Expert group recommendation on inhaled mucoactive drugs in pediatric respiratory diseases: an Indian perspective.

Background: Currently, there are no guidelines or consensus statements about the usage of inhaled mucoactive drugs in pediatric respiratory disease conditions from an Indian perspective. Objective: To develop a practical consensus document to help pediatricians in clinical decision-making when choosing an appropriate mucoactive drug for the management of specific respiratory disease conditions. Methods: A committee of nine experts with significant experience in pediatric respiratory disease conditions and a microbiological expert constituted the panel. An electronic search of the PubMed/MEDLINE, Cochrane Library, Scopus, and Embase databases was undertaken to identify relevant articles. Various combinations of keywords such as inhaled, nebulized, mucoactive, mucolytic, mucokinetic, expectorants, mucoregulators, mucociliary clearance, respiratory disorders, pediatric, cystic fibrosis (CF), non-CF bronchiectasis, acute wheezing, asthma, primary ciliary dyskinesia (PCD), critically ill, mechanical ventilation, tracheomalacia, tracheobronchomalacia, esophageal atresia (EA), tracheoesophageal fistula (TEF), acute bronchiolitis, sputum induction, guideline, and management were used. Twelve questions were drafted for discussion. A roundtable meeting of experts was conducted to arrive at a consensus. The level of evidence and class of recommendation were weighed and graded. Conclusions: Inhaled mucoactive drugs (hypertonic saline, dry powder mannitol, and dornase alfa) can enhance mucociliary clearance in children with CF. Experts opined that hypertonic saline could be beneficial in non-CF bronchiectasis, acute bronchiolitis, and PCD. The current state of evidence is inadequate to support the use of inhaled mucoactive drugs in asthma, acute wheezing, tracheomalacia, tracheobronchomalacia, and EA with TEF.

Assessment of Blood Lead Level of School Children in 10 Cities of India: A Cross-Sectional Study.

OBJECTIVES: To assess the blood lead level (BLL) of school children in 10 cities of India. METHODS: This multi-centric cross-sectional study enrolled participants from randomly selected schools. Data on demographic details, socioeconomic status (SES) and anthropometric indicators was collected. Samples were collected for assessment of lead level in blood. Inductively coupled plasma-optical emission spectrometry technique was used to assess BLL. RESULTS: From April 2019 through February 2020, 2247 participants were recruited from sixty schools (62.6% government schools) with equal gender distribution. The overall median (interquartile range) BLL was 8.8 (4.8, 16.4) µg/dl. The highest median (interquartile range) BLL was in Manipal 30.6 (23.0, 46.7) and lowest in Dibrugarh 4.8 (3.2, 7.0). Overall, 82.5% of participants had BLL above ≤4 µg/dl. Significant negative correlation was observed between BLL and SES (correlation= -0.24, p <0.001), anthropometric indicators (correlation= -0.11, p <0.001), hemoglobin level (correlation= -0.045, p = 0.03) and multivariate regression model showed association with gender, SES and anthropometric indicators. CONCLUSIONS: BLL are elevated in urban school going children and there is intercity variation. Hence, urgent focus is needed to reduce exposure to lead in India.

Association of dietary intake with micronutrient deficiency in Indian school children: a cross-sectional study.

Adequate nutrition is necessary during childhood and early adolescence for adequate growth and development. Hence, the objective of the study was to assess the association between dietary intake and blood levels of minerals (calcium, iron, zinc, and selenium) and vitamins (folate, vitamin B12, vitamin A, and vitamin D) in urban school going children aged 6-16 years in India, in a multicentric cross-sectional study. Participants were enrolled from randomly selected schools in ten cities. Three-day food intake data was collected using a 24-h dietary recall method. The intake was dichotomised into adequate and inadequate. Blood samples were collected to assess levels of micronutrients. From April 2019 to February 2020, 2428 participants (50⋅2 % females) were recruited from 60 schools. Inadequate intake for calcium was in 93⋅4 % (246⋅5 ± 149⋅4 mg), iron 86⋅5 % (7⋅6 ± 3⋅0 mg), zinc 84⋅0 % (3⋅9 ± 2⋅4 mg), selenium 30⋅2 % (11⋅3 ± 9⋅7 mcg), folate 73⋅8 % (93⋅6 ± 55⋅4 mcg), vitamin B12 94⋅4 % (0⋅2 ± 0⋅4 mcg), vitamin A 96⋅0 % (101⋅7 ± 94⋅1 mcg), and vitamin D 100⋅0 % (0⋅4 ± 0⋅6 mcg). Controlling for sex and socioeconomic status, the odds of biochemical deficiency with inadequate intake for iron [AOR = 1⋅37 (95 % CI 1⋅07-1⋅76)], zinc [AOR = 5⋅14 (95 % CI 2⋅24-11⋅78)], selenium [AOR = 3⋅63 (95 % CI 2⋅70-4⋅89)], folate [AOR = 1⋅59 (95 % CI 1⋅25-2⋅03)], and vitamin B12 [AOR = 1⋅62 (95 %CI 1⋅07-2⋅45)]. Since there is a significant association between the inadequate intake and biochemical deficiencies of iron, zinc, selenium, folate, and vitamin B12, regular surveillance for adequacy of micronutrient intake must be undertaken to identify children at risk of deficiency, for timely intervention.

