Comparison of the efficacy of esophageal balloon dilatation and Botox injection, with esophageal balloon dilatation alone, in children with achalasia referred to Mofid children hospital (2020-2023)

Comparison of the efficacy of esophageal balloon dilatation and Botox injection, with esophageal balloon dilatation alone, in children with achalasia referred to Mofid children hospital (2020-2023) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparison of the efficacy of esophageal balloon dilatation and Botox injection, with esophageal balloon dilatation alone, in children with achalasia referred to Mofid children hospital (2020-2023) Naghi Dara, Mohammad Aghaei, Amirhossein Hosseini, yasaman zarinfar, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4854073/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Aug, 2025 Read the published version in Scientific Reports → Version 1 posted 13 You are reading this latest preprint version Abstract Background: Achalasia is an esophageal motility disorder with symptoms like regurgitation, dysphagia, anorexia, and chronic cough. Effective treatments include pneumatic dilatation and myotomy. This study evaluated the combined use of botulinum toxin (Botox) injection and esophageal balloon dilation versus balloon dilation alone, analyzing recovery rates for gastrointestinal and non-gastrointestinal symptoms. Study method: This clinical trial involved an intervention group and historical controls. Patients with symptomatic achalasia referred to Mofid Hospital (2020-2023) received balloon dilatation with Botox injection. Historical controls had balloon dilatation alone. Botox was injected at four points in the Lower Esophageal Sphincter (LES) before balloon dilatation. Symptoms and growth parameters were monitored every three months for a year, then every six months, with annual follow-ups for three years. The study included 37 intervention and 31 control patients, and data were analyzed using SPSS 24 software. Results: From the onset of the study to the 36th month, the intervention group showed greater symptom improvement than the control group: nausea or vomiting (19%), regurgitation (21%), dysphagia to liquids (37%), dysphagia to solids (10%), globus sensation (10%), anorexia (2.14%), weight loss (18%), halitosis (15%), cough (44%), aspiration (18%), and refusal to eat (7%). Exceptions were chest pain (same in both groups) and heartburn (14% better in the control group). At 6 and 12 months, the intervention group improved in abdominal tenderness (4.2%), wheezing (7.11%), and coarse rales (20.9%). Radiological signs improved more in the intervention group: esophageal dilatation (11.6%), rat tail/bird beak sign (31.7%), tertiary contractions (10.4%), and reduced air-fluid level in the esophagus (upper to middle third: 17%, middle to lower third: 35.8%), except for the sigmoid esophagus (same in both groups). At 36 months, growth criteria in the intervention group increased: weight (4 kg), length (5.35 cm), BMI (1.47 units), Z score (0.65 units), and percentile (5.65 units). Conclusion: The combined balloon and Botox treatment has shown effectiveness in improving disease symptoms, physical examination results, growth criteria, and radiological findings. Further studies are recommended to potentially establish this approach as a national protocol. Health sciences/Medical research Health sciences/Medical research/Paediatric research achalasia balloon dilatation Botox children effectiveness Figures Figure 1 Figure 2 Introduction Achalasia is a primary esophageal motility disorder whose etiology remains elusive. It is characterized by the failure of the lower esophageal sphincter to relax and by the diminished or absent esophageal peristalsis, both contributing to a functional obstruction at the distal esophagus. Clinically, Achalasia presents with regurgitation and dysphagia for both solids and liquids and may be associated with malnutrition or a chronic cough. Residual food within the esophagus can lead to esophagitis ( 1 ). If achalasia is not treated, the patients suffer from acute and chronic malnutrition and their mental and physical condition will be at risk. The most effective current treatment options include two methods pneumatic dilatation or myotomy method( 2 ). In previous studies, the effects of dilation balloon alone and Botox injection alone have been investigated, and research on the simultaneous injection of Botox and dilatation balloon has been carried out to a small extent. Botox injection into the LES during endoscopy is an effective treatment by inhibiting the release of acetylcholine from nerve terminals. Botox injection in the LES is an attempt to treat achalasia, and instead of disrupting the sphincter mechanically or surgically with existing treatments, it reduces LES pressure. Its foundation is based on the action of Botox, which reduces LES pressure by preventing the release of acetylcholine at the level of cholinergic synapses, thus reestablishing a balance by reducing nitric oxide. The administration technique entails injecting Botox at a dosage of 10 units per kilogram of body weight, not exceeding 100 units, distributed across four quadrants just above the squamocolumnar junction, utilizing a sclerotherapy injection needle. Adverse events associated with this procedure are very rare. While immediate response is seen in most patients after injection of Botox into the LES can be both diagnostic and therapeutic. After administration of a Botox injection, patients typically experience an alleviation of symptoms for an average duration of four months. Consequently, it is frequently necessary to undertake repeated treatments on an annual basis( 3 ). In addition, Botox injection monotherapy results in permanent symptom relief in approximately 10–40% of adult cases( 4 ), consequently, these patients necessitate surgical intervention. Botox injection alone reduces the symptoms of achalasia in up to 60% of cases, but there are few studies about the simultaneous injection of Botox and dilation balloon in children and few clinical trials have been conducted so far. This dual therapy has been shown to reduce dysphagia, improve nutritional status, and correct malnutrition due to decreased food intake. Radiographically, it is associated with a reduction in esophageal diameter and a decrease in the height of the liquid-air interface secondary to functional obstruction. It is imperative to investigate whether the concurrent administration of Botox injection and balloon dilation, as opposed to balloon dilation alone, effectively reduces the symptoms of the disease, reduces dysphagia, enhances nutritional uptake, and rectifies malnutrition resulting from diminished food consumption. Additionally, it warrants examination whether this combined treatment modality contributes to a reduction in the esophageal diameter and a decrease in the height of the liquid-air interface secondary to functional obstruction, as observed radiographically( 2 , 5 ). Patients with achalasia often require hospitalization for esophageal balloon dilation at intervals of a few months. The concurrent administration of Botox may decrease the frequency of hospitalizations annually, thereby reducing the risks associated with anesthesia, lowering patient healthcare costs, and enhancing the overall quality of life. Given that this center (Mofid Children Hospital) is one of the main referral centers for achalasia patients in Iran and considering the scarcity of studies conducted on pediatric populations globally, the new method presented can be suggested as a more effective and practical method. The purpose of this study is to evaluate the rate of improvement in both gastrointestinal and non-gastrointestinal symptoms in patients with achalasia undergoing concurrent balloon dilatation and Botox injection at the same time, as opposed to balloon dilation alone. This research aims to ascertain the reasons for the patients’ visits and the nature of gastrointestinal complication and the indications for performing endoscopy in these patients, thereby facilitating the determination of the most effective treatment modality. Furthermore, the study compares the efficacy of combined Botox injections and balloon dilation against balloon dilation monotherapy in achalasia patients, considering variables such as age, sex, duration of recovery, nutritional status, and the severity and incidence of the condition.in this study we compare the recovery rates using growth parameters (weight, height, and body mass index (BMI)), clinical and radiological findings, between the group receiving balloon dilation with Botox injection (intervention group) and the group undergoing balloon dilation alone (control group). Additionally, the complications and prognostic factors post-treatment with balloon dilation and Botox injection in comparison to balloon dilation monotherapy are investigated. The implementation of this study has been associated with an extended recovery period for clinical symptoms, a reduction in hospitalizations, anesthesia-related complications, and overall costs for achalasia patients, culminating in an enhanced quality of life. Methods and materials Study design: The present study is a clinical trial with a historical control group. The intervention group was selected from patients diagnosed with esophageal achalasia in need of treatment, who were referred to the endoscopy department of Mofid Children's Hospital. For this group, balloon dilatation was performed simultaneously with Botox injection. The historical control group was selected from patients with achalasia who underwent balloon dilatation alone in Mofid Hospital between 2014 and 2021. The aim was to assess the comparative effectiveness of simultaneous balloon dilation and Botox injection versus balloon dilation alone. Inclusion Criteria: Patients diagnosed with esophageal achalasia and aged three months to 14 years presenting with symptoms of dysphagia, weight loss, respiratory symptoms, and chest pain due to food aspiration, and exhibiting signs of failure to thrive (FTT), abdominal pain, chest pain, or dental caries. Exclusion Criteria: Patients who underwent balloon dilation for reasons other than achalasia, such as anastomotic stricture following esophageal atresia, syndromic FTTs, abdominal pain from alternative etiologies, and chest pain attributable to cardiac conditions. Diagnosis criteria: Patients with the diagnosis of esophageal achalasia included in the study based on the diagnosis criteria mentioned below: 1-High-Resolution Esophageal Manometry : The criterion standard for diagnosing achalasia is high-resolution esophageal manometry . It shows incomplete relaxation of the esophagogastric junction (EGJ) coupled with the absence of organized peristalsis in the esophageal body. Three achalasia subtypes have been defined based on high-resolution manometry findings in the esophageal body: type I (classic achalasia) with low-pressure contractions , type II (achalasia with pan-esophageal pressurization) , and type III (spastic achalasia) . 2-Endoscopic and Radiographic Finding Endoscopic findings include retained saliva with puckering of the gastroesophageal junction. Esophagram (barium swallow) may show a dilated esophagus with bird beaking as an important diagnostic clue.(6-8) Study population: The study population consisted of pediatric patients referred to Mofid Children's Hospital, who were ranging from 3 months old to 14 years old, diagnosed with esophageal achalasia. participants were selected based on predefined inclusion criteria . According to other studies about rare diseases, 37 people were in the intervention group and 31 people were in the control group. The study population consisted of pediatric patients referred to Mofid Children’s Hospital, ranging from 3 months to 14 years of age, diagnosed with esophageal achalasia. Participants were selected based on predefined inclusion criteria. Drawing from literature on rare diseases, the intervention group included 37 individuals, while the control group comprised 31. Data collection and variables: The data collection tools comprised a questionnaire and a researcher-developed checklist, encompassing variables such as age, sex, growth metrics upon presentation, medical history, and physical examination findings pertinent to achalasia. Additional data included radiological assessments pre- and post-endoscopy, balloon dilation outcomes, and the presence or absence of Botox injections. The study also tracked changes in weight and height, the nature and frequency of procedures performed, as per patient records. This research compiled data over a span of three years.Data were derived from patient files , clinical evaluations, radiologist reports on esophageal contrast studies and the information obtained from the parents. The data related to the symptoms of the disease and growth criteria up to three years, and clinical and radiological findings over the same period reviewed . In the initial year of the study the patients were assessed of symptoms and physical examination and the growth criteria (weight, height, BMI, Z Score, and Percentile) every 3 months and radiological studies (with contrast material) were evaluated every 6 months. Subsequent evaluations of clinical symptoms and growth metrics occurred annually in the second and third years . Clinical and radiological findings were extracted and analyzed biannually for one year. The first phase of the study spanned from 2014 to 2019, with the second phase extending from July 2020 to July 2023. The research was conducted in the endoscopy unit of Mofid Children’s Hospital. Intervention group patients exhibited symptomatic achalasia, confirmed through clinical and radiological evidence, and received treatment via endoscopy under general anesthesia. Botox was administered intramuscularly in the distal esophagus at four junctures between squamous and columnar epithelium, using a sclerotherapy needle, at a dosage of 10 U/kg (capped at 100 units), followed by balloon dilation. The dilation balloon pressure ranged from 15 to 35 mmHg, sufficient to induce esophageal rupture. The historical control group consisted of patients with achalasia who underwent esophageal balloon dilation as a standalone treatment between 2014 and 2021, with their data retrospectively collected and analyzed. The symptoms of the disease that were examined include: Nausea/Vomiting Regurgitation Liquid dysphagia Solid dysphagia Globus sensation Anorexia Weight loss Halitosis Chest pain Heartburn Cough Aspiration Feeding refusal Clinical signs were: Abdominal tenderness Wheezing Coarse rales Dental caries Radiological signs included: Dilated esophagus Sigmoid esophagus Bird beak/Rat tail appearance Tertiary contractions Air-fluid levels Growth metrics were: Weight Height BMI Percentile Z-score Statical analysis: After collecting information related to disease symptoms, physical examination, radiological findings, and growth criteria, at the mentioned times, data analysis was done using SPSS version 24 software. Regression analysis is used to analyze