Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia.

OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

Effect of chest shielding during phototherapy for hyperbilirubinemia on symptomatic patent ductus arteriosus - a double-blind randomized placebo-controlled trial.

BACKGROUND: Meta-analysis of randomized trials suggests that phototherapy is associated with patent ductus arteriosus (PDA). We hypothesized that chest shielding during phototherapy would decrease the incidence of symptomatic PDA (sPDA) compared to sham shielding. METHODS: A single center, double-blind, randomized, placebo-controlled trial was performed to evaluate the effect of chest shielding during phototherapy on sPDA in infants ≤ 29 weeks gestational age (GA) or with birth weight (BW) ≤ 1000 g. Infants were randomized to either chest shield (with aluminum foil, intervention group) or sham shield (without aluminum foil, control group) during phototherapy. The primary outcome was sPDA during the period 24 h after phototherapy initiation until 3 days after phototherapy cessation. RESULTS: 160 infants were randomized with 10 infants withdrawn from each group due to shield placement after phototherapy initiation. Of 140 infants analyzed, the mean GA and BW was 26.6 weeks and 872 g, respectively. There was no difference in the incidence of sPDA between the intervention (n = 70) and control group (n = 70) (10% vs 11%, respectively, adjusted odds ratio 0.78, 95% CI:0.33-1.82; p = 0.57). CONCLUSIONS: Chest shielding during phototherapy had no effect on sPDA in infants ≤ 29 weeks GA or with BW ≤ 1000 g. TRIAL REGISTRATION: http://clinicaltrials.gov , Identifier: NCT02552927. IMPACT: Meta-analysis of randomized clinical trials suggests that chest shielding during phototherapy used for hyperbilirubinemia may decrease the incidence of patent ductus arteriosus. The effect of chest shielding during phototherapy on symptomatic patent ductus arteriosus has not been evaluated in a double-blind randomized trial. In this double-blind, randomized, placebo-controlled trial, chest shielding during phototherapy was not associated with a decreased incidence of symptomatic patent ductus arteriosus in premature infants.

SARS-CoV-2 seroprevalence in patients with autoimmune rheumatic diseases versus family controls: a multi-city cross-sectional survey.

There is uncertainty regarding the effect of the SARS-CoV-2 infection on patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressive drugs. We did a multicity cross-sectional seroprevalence study conducted in five different cities in India before COVID-19 immunization. Patients with a diagnosis of AIRD and DMARDs were included. Relatives of the patients, preferably staying in the same household with no known rheumatic diseases served as controls. Serum IgG antibodies to SARS-CoV-2 Receptor Binding Domain (RBD) of the spike protein and nucleoprotein (NP) were assayed in eight hundred and eighty nine sera (subjects with disease = 379 and in subjects without disease = 510). IgG antibodies to either RBD and/or NP were positive in 135 (36%) subjects with AIRD as compared to 196 (38%) controls. The seroprevalence of anti-RBD and anti-NP varied between different cities but was not significantly different between subjects with and without disease in Mumbai, Ahmedabad, Bengaluru and Bhubaneswar. However, the occurrence of IgG antibodies to RBD was significantly (p < 0.05) lower in subjects with disease (28/65;43%) as compared to subjects without disease (42/65;65%) in Kolkata, where the positivity rate was lower in connective tissue disease group than in inflammatory arthritis group. Overall, patients with rheumatic diseases on DMARDs have IgG antibodies to RBD and NP of SARSCoV-2 at a comparable level with that of subjects without disease, but the level of antibodies to RBD is lower in patients with connective tissue disease on immunosuppressive drugs in one centre.

Bilirubin-Displacing Effect of Ceftriaxone in Infants With Unconjugated Hyperbilirubinemia Born at Term.