Micronutrients and cognitive functions among urban school-going children and adolescents: A cross-sectional multicentric study from India.

BACKGROUND: Micronutrient deficiency (MD) is associated with deficits in cognitive functioning of children. However, no comprehensive multicentric study has been conducted in India to explore the role of multiple MD in cognition of children and adolescents. The present study aimed to explore association of MD with level of general intelligence and specific cognitive functions, in urban school-going children and adolescents across ten cities of India. METHOD: Cross-sectional multicentric study, enrolled participants aged 6-16 years. Blood samples were collected for biochemical analysis of calcium, iron, zinc, selenium, folate, vitamin A, D and B12. Colored Progressive Matrices / Standard Progressive Matrices (CPM/SPM), Coding, Digit Span and Arithmetic tests were used for the assessment of cognitive functions of participants. Height and weight measures were collected along with socio-economic status. RESULTS: From April-2019 to February-2020, 2428 participants were recruited from 60 schools. No MD was found in 7.0% (134/1918), any one MD in 23.8% (457/1918) and ≥ 2 MD in 69.2% (1327/1918) participants. In presence of ≥ 2 MD, adjusted odds ratio (OR) for borderline or dull normal in CPM/SPM was 1.63, (95% CI: 1.05-2.52), coding was 1.66 (95% CI: 1.02-2.71), digit span was 1.55 (95% CI: 1.06-2.25) and arithmetic was 1.72 (95% CI: 1.17-2.53), controlling for gender, socioeconomic status and anthropometric indicators. CONCLUSION: Since ≥ 2 MD were found in more than 2/3rd of participants and was associated with impairment in cognitive function, attempts must be made to ameliorate them on priority in school going children in India. TRIAL REGISTRATION NUMBER: CTRI/2019/02/017783.

Texture and rheological features of strain and pH sensitive chitosan-imine graphene-oxide composite hydrogel with fast self-healing nature.

Here we report a smart Chitosan-isophthalaldehyde-Graphene oxide (CS-ISD-GO) hydrogel as a "multicomponent hydrogel". We witnessed an unprecedented pH responsive changes in viscoelasticity, stretchability, adhesiveness, self-healing and self-adaptability upon changing the pH and concentration of CS and ISD that was authenticated by texture and rheological analysis. The GO provides physical crosslinks and antibacterial properties to the hydrogel. Taking the advantage of dynamic nature of covalent and non-covalent interactions, we tuned the hydrogel adhesion and stretchability in response to the pH changes. Further self-healing of hydrogels was fully investigated by measuring thixotropic response over more than three cycles of strain sweep and real time optical imaging and video recording techniques. The recorded videos display 100 % self-healing response within a time frame of 2-6 min. These properties were observed only over small range of pH (4.5-5.5). The hydrogel becomes mechanically strong above pH 5.5 and becomes unstable above pH 7 leading to subsequent disintegration. The characterization of hydrogel was carried by FTIR, FESEM and TGA analysis. In addition, the hydrogel was reduced using NaBH4 for drug release. The reduced gel appears to be stable at lower pH values also. The reduced hydrogel may potentially be used for drug release purpose with low toxicity.

Prevalence of specific micronutrient deficiencies in urban school going children and adolescence of India: A multicenter cross-sectional study.