the data. For important qualitative variables, logistic regression analysis is used, and for quantitative important variables, linear regression analysis is used. For quantitative variables (such as weight, height, and BMI) that have been repeated at different times (such as time zero, three months, six months, and three years), repeated measure analysis is used, in other words, measurements are analyzed repeatedly. Ethical Considerations: In this study, adherence to the Helsinki Declaration was meticulously ensured at all stages, from data collection through to the finalization of the thesis and dissemination of the research findings. The integrity of scientific processes and the confidentiality of patient information were stringently maintained throughout. The research protocols involving human subjects were rigorously aligned with the ethical standards set forth by both the institutional and national research committees, specifically the Research Ethics Committee of Shahid Beheshti University of Medical Sciences (approval number: IR.SBMU.MSP.REC.1400.636). This study was conducted in strict compliance with the ethical principles outlined in the 1964 Helsinki Declaration and its subsequent updates. No animal studies were conducted by any of the authors for this article. Clinical Trial Registration : This study has been registered with a publicly accessible primary register that participates in the Iranian Registry of Clinical Trials. The clinical trial registration number is IRCT20240629062273N1, with the first trial registration date at 23/07/2024. Informed Consent : Informed consent was obtained from all individual participants included in the study. For participants who are minors, informed consent was obtained from their parents and/or legal guardians. Results After reviewing 189 patient files among children referred to Mofid Hospital, 115 cases with balloon dilatation and 64 cases with achalasia. According to the inclusion criteria, 37 patients were in the intervention group and 31 patients were in the control group. The intervention group, consisting of 19 boys and 18 girls, received both balloon dilation and Botox injections, while the control group, comprising 21 boys and 10 girls, received only balloon dilation. At the study’s onset, the average weight of the children was 26 kg in the intervention group and 12.5 kg in the control group. Notably, 10 patients were diagnosed with Addison’s syndrome and Alacrima (Allgrove syndrome or triple A), with an equal distribution across both groups. Endoscopic procedures and Botox administrations were recorded as follows: In the intervention group, 23 patients received Botox injection once, 8 patients received twice, 4 patients received three times, and 2 patients received four times. The average intervals between the first and second, second and third, and third and fourth injections were 6.5 months, 4 months, and 15 months, respectively. In the control group, balloon dilations were performed once for 13 patients, twice for 5, thrice for 4, four times for 6, five times for 2, and ten times for one patient. The intervals between successive dilations ranged from 1.5 to 3 months. Data analysis included symptoms of the disease, clinical and radiological signs, and growth parameters over a three-year period. Symptoms and growth parameters (weight, height, Body, BMI, Z-score, and percentile) were recorded every three months in the first year. In the second and third year, this information was obtained annually. Clinical findings (signs) and radiological findings were extracted and analyzed every 6 months for one year. Table 1 presents a detailed comparison of clinical and radiographic signs and symptoms between two groups (intervention and control) over 36 months. The intervention group received a combination of a dilation balloon and Botox injection, while the control group received only the dilation balloon treatment. Nausea and Vomiting (N/V): The intervention group showed a decrease from 48.1% to 22.7%, indicating a significant improvement. The control group, however, had an increase from 51.9% to 77.3%, suggesting worsening of symptoms or less effective treatment. Regurgitation: In the intervention group, there was a notable decrease from 54.3% to 21.1%. The control group saw an increase from 45.7% to 78.9%, again indicating that the intervention was more effective. Dysphagia (Liquid and Solid): Both types of dysphagia showed better outcomes in the intervention group. Liquid dysphagia decreased from 51.4% to 26.3%, and solid dysphagia from 75.7% to 24.3%. The control group had less improvement. Globus Sensation: A decrease from 21.6% to 8.1% was observed in the intervention group, while the control group had a slight increase from 16.1% to 16.1%. Anorexia and Weight Loss: Both symptoms improved more in the intervention group, with anorexia decreasing from 51.4% to 18.9% and weight loss from 64.9% to 21.6%. Halitosis, Chest Pain, and Heartburn: These symptoms also showed more significant improvement in the intervention group compared to the control group. Radiographic Features: Dilated Esophagus: The intervention group saw a reduction from 89.2% to 56.8%, while the control group’s reduction was from 90.3% to 67.7%. Sigmoid Esophagus and Bird Beak/Rat Tail: Both conditions showed greater improvement in the intervention group. Tertiary Contractions: The intervention group had a decrease from 27% to 10.8%, while the control group decreased from 32.3% to 22.6% (presented in figure a and b). Air Fluid Level: This feature was assessed with a grading system from 0 to 3. The intervention group showed an increase in grade 0 from 0% to 45.9%, indicating an improvement. The control group had an increase in grade 0 from 0% to 48.4% (presented in figure a and b). Table 2 shows the analysis of the growth factors between the intervention group (receiving a dilation balloon combined with Botox injection) and the control group (receiving a dilation balloon alone) over 36 months revealing significant differences in growth trajectories. Weight: The intervention group showed a consistent increase in weight from 24.96 kg to 41.32 kg, indicating a positive growth trend. The control group had a more modest increase from 13.72 kg to 18.47 kg. Length/Height: The intervention group’s length increased from 119.48 cm to 143.21 cm, suggesting normal growth progression. The control group’s length also increased but at a slower rate, from 94.00 cm to 111.93 cm. BMI: The intervention group’s BMI increased from 16.00 to 18.95, remaining within a healthy range throughout the study period. The control group’s BMI showed minimal variation, starting at 13.93 and ending at 15.01. Percentile: The intervention group’s percentile scores improved from 24.36 to 56.18, reflecting better growth compared to the control group. The control group’s percentile scores also improved but remained lower, from 15.73 to 32.82. Z-Score: The intervention group’s Z-score improved from -1.36 to 0.188, moving towards the average for the population. The control group’s Z-score remained relatively stable, with a slight improvement from -1.50 to -0.87. To check that at the end of three years of follow-up, in someone who had or did not have regurgitation, what confounding factors besides the intervention and control factors have a role that can increase or decrease the amount of regurgitation, the variables of the group, age, gender, number of times referral, the number of balloon dilatation, triple-A accompaniment, and primary regurgitation at the beginning of the study were entered into the Logistic regression model to determine the degree of their relationship and the degree of confounding about each other to determine the true effect of the intervention (balloon and Botox at the same time). According to Table 3, in the regression model, the above confounding factors were excluded from the study and only the main variables remained, and the effect of the confounders was adjusted in this way. By entering the variables that we assumed to be confounding, in the logistic regression model, our final result is the regurgitation of the 36th month, which is an independent variable. The group variable and the number of balloon times remained in the model, but the rest of the variables were removed from the model. Patients who underwent balloon alone were 8.7 times more likely to have regurgitation after three years. When the number of times the balloon is increased, the chance of regurgitation increases by 49%. According to Table 4, In the case of Nausea/Vomiting, after removing other variables from the regression model, only the balloon group, Botox balloon, and gender remain. The chance of remaining nausea/vomiting at the end of the 36th month, in the balloon dilatation group alone, is 11 times higher than in the intervention group. The chance of having nausea/vomiting in the female group is 3.8 times higher than that of males. In the case of the Weight variable, after removing other variables from the model, the initial weight and age variables remain. In children who received balloon and Botox, compared to those who received balloon alone, the average weight gain was 5.6 kg higher than the average of the control group. The average initial weight in the intervention group has reached from 24 to 41 in the 36th month (the difference is 17 kg) and the control group has reached from 13 to 18 (the difference is 5 kg). The average weight in the 36th month was 41 in the intervention group and 18 in the balloon group, and this difference (23 kg) in the baseline was 11 kg. Regarding the Length variable, we entered the base height and 36th-month height, age, and gender in the regression model, the age and gender variables were removed from the model. In the intervention group, three years after the intervention, in the 36th month, the average height increased by almost 8 units (cm). Regarding the BMI variable, in the intervention group, compared to the control group, three years after the intervention, the average BMI increased by 1.65 units. As for the Z score variable in the intervention group, compared to the control group, three years after the intervention, it increased by 0.96 points. Discussion This research investigated the effect of simultaneous treatment with Botox and balloon dilation compared to balloon dilation alone in children with esophageal achalasia. The study found that the combined treatment resulted in better improvement in most of the disease symptoms, radiological signs, and growth criteria (including weight, height, BMI, Z score, and percentile) compared to the control group. Additionally, the intervention group showed superiority based on age and gender. The study explored the simultaneous and combined effects of these two different treatment methods in a group of children. Previous research has primarily focused on the effects of Botox and balloon dilation as separate interventions in adults, and only a few studies conducted on pediatric patients. To date, no similar study was done. In this study, more precise criteria for review and comparison, with a follow-up period extending over three years. In contrast, related research has tended to employ broader review methodologies, resulting in less precise outcomes. The recent studies indicates that the methods that have been investigated, in case of no response to medication alone or balloon dilatation alone, have finally ended in myotomy surgery, but the present study suggests a third solution which, if implemented, could significantly reduce the necessity for surgical intervention. Mario Costantini et al discuss the various treatment options for esophageal achalasia, acknowledging the role of Botox injections and pneumatic dilation as traditional therapies, which have been challenged by surgical approaches but remain relevant for certain patient populations(9). Also, Zaheer Nabi et al conducted a study evaluating the long-term outcomes of per-oral endoscopic myotomy (POEM) in children and adolescents with achalasia cardia suggests that POEM is a durable treatment modality for achalasia in the pediatric population, irrespective of the subtype of achalasia and history of prior treatment(10). Elizabeth Brindise et al. in their comprehensive review, discuss the successes of endoscopic treatment options for achalasia, which include Botox injection, pneumatic dilation, and POEM. The article provides a detailed overview of these treatments and delves into recent advancements, underscoring their continued recommendation for patients with achalasia. This is particularly pertinent for individuals who are medically unfit for more invasive therapies(11). Also, some studies are challenging our results. Froukje B. van Hoeij et al conducted a systematic review and meta-analysis on the efficacy and safety of pneumatic dilation in achalasia indicating that while pneumatic dilation is a valid treatment option, there may be variability in long-term outcomes, and some patients may require additional interventions (12). Linda Nguyen et al conducted a randomized controlled trial comparing Botox injection to pneumatic dilation for the treatment of achalasia they suggest that endoscopic treatments like pneumatic dilation and Botox injections offer less invasive management of achalasia with varying degrees of symptom relief and recurrence rates. Surgical intervention, while more invasive, provides a longer-lasting solution but carries a higher risk of complications such as reflux (13). Froukje B. van Hoeij et al in another study published in 2017 examine the complications associated with Botox injections for esophageal motility disorders. It suggests that while the procedure is considered effective and low risk for short-term symptom relief, it is not without risks, including rare but serious complications such as acute mediastinitis (13). The intervention group exhibited a significant improvement in symptoms compared to the control group, with notable advancements in nausea, regurgitation, and dysphagia. These findings align with the systematic review by Pandolfino and Gawron, which emphasizes the efficacy of interventions targeting the lower esophageal sphincter in achalasia(14). However, the absence of improvement in chest pain and the unexpected higher improvement in heartburn symptoms in the control group present an intriguing divergence from the norm. This could be compared to the findings of Patel et al., who reported variable responses to treatment based on achalasia subtypes, suggesting a potential influence of subtype-specific pathophysiology on symptom manifestation and treatment response(15). Most radiological signs improved in the intervention group, with significant changes in esophageal dilatation and the rat tail/bird beak sign. These improvements are critical indicators of successful intervention, as highlighted in the European achalasia trial(16). On the contrary, the similar outcomes for the sigmoid esophagus between both groups challenge the expected results, which could be contrasted with the long-term outcomes study by Jung et al., where balloon