OBJECTIVE: To evaluate the effect of intravenous (IV) ceftriaxone on free bilirubin concentrations in infants with unconjugated hyperbilirubinemia born at term. STUDY DESIGN: A prospective study was performed with subjects serving as their own controls. Our inclusion criteria were infants born at term <7 days old with sepsis and receiving IV antibiotics for >3 days and resolving hyperbilirubinemia with total serum bilirubin levels between 6 and12 mg/dL by day 4 of life. Free bilirubin concentrations were measured by the peroxidase method using a UB analyzer and a Zone Fluidics device before (baseline) and 15 minutes after (follow-up) IV ceftriaxone administration on postnatal days 4 to 6. Paired measurements of free bilirubin were analyzed using a Student paired t-test or Wilcoxon signed-rank test. RESULTS: In total, 27 infants were studied. The mean free bilirubin (µg/dL) at follow-up was not different from that at baseline when measured by the UB analyzer (P = .78). The mean free bilirubin was significantly lower at follow-up compared with baseline when measured by the Zone Fluidics device (P = .02). The ratio of a free bilirubin with and without ceftriaxone, an index of displacing effect, was 1.02 (95% CI 0.89-1.14) using the UB analyzer and 0.58 (95% CI 0.30-0.86) using the Zone Fluidics device. CONCLUSIONS: Ceftriaxone is not associated with a bilirubin-displacing effect in infants with a mild unconjugated hyperbilirubinemia. Home therapy with once-daily intramuscular ceftriaxone may be an alternative option for management of sepsis in asymptomatic infants with a mild unconjugated hyperbilirubinemia born at term.

Developmental influence of unconjugated hyperbilirubinemia and neurobehavioral disorders.

Bilirubin-induced brain injury in the neonatal period has detrimental effects on neurodevelopment that persist into childhood and adulthood, contributing to childhood developmental disorders. Unconjugated bilirubin is a potent antioxidant that may be useful for protecting against oxidative injuries, but it becomes a potent neurotoxin once it crosses the blood brain barrier. Because bilirubin toxicity involves a myriad of pathological mechanisms, can damage most types of brain cells, and affects brain circuits or loops that influence cognition, learning, behavior, sensory, and language, the clinical effects of bilirubin-induced neurotoxicity are likely to be manifold. One possible effect that several experts have identified is bilirubin-induced neurological dysfunction (subtle kernicterus). However, the underlying biological mechanisms or pathways by which subtle kernicterus could lead to developmental disorders has not been elucidated previously. Our aim in this review is to describe a spectrum of developmental disorders that may reflect subtle kernicterus and outline plausible biological mechanisms for this possible association. We review existing evidence that support or refute the association between unconjugated hyperbilirubinemia and developmental disorders, and limitations associated with these studies.

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants.

OBJECTIVE: To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. STUDY DESIGN: In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day. RESULTS: For the 166 infants studied, peak UB significantly correlated with concomitant Ka (r = -0.44, P = .001) but not with concomitant TSB or BAMR after adjusting for GA. On multiple regression analyses, there was a significant association of concomitant Ka (-0.06, 95% CI -0.08 to -0.04, P = .0001), but not concomitant TSB or BAMR with peak UB after controlling for GA, birth weight, race, and sex. GA group was a significant effect modifier for the association between Ka and peak UB (0.03, 95% CI 0.02-0.04, P < .001). Interaction analyses showed the association between concomitant Ka and peak UB was significant for the 24-30 weeks GA group infants, but not for the 301/7-33 weeks GA group infants. CONCLUSIONS: Peak UB was primarily associated with a decrease in binding affinity in infants ≤30 weeks GA. Interventions aimed at improving binding affinity may be important in decreasing the risk of bilirubin-induced neurotoxicity.

Auditory toxicity in late preterm and term neonates with severe jaundice.