INTRODUCTION: Childhood and adolescence require adequate amount of micronutrients for normal growth and development. The primary objective of study was to assess the prevalence of deficiencies of Vitamins (Vitamin A, 25 Hydroxy Vitamin D, Vitamin B12 and Folate) and minerals (Calcium, Zinc, Selenium and Iron), among urban school going children aged 6-11 and 12-16 years in ten cities of India. Secondary objective was to find the association between micronutrient deficiencies with sociodemographic and anthropometric indicators. METHODS: A multi-center cross-sectional study was conducted across India. Participants in the age groups of 6 to 11 years (group 1) and 12 to 16 years (group 2) were selected from randomly chosen schools from each center. Data on socio economic status, anthropometric measures was collected. Blood samples were collected for biochemical analysis of micronutrients. Point estimates and 95% confidence intervals was used to assess the prevalence of deficiencies. Associations were observed using chi square, student t test and ANOVA test. RESULTS: From April 2019 to February 2020, 2428 participants (1235 in group 1 and 1193 group 2) were recruited from 60 schools across ten cites. The prevalence of calcium and iron deficiency was 59.9% and 49.4% respectively. 25 Hydroxy Vitamin D deficiency was seen in 39.7% and vitamin B12 in 33.4% of subjects. Folate, Selenium and Zinc were deficient in 22.2%, 10.4% and 6.8% of subjects respectively. Vitamin A deficiency least (1.6%). Anemia was prevalent in 17.6% subjects and was more common among females. CONCLUSION: One or more micronutrient deficiencies are found in almost one half of school going children in urban area. Hence efforts must be made to combat these on priority. TRIAL REGISTRATION NUMBER: CTRI/2019/02/017783.

Viscoelastic and smart swelling disposition of Carboxymethylcellulose based hydrogels substantiated by Gemini surfactant and in-vitro encapsulation and controlled release of Quercetin.

CMC-SA-12-E2-12 hydrogels were prepared from Carboxymethylcellulose (CMC), succinic acid (SA) (biocompatible cross-linker) and Ethane-1,2-diyl-bis(N, N-dimethyl-N-dodecylammoniumacetoxy) (referred as 12-E2-12) (0.0006, 0.0015, 0.003, 0.0045 mMoles) by thermal treatment with economical and easy solution polymerization strategy. The CMC-SA-12E2-12 hydrogels were characterized for mechanical and viscoelastic properties like self-healing, viscosity and modulus using rheological analysis. Further the structural, morphological and thermal properties were investigated by FTIR, SEM and TGA analysis. The investigation revealed significant modulation in mechanical, viscoelastic, self-healing and drug release behavior with the addition of 12-E2-12. The CMC-SA-12-E2-12 hydrogels were investigated for drug release studies in PBS 7.4 for 48 h using Quercetin dihydrate. The results showed sustained release behavior at optimised concentration values of surfactant. Release data fitted nicely to the Higuchi model and hence the release could be seen to be diffusion controlled phenomenon or Fickian diffusion. The biocompatibility of cross-linker and surfactant may potentially make the hydrogels suitable for drug delivery applications.

First report of powdery mildew caused by Phyllactinia pyri-serotinae Sawada on pear (Pyrus communis L.) from India.