dilation and Botox injection showed differing impacts on esophageal morphology(17). The intervention group’s growth criteria, including weight and BMI, showed marked increases, underscoring the potential of combined treatments to enhance overall patient growth and development. This is supported by the overview provided by Patel, Lappas, and Vaezi, which discusses the nutritional implications of achalasia and its treatments(15). Nevertheless, the study by Moonen et al. presents a conflicting perspective, suggesting that the type of achalasia may significantly influence the long-term growth outcomes, a factor that should be considered when interpreting these results(16). The research’s outcomes have successfully achieved its purposes. Specifically, the concurrent administration of Botox and balloon dilation has resulted in a reduction in both hospital visits and the frequency of anesthesia and balloon dilatations, yielding economic and medical benefits for patients. Further investigation into the long-term adverse effects of Botox and the fibrosis at the injection site may lead to the formulation and exploration of new hypotheses. A particularly salient hypothesis involves the longitudinal assessment of the same cohort based on developmental benchmarks and quality of life over intervals of five and ten years, thereby elucidating the enduring impact of the combined Botox and balloon therapy. The significance of this study’s findings lies in the observed synergistic effect of the integrated treatment approach. The minimal complications and constraints associated with this modality, coupled with the widespread availability of the requisite medication and the procedural ease of injection and balloon dilation, facilitate its implementation across all facilities equipped with endoscopic apparatus. Limitations and suggestions : The rarity of achalasia caused a relatively small sample size, which means that the findings may not apply to everyone. Comparisons with past treatments can bias the results. This study looked differently at chest pain and heartburn, so treatment may not help all symptoms; because the patients in the control group were selected as historical control, there was a limitation in completing the information in the file, which was collected by long follow-ups, asking the parents, and checking the previous documents in the patient's files. It is suggested that access to the medical records of the patients is not limited to the hospital and through the site while maintaining the confidentiality of the patient's files, the accesses become easier and faster. Because of the encouraging results, further studies into this combined treatment approach are guaranteed, so it is suggested to investigate more about this type of intervention, and the investigation will be done over a longer period so that this treatment method is used as an international protocol of treatment. Also, future trials should investigate why symptoms differ to develop better programs for each individual. Further studies can elucidate the sustained efficacy of the treatment. Conclusion The findings of this study demonstrate that the combined treatment of Botox injection and balloon dilation is better than balloon dilation alone. This result is supported by evidence showing improvement in disease symptoms, relief of symptoms, increase in growth indicators, and improvement in radiological signs. A comprehensive analysis suggests that the combination of Botox with dilatation can potentially provide a more effective treatment protocol for achalasia. Declarations Ethics approval and consent to participate: The study was approved by the relevant local ethics committees ( IR.SBMU.MSP.REC.1400.636) Informed consent was obtained from all individual participants included in the study. For our participants who were pediatrics, informed consent was obtained from their parents and/or legal guardians. Availability of data and materials: The data generated by and used in the study is available from the corresponding author upon reasonable request. Competing interests: Declaration of competing interest, no financial disclosures or conflicts of interest for any of the authors. Funding: This study was funded by Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Authors' contributions: ND, MA and MH participated in the study design. BO, AS, AH and AD participated in the acquisition and interpretation of all data. AS, AH, FI, MA wrote the first draft of manuscript. YZ, ND and MH critically revised the manuscript. All the authors have read the journal’s authorship agreement, and the manuscript has been reviewed by and approved by all named authors. 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Indications, success, and adverse event rates of pediatric endoscopic retrograde cholangiopancreatography (ERCP): a systematic review and meta-analysis. BMC pediatrics. 2023;23(1):596. Khashab MA, Vela MF, Thosani N, Agrawal D, Buxbaum JL, Fehmi SMA, et al. ASGE guideline on the management of achalasia. Gastrointestinal endoscopy. 2020;91(2):213-27. e6. Vaezi MF, Pandolfino JE, Yadlapati RH, Greer KB, Kavitt RT. ACG clinical guidelines: diagnosis and management of achalasia. Official journal of the American College of Gastroenterology| ACG. 2020;115(9):1393-411. Jarzębicka D, Czubkowski P, Sieczkowska-Gołub J, Kierkuś J, Kowalski A, Stefanowicz M, Oracz G. Achalasia in children—clinical presentation, diagnosis, long-term treatment outcomes, and quality of life. Journal of Clinical Medicine. 2021;10(17):3917. Costantini M, Salvador R, Costantini A. Esophageal Achalasia: Pros and Cons of the Treatment Options. World Journal of Surgery. 2022;46(7):1554-60. 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Moonen A, Annese V, Belmans A, Bredenoord AJ, des Varannes SB, Costantini M, et al. Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy. Gut. 2016;65(5):732-9. Jung HE, Lee JS, Lee TH, Kim JN, Hong SJ, Kim JO, et al. Long-term outcomes of balloon dilation versus botulinum toxin injection in patients with primary achalasia. The Korean Journal of Internal Medicine. 2014;29(6):738. Tables Table 1, Comparison of clinical and radiographic signs and symptoms in the intervention and control groups as a follow-up every 6 months in both intervention groups (dilation balloon combined with botox injection) and control (dilation balloon alone) ‍ variables Groups 0 months 6 months 12 months 24 months 36 months Sign/symptom N/V Intervention 25(48.1) 9(32.1) 7(29.2) 5 (25) 5(22.7) Control 27(51.9) 19(67.9) 17(70.8) 15 (75) 17(77.3) Regurgitation Intervention 19(54.3) 7 (38.9) 5 (33.3) 33(67.3) 4 (21.1) Control 16(45.7) 11(61.1) 10(66.7) 12 (80) 15(78.9) Liquid dysphagia Intervention 19(51.4) 8(40) 5 (33.3) 4(25) 5 (26.3) Control 18(48.6) 12(60) 10(66.7) 12(75) 14(73.7) Solid dysphagia Intervention 28(75.7) 9(24.3) 7 (18.9) 7 (18.9) 9(24.3) Control 21(67.7) 15(48.40 13(41.9) 14(45.2) 13(41.9) Globus sensation Intervention 8 (21.6) 3(8.1) 2 (5.4) 2 (5.4) 3(8.1) Control 5 (16.1) 3(9.7) 3(9.7) 4 (12.9) 5 (16.1) anorexia Intervention 19(51.4) 10(27) 9 (24.3) 7(18.9) 7(18.9) Control 17(54.8) 12(38.7) 11(35.5) 13(41.9) 13(41.9) Weight loss Intervention 24(64.9) 9(24.3) 8 (21.6) 8 (21.6) 8 (21.6) Control 21(67.7) 13 (41.9) 15(78.9) 15(78.9) 16(45.7) halitosis Intervention 23(62.2) 10(27) 9 (24.3) 8 (21.6) 9 (24.3) Control 19(61.3) 14(45.2) 14(45.2) 16(45.7) 16(45.7) Chest pain Intervention 13 (35.1 5 (13.5) 7 (18.9) 8 (21.6) 8 (21.6) Control 9 (29) 5 (13.5) 5 (13.5) 6 (19.4) 6 (19.4) Hurt burn Intervention 2 (28.6) 0(0) 0(0) 1(14.3) 0(0) Control 7(22.6) 5 (16.1) 5(16.1) 4(12.9) 5(16.1) cough Intervention 18(48.6) 7(18.9) 6 (16.2) 6 (16.2) 7(18.9) Control 19(61.3) 12 (38.7) 11(35.5) 13(41.9) 15(48.4) aspiration Intervention 17(45.9) 5 (13.5) 5 (13.5) 5 (13.5) 6 (16.2) Control 15(48.4) 9(29) 8(25.8) 10(32.3) 12(38.7) Refuse of feeding Intervention 8 (21.6) 4 (10.8) 3 (8.1) 3 (8.1) 5 (13.5) Control 7 (22.1) 5 (16.1) 5 (16.1) 6 (19.4) 6 (19.4) Alacrimation Intervention 4 (10.8) 4 (10.8) 3(8.1) Control 5 (16.1) 5 (16.1) 5 (16.1) Abdominal tenderness Intervention 9 (24.3) 4 (10.8) 3(8.1) Control 8 (25.8) 6(19.4) 6(19.4) wheezing Intervention 13(35.1) 5 (13.5) 5 (13.5) Control 12(38.7) 9(29) 9(29) Coarse rales Intervention 17(45.9) 7 (18.9) 6 (16.2) Control 14(45.2) 9(29) 10(32.3) Dental caries Intervention 19(51.4) 16(43.2) Control 11(35.5) 13(41.9) Radiologic features Dilated esophagus Intervention 33(89.2) 24 (64.9) 21(56.8) Control 28(90.3) 23 (74.2) 21(67.7) Sigmoid esophagus Intervention 10 (27) 8(21.6) 5 (13.5) Control 9(29) 9(29) 6 (19.4) Bird beak / Rat tail Intervention 32(86.5) 18(48.6) 10 (27) Control 27(87.1 ) 22(71) 19(61.3) Gastric ulcer Intervention 2 (5.4) Control 1(3.2) tertiary contractions Intervention 10 (27) 6 (16.2) 4 (10.8) Control 10(32.3) 8 (25.8) 7( 22.6 ) Air fluid level intervention 0 0(0) 8(21.6) 17(45.9) 1 3(8.1) 16 (43.2) 14(37.8) 2 21(56.8) 8(21.6) 6 (16.2) 3 13(35.1) 5 (13.5) 0(0) control 0 0(0) 1(3.2) 15(48.4) 1 4(12.9) 9(29) 6 (19.4) 2 16(51.6) 15(48.4) 6 (19.4) 3 11(35.5) 6(19.4) 4(12.9) Table 2, Comparison of growth factors in the intervention and control groups as a follow-up every 6 months in both intervention groups (dilation balloon combined with botox injection) and control (dilation balloon alone) Growth factors Groups 0 months 3 months 6 months 9 months 12 months 24 months 36 months weight intervention 24.96 (15.36) 26.60 (15.84) 28.26 (16.21) 29.94 (16.75) 31.66 (17.31) 37.24 (17.84) 41.32 (18.91) control 13.72 (7.36) 14.42 (7.53) 15.15 (7.70) 15.86 (7.90) 16.44 (8.04) 17.45 (6.72) 18.47 (5.79) length intervention 119.48 (30.76) 121.85 (30.26) 124.02 (29.55) 126.06 (28.93) 128.32 (28.61) 137.34 (26.31) 143.21 (24.54) control 94.00 (23.19) 96.00 (22.75) 98.19 (22.12) 100.06 (12.46) 101.77 (20.92) 106.70 (18.06) 111.93 (17.71) BMI intervention 16.00 (3.32) 16.42 (3.21) 16.82 (3.20) 17.35 (3.21) 17.77 (3.20) 18.45 (3.30) 18.95 (3.46) control 13.93 (1.37) 14.18 (1.33) 15.11 (3.61) 14.91 (2.02) 15.10 (2.05) 14.85 (1.47) 15.01 (1.70) percentile intervention 24.36 (29.56) 30.80 (30.26) 36.33 (32.28) 43.29 (32.30) 48.59 (32.54) 53.45 (28.49) 56.18 (27.12) control 15.73 (19.26) 18.77 (21.39) 22.99 (26.07) 24.82 (26.94) 28.15 (27.79) 29.52 (27.09) 32.82 (28.78) Z score intervention -1.36 (1.68) -0.96 (1.40) -0.60 (1.27) -0.27 (1.21) -0.08 (1.20) 0.08 (0.95) 0.188 (0.87) control -1.50 (1.77) -1.29 (1.66) -1.10 (1.58) -0.96 (1.57) -0.84 (1.54) -0.96 (1.33) -0.87 (1.41) Table 3, Effectiveness of Balloon Dilatation on Gastrointestinal Symptoms in Pediatric Patients: A Statistical Analysis” P. Value O.R (95% CI) Variable < 0.001 11.244 ) 2.959-42.721 ( Balloon N/V --- Balloon &Botox 0.043 3.813 ) 1.044-13.927 ( Gender (female) < 0.001 8.76 ) 2.365-32.453 ( Balloon Regurgitation --- Balloon &Botox 0.062 3.292 ) 0.94-11.527 ( Regurgitation (Baseline) Table 4 Regression Analysis of Growth Outcomes in Pediatric Patients: Baseline Versus 36-Month Follow-Up P. Value B (95% CI) Variable <0.001 0.988 (0.838-1.159) Weight (Baseline) Weight 36 th month <0.001 5.619 (3.592-7.645) Intervention --- Control 0.012 0.051 (0.012-0.091) Age(month) <0.001 0.794 (0.752-0.836) L (Baseline) Length 36 th month <0.001 7.992 (5.467-10.516) Intervention --- Control <0.001 0.776 (0.609-0.944) BMI (Baseline) BMI 36th month 0.002 1.655 (0.661-2.649) Intervention --- Control 0.003 0.017(0.006-0.027) Age (Month) <0.001 0.393 (0.242-0.543) Z (Baseline) Z 36 th month <0.001 0.967 (0.454-1.480) Intervention --- Control Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Aug, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 23 Sep, 2024 Reviews received at journal 23 Sep, 2024 Reviewers agreed at journal 13 Sep, 2024 Reviews received at journal 13 Sep, 2024 Reviewers agreed at journal 13 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviews received at journal 10 Sep, 2024 Reviewers agreed at journal 10 Sep, 2024 Reviewers invited by journal 09 Sep, 2024 Editor assigned by journal 09 Sep, 2024 Editor invited by journal 25 Aug, 2024 Submission checks completed at journal 22 Aug, 2024 First submitted to journal 03 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4854073","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":355387263,"identity":"fa73673d-c4a4-41a2-80b1-107d3338cd18","order_by":0,"name":"Naghi Dara","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Naghi","middleName":"","lastName":"Dara","suffix":""},{"id":355387264,"identity":"c2dbc8c3-bbeb-4420-bf2f-3597c3e9898b","order_by":1,"name":"Mohammad Aghaei","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Aghaei","suffix":""},{"id":355387265,"identity":"e3f63f82-020a-4b45-873c-f8973ecf53d6","order_by":2,"name":"Amirhossein Hosseini","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Amirhossein","middleName":"","lastName":"Hosseini","suffix":""},{"id":355387266,"identity":"77764b2d-cb37-48af-af7e-feb4867fb2ce","order_by":3,"name":"yasaman zarinfar","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"yasaman","middleName":"","lastName":"zarinfar","suffix":""},{"id":355387267,"identity":"9065f54e-bf76-41eb-af00-0f9a605d98dd","order_by":4,"name":"Arshia Dara","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Arshia","middleName":"","lastName":"Dara","suffix":""},{"id":355387268,"identity":"3088412b-f30c-4e03-bc42-589e2a0b33cc","order_by":5,"name":"Aliakbar Sayyari","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Aliakbar","middleName":"","lastName":"Sayyari","suffix":""},{"id":355387269,"identity":"48174baf-f603-41db-91b8-1b9e9dca800d","order_by":6,"name":"Beheshteh Olang","email":"","orcid":"","institution":"Karolinska university hospital","correspondingAuthor":false,"prefix":"","firstName":"Beheshteh","middleName":"","lastName":"Olang","suffix":""},{"id":355387270,"identity":"6d1fee3f-d4b7-434e-84b4-a1f61f1802d7","order_by":7,"name":"Mitra Khalili","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mitra","middleName":"","lastName":"Khalili","suffix":""},{"id":355387271,"identity":"bcddd46c-e7fd-4170-b9f4-95ba6452f317","order_by":8,"name":"Farid Imanzadeh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYDCCA4wNUAYP4wMYmyGBSC3MBkRqgTN42CTgWvABvtuHWzf83FEnz3e891jlzx3bEhvYDz9geLgHtxbJc4ltN3vPsBnOPHMu7TbvmduJDTxpBgwJz3BrMTjD2HaDt42HccONHLPbjG1ALQw5QL8cwK/l5t82CfsN99+YFf4EaeF/Q1jLbd42g8QNN3jMGHhBWiQI2CIJ0iLblpA880yOsTTQL8ZtEs8MDuDTwneG/dnNt211tn3Hzxh+/Lnjtmw/f/LDhz/waMEEbAxIkTUKRsEoGAWjgDwAADMlXqEHHg7jAAAAAElFTkSuQmCC","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Farid","middleName":"","lastName":"Imanzadeh","suffix":""},{"id":355387272,"identity":"ad92b89b-7229-4c37-8d58-399e8ad2af5d","order_by":9,"name":"Mahmoud hajipour","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"hajipour","suffix":""}],"badges":[],"createdAt":"2024-08-03 15:52:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4854073/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4854073/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-81781-5","type":"published","date":"2025-08-25T15:57:07+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66673829,"identity":"92b3ecb0-dcaa-4d10-be21-feb40b6fa2ab","added_by":"auto","created_at":"2024-10-15 10:54:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1104416,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure a\u003c/strong\u003e: Clinical progression of esophageal achalasia in a 9-year-old boy before and after treatment. The pre-treatment image shows an air-fluid level (A.F), tertiary movements (T), and a dilated esophagus (D), culminating in a beak-like appearance (B) at the gastroesophageal junction. The post-treatment image demonstrates the resolution of these features following balloon dilatation and Botox injection. Original blots/gels are presented in Figure a.