AIM: Jaundice may cause auditory toxicity (auditory neuropathy and hearing loss). However, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. We compared TSB, bilirubin:albumin molar ratio (BAMR), and unbound bilirubin for their association with auditory toxicity in neonates with severe jaundice (TSB ≥342µmol/L, or that met exchange transfusion). METHOD: Neonates greater or equal to 34 weeks gestational age with severe jaundice during the first 2 postnatal weeks were eligible for prospective cohort study, unless they had craniofacial malformations, chromosomal disorders, toxoplasmosis, other infections, rubella, cytomegalovirus, herpes simplex infections, surgery, or family history of congenital deafness. RESULTS: Twenty-eight out of 100 neonates (mean gestational age 37.4wks; 59 males, 41 females) had auditory toxicity. Peak unbound bilirubin, but not peak TSB and BAMR, was associated with auditory toxicity (p<0.05) in neonates with severe (TSB <427.5µmol/L) and extreme hyperbilirubinemia (TSB ≥427.5µmol/L). Area under the receiver operating characteristic curve for unbound bilirubin (0.78) was significantly greater (p=0.03) than TSB (0.54) among neonates with severe but not extreme hyperbilirubinemia. INTERPRETATION: Unbound bilirubin is more strongly associated with auditory toxicity than TSB and/or BAMR in greater or equal to 34 weeks gestational age neonates with severe jaundice. Unbound bilirubin is a better predictor than TSB in neonates with severe hyperbilirubinemia.

Meta-Analysis of the Effect of Chest Shielding on Preventing Patent Ductus Arteriosus in Premature Infants.

Objective This study aims to perform a meta-analysis of randomized studies to evaluate if chest shielding during phototherapy is associated with decreased incidence of patent ductus arteriosus (PDA) in premature infants. Design/Methods We used published guidelines for the meta-analysis of clinical trials. The search strategy included electronic searches of CINAHL, CENTRAL Cochrane Library, MEDLINE, PubMed, and abstracts presented at the Pediatric Academic Societies. Inclusion criteria were randomized controlled trials (RCTs), quasi-RCTs or cluster RCTs published in English and involving chest shielding during phototherapy in premature infants with PDA as an outcome. Exclusion criteria involved case reports, case series, and multiple publications from the same author. Heterogeneity testing using Q statistics was performed to evaluate the variance between studies. Results Two RCTs met study criteria. There was heterogeneity (I2: 55.4%) between the two trials. Meta-analysis of RCTs using the random effect model demonstrated that chest shielding during phototherapy was associated with decreased incidence of PDA (odds ratio: 0.47, 95% confidence interval: 0.23-0.96). There was no publication bias on Eggers test. Heterogeneity was seen in gestational age, gender, prophylactic use of postnatal indomethacin, duration of phototherapy, and assessment of PDA. Conclusion Chest shielding during phototherapy may be associated with decreased incidence of PDA among premature infants.

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice.

OBJECTIVE: This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). STUDY DESIGN: Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. RESULTS: Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). CONCLUSIONS: Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice.

Unbound unconjugated hyperbilirubinemia is associated with central apnea in premature infants.

OBJECTIVE: To evaluate whether jaundice, indexed by unbound bilirubin (UB), is associated with central apnea in premature infants. STUDY DESIGN: A prospective observational study was performed with 27-33 weeks' gestational age infants who were not requiring either mechanical ventilation or noninvasive ventilation with continuous positive airway pressure beyond 24 hours after birth. Infants with congenital infections, chromosomal disorders, craniofacial anomalies, and/or family history of hearing loss were excluded. Total serum bilirubin and UB were measured twice daily during the first postnatal week and then when clinically indicated. Central apnea was evaluated by visual inspection of continuous, electronic cardiorespiratory recordings until 2 weeks of age. RESULTS: One hundred infants were subdivided into 2 groups via median peak UB level: the high UB group (greater than median) and low UB group (less than median). The high UB group had an increased frequency of apnea events during the first 2 weeks compared with infants in the low UB group. After we controlled for confounders, the high UB group had more events of apnea during the first 2 postnatal weeks compared with the low UB group (incidence rate ratio: 1.9, 95% CI 1.2-3.2). CONCLUSIONS: Our findings suggest that jaundice, as indexed by UB, is associated with central apnea in premature infants.

Central auditory processing disorder profile in premature and term infants.