In August 2020 powdery mildew was observed on pear cv. Fertility at the University research field in Shalimar, Srinagar (J&K), India (34° 08' 30.5'' N and 74° 51' 42.0'' E) with a disease incidence up to 30% (100 leaves observed from ten trees). White irregularly shaped fungal colonies were observed on the abaxial leaf surface which latter covered the whole leaf surface and developed black chasmothecia. The affected leaves appeared brittle, slightly curved upwards and dropped prematurely. Mycelium was hypophyllous, septate and measured 2.0 to 5.0 µm in width. Appressoria were nipple shaped, solitary or present in opposite pairs. Conidiophores were erect, up to 440.0 µm long (n=50), mostly centrally on upper surface of mother cells. Conidiophore foot-cells were filiform, followed by 1 to 3 shorter cells, producing single conidia at the tip. Conidia were hyaline, lanceolate, with a non-papillate rounded apex, measuring55.5 to 81.4 × 14.8 to 22.5 µm (n=50) and devoid of any conspicuous fibrosin bodies. Germ tube was, filiform, twisted, arose basally and measured 2.0 to 5.0 µm in width. Chasmothecia were hypophyllous, black, scattered, globose and measured 195.0 to 255.0 µm in diameter (n=50) having 8 to 12 equatorial, acicular, up to 270.0 µm length appendages with 25.9 to 44.4 µm diameter bulbous base (n=50) and obtuse or subacute apex. Asci in a chasmothecium were clavate to saccate, 62.9 to 81.4 × 18.5 to 22.2 µm (n=50), stalked, and two- spored. Ascospores were 33.3 to 40.7 × 12.9 to 18.5 µm (n=50), pale yellowish or golden brown in color. All morphological features were consistent with Phyllactinia pyri-serotinae (Braun and Cook 2012). To confirm the fungus identity at molecular level, DNA of two isolates was extracted from chasmothecia. The internal transcribed spacer (ITS) sequence of ribosomal DNA was amplified with the primers ITS1 and ITS4 (White et al. 1990) and sequenced. The ITS sequences submitted to NCBI GenBank under Accession No. MZ505441 and MZ505442 have 97 (416/427) & 96 (424/440) per cent and 99 (424/430) & 98 (428/438) per cent base pair matching, with that of P. pyri-serotinae isolates from Japan (AB080521 and AB985507), respectively. Thus, the pathogen was identified as Phyllactinia pyri-serotinae Sawada based on morphological and molecular sequence analyses. The pathogenicity tests of both the isolates were carried out on one year old pear saplings (cv. Fertility) and repeated twice. The inoculum was prepared by collecting P. pyri-serotinae conidia in sterile distilled water from infected pear leaves. Three saplings were inoculated by spraying (15ml per sapling) the inoculum (3 x 105 spores ml-1) on leaf surfaces, while same number of saplings sprayed with sterile distilled water served as non-inoculated controls. After 15 days of incubation at 25oC in a green house, similar symptoms as observed on naturally infected plants were observed on inoculated plants and uninoculated plants remained symptomless. The pathogen of interest observed on inoculated plants was morphologically characterized and found to be similar to P. pyri-serotinae. The voucher specimen was deposited in the Herbarium Crytogamae Indiae Orientalis (HCIO), IARI, New Delhi under accession number 52213. Pear is the third most important temperate fruit grown in India (Chattopadhyay 2009) and our study reveal P. pyri-serotinae as the new causal agent of powdery mildew in addition to P. guttata (Dhar and Shah 1982) under Indian conditions.

Rickettsial Infections among the Undifferentiated Febrile Patients Attending a Tertiary Care Teaching Hospital of Northern India: A Longitudinal Study.

BACKGROUND: Acute undifferentiated febrile illness (AUFI) is one of the most daunting challenges a physician faces in such settings. Among AUFI, rickettsial infections are most common and related infections (such as anaplasmosis, ehrlichiosis, and Q fever) which are caused by an unusual type of bacteria that can live only inside the cells of another organism. The present study was therefore planned with an objective to estimate the prevalence of rickettsial infection among patients of undifferentiated fever and to determine any association of socio-demographic characteristics with rickettsial disease. MATERIALS AND METHODS: Patients presenting with febrile illness and admitted or attending out-patient department of Sher-i-Kashmir Institute of Medical Sciences, Srinagar was approached and recruited in the study. Weil Felix Assay, enzyme-linked immunosorbent assay and indirect immunofluorescence assay were done to detect the anti-rickettsial antibodies. Serological evidence of a fourfold increase in IgG-specific antibody titer reactive with spotted fever group rickettsial antigen by indirect immunofluorescence antibody assays between paired serum specimens was considered a confirmatory diagnosis for the rickettsial disease. RESULTS: Most of the patients were males 61.6%, and most 46.2% were in the age group of 20 -39 years. Most of the patients, 80.8% belonged to rural areas, and 48% belonged to the upper middle (II) class of the socio-economic class according to modified Kuppuswamy scale. Of the studied participants, a majority, 47.0%, were determined undiagnosed, while 15.4% studied participants were diagnosed to have a rickettsial disease. In patients positive for typhus group, 67.8% were IgM positive, 28.5% were IgG positive, and only 3% were positive for IgM and IgG. In patients positive for Scrub Typhus Group, 32.7% were positive for IgM, and 62.0% were positive for IgG, and only 5.0% were positive for both IgM and IgG. In patients positive for spotted fever group, 36.1% were positive for IgM, and 58.5% were positive for IgG, and only 5.5% were positive for both IgM and IgG. The prevalence of rickettsial disease was found to be 11.3%. CONCLUSION: Rickettsial diseases, typhoid and brucellosis, were the most prevalent diseased diagnosed among patients reporting to hospitals with undifferentiated febrile illness. Clinicians must consider rickettsial diseases as one of the differential diagnosis while treating patients with fever.

