Computational analysis of nasal airflow and its alteration by a nasal dilator.

Nasal airflow obstruction correlates with several ailments, such as higher patency, increased friction at the mucosal wall or the so-called Little's area, improper air conditioning, and snoring. Nasal dilators are frequently employed, mainly due to their ease of access and use, combined with their non-permanent and non-surgical nature. Their overall efficacy, however, has not been clearly demonstrated so far, with some studies reporting conflicting outcomes, mainly because being based on subjective evaluations. This study employs Computational Fluid Dynamics simulations to analyze the flow inside a real nose, performs an objective assessment of a nasal dilator's effect in terms of airflow and air conditioning, reporting flow paths, friction levels, heat and water fluxes and detailed temperature and humidity distributions. Coincidentally, the studied nose presents a septal deviation, with one nostril being wider than the other. The tubes of the dilator used in both nostrils are identical, as with any standard commercial dilator. Consequently, the dilator widens one nostril, as intended, but results in an obstruction in the other. This allows simultaneously addressing two situations, the nominal function of the dilator, as well as an off-design case. Results indicate a 24 % increase in nasal patency in the design situation. The effect, however, is limited, as quantified by appropriate measures, such as the flow-generated friction at the nose surfaces and the temperature fluxes. Hence, the effect of such a dilator in nominal conditions is perhaps not as large as might be hoped. In the off-design situation, nasal resistance increases by 62 %, an undesirable effect, illustrating the consequences of using an inappropriate dilator.

Clinical outcomes of serial endoscopic balloon dilation for duodenal Crohn's disease-associated strictures.

BACKGROUND: Endoscopic balloon dilation (EBD) is a safe and effective treatment for Crohn's disease (CD)-associated strictures. However, serial EBDs have rarely been reported. This study aimed to evaluate the efficacy and safety of serial EBDs for treating CD-associated duodenal strictures compared with intermittent EBDs. METHODS: Patients with CD-associated duodenal strictures who underwent EBD were recruited. The clinical data, stricture characteristics, number of EBDs, dilation diameter, complications, surgical interventions, and follow-up periods were recorded. Patients were divided into a serial dilation group and an intermittent dilation group to analyze the differences in safety and efficacy. RESULTS: Forty-five patients with duodenal CD-associated strictures underwent a total of 139 dilations. A total of 23 patients in the serial dilation group underwent 72 dilations, for a median of 3 (range 3 ~ 4) dilations per patient, and 22 patients in the intermittent dilation group underwent 67 dilations, for a median of 3 (range 1 ~ 6) dilations per patient. Technical success was achieved in 97.84% (136/139) of the patients. During the follow-up period, three patients in the intermittent dilation group underwent surgery, and the total clinical efficacy was 93.33% (42/45). No difference in safety or short-term efficacy was noted between the two groups, but serial EBDs exhibited significantly greater clinical efficacy between 6 months and 2 years. No significant difference in recurrence-free survival was observed, but the median longest recurrence-free survival and recurrence-free survival after the last EBD in the serial dilation group were 693 days (range 298 ~ 1381) and 815 days (range 502 ~ 1235), respectively, which were significantly longer than the 415 days (range 35 ~ 1493) and 291 days (range 34 ~ 1493) in the intermittent dilation group (p = 0.013 and p = 0.000, respectively). At the last follow-up, the mean diameter of the duodenal lumen was 1.17 ± 0.07 cm in the serial dilation group, which was greater than the 1.11 ± 0.10 cm in the intermittent dilation group (p = 0.018). We also found that the Simple Endoscopic Score for Crohn's Disease was associated with an increased risk of surgical intervention (HR 2.377, 95% CI 1.125-5.020; p = 0.023) and recurrence at 6 months after the last EBD (HR 0.698, 95% CI 0.511-0.953; p = 0.024), as assessed by univariate analysis. CONCLUSIONS: Compared to the intermittent EBDs, serial EBDs for duodenal CD-associated strictures exhibit greater clinical efficacy within two years and could delay stricture recurrence. We suggest that serial EBDs can be a novel option for endoscopic treatment of duodenal CD-associated strictures.

One-step tract dilation using a novel long balloon catheter during endoscopic ultrasound-guided hepaticogastrostomy.

Tract dilation prior to stent placement is an important step in endoscopic ultrasound-guided hepaticogastrostomy. Mukai and colleagues describe their use of a novel catheter with a longer balloon, which enables one-step tract dilation of the gastric wall, liver parenchyma, and bile duct wall, shortening the procedure and reducing bile leakage.