OBJECTIVE: The aim of this study is to compare central auditory processing disorder (CAPD) profile between children born prematurely and at term. METHODS: A retrospective study involving children 7 to 13 years of age who were referred for CAPD evaluation over the past 3 years. Parental reports and medical records were used to collect information. Children with a score ≥ two standard deviations below the mean for at least one ear on at least two different CAPD tests were considered to have CAPD. RESULTS: A total of 82 children were evaluated for CAPD of which 22 met exclusion criteria, resulting in 60 children with CAPD (15 premature and 45 term). Premature children had higher prevalence of cesarean section delivery and neonatal jaundice compared with term children. Premature children had a higher total number of failed CAPD tests compared with the term children. Among CAPD tests, there was an increased frequency of abnormal Phonemic Synthesis test (PST) and decreased frequency of abnormal Staggered Spondaic Word test (SSW) among premature children compared with term children. CONCLUSION: Premature children differ in CAPD profile compared with term children. Findings suggest possible etiological differences for CAPD such as jaundice or differential susceptibility of premature children for altered PST and SSW performance when compared with the term children.

Cumulative amount of intravenous lipid intake and parenteral nutrition-associated cholestasis in neonates with gastrointestinal surgical disorders.

OBJECTIVE: To evaluate if cumulative amount of intravenous lipid (IL) intake is associated with severity of parenteral nutrition (PN)-associated cholestasis (PNAC) in neonates with gastrointestinal surgical disorders (GISD). STUDY DESIGN: The authors performed a retrospective study including 36 neonates > 34 weeks gestational age with GISD. Neonates with metabolic liver disorders, chromosomal disorders, TORCH infections, which includes toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus (CMV), and herpes, biliary tract anomalies, or direct hyperbilirubinemia (DHB) within first postnatal week were excluded. RESULTS: There was no significant difference in clinical factors between three groups of neonates: (1) without PNAC (n = 13), (2) with mild-to-moderate PNAC (DHB 1-5 mg/dL, n = 12), and (3) with severe PNAC (DHB > 5 mg/dL or PNAC with elevated amino-transaminases, n = 11) except for duration of enteral starvation and PN. Using ordered logistic regression, cumulative amount of IL, glucose, and protein intake were independently associated with severity of PNAC (p < 0.05). Comparing macronutrients as predictors of severe PNAC using receiver operating characteristic curves, the area under the curve for IL (0.583) intake was significantly larger (p = 0.008) compared with intravenous protein (0.257) and glucose (0.431) intake. CONCLUSIONS: IL intake is associated with and is a better predictor of severity of PNAC in neonates with GISD.

Effectiveness of generic tofacitinib in idiopathic inflammatory myositis (IIM)-a retrospective analysis from Indian Myositis Registry (MyoIN).

OBJECTIVES: Determine domain-based-outcomes and steroid-sparing efficacy of generic tofacitinib in IIM. METHODS: This is a multicenter retrospective study wherein clinical phenotype, autoantibody profile, prior immunosuppressives, and outcomes at 3, 6, and 12 months were retrieved for IIM patients prescribed tofacitinib. Overall clinical response was assessed as complete or partial remission as per physician judgment. Changes in cutaneous and calcinosis domain were recorded as per physician global assessment (PGA), lung domain as per medical research council (MRC) dyspnea scale, and muscle strength by Manual Muscle Testing-8 (MMT-8). RESULTS: Forty-two patients of IIM with mean age 38.7 ± 16 years; (76.2% (N = 32) women), median duration of illness 48 (19;88) months were included. Commonest indication for initiating tofacitinib was either for refractory or as steroid sparing for cutaneous domain (N = 25/42, 59.5%) followed by calcinosis (N = 16/42, 38%). Overall complete and/or partial remission was achieved in 23/37 (64.8%), 30/35 (85.7%), and 29/30 (96.6%) patients at 3, 6, and 12 months, respectively. At 12-month follow-up, there was a reduction in prednisolone dose, with absolute decrease from a daily dose of 17.5 mg (IQR 5;50) to 2.5 mg (IQR 0;5) (p < 0.001). Individual domain assessments revealed improvement in cutaneous domain [16/25 (64%)] and calcinosis [6/15 (40%)]. Adverse effects included herpes zoster (N = 2/42, 4.8%) and dyslipidemia (N = 4/42, 9.5%). CONCLUSIONS: Treatment with generic tofacitinib significantly reduces the daily dose of corticosteroids and is effective in cutaneous domain including calcinosis in IIM. KEY POINTS: • This multicenter retrospective study is the first real-world data from India, elucidating steroid sparing efficacy of generic tofacitinib in patients with inflammatory myositis. • Domain-based outcome assessment suggests good clinical improvement especially in cutaneous domain, even those with refractory disease. • Modest benefits were evident in calcinosis, but its effect on the muscle and pulmonary domain appears limited.