\u003c/p\u003e","description":"","filename":"figurea.png","url":"https://assets-eu.researchsquare.com/files/rs-4854073/v1/5ffaba5e44f08dafe2f3a66f.png"},{"id":66673834,"identity":"1deb2405-0efd-43ce-bc6f-bf5adbf91a85","added_by":"auto","created_at":"2024-10-15 10:54:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2673978,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure b\u003c/strong\u003e: Clinical progression of esophageal achalasia in a 10-year-old girl before and after treatment. The pre-treatment image illustrates an air-fluid level (A.F) and a dilated esophagus (D), with a beak-like appearance (B) at the gastroesophageal junction. The post-treatment image shows the therapeutic effects of balloon dilatation and Botox injection, with improved esophageal structure. Original blots/gels are presented in Figure b.\u003c/p\u003e","description":"","filename":"figureb.png","url":"https://assets-eu.researchsquare.com/files/rs-4854073/v1/af8cb93a35f737025eaeea43.png"},{"id":90345120,"identity":"4bf4be0c-f93f-4af4-8d51-4f8e9ff62d43","added_by":"auto","created_at":"2025-09-01 16:10:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8918373,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4854073/v1/3c93be28-9845-4037-a0fa-0bd0ce71cbf8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of the efficacy of esophageal balloon dilatation and Botox injection, with esophageal balloon dilatation alone, in children with achalasia referred to Mofid children hospital (2020-2023)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAchalasia is a primary esophageal motility disorder whose etiology remains elusive. It is characterized by the failure of the lower esophageal sphincter to relax and by the diminished or absent esophageal peristalsis, both contributing to a functional obstruction at the distal esophagus. Clinically, Achalasia presents with regurgitation and dysphagia for both solids and liquids and may be associated with malnutrition or a chronic cough. Residual food within the esophagus can lead to esophagitis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). If achalasia is not treated, the patients suffer from acute and chronic malnutrition and their mental and physical condition will be at risk. The most effective current treatment options include two methods pneumatic dilatation or myotomy method(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn previous studies, the effects of dilation balloon alone and Botox injection alone have been investigated, and research on the simultaneous injection of Botox and dilatation balloon has been carried out to a small extent. Botox injection into the LES during endoscopy is an effective treatment by inhibiting the release of acetylcholine from nerve terminals. Botox injection in the LES is an attempt to treat achalasia, and instead of disrupting the sphincter mechanically or surgically with existing treatments, it reduces LES pressure. Its foundation is based on the action of Botox, which reduces LES pressure by preventing the release of acetylcholine at the level of cholinergic synapses, thus reestablishing a balance by reducing nitric oxide. The administration technique entails injecting Botox at a dosage of 10 units per kilogram of body weight, not exceeding 100 units, distributed across four quadrants just above the squamocolumnar junction, utilizing a sclerotherapy injection needle. Adverse events associated with this procedure are very rare. While immediate response is seen in most patients after injection of Botox into the LES can be both diagnostic and therapeutic. After administration of a Botox injection, patients typically experience an alleviation of symptoms for an average duration of four months. Consequently, it is frequently necessary to undertake repeated treatments on an annual basis(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition, Botox injection monotherapy results in permanent symptom relief in approximately 10\u0026ndash;40% of adult cases(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), consequently, these patients necessitate surgical intervention. Botox injection alone reduces the symptoms of achalasia in up to 60% of cases, but there are few studies about the simultaneous injection of Botox and dilation balloon in children and few clinical trials have been conducted so far. This dual therapy has been shown to reduce dysphagia, improve nutritional status, and correct malnutrition due to decreased food intake. Radiographically, it is associated with a reduction in esophageal diameter and a decrease in the height of the liquid-air interface secondary to functional obstruction. It is imperative to investigate whether the concurrent administration of Botox injection and balloon dilation, as opposed to balloon dilation alone, effectively reduces the symptoms of the disease, reduces dysphagia, enhances nutritional uptake, and rectifies malnutrition resulting from diminished food consumption. Additionally, it warrants examination whether this combined treatment modality contributes to a reduction in the esophageal diameter and a decrease in the height of the liquid-air interface secondary to functional obstruction, as observed radiographically(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Patients with achalasia often require hospitalization for esophageal balloon dilation at intervals of a few months. The concurrent administration of Botox may decrease the frequency of hospitalizations annually, thereby reducing the risks associated with anesthesia, lowering patient healthcare costs, and enhancing the overall quality of life. Given that this center (Mofid Children Hospital) is one of the main referral centers for achalasia patients in Iran and considering the scarcity of studies conducted on pediatric populations globally, the new method presented can be suggested as a more effective and practical method.\u003c/p\u003e \u003cp\u003eThe purpose of this study is to evaluate the rate of improvement in both gastrointestinal and non-gastrointestinal symptoms in patients with achalasia undergoing concurrent balloon dilatation and Botox injection at the same time, as opposed to balloon dilation alone. This research aims to ascertain the reasons for the patients\u0026rsquo; visits and the nature of gastrointestinal complication and the indications for performing endoscopy in these patients, thereby facilitating the determination of the most effective treatment modality. Furthermore, the study compares the efficacy of combined Botox injections and balloon dilation against balloon dilation monotherapy in achalasia patients, considering variables such as age, sex, duration of recovery, nutritional status, and the severity and incidence of the condition.in this study we compare the recovery rates using growth parameters (weight, height, and body mass index (BMI)), clinical and radiological findings, between the group receiving balloon dilation with Botox injection (intervention group) and the group undergoing balloon dilation alone (control group). Additionally, the complications and prognostic factors post-treatment with balloon dilation and Botox injection in comparison to balloon dilation monotherapy are investigated. The implementation of this study has been associated with an extended recovery period for clinical symptoms, a reduction in hospitalizations, anesthesia-related complications, and overall costs for achalasia patients, culminating in an enhanced quality of life.\u003c/p\u003e"},{"header":"Methods and materials","content":"\u003cp\u003e\u003cstrong\u003eStudy design:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study is a clinical trial with a historical control group. The intervention group was selected from patients diagnosed with esophageal achalasia in need of treatment, who were referred to the endoscopy department of Mofid Children\u0026apos;s Hospital. For this group, balloon dilatation was performed simultaneously with Botox injection. The historical control group was selected from patients with achalasia who underwent balloon dilatation alone in Mofid Hospital between 2014 and 2021. The aim was to assess the comparative effectiveness of simultaneous balloon dilation and Botox injection versus balloon dilation alone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion Criteria:\u003c/strong\u003e Patients\u003cstrong\u003e diagnosed with esophageal achalasia and\u003c/strong\u003e aged three months to 14 years presenting with symptoms of dysphagia, weight loss, respiratory symptoms, and chest pain due to food aspiration, and exhibiting signs of failure to thrive (FTT), abdominal pain, chest pain, or dental caries.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria:\u003c/strong\u003e Patients who underwent balloon dilation for reasons other than achalasia, such as anastomotic stricture following esophageal atresia, syndromic FTTs, abdominal pain from alternative etiologies, and chest pain attributable to cardiac conditions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnosis criteria: \u003c/strong\u003ePatients with the diagnosis of esophageal achalasia included in the study based on the diagnosis criteria mentioned below:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1-High-Resolution Esophageal Manometry\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe criterion standard for diagnosing achalasia is\u003cstrong\u003e \u003cstrong\u003ehigh-resolution esophageal manometry\u003c/strong\u003e\u003c/strong\u003e. It shows \u003cstrong\u003eincomplete relaxation of the esophagogastric junction (EGJ)\u003c/strong\u003ecoupled with the \u003cstrong\u003eabsence of organized peristalsis\u003c/strong\u003ein the esophageal body.\u003c/p\u003e\n\u003cp\u003eThree achalasia subtypes have been defined based on high-resolution manometry findings in the esophageal body: \u003cstrong\u003etype I (classic achalasia) with low-pressure contractions\u003c/strong\u003e\u003cstrong\u003e, \u003cstrong\u003etype II (achalasia with pan-esophageal pressurization)\u003c/strong\u003e, \u003c/strong\u003eand\u003cstrong\u003e \u003cstrong\u003etype III (spastic achalasia)\u003c/strong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2-Endoscopic and Radiographic Finding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e Endoscopic findings\u003c/strong\u003e include \u003cstrong\u003eretained saliva\u003c/strong\u003e with puckering of the gastroesophageal junction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEsophagram (barium swallow)\u003c/strong\u003e may show a \u003cstrong\u003edilated esophagus with bird beaking\u003c/strong\u003e as an important diagnostic clue.(6-8)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population: The study population consisted of pediatric patients referred to Mofid Children\u0026apos;s Hospital, who were ranging from 3 months old to 14 years old, diagnosed with esophageal achalasia. participants were selected \u003c/strong\u003ebased on predefined inclusion criteria\u003cstrong\u003e. According to other studies about rare diseases, 37 people were in the intervention group and 31 people were in the control group. \u003c/strong\u003eThe study population consisted of pediatric patients referred to Mofid Children\u0026rsquo;s Hospital, ranging from 3 months to 14 years of age, diagnosed with esophageal achalasia. Participants were selected based on predefined inclusion criteria. Drawing from literature on rare diseases, the intervention group included 37 individuals, while the control group comprised 31.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and variables: \u003c/strong\u003eThe data collection tools comprised a questionnaire and a researcher-developed checklist, encompassing variables such as age, sex, growth metrics upon presentation, medical history, and physical examination findings pertinent to achalasia. Additional data included radiological assessments pre- and post-endoscopy, balloon dilation outcomes, and the presence or absence of Botox injections. The study also tracked changes in weight and height, the nature and frequency of procedures performed, as per patient records. This research compiled data over a span of three years.Data were derived from patient files\u003cstrong\u003e, clinical evaluations, radiologist reports on esophageal contrast studies and the information obtained from the parents. The data related to the symptoms of the disease and growth criteria up to three years, \u003c/strong\u003eand clinical and radiological findings over the same period reviewed\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e In the initial year of the study the patients were assessed of symptoms and physical examination and the growth criteria (weight, height, BMI, Z Score, and Percentile) every 3 months and radiological studies (with contrast material) were evaluated every 6 months. \u003c/strong\u003eSubsequent evaluations of clinical symptoms and growth metrics occurred annually in the second and third years\u003cstrong\u003e. Clinical and radiological findings were extracted and analyzed biannually for one year. \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe first phase of the study spanned from 2014 to 2019, with the second phase extending from July 2020 to July 2023. The research was conducted in the endoscopy unit of Mofid Children\u0026rsquo;s Hospital. Intervention group patients exhibited symptomatic achalasia, confirmed through clinical and radiological evidence, and received treatment via endoscopy under general anesthesia. Botox was administered intramuscularly in the distal esophagus at four junctures between squamous and columnar epithelium, using a sclerotherapy needle, at a dosage of 10 U/kg (capped at 100 units), followed by balloon dilation. The dilation balloon pressure ranged from 15 to 35 mmHg, sufficient to induce esophageal rupture. The historical control group consisted of patients with achalasia who underwent esophageal balloon dilation as a standalone treatment between 2014 and 2021, with their data retrospectively collected and analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe symptoms of the disease that were examined include:\u003c/strong\u003e\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eNausea/Vomiting\u003c/li\u003e\n\u003cli\u003eRegurgitation\u003c/li\u003e\n\u003cli\u003eLiquid dysphagia\u003c/li\u003e\n\u003cli\u003eSolid dysphagia\u003c/li\u003e\n\u003cli\u003eGlobus sensation\u003c/li\u003e\n\u003cli\u003eAnorexia\u003c/li\u003e\n\u003cli\u003eWeight loss\u003c/li\u003e\n\u003cli\u003eHalitosis\u003c/li\u003e\n\u003cli\u003eChest pain\u003c/li\u003e\n\u003cli\u003eHeartburn\u003c/li\u003e\n\u003cli\u003eCough\u003c/li\u003e\n\u003cli\u003eAspiration\u003c/li\u003e\n\u003cli\u003eFeeding refusal\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eClinical signs were:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eAbdominal tenderness\u003c/li\u003e\n\u003cli\u003eWheezing\u003c/li\u003e\n\u003cli\u003eCoarse rales\u003c/li\u003e\n\u003cli\u003eDental caries\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eRadiological signs included:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eDilated esophagus\u003c/li\u003e\n\u003cli\u003eSigmoid esophagus\u003c/li\u003e\n\u003cli\u003eBird beak/Rat tail appearance\u003c/li\u003e\n\u003cli\u003eTertiary contractions\u003c/li\u003e\n\u003cli\u003eAir-fluid levels\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eGrowth metrics were:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eWeight\u003c/li\u003e\n\u003cli\u003eHeight\u003c/li\u003e\n\u003cli\u003eBMI\u003c/li\u003e\n\u003cli\u003ePercentile\u003c/li\u003e\n\u003cli\u003eZ-score\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eStatical analysis: \u003c/strong\u003eAfter collecting information related to disease symptoms, physical examination, radiological findings, and growth criteria, at the mentioned times, data analysis was done using SPSS version 24 software. Regression analysis is used to analyze the data. For important qualitative variables, logistic regression analysis is used, and for quantitative important variables, linear regression analysis is used. For quantitative variables (such as weight, height, and BMI) that have been repeated at different times (such as time zero, three months, six months, and three years), repeated measure analysis is used, in other words, measurements are analyzed repeatedly.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Considerations: \u003c/strong\u003eIn this study, adherence to the Helsinki Declaration was meticulously ensured at all stages, from data collection through to the finalization of the thesis and dissemination of the research findings. The integrity of scientific processes and the confidentiality of patient information were stringently maintained throughout. The research protocols involving human subjects were rigorously aligned with the ethical standards set forth by both the institutional and national research committees, specifically the Research Ethics Committee of Shahid Beheshti University of Medical Sciences (approval number: IR.SBMU.MSP.REC.1400.636). This study was conducted in strict compliance with the ethical principles outlined in the 1964 Helsinki Declaration and its subsequent updates. No animal studies were conducted by any of the authors for this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration\u003c/strong\u003e: This study has been registered with a publicly accessible primary register that participates in the Iranian Registry of Clinical Trials. The clinical trial registration number is IRCT20240629062273N1, with the first trial registration date at 23/07/2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e: Informed consent was obtained from all individual participants included in the study. For participants who are minors, informed consent was obtained from their parents and/or legal guardians.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAfter reviewing 189 patient files among children referred to Mofid Hospital, 115 cases with balloon dilatation and 64 cases with achalasia. According to the inclusion criteria, 37 patients were in the intervention group and 31 patients were in the control group.\u0026nbsp;The intervention group, consisting of 19 boys and 18 girls, received both balloon dilation and Botox injections, while the control group, comprising 21 boys and 10 girls, received only balloon dilation.\u0026nbsp;At the study’s onset, the average weight of the children was 26 kg in the intervention group and 12.5 kg in the control group. Notably, 10 patients were diagnosed with Addison’s syndrome and Alacrima (Allgrove syndrome or triple A), with an equal distribution across both groups.\u003c/p\u003e\n\u003cp\u003eEndoscopic procedures and Botox administrations were recorded as follows: In the intervention group, 23 patients received Botox injection once, 8 patients received twice, 4 patients received three times, and 2 patients received four times. The average intervals between the first and second, second and third, and third and fourth injections were 6.5 months, 4 months, and 15 months, respectively. In the control group, balloon dilations were performed once for 13 patients, twice for 5, thrice for 4, four times for 6, five times for 2, and ten times for one patient. The intervals between successive dilations ranged from 1.5 to 3 months.\u003c/p\u003e\n\u003cp\u003eData analysis included symptoms of the disease, clinical and radiological signs, and growth parameters over a three-year period. Symptoms and growth parameters (weight, height, Body, BMI, Z-score, and percentile) were recorded every three months in the first year.\u0026nbsp;In the second and third year, this information was obtained annually. Clinical findings (signs) and radiological findings were extracted and analyzed every 6 months for one year.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Table 1 presents a detailed comparison of clinical and radiographic signs and symptoms between two groups (intervention and control) over 36 months. The intervention group received a combination of a dilation balloon and Botox injection, while the control group received only the dilation balloon treatment.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Nausea and Vomiting (N/V): The intervention group showed a decrease from 48.1% to 22.7%, indicating a significant improvement. The control group, however, had an increase from 51.9% to 77.3%, suggesting worsening of symptoms or less effective treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegurgitation: In the intervention group, there was a notable decrease from 54.3% to 21.1%. The control group saw an increase from 45.7% to 78.9%, again indicating that the intervention was more effective.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDysphagia (Liquid and Solid): Both types of dysphagia showed better outcomes in the intervention group. Liquid dysphagia decreased from 51.4% to 26.3%, and solid dysphagia from 75.7% to 24.3%. The control group had less improvement.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGlobus Sensation: A decrease from 21.6% to 8.1% was observed in the intervention group, while the control group had a slight increase from 16.1% to 16.1%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnorexia and Weight Loss: Both symptoms improved more in the intervention group, with anorexia decreasing from 51.4% to 18.9% and weight loss from 64.9% to 21.6%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHalitosis, Chest Pain, and Heartburn: These symptoms also showed more significant improvement in the intervention group compared to the control group.\u003c/p\u003e\n\u003cp\u003eRadiographic Features: Dilated Esophagus: The intervention group saw a reduction from 89.2% to 56.8%, while the control group’s reduction was from 90.3% to 67.7%.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Sigmoid Esophagus and Bird Beak/Rat Tail: Both conditions showed greater improvement in the intervention group. Tertiary Contractions: The intervention group had a decrease from 27% to 10.8%, while the control group decreased from 32.3% to 22.6% (presented in figure a and b).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAir Fluid Level: This feature was assessed with a grading system from 0 to 3. The intervention group showed an increase in grade 0 from 0% to 45.9%, indicating an improvement. The control group had an increase in grade 0 from 0% to 48.4% (presented in figure a and b).\u003c/p\u003e\n\u003cp\u003eTable 2 shows the analysis of the growth factors between the intervention group (receiving a dilation balloon combined with Botox injection) and the control group (receiving a dilation balloon alone) over 36 months revealing significant differences in growth trajectories. Weight: The intervention group showed a consistent increase in weight from 24.96 kg to 41.32 kg, indicating a positive growth trend. The control group had a more modest increase from 13.72 kg to 18.47 kg. Length/Height: The intervention group’s length increased from 119.48 cm to 143.21 cm, suggesting normal growth progression. The control group’s length also increased but at a slower rate, from 94.00 cm to 111.93 cm. BMI: The intervention group’s BMI increased from 16.00 to 18.95, remaining within a healthy range throughout the study period. The control group’s BMI showed minimal variation, starting at 13.93 and ending at 15.01. Percentile: The intervention group’s percentile scores improved from 24.36 to 56.18, reflecting better growth compared to the control group. The control group’s percentile scores also improved but remained lower, from 15.73 to 32.82. Z-Score: The intervention group’s Z-score improved from -1.36 to 0.188, moving towards the average for the population. The control group’s Z-score remained relatively stable, with a slight improvement from -1.50 to -0.87.\u003c/p\u003e\n\u003cp\u003eTo check that at the end of three years of follow-up, in someone who had or did not have regurgitation, what confounding factors besides the intervention and control factors have a role that can increase or decrease the amount of regurgitation, the variables of the group, age, gender, number of times referral, the number of balloon dilatation, triple-A accompaniment, and primary regurgitation at the beginning of the study were entered into the Logistic regression model to determine the degree of their relationship and the degree of confounding about each other to determine the true effect of the intervention (balloon and Botox at the same time). According to Table 3, in the regression model, the above confounding factors were excluded from the study and only the main variables remained, and the effect of the confounders was adjusted in this way. By entering the variables that we assumed to be confounding, in the logistic regression model, our final result is the regurgitation of the 36th month, which is an independent variable. The group variable and the number of balloon times remained in the model, but the rest of the variables were removed from the model. Patients who underwent balloon alone were 8.7 times more likely to have regurgitation after three years. When the number of times the balloon is increased, the chance of regurgitation increases by 49%.\u003c/p\u003e\n\u003cp\u003eAccording to Table 4, In the case of Nausea/Vomiting, after removing other variables from the regression model, only the balloon group, Botox balloon, and gender remain. The chance of remaining nausea/vomiting at the end of the 36th month, in the balloon dilatation group alone, is 11 times higher than in the intervention group. The chance of having nausea/vomiting in the female group is 3.8 times higher than that of males.\u003c/p\u003e\n\u003cp\u003eIn the case of the Weight variable, after removing other variables from the model, the initial weight and age variables remain. In children who received balloon and Botox, compared to those who received balloon alone, the average weight gain was 5.6 kg higher than the average of the control group. The average initial weight in the intervention group has reached from 24 to 41 in the 36th month (the difference is 17 kg) and the control group has reached from 13 to 18 (the difference is 5 kg). The average weight in the 36th month was 41 in the intervention group and 18 in the balloon group, and this difference (23 kg) in the baseline was 11 kg.\u003c/p\u003e\n\u003cp\u003eRegarding the Length variable, we entered the base height and 36th-month height, age, and gender in the regression model, the age and gender variables were removed from the model. In the intervention group, three years after the intervention, in the 36th month, the average height increased by almost 8 units (cm). Regarding the BMI variable, in the intervention group, compared to the control group, three years after the intervention, the average BMI increased by 1.65 units. As for the Z score variable in the intervention group, compared to the control group, three years after the intervention, it increased by 0.96 points.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis research investigated the effect of simultaneous treatment with Botox and balloon dilation compared to balloon dilation alone in children with esophageal achalasia. The study found that the combined treatment resulted in better improvement in most of the disease symptoms, radiological signs, and growth criteria (including weight, height, BMI, Z score, and percentile) compared to the control group. Additionally, the intervention group showed superiority based on age and gender. The study explored the simultaneous and combined effects of these two different treatment methods in a group of children.\u003c/p\u003e\n\u003cp\u003ePrevious research has primarily focused on the effects of Botox and balloon dilation as separate interventions in adults, and only a few studies conducted on pediatric patients. To date, no similar study was done. In this study, more precise criteria for review and comparison, with a follow-up period extending over three years. In contrast, related research has tended to employ broader review methodologies, resulting in less precise outcomes. The recent studies indicates that the methods that have been investigated, in case of no response to medication alone or balloon dilatation alone, have finally ended in myotomy surgery, but the present study suggests a third solution which, if implemented, could significantly reduce the necessity for surgical intervention. Mario Costantini et al discuss the various treatment options for esophageal achalasia, acknowledging the role of Botox injections and pneumatic dilation as traditional therapies, which have been challenged by surgical approaches but remain relevant for certain patient populations(9). Also, Zaheer Nabi et al conducted a study evaluating the long-term outcomes of per-oral endoscopic myotomy (POEM) in children and adolescents with achalasia cardia suggests that POEM is a durable treatment modality for achalasia in the pediatric population, irrespective of the subtype of achalasia and history of prior treatment(10). Elizabeth Brindise et al. in their comprehensive review, discuss the successes of endoscopic treatment options for achalasia, which include Botox injection, pneumatic dilation, and POEM. The article provides a detailed overview of these treatments and delves into recent advancements, underscoring their continued recommendation for patients with achalasia. This is particularly pertinent for individuals who are medically unfit for more invasive therapies(11).