Degrees of Inflammation in the Treatment of Subglottic Stenosis in a Rabbit Model: Histopathological Assessment of a Novel Bioabsorbable Ultra-high Ductility Magnesium Alloy Stent.

OBJECTIVE: Utilizing a novel histopathological scoring system and subglottic stenosis (SGS) rabbit model, we aimed to compare degrees of inflammation and severity of narrowing in the subglottis between two minimally invasive therapeutic modalities: endoscopic balloon dilation (EBD) alone versus EBD with placement of a bioabsorbable ultra-high ductility magnesium (UHD-Mg) alloy stent. METHODS: SGS was induced endoscopically via microsuspension laryngoscopy in 23 New Zealand white rabbits. The control group (n = 11) underwent EBD alone, the study arm (n = 12) underwent EBD with implantation of bioabsorbable UHD-Mg alloy stents. Rabbits were euthanized at 2-, 3-, and 6-weeks after SGS induction, coinciding with wound healing stages. Using Optical Coherence Tomography (OCT), cross-sectional areas of airways were compared to calculate the mean percentage of intraluminal area at sequential time points. A novel histopathological scoring system was used to analyze frozen sections of laryngotracheal complexes. The degree of inflammation was quantified by scoring changes in inflammatory cell infiltration, epithelial ulceration/metaplasia, subepithelial edema/fibrosis, and capillary number/dilation. Univariate analysis was utilized to analyze these markers. RESULTS: We found rabbits implanted with the bioabsorbable UHD-Mg alloy stent had statistically significantly higher scores in categories of hyperplastic change (stents vs controls: 1.48 vs 0.46 p < 0.001), squamous metaplasia (22 vs 5 p < 0.001), and neutrophils/fibrin in lumen (31 vs 8, p < 0.001). Rabbits who received EBD alone had higher scores of subepithelial edema and fibrosis (2.70 vs 3.49, p < 0.0256). The stented rabbits demonstrated significantly increased mean percent stenosis by intraluminal mean area compared to controls at 2 weeks (88.56 vs 58.98, p = 0.032), however at all other time points there was no significant difference between intraluminal subglottic stenosis by mean percent stenosis area. DISCUSSION: Rabbits with SGS treated with UHD-Mg alloy stents demonstrated histopathologic findings suggestive of lower levels of tracheal fibrosis. This could indicate a reduced tendency towards the development of stenosis when compared to EBD alone. There was not a difference in luminal size between stent and non-stented rabbits at the six-week end point. Histologically, however, overall the use of bioabsorbable UHD-Mg alloy stenting elicited a greater tissue response at the level of the superficial mucosa rather than fibrosis of the lamina propria seen in the stented rabbits. This suggests more favorable healing and less of a tendency towards fibrosis and stenosis even though there may not be a benefit from a luminal size standpoint during this early healing period. Compared to known complications of currently available non-bioabsorbable metal or silicone-based stents, this proof-of-concept investigation highlights the potential use of a novel biodegradable UHD-Mg stent as a therapeutic modality for pediatric SGS.

Ultrasound-guided renal puncture followed by endoscopically guided tract dilatation vs standard fluoroscopy-guided percutaneous nephrolithotomy for non-opaque renal stones; a randomized clinical trial.

This study was designed to evaluate the non-inferiority of ultrasound puncture followed by endoscopically guided tract dilatation compared to the standard fluoroscopy-guided PCNL. Forty patients with non-opaque kidney stones eligible for PCNL were randomly divided into two groups. The standard fluoroscopy-guided PCNL using the Amplatz dilator was performed in the XRAY group. In the SONO group, the Kidney was punctured under an ultrasound guide followed by tract dilatation using a combination of the Amplatz dilator based on the tract length and an endoscopically guided tract dilatation using a bi-prong forceps in cases of short-advancement. The primary outcome was successful access. In 90% of cases in the XRAY and 95% in the SONO group access dilatation process was performed uneventfully at the first attempt (p = 0.5). In 45% of cases in the SONO group, bi-prong forceps were used as salvage for short-advancement. In one case in the X-ray group over-advancement occurred. One month after surgery, the stone-free rate on the CT-scan was 75% for the X-ray group and 85% for the SONO group (p = 0.4). There were no significant differences in operation time, hospitalization duration, transfusion, or complication rates between the two groups. We conclude that ultrasound-guided renal puncture, followed by endoscopically guided tract dilatation can achieve a high success rate similar to X-ray-guided PCNL while avoiding the harmful effects of radiation exposure and the risk of over-advancement.

The Efficacy and Safety of Endoscopic Balloon Dilatation in the Treatment of Functional Post-Sleeve-Gastrectomy Stenosis.

Background and Objectives: Functional gastric stenosis, a consequence of sleeve gastrectomy, is defined as a rotation of the gastric tube along its longitudinal axis. It is brought on by gastric twisting without the anatomical constriction of the gastric lumen. During endoscopic examination, the staple line is deviated with a clockwise rotation, and the stenosis requires additional endoscopic manipulations for its transposition. Upper gastrointestinal series show the gastric twist with an upstream dilatation of the gastric tube in some patients. Data on its management have remained scarce. The objective was to assess the efficacy and safety of endoscopic balloon dilatation in the management of functional post-sleeve gastrectomy stenosis. Patients and Methods: Twenty-two patients with functional post-primary-sleeve-gastrectomy stenosis who had an endoscopic balloon dilatation between 2017 and 2023 were included in this retrospective study. Patients with alternative treatment plans and those undergoing endoscopic dilatation for other forms of gastric stenosis were excluded. The clinical outcomes were used to evaluate the efficacy and safety of balloon dilatation in the management of functional gastric stenosis. Results: A total of 45 dilatations were performed with a 30 mm balloon in 22 patients (100%), a 35 mm balloon in 18 patients (81.82%), and a 40 mm balloon in 5 patients (22.73%). The patients' clinical responses after the first balloon dilatation were a complete clinical response (4 patients, 18.18%), a partial clinical response (12 patients, 54.55%), and a non-response (6 patients, 27.27%). Nineteen patients (86.36%) had achieved clinical success at six months. Three patients (13.64%) who remained symptomatic even after achieving the maximal balloon dilation of 40 mm were considered failure of endoscopic dilatation, and they were referred for surgical intervention. No significant adverse events were found during or following the balloon dilatation. Conclusions: Endoscopic balloon dilatation is an effective and safe minimally invasive procedure in the management of functional post-sleeve-gastrectomy stenosis.

Comparative Analysis of Silicone Tube Intubation Versus Probing and Balloon Dilation for Congenital Nasolacrimal Duct Obstruction: A Systematic Review and Meta-Analysis.

OBJECTIVE: Congenital nasolacrimal duct obstruction (CNLDO) is a pediatric disorder with a wide range of pathology. If untreated, the condition may end up with serious complications. Multiple treatment options for CNLDO exist throughout the literature, and there is an ongoing debate on the best intervention for each disease subgroup and the best timing of such interventions. This study compares the success and failure rates of silicone tube intubation (STI) against probing and balloon dilation (BD). METHODS: The authors searched the literature for relevant articles using PubMed, Scopus, web of Science, and Cochrane Library until January 2024. Using RevMan 5.4, the authors compared STI's success and failure rates to probing and BD using risk ratios (RRs) and a random-effect model. In addition, the complication rate of monocanalicular intubation (MCI) versus bicanalicular intubation (BCI) was investigated. The authors used the leave-one-out method to check for influential studies and to resolve heterogeneity. RESULTS: The screening process resulted in 23 eligible articles for inclusion in the authors' review. Silicone tube intubation had a higher chance of resolving the symptoms of CNLDO than probing (RR = 1.11; 95% CI: 1.04, 1.20; P = 0.004) while having less risk of surgical failure (RR = 0.48; 95% CI: 0.30, 0.76; P = 0.002]. Monocanalicular intubation showed no statistically significant difference when compared with BCI in terms of surgical success and failure; however, MCI had a lower risk of complications (RR = 0.68; 95% CI: 0.48, 0.97; P = 0.04). In addition, STI did not demonstrate any significant difference from BD. CONCLUSION: There was no significant difference in success/failure between MCI and BCI; monocanalicular had fewer complications. Silicone tube intubation did better in terms of surgical success than probing, especially in children over 12 months, suggesting that it is the preferred intervention for older patients with CNLDO.

Safety and efficacy of EsoFLIP dilation in patients with esophageal dysmotility: a systematic review.

Esophageal manometry is utilized for the evaluation and classification of esophageal motility disorders. EndoFlip has been introduced as an adjunctive test to evaluate esophagogastric junction (EGJ) distensibility. Treatment options for achalasia and EGJ outflow obstruction (EGJOO) include pneumatic dilation, myotomy, and botulinum toