical research if their child was seriously ill than if healthy, indicating the need to educate the society about the need for clinical research so that they could take more informed decisions.

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.

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: Local anesthetic agent is not usually used to reduce pain experienced by children undergoing venepuncture. This study was undertaken 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 5-12 yr 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: 1 min; 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.