\u003c/p\u003e\n\u003cp\u003eAlso, some studies are challenging our results. Froukje B. van Hoeij et al conducted a systematic review and meta-analysis on the efficacy and safety of pneumatic dilation in achalasia indicating that while pneumatic dilation is a valid treatment option, there may be variability in long-term outcomes, and some patients may require additional interventions (12). Linda Nguyen et al conducted a \u003cstrong\u003erandomized controlled trial\u003c/strong\u003e comparing Botox injection to pneumatic dilation for the treatment of achalasia they suggest that endoscopic treatments like pneumatic dilation and Botox injections offer less invasive management of achalasia with varying degrees of symptom relief and recurrence rates. Surgical intervention, while more invasive, provides a longer-lasting solution but carries a higher risk of complications such as reflux (13). Froukje B. van Hoeij et al in another study published in 2017 examine the complications associated with Botox injections for esophageal motility disorders. It suggests that while the procedure is considered effective and low risk for short-term symptom relief, it is not without risks, including rare but serious complications such as acute mediastinitis (13).\u003c/p\u003e\n\u003cp\u003eThe intervention group exhibited a significant improvement in symptoms compared to the control group, with notable advancements in nausea, regurgitation, and dysphagia. These findings align with the systematic review by Pandolfino and Gawron, which emphasizes the efficacy of interventions targeting the lower esophageal sphincter in achalasia(14). However, the absence of improvement in chest pain and the unexpected higher improvement in heartburn symptoms in the control group present an intriguing divergence from the norm. This could be compared to the findings of Patel et al., who reported variable responses to treatment based on achalasia subtypes, suggesting a potential influence of subtype-specific pathophysiology on symptom manifestation and treatment response(15).\u003c/p\u003e\n\u003cp\u003eMost radiological signs improved in the intervention group, with significant changes in esophageal dilatation and the rat tail/bird beak sign. These improvements are critical indicators of successful intervention, as highlighted in the European achalasia trial(16). On the contrary, the similar outcomes for the sigmoid esophagus between both groups challenge the expected results, which could be contrasted with the long-term outcomes study by Jung et al., where balloon dilation and Botox injection showed differing impacts on esophageal morphology(17).\u003c/p\u003e\n\u003cp\u003eThe intervention group’s growth criteria, including weight and BMI, showed marked increases, underscoring the potential of combined treatments to enhance overall patient growth and development. This is supported by the overview provided by Patel, Lappas, and Vaezi, which discusses the nutritional implications of achalasia and its treatments(15). Nevertheless, the study by Moonen et al. presents a conflicting perspective, suggesting that the type of achalasia may significantly influence the long-term growth outcomes, a factor that should be considered when interpreting these results(16).\u003c/p\u003e\n\u003cp\u003eThe research’s outcomes have successfully achieved its purposes. Specifically, the concurrent administration of Botox and balloon dilation has resulted in a reduction in both hospital visits and the frequency of anesthesia and balloon dilatations, yielding economic and medical benefits for patients. Further investigation into the long-term adverse effects of Botox and the fibrosis at the injection site may lead to the formulation and exploration of new hypotheses. A particularly salient hypothesis involves the longitudinal assessment of the same cohort based on developmental benchmarks and quality of life over intervals of five and ten years, thereby elucidating the enduring impact of the combined Botox and balloon therapy. The significance of this study’s findings lies in the observed synergistic effect of the integrated treatment approach. The minimal complications and constraints associated with this modality, coupled with the widespread availability of the requisite medication and the procedural ease of injection and balloon dilation, facilitate its implementation across all facilities equipped with endoscopic apparatus.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations and suggestions\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe rarity of achalasia caused a relatively small sample size, which means that the findings may not apply to everyone. Comparisons with past treatments can bias the results. This study looked differently at chest pain and heartburn, so treatment may not help all symptoms; because the patients in the control group were selected as historical control, there was a limitation in completing the information in the file, which was collected by long follow-ups, asking the parents, and checking the previous documents in the patient's files. It is suggested that access to the medical records of the patients is not limited to the hospital and through the site while maintaining the confidentiality of the patient's files, the accesses become easier and faster. Because of the encouraging results, further studies into this combined treatment approach are guaranteed, so it is suggested to investigate more about this type of intervention, and the investigation will be done over a longer period so that this treatment method is used as an international protocol of treatment. Also, future trials should investigate why symptoms differ to develop better programs for each individual. Further studies can elucidate the sustained efficacy of the treatment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe findings of this study demonstrate that the combined treatment of Botox injection and balloon dilation is better than balloon dilation alone. This result is supported by evidence showing improvement in disease symptoms, relief of symptoms, increase in growth indicators, and improvement in radiological signs. A comprehensive analysis suggests that the combination of Botox with dilatation can potentially provide a more effective treatment protocol for achalasia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study was approved by the relevant local ethics committees (\u003cstrong\u003eIR.SBMU.MSP.REC.1400.636)\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all individual participants included in the study. For our participants who were pediatrics, informed consent was obtained from their parents and/or legal guardians.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe data generated by and used in the study is available from the corresponding author upon reasonable request.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eDeclaration of competing interest, no financial disclosures or conflicts of interest for any of the authors.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was funded by Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children\u0026rsquo;s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e ND, MA and MH participated in the study design. BO, AS, AH and AD participated in the acquisition and interpretation of all data. AS, AH, FI, MA wrote the first draft of manuscript. YZ, ND and MH critically revised the manuscript. All the authors have read the journal\u0026rsquo;s authorship agreement, and the manuscript has been reviewed by and approved by all named authors.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eThe authors gratefully acknowledge the patients, parents of Mofid Children\u0026rsquo;s hospital. Also, we are grateful to the staffs of Pediatric Gastroenterology, Hepatology and Nutrition Research Center.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBehrman RE, Vaughan V, III. Nelson textbook of pediatrics1983.\u003c/li\u003e\n\u003cli\u003eWyllie R, Hyams JS. Pediatric Gastrointestinal and Liver Disease E-Book: Elsevier Health Sciences; 2010.\u003c/li\u003e\n\u003cli\u003ePatti MG, Feo CV, Arcerito M, De Pinto M, Tamburini A, Diener U, et al. Effects of previous treatment on results of laparoscopic Heller myotomy for achalasia. Digestive diseases and sciences. 1999;44:2270-6.\u003c/li\u003e\n\u003cli\u003eHurwitz M, Bahar RJ, Ament ME, Tolia V, Molleston J, Reinstein LJ, et al. Evaluation of the use of botulinum toxin in children with achalasia. Journal of pediatric gastroenterology and nutrition. 2000;30(5):509-14.\u003c/li\u003e\n\u003cli\u003eHosseini A, Sohouli MH, Sharifi E, Sayyari A, Sridharan K, Tajalli S, et al. Indications, success, and adverse event rates of pediatric endoscopic retrograde cholangiopancreatography (ERCP): a systematic review and meta-analysis. BMC pediatrics. 2023;23(1):596.\u003c/li\u003e\n\u003cli\u003eKhashab MA, Vela MF, Thosani N, Agrawal D, Buxbaum JL, Fehmi SMA, et al. ASGE guideline on the management of achalasia. Gastrointestinal endoscopy. 2020;91(2):213-27. e6.\u003c/li\u003e\n\u003cli\u003eVaezi MF, Pandolfino JE, Yadlapati RH, Greer KB, Kavitt RT. ACG clinical guidelines: diagnosis and management of achalasia. Official journal of the American College of Gastroenterology| ACG. 2020;115(9):1393-411.\u003c/li\u003e\n\u003cli\u003eJarzębicka D, Czubkowski P, Sieczkowska-Gołub J, Kierkuś J, Kowalski A, Stefanowicz M, Oracz G. Achalasia in children\u0026mdash;clinical presentation, diagnosis, long-term treatment outcomes, and quality of life. Journal of Clinical Medicine. 2021;10(17):3917.\u003c/li\u003e\n\u003cli\u003eCostantini M, Salvador R, Costantini A. Esophageal Achalasia: Pros and Cons of the Treatment Options. World Journal of Surgery. 2022;46(7):1554-60.\u003c/li\u003e\n\u003cli\u003eNabi Z, Ramchandani M, Basha J, Goud R, Darisetty S, Reddy DN. POEM is a durable treatment in children and adolescents with achalasia cardia. Frontiers in Pediatrics. 2022;10:812201.\u003c/li\u003e\n\u003cli\u003eBrindise E, Khashab M, El Abiad R. How to Endoscopically Treat Achalasia: to Balloon, Inject, or Incise? Current Treatment Options in Gastroenterology. 2022;20(1):34-45.\u003c/li\u003e\n\u003cli\u003evan Hoeij FB, Prins LI, Smout AJ, Bredenoord AJ. Efficacy and safety of pneumatic dilation in achalasia: A systematic review and meta‐analysis. Neurogastroenterology \u0026amp; Motility. 2019;31(7):e13548.\u003c/li\u003e\n\u003cli\u003evan Hoeij FB, Tack JF, Pandolfino JE, Sternbach JM, Roman S, Smout AJ, Bredenoord AJ. Complications of botulinum toxin injections for treatment of esophageal motility disorders. Diseases of the Esophagus. 2017;30(3).\u003c/li\u003e\n\u003cli\u003ePandolfino JE, Gawron AJ. Achalasia: a systematic review. Jama. 2015;313(18):1841-52.\u003c/li\u003e\n\u003cli\u003ePatel DA, Lappas BM, Vaezi MF. An overview of achalasia and its subtypes. Gastroenterology \u0026amp; hepatology. 2017;13(7):411.\u003c/li\u003e\n\u003cli\u003eMoonen A, Annese V, Belmans A, Bredenoord AJ, des Varannes SB, Costantini M, et al. Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy. Gut. 2016;65(5):732-9.\u003c/li\u003e\n\u003cli\u003eJung HE, Lee JS, Lee TH, Kim JN, Hong SJ, Kim JO, et al. Long-term outcomes of balloon dilation versus botulinum toxin injection in patients with primary achalasia. The Korean Journal of Internal Medicine. 2014;29(6):738.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1, Comparison of clinical and radiographic signs and symptoms in the intervention and control groups as a follow-up every 6 months in both intervention groups (dilation balloon combined with botox injection) and control (dilation balloon alone)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"664\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.371601208459214%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.371601208459214%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026zwj;\u003c/span\u003evariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803625377643504%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e0 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.574018126888218%\" valign=\"top\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e36 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.371601208459214%\" rowspan=\"36\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSign/symptom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.371601208459214%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eN/V\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803625377643504%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e25(48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.574018126888218%\" valign=\"top\"\u003e\n \u003cp\u003e9(32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e7(29.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e5 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e5(22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e27(51.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e19(67.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e17(70.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e15 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e17(77.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRegurgitation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e19(54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e7 (38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e33(67.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e4 (21.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e16(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e11(61.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e10(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e12 (80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e15(78.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eLiquid dysphagia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e19(51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e8(40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e4(25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e18(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e12(60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e10(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e12(75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e14(73.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSolid dysphagia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e28(75.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e9(24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e7 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e7 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e9(24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e21(67.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e15(48.