Blood Pressure-to-Height Ratio as a Screening Tool for Hypertension in Children.

OBJECTIVE: To test whether blood pressure-to-height ratio (BPHR) can be used to screen for hypertension in children. METHODS: Data regarding blood pressure and other variables was recorded for 2702 school children between the ages of 10-16 years as a part of a nutritional survey. RESULTS: The optimal thresholds for defining hypertension in boys were 0.76 for systolic BPHR and 0.50 for diastolic BPHR; the respective threshold in girls were 0.80 and 0.52. CONCLUSION: BPHR can be used as an effective screening test for diagnosing both hypertension and prehypertension in children aged 10-16 years.

Clinical and mutation profile of children with cystic fibrosis in Jammu and Kashmir.

OBJECTIVE: To study the clinical and mutation profiles of children with cystic fibrosis in Jammu and Kashmir. METHODS: One hundred consecutive patients presenting with one or more phenotypic features suggestive of cystic fibrosis (CF) were screened by quantitative sweat chloride testing. For patients with positive/equivocal test result on two occasions, CFTR gene mutation analysis was done by polymerase chain reaction. RESULTS: Of the 100 patients, 18 (10 females) were diagnosed to have CF at a median age of 10.5 y (IQR 4.75-15.25 y) while the median age at the onset of symptoms was 12 mo (IQR 4-63 mo) with a delay in diagnosis by 102.4±80.5 months. Clinical features at presentation included failure to thrive (94.4%), chronic cough (78%), recurrent pneumonia (61%), persistent pneumonia (11%), and chronic diarrhea (50%). Positive sweat chloride (>60 meq/L) was seen in 14 (14%) patients and 4 (4%) patients had equivocal (40-60 meq/L) value on two different occasions. Mutational analysis done in 15 patients showed DeltaF508 mutation in 20% (3/15) patients in homozygous form and in 13% (2/15) patients in heterozygous form. Intron 19 mutation 3849+10kb C>T was found in 40% (6/15) in heterozygous form. One (6.6%) patient had DeltaF508 and 3849+10kbC>T mutations in compound heterozygous form. Patients with equivocal sweat chloride and 3849+10kbC>T mutation had delayed onset of pulmonary involvement. CONCLUSION: 3849 +10kbC>T mutation appears to be common in children with cystic fibrosis in Jammu and Kashmir followed by DeltaF508, although the data are quite limited. Although presentation is delayed and sweat chloride is in the equivocal range, severe lung involvement may occur in these patients.

Effect of second dose of measles vaccine on measles antibody status: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of the second dose of measles vaccine on measles antibody status during childhood. SETTING: Immunization centre of Under-five Clinic of the Department of Community Medicine at a tertiary-hospital. STUDY DESIGN: Randomized Controlled trial. SUBJECTS: Children from 6 years to 17 year old. 188 with simple obesity, and 431 with obesity and metabolic abnormalities. 274 age and gender-matched healthy children as controls. METHODS: Blood samples were collected from all subjects for baseline measles serology by heel puncture at 9-12 months of age. All subjects were given the first dose of measels vaccine. At second visit (3-5 months later), after collecting the blood sample from all, half the children were randomized to receive the second dose of measles vaccine (study group), followed by collection of the third sample six weeks later in all the subjects. RESULTS: A total of 78 children were enrolled and 30 children in each group could be analyzed. 11(36.6%) children in the study group and 13 (43.3%) children in the control group had protective levels of measles IgG at baseline. Around 93.3% of children in the study group had protective measles antibody titers as against 50% in the control group at the end of the trial. The Geometric Mean Titre (GMT) of measles IgG increased from 14.8 NTU/mL to 18.2 NTU/mL from baseline to six weeks following receipt of the second dose of the vaccine in the study group, as compared to a decrease from 16.8 NTU/mL to 12.8 NTU/mL in the control group. CONCLUSION: A second dose of measles vaccine boosts the measles antibody status in the study population as compared to those who receive only a single dose.

