key: cord-0722707-ol7cb0g0 authors: Kawade, Anand; Dayma, Girish; Apte, Aditi; Roy, Sudipto; Gondhali, Arun; Juvekar, Sanjay; Bavdekar, Ashish title: Assessment of perceived distress due to nasopharyngeal swab collection in healthy Indian infants participating in a clinical trial date: 2021-12-26 journal: Paediatr Neonatal Pain DOI: 10.1002/pne2.12068 sha: 71437f9450ae47cd5f76be84a8721be64db9bbd6 doc_id: 722707 cord_uid: ol7cb0g0 Routinely children are exposed to various procedures as a part of clinical care and/or research participation. Public health strategies to contain current COVID‐19 pandemic demanded massive nasopharyngeal swab testing but limited data exist to confirm the extent of the pain and distress that result from this procedure. These data could help clinicians to formulate mitigation strategies, influence public health directives, and inform review boards/ethics committees to decide on risk‐benefit ratio of the procedure. Hence, an observational study to assess perceived distress was nested in a phase IV alternate and reduced dose schedule trial of the pneumococcal conjugate vaccine (PCV) in which nasopharyngeal swab (NPS) was used to collect nasopharyngeal secretions as part of the study procedure. Out of 805 infant participants enrolled in the main study, a total of 425 infants were enrolled and observed for procedural distress at 18 weeks and 10 months of age using the Face Leg Activity Cry and Consolability (FLACC) Scale. The FLACC score and duration of cry were recorded. The mean FLACC score changed substantially from preprocedural to procedure in both age groups (from 0.08 to 5.8 at 18 weeks and from 0.5 to 7.007 at 10 months. P = <.0001). The proportion of infants experiencing higher FLACC scores (7‐10) indicating severe distress increased significantly from 22% (n = 95) at 18 weeks to 61% (n = 248) at 10 months (P < .0001). The mean duration of cry was significantly increased from 23.03 seconds at 18 weeks to 52.6 seconds at 10 months (P = .00). Nasopharyngeal swab collection produced substantial distress which increased with age. Adequate training of sample collectors and supporting parent engagement during procedure could help in reducing the distress. In a clinical setting, various sampling procedures need to be carried out for establishing a definitive diagnosis of an illness, while in a research setting, these procedures need to be performed to assess eligibility for study participation, as a part of routine clinical care and for ascertainment of study outcomes. Some of these procedures, such as blood collection, insertion of catheters, cannulation, parental injections, nasal swabs, and nasopharyngeal swab collection, are associated with varying degrees of pain and distress, especially in children. Although, pain is an important cause of distress, assessment and differentiation of pain, and distress in infant is inherently difficult due to their inability to self-report. 1,2 Current definition of pain which describes pain as "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage" put less emphasis on actual tissue damage and recognizes pain in absence of injury. 3 In infants the responsibility of assessing pain and distress often falls to the professional or lay care provider, whose knowledge, expertise, and beliefs influence their judgements. Therefore, various observational pain scales are used to provide more objective and standardized assessment of pain. These scales are validated in specific context of pain type, age groups, and clinical setting. The Children Hospital of Eastern Ontario Pain Scale (CHEOPS), The Evaluation Enfant Douleur (EVENDOL), and The Faces, Legs, Activity, Cry, and Consolability (FLACC) scale are validated and recommended for evaluation of procedural pain in infants. [3] [4] [5] Use of nasopharyngeal swab, nasal wash, nasal aspirate, and mid turbinate sampling is common methods for diagnosing respiratory infections and ascertaining colonizing microorganisms with comparable sensitivity. [6] [7] [8] Use of flocked swab for nasopharyngeal sample collection is considered easy, flexible, and a preferred method for detecting an organism from the upper respiratory tract in children compared to nasal wash or nasopharyngeal aspirates due to reduced risk of aspiration. 9,10 During current COVID-19 pandemic, nasopharyngeal swab collection had become more commonly and routinely done procedure for clinical care management. 11 However, there are little data on the level of pain and distress associated with nasopharyngeal swab collection in a young infant. While in clinical practice, accurate assessment of pain and distress is important for clinical management; in research settings, assessment of risk and benefits associated with study procedures is an essential part of ethical review and institutional ethics committees (IEC) are responsible for evaluating whether the procedural risk is reasonable in relation to the knowledge gained. 12 Thus, this study was conducted to quantify the level of distress associated with nasopharyngeal swab collection in healthy infant. This will help inform primary care taker, clinicians, researchers to formulate appropriate alleviation strategies, and public health experts and policy makers to decide on compliance with testing during pandemic. This was an observational study nested within a clinical trial on alternate and reduced dose schedule of pneumococcal conjugate vaccines (PCV), which is hereafter referred to as the parent study. The parent study was conducted at Vadu Rural Health Program of KEM Hospital Research Centre, Pune, India from July 2016 to May 2018 to determine the nasopharyngeal pneumococcal carriage reduction and immunogenicity with reduced and alternate dose schedule of PCV in infancy. During this study, total 805 healthy infants were enrolled at the age of 6-8 weeks and followed till the age of 18 months. Nasopharyngeal swabs and blood samples were collected at different timepoints to assess primary (carriage reduction) and secondary (immunogenicity) endpoints. After ethics committee approval, infants already enrolled and whose 18 weeks' visit was due, were invited in succession to participate until a total 425 infants were enrolled. Since this was an observational study, all invited participants agreed to participate. All participants underwent the procedure at 18 weeks and 10 months of age, and the FLACC scale was used to assess the level of distress experienced before and during the procedure. Valid observational scales are needed to assess pain and distress in infant who lack the verbal ability to self-report. The Face, Legs, Activity Cry, and Consolability scale (FLACC) scale is one of the most well-known, widely used observational scale and is recommended for procedural pain measurement. 