Latent iron deficiency in utero is associated with abnormal auditory neural myelination in ≥ 35 weeks gestational age infants.

OBJECTIVE: To determine whether cord serum ferritin level is associated with auditory brainstem evoked response interpeak latencies, an index of auditory neural myelination, in infants at ≥ 35 weeks gestational age (GA). STUDY DESIGN: This prospective study compared auditory neural myelination in infants with latent iron deficiency (cord serum ferritin, 11-75 ng/mL) and infants with normal iron status (cord serum ferritin, >75 ng/mL) at birth. Our inclusion criteria were infants born at ≥ 35 weeks GA who had cord blood collected soon after birth and had 1 or more of the following risk factors for poor in utero iron status: maternal diabetes mellitus, pregnancy-induced hypertension, and intrauterine growth restriction. Cord serum ferritin level was measured using the chemiluminescence immunoassay method. Auditory brainstem evoked response was measured using 80-dB normal hearing level click stimuli at a rate of 69.9/second within 48 hours after birth to evaluate interpeak latencies, a measure of nerve conduction velocity or myelination. RESULTS: Of the 45 infants studied, 12 had latent iron deficiency. On repeated-measures ANCOVA using interpeak latencies I-III, III-V, and I-V as multiple outcomes, infants with latent iron deficiency had significantly prolonged interpeak latencies (P = .01) compared with infants with normal iron status after controlling for confounders. CONCLUSION: In utero latent iron deficiency is associated with abnormal auditory neural myelination at birth in infants born at ≥ 35 weeks GA.

Monitoring apnea of prematurity: validity of nursing documentation and bedside cardiorespiratory monitor.

OBJECTIVE: To compare apnea events recorded by bedside cardiorespiratory monitor and nursing documentation with those detected by visual inspection of continuous electronic cardiorespiratory waveform. METHODS: In a prospective observational study, 20 nonventilated infants of 28 to 33 weeks' gestational age were monitored for apnea during the first 2 postnatal weeks. Apnea was defined as a respiratory pause > 20 seconds or > 15 seconds if associated with a heart rate < 80/min or oxygen saturation < 85%. True apnea was defined as one for which visual inspection of continuous electronic cardiorespiratory waveform on the central monitor verified apnea. RESULTS: The number of apnea episodes recorded by nursing documentation and bedside monitors were 207 and 418, respectively. Only 7.7% of apnea events recorded by nursing documentation were confirmed as true apnea compared with 50.4% of apnea recorded by bedside monitors and the difference was statistically significant. Of true apnea (n = 211) episodes recorded on central monitors, 99% were recorded by bedside monitors but only 7.6% of apnea occurrences were recorded by nursing personnel. CONCLUSIONS: Nursing documentation does not provide accurate monitoring of apnea. Although bedside monitors have better sensitivity and specificity than nursing documentation, future research should be directed to improve the specificity of bedside monitoring.

Effectiveness and safety of generic tofacitinib in spondyloarthritis: A real-world retrospective analysis from India.