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e13(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e14(45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e13(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGlobus sensation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e2 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e2 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e3(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e3(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e4 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eanorexia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e19(51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e10(27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e9 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e7(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e7(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e17(54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e12(38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e11(35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e13(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e13(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eWeight loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e24(64.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e9(24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e21(67.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e13 (41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e15(78.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e15(78.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e16(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ehalitosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e23(62.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e10(27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e9 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e9 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e19(61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e14(45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e14(45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e16(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e16(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eChest pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e13 (35.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e7 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e9 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e6 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e6 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHurt burn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e2 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e1(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e7(22.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5(16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e4(12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5(16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ecough\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e18(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e7(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e6 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e6 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e7(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e19(61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e12 (38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e11(35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e13(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e15(48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003easpiration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e17(45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e6 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e15(48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e8(25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e10(32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e12(38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eRefuse of feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e3 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e3 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e7 (22.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e6 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e6 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAlacrimation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e5 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAbdominal tenderness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e9 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e8 (25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e6(19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e6(19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ewheezing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e13(35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e12(38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCoarse rales\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e17(45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e7 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e6 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e14(45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e10(32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDental caries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e19(51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e16(43.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e11(35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e13(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.371601208459214%\" rowspan=\"18\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRadiologic features\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.371601208459214%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDilated esophagus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803625377643504%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e33(89.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.574018126888218%\" valign=\"top\"\u003e\n \u003cp\u003e24 (64.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e21(56.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.969788519637461%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e28(90.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e23 (74.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e21(67.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSigmoid esophagus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e10 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e8(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e6 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eBird beak / Rat tail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e32(86.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e18(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e10 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e27(87.1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e22(71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e19(61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGastric ulcer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e2 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e1(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003etertiary contractions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.915904936014627%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e10 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e6 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.685185185185187%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e10(32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e8 (25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e7(\u003cspan dir=\"RTL\"\u003e22.6\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.02376599634369%\" rowspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAir fluid level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.957952468007313%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eintervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.957952468007313%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.79707495429616%\" valign=\"top\"\u003e\n \u003cp\u003e8(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e17(45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.06581352833638%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.793733681462141%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.276762402088774%\" valign=\"top\"\u003e\n \u003cp\u003e16 (43.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e14(37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.793733681462141%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e21(56.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.276762402088774%\" valign=\"top\"\u003e\n \u003cp\u003e8(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e6 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.793733681462141%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e13(35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.276762402088774%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.342592592592593%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.342592592592593%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.203703703703702%\" valign=\"top\"\u003e\n \u003cp\u003e1(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e15(48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.277777777777779%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.793733681462141%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e4(12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.276762402088774%\" valign=\"top\"\u003e\n \u003cp\u003e9(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e6 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.793733681462141%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e16(51.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.276762402088774%\" valign=\"top\"\u003e\n \u003cp\u003e15(48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e6 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.793733681462141%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e11(35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.276762402088774%\" valign=\"top\"\u003e\n \u003cp\u003e6(19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e4(12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.232375979112273%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2, Comparison of growth factors in the intervention and control groups as a follow-up every 6 months in both intervention groups (dilation balloon combined with botox injection) and control (dilation balloon alone)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"685\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.837481698389457%\" valign=\"top\"\u003e\n \u003cp\u003eGrowth factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.348462664714495%\" valign=\"top\"\u003e\n \u003cp\u003eGroups\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e0 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e9 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e36 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.837481698389457%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.348462664714495%\" valign=\"top\"\u003e\n \u003cp\u003eintervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e24.96 (15.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e26.60 (15.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e28.26 (16.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e29.94 (16.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e31.66 (17.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e37.24 (17.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e41.32 (18.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.253521126760564%\" valign=\"top\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e13.72 (7.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e14.42 (7.53)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e15.15 (7.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e15.86 (7.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e16.44 (8.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e17.45 (6.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e18.47 (5.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.837481698389457%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003elength\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.348462664714495%\" valign=\"top\"\u003e\n \u003cp\u003eintervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e119.48 (30.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e121.85 (30.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e124.02 (29.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e126.06 (28.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e128.32 (28.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e137.34 (26.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e143.21 (24.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.253521126760564%\" valign=\"top\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e94.00 (23.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e96.00 (22.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e98.19 (22.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e100.06 (12.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e101.77 (20.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e106.70 (18.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e111.93 (17.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.837481698389457%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.348462664714495%\" valign=\"top\"\u003e\n \u003cp\u003eintervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e16.00 (3.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e16.42 (3.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e16.82 (3.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e17.35 (3.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e17.77 (3.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e18.45 (3.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e18.95 (3.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.253521126760564%\" valign=\"top\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e13.93 (1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e14.18 (1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e15.11 (3.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e14.91 (2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e15.10 (2.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e14.85 (1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e15.01 (1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.837481698389457%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003epercentile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.348462664714495%\" valign=\"top\"\u003e\n \u003cp\u003eintervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e24.36 (29.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e30.80 (30.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e36.33 (32.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e43.29 (32.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e48.59 (32.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e53.45 (28.