13 Although the FLACC scale was designed to assess postoperative pain, a recent review supports the reliability and sensitivity of the FLACC scale for procedural pain assessment with limited capacity to differentiate between pain and non-pain-related distress, thus measuring composite of pain and distress. 14, 15 The FLACC scale comprised of 5 items each scored 0-2 the sum of which provides a score between 0 and 10; wherein 0 indicates no pain and distress and 10 indicates maximum pain and distress. Although there is no evidence that the FLACC scale is a ratio scale of measurement, for analysis purpose, it was treated as a ratio and commonly accepted scores were used as cut-offs for varying severity. The score of 0 was termed as no pain/distress "(Relaxed/comfortable); score between 1-3 was termed as mild; 4-6 as a moderate; and 7-10 as a severe 16 (Table S1 ). All participants underwent the procedure at 18 weeks and 10 months of age, and the FLACC scale was used to assess the level of distress experienced before and during the procedure. The preprocedural phase was considered as 2-5 minutes before the start of the procedure, and the procedural phase was considered to begin with introducing the swab into the nostril until removing the swab from the nostril. The independent observer had recorded the scores in each of the FLACC categories and documented the highest score achieved during the entire procedural phase. The duration between the start of the cry from the time the swab was introduced into the infant's nostril until the cry had not been audible for at least five seconds was recorded as the duration of cry. The FLACC score and duration of cry were noted by a trained observer independent of the swab collector at both the age groups. The English version of the FLACC scale was used to capture the data as the independent observer was well versed in the English language. Assuming that 50% of children would experience significant pain and distress (score >= 7 on FLACC scale) due to nasopharyngeal swab collection and considering 95% confidence interval with 5% absolute error, the sample size was calculated as 384 and adding 10% dropout; the sample size was 423 which was rounded off to 425. All the data analysis was done using STATA 15.0 version. The study was approved by the KEM Hospital Research Centre Ethics Committee. As this was an observational study within the main PCV study, verbal consent was sought from the parents before administering the FLACC scale. Of the total 425 participants enrolled at 18 weeks of age, 406 (95.9%) successfully completed the study at 10 months. We were unable to collect the data from 19 participants (Figure 1 ). At 18 weeks, 50.8% (n = 215) of participants were female and participants' mean age, weight and height were 135.1 days, 6.2 kg, and 62.3 cm, respectively; while at 10 months 51.2% (n = 208) were female and participants' mean age, weight, and height were-304.4 days, 7.9 kg, and 70.3 cm, respectively (Table 1 ). The preprocedural and procedural mean FLACC scores at 18 weeks Similarly, comparison of preprocedural and procedural scores of both timepoints showed statistically significant (P < .001) differences. At 18 weeks, before the start of procedure, 98% of children In infants, the cry is the most audio-visible activity and is an im- (Table 2 ). To our knowledge, this is the first Indian study assessing the levels of distress due to nasopharyngeal swab collection in healthy infants. This study results showed that nasopharyngeal swab collection caused a substantial distress which increased with the age. These results are in concordance with the studies done previously. In this study, we had sampled each of participant twice; at ages of 18 weeks and 10 months and our results showed higher scores at 10 months. Although these differences were statistically significant, we need more studies to conclude on clinical importance of these findings. et al reported that FLACC scores during the procedural phase were highest in the youngest age group and lowest in the oldest age group. 14 This different result could be explained by the fact that the behavioral responses to pain and distress are influenced by previous pain experiences, its' context, and sociocultural factors. 5 Therefore, it is difficult to conclude on the effect of age despite repeat sampling. In our study, mean cry duration also changed significantly. Similar The study's major strength is sample size of the cohort. Twice sampling of a participant to ascertain the effect of age on perception of distress could have been another strength but to limit by the fact that pain and distress responses are modified by previous painful/ distressful experience. This was a single-center study and had limited generalizability. This study had not used any comparison group like different swab collectors, different FLACC assessors and control group undergoing less/ no painful and distressful procedure, for example, measuring SPO2 by Pulse Oximeter. This study provides the objective assessment of pain and distress a child can foresee during routine procedures like NPS collection and emphasize the need for appropriate training, supports engagement of care takers, and use of alleviation measures. Though this study was conducted before pandemic, the findings of the study are important in pandemic context and could prompt the policy maker to think of pain/distress relieving measure to increase procedural compliance and public health behavior. These results could also help inform the review boards to decide on risk-benefit ratio of the procedure while reviewing the trial protocols. Nasopharyngeal swab collection produced substantial distress in infants, which increased with age. Alternative bio-sampling could help in getting maximum community response to public health strategies especially during pandemic. Additionally adequate training of swab collector and care taker engagement during procedure could help in minimizing the distress. We would like to thank the following members from the KEM Hospital research center, Pune India: Diana Kekan for clinical data acquisition; Poonam Vallal for assessing FLACC scores and cry duration; and Tathagata Bhattacharjee for data management. We are in debt to all the study participants and their family members to agree to participate in this study and provide their valuable data. None. 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