BACKGROUND: Clinical trial evidence demonstrates the efficacy of tofacitinib in ankylosing spondylitis and psoriatic arthritis (PsA). Real-world data from spondyloarthritis (SpA) patients are scarce; there are few reports of its effectiveness and safety from low- to middle-income countries like India, despite its widespread usage. METHODS: This was a retrospective analysis of clinical and laboratory records of 100 patients with SpA prescribed generic tofacitinib from a single center in Mumbai, India. Disease activity was measured using the Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (ASDAS-CRP) in all patients, along with disease-specific outcome measures in the subgroups. We used paired t test for response to tofacitinib. We compared Δ ASDAS-CRP in patients with active peripheral arthritis and in patients without. We defined clinical tofacitinib failure as the physician's decision to change or add a disease-modifying antirheumatic drug (DMARD), and performed logistic regression to identify factors associated with tofacitinib failure. RESULTS: Among 100 patients (71 male, median age 42.5 years), 57 had axial SpA, 10 had peripheral SpA, 4 had inflammatory bowel disease-SpA and 29 had PsA. One-third had received biologic DMARDs previously. Patients received tofacitinib for a median of 192 days. There was a significant improvement in ASDAS-CRP in all types of SpA. Patients with active peripheral arthritis had a significantly greater fall in ASDAS-CRP. There were no serious adverse events, 19 patients had mild COVID-19; no patient had tuberculosis. Ten patients had tofacitinib failure; no baseline parameter could predict failure. INTERPRETATION: In the real-world setting, generic tofacitinib showed good effectiveness and tolerable safety profile in Indian patients with SpA.

Optimum click rate for neurodevelopmental evaluation using auditory brainstem response in premature infants.

OBJECTIVE: To determine the optimal click rate (CR) for neurodevelopmental assessment using auditory brainstem evoked response (ABR) in preterm infants. STUDY DESIGN: A prospective study was performed in 17 preterm infants at 34 weeks' postmenstrual age. Three separate ABRs were performed a few minutes apart on each subject using three different click rates (CRs): 19.9/s, 29.9/s, and 69.9/s. An ABR response with waves I, III, and V identifiable and measurable was defined as a pass response. The CR associated with the highest frequency of pass responses was considered optimal, or if two CRs were tied for the highest frequency, then the faster of the two CR was deemed best. RESULTS: The frequency of pass responses for 29.9/s and 19.9/s CR was 100% and was significantly higher compared with 82% frequency with 69.9/s CR. There was no difference in latencies, interpeak latencies, and amplitudes of waves between 19.9/s and 29.9/s CR; however, standard deviations of interpeak latencies were larger with 19.9/s compared with 29.9/s CR. CONCLUSION: Our data suggest that 29.9/s is the optimal CR for neurodevelopmental assessment using ABR. Because of smallest variance in interpeak latencies, the sample size requirement will be lowest using 29.9/s CR with secondary reduction in cost and time.

Real-world evidence of the effectiveness and safety of generic tofacitinib in rheumatoid arthritis patients: a retrospective, single-centre analysis from Western India.

Generic tofacitinib has been available in India for more than a year and is widely used in rheumatoid arthritis (RA) therapy. There is scarce real-world data on its effectiveness and safety from India, especially given infection endemicity. We retrospectively analysed records (demographic and clinical information, haematology and biochemistry, adverse events) of patients prescribed generic tofacitinib from a single centre in Mumbai, India. Disease activity was calculated using the disease activity score-28 and erythrocyte sedimentation rate (DAS28-ESR) and other tools, and we used paired T-tests for significant response. We defined clinical tofacitinib failure as a composite outcome, including clinician's decision to change to an alternative disease-modifying anti-rheumatic drug (DMARD) or flare after self-withdrawal. We performed logistic regression and survival analysis for determinants of clinical failure. We reviewed records of 102 patients (92 female; median age: 53 years) with mean RA duration of 146 months. Thirteen had prior treatment with innovator tofacitinib. There was significant improvement in disease activity parameters at a mean duration of 186 days. No serious adverse events were reported; 4 patients had tuberculosis and 19 patients had mild COVID-19 while on treatment. Clinical failure was seen in 25 patients, and mean time to failure on survival analysis was 357 days. No baseline characteristic predicted clinical failure. Generic tofacitinib showed good effectiveness and a tolerable adverse effect profile, despite tuberculosis endemicity and COVID-19. Setting up registries would be valuable in gaining more data on generic tofacitinib. Key Points • There is scarce data from India regarding the use of tofacitinib in rheumatoid arthritis, despite widespread use. • In this retrospective analysis of 102 patients at a single centre, we found tofacitinib monotherapy was efficacious and tolerable. • Tuberculosis was detected in four and nineteen patients had mild covid.