Antiphospholipid syndrome in a neonate.

Antiphospholipid syndrome presenting in the neonatal period is very rare. Although antiphospholipid antibodies from mothers with antiphospholipid syndrome can cross the placenta and put their neonates at risk, the occurrence of thrombotic complications in these neonates is uncommon. We present a 10-day-old neonate who developed Klebsiella sepsis with arterial gangrene of the left lower limb. Investigations revealed thrombosis of the left femoral artery with both the mother and the neonate positive for antiphospholipid antibodies. In conclusion, passive transfer of antiphospholipid antibodies from mothers to their offspring can be associated with significant complication in the presence of secondary risk factors.

Pulmonary thromboembolism as the initial manifestation in a child with antiphospholipid syndrome in the emergency department.

Antiphospholipid syndrome is characterized by recurrent arterial or venous thrombosis at any level of the vascular tree and the presence of circulating antiphospholipid antibodies. The syndrome may be idiopathic or secondary to an underlying autoimmune disorder. The disease is uncommon in children, and manifestations are diverse and underreported. We report the case of a 10-year-old boy who presented with features of pulmonary thromboembolism in the emergency department. Subsequently, he proved to have systemic lupus erythematosus with circulating antiphospholipid antibodies. He had no signs of systemic lupus erythematosus at presentation. In conclusion, antiphospholipid syndrome should also be kept as a possibility in children presenting for the first time with pulmonary thromboembolism in the emergency department.

Physiological and biochemical changes associated with flower development and senescence in so far unexplored Helleborus orientalis Lam. cv. Olympicus.

The so far unexplored H. Orientalis cv. Olympicus exhibits a unique pattern of flower senescence, involving re-greening of creamy white petaloid sepals at the later stages. The greenish sepals become photosynthetically competent immediately after pollination and persist until the seeds are set. After the seed set, the entire (green) flower abscises from the plant. Flower development of Helleborus orientalis cv. Olympicus growing in the open was divided into six stages (I-VI) from tight bud stage to the senescent stage. The average life span of an individual flower after it is fully open is about 6 days. Membrane permeability of sepal tissues estimated as electrical conductivity of leachates increased during senescence. The content of sugars and soluble proteins in the sepal tissues increased during flower opening and declined thereafter during senescence. The protease activity increased as the flower progressed towards senescence. From the present study, it becomes evident that decline in the sugar status and elevation in specific protease activity leading to degradation of proteins are the important factors regulating development and senescence in H. orientalis flowers. Although the tissue content of soluble proteins registered an overall quantitative decrease but SDS-PAGE of protein extract from sepal tissues suggested a decrease in the expression of high molecular weight proteins and an increase in low molecular weight proteins during flower development and senescence. At this stage it is not known whether the polypeptides that increased during senescence play an important role in the senescence of Helleborus orientalis flowers. The increase in these polypeptides during flower senescence is of particular interest because they may be linked to flower longevity. Understanding the nature of these proteins can provide new insights into the pathways that execute senescence and the post-transcriptional regulation of senescence in this flower system.

Acute intermittent porphyria with transient cortical blindness.

Acute intermittent porphyria is a hereditary disorder characterized by deficient activity of the enzyme porphobilinogen deaminase. It manifests with occasional neurovisceral crises due to overproduction of porphyrin precursors. We report a 12 year old male child with acute intermittent porphyria, who presented with encephalopathy and transient blindness of cerebral origin.

Experience with oral mexiletine in primary erythromelalgia in children.

Primary erythromelalgia is characterized by burning pain, redness, and warmth in the extremities. We present two cases of primary erythromelalgia both of whom presented with a history of several months of severe burning pain in both hands and feet. Both patients had received multiple pain medications with no improvement in symptoms. Pain was relieved by putting affected parts in ice cold water, which resulted in immersion injury of the affected parts. Both patients stopped taking part in school and social activities. We tried oral mexiletine, a class Ib antiarrythmic agent, in view of its reported role in various chronic painful conditions. Dramatic improvement was observed with its use. Both patients improved after several weeks of use, and there were fewer soaking episodes. We observed no adverse effects with mexilitine therapy.