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e56.18 (27.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.253521126760564%\" valign=\"top\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e15.73 (19.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e18.77 (21.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e22.99 (26.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e24.82 (26.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e28.15 (27.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e29.52 (27.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e32.82 (28.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.837481698389457%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eZ score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.348462664714495%\" valign=\"top\"\u003e\n \u003cp\u003eintervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e-1.36 (1.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e-0.96 (1.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.248901903367496%\" valign=\"top\"\u003e\n \u003cp\u003e-0.60 (1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e-0.27 (1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e-0.08 (1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e0.08 (0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.66325036603221%\" valign=\"top\"\u003e\n \u003cp\u003e0.188 (0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.253521126760564%\" valign=\"top\"\u003e\n \u003cp\u003econtrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e-1.50 (1.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e-1.29 (1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.32394366197183%\" valign=\"top\"\u003e\n \u003cp\u003e-1.10 (1.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e-0.96 (1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e-0.84 (1.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e-0.96 (1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.619718309859154%\" valign=\"top\"\u003e\n \u003cp\u003e-0.87\u003c/p\u003e\n \u003cp\u003e(1.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3, Effectiveness of Balloon Dilatation on Gastrointestinal Symptoms in Pediatric Patients: A Statistical Analysis\u0026rdquo;\u003c/p\u003e\n\u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"661\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.969742813918305%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eP. Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.91376701966717%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eO.R (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.11649016641452%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.96969696969697%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e11.244 \u003cspan dir=\"RTL\"\u003e)\u003c/span\u003e2.959-42.721\u003cspan dir=\"RTL\"\u003e(\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.515151515151516%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBalloon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.515151515151516%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eN/V\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.21243523316062%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e---\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.78756476683938%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBalloon \u0026amp;Botox\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.482625482625483%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.1042471042471%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e3.813 \u003cspan dir=\"RTL\"\u003e)\u003c/span\u003e1.044-13.927\u003cspan dir=\"RTL\"\u003e(\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.413127413127413%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eGender (female)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.96969696969697%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e8.76 \u003cspan dir=\"RTL\"\u003e)\u003c/span\u003e2.365-32.453\u003cspan dir=\"RTL\"\u003e(\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.515151515151516%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBalloon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.515151515151516%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eRegurgitation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"63.21243523316062%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e---\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.78756476683938%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBalloon \u0026amp;Botox\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.482625482625483%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.1042471042471%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e3.292 \u003cspan dir=\"RTL\"\u003e)\u003c/span\u003e0.94-11.527\u003cspan dir=\"RTL\"\u003e(\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.413127413127413%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eRegurgitation\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(Baseline)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 Regression Analysis of Growth Outcomes in Pediatric Patients: Baseline Versus 36-Month Follow-Up\u003c/p\u003e\n\u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"761\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.630749014454665%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eP. Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.89618922470434%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eB (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"40.473061760841%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.603674540682416%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.84514435695538%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.988 (0.838-1.159)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.94750656167979%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eWeight (Baseline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.603674540682416%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eWeight 36\u003csup\u003eth\u003c/sup\u003e month\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.950413223140497%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.925619834710744%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5.619 (3.592-7.645)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.123966942148762%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"66.07142857142857%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.92857142857143%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.950413223140497%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.925619834710744%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.051 (0.012-0.091)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.123966942148762%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eAge(month)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.603674540682416%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.84514435695538%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.794 (0.752-0.836)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.94750656167979%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eL (Baseline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.603674540682416%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eLength 36\u003csup\u003eth\u003c/sup\u003e month\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.950413223140497%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.925619834710744%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.992 (5.467-10.516)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.123966942148762%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"66.07142857142857%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e---\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.92857142857143%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.603674540682416%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.84514435695538%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.776 (0.609-0.944)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.94750656167979%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBMI (Baseline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.603674540682416%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBMI 36th month\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.950413223140497%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.925619834710744%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e1.655 (0.661-2.649)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.123966942148762%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"66.07142857142857%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.92857142857143%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.950413223140497%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.925619834710744%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.017(0.006-0.027)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.123966942148762%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eAge (Month)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.603674540682416%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.84514435695538%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.393 (0.242-0.543)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.94750656167979%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eZ (Baseline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.603674540682416%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eZ 36\u003csup\u003eth\u003c/sup\u003e month\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.950413223140497%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.925619834710744%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.967 (0.454-1.480)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.123966942148762%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"66.07142857142857%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.92857142857143%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"achalasia, balloon dilatation, Botox, children, effectiveness","lastPublishedDoi":"10.21203/rs.3.rs-4854073/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4854073/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAchalasia is an esophageal motility disorder with symptoms like regurgitation, dysphagia, anorexia, and chronic cough. Effective treatments include pneumatic dilatation and myotomy. This study evaluated the combined use of botulinum toxin (Botox) injection and esophageal balloon dilation versus balloon dilation alone, analyzing recovery rates for gastrointestinal and non-gastrointestinal symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy method: \u003c/strong\u003eThis clinical trial involved an intervention group and historical controls. Patients with symptomatic achalasia referred to Mofid Hospital (2020-2023) received balloon dilatation with Botox injection. Historical controls had balloon dilatation alone. Botox was injected at four points in the Lower Esophageal Sphincter (LES) before balloon dilatation. Symptoms and growth parameters were monitored every three months for a year, then every six months, with annual follow-ups for three years. The study included 37 intervention and 31 control patients, and data were analyzed using SPSS 24 software.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eFrom the onset of the study to the 36th month, the intervention group showed greater symptom improvement than the control group: nausea or vomiting (19%), regurgitation (21%), dysphagia to liquids (37%), dysphagia to solids (10%), globus sensation (10%), anorexia (2.14%), weight loss (18%), halitosis (15%), cough (44%), aspiration (18%), and refusal to eat (7%). Exceptions were chest pain (same in both groups) and heartburn (14% better in the control group). At 6 and 12 months, the intervention group improved in abdominal tenderness (4.2%), wheezing (7.11%), and coarse rales (20.9%). Radiological signs improved more in the intervention group: esophageal dilatation (11.6%), rat tail/bird beak sign (31.7%), tertiary contractions (10.4%), and reduced air-fluid level in the esophagus (upper to middle third: 17%, middle to lower third: 35.8%), except for the sigmoid esophagus (same in both groups). At 36 months, growth criteria in the intervention group increased: weight (4 kg), length (5.35 cm), BMI (1.47 units), Z score (0.65 units), and percentile (5.65 units).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe combined balloon and Botox treatment has shown effectiveness in improving disease symptoms, physical examination results, growth criteria, and radiological findings. Further studies are recommended to potentially establish this approach as a national protocol.\u003c/p\u003e","manuscriptTitle":"Comparison of the efficacy of esophageal balloon dilatation and Botox injection, with esophageal balloon dilatation alone, in children with achalasia referred to Mofid children hospital (2020-2023)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 10:54:30","doi":"10.21203/rs.3.rs-4854073/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-23T10:45:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-23T08:53:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66211275188845089853349799838798264508","date":"2024-09-13T12:08:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-13T10:11:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117093212328593561331656954748898633524","date":"2024-09-13T05:22:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338973567713602113916014935599783017568","date":"2024-09-12T03:22:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-10T10:51:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"260221945428099481450211901982367974207","date":"2024-09-10T09:42:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-10T03:16:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-09T10:13:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-26T03:23:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-22T09:39:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-03T15:50:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8fff0c63-83d3-47bc-abae-a8be9a169f34","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":37779914,"name":"Health sciences/Medical research"},{"id":37779915,"name":"Health sciences/Medical research/Paediatric research"}],"tags":[],"updatedAt":"2025-09-01T16:07:22+00:00","versionOfRecord":{"articleIdentity":"rs-4854073","link":"https://doi.org/10.1038/s41598-024-81781-5","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-08-25 15:57:07","publishedOnDateReadable":"August 25th, 2025"},"versionCreatedAt":"2024-10-15 10:54:30","video":"","vorDoi":"10.1038/s41598-024-81781-5","vorDoiUrl":"https://doi.org/10.1038/s41598-024-81781-5","workflowStages":[]},"version":"v1","identity":"rs-4854073","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4854073","identity":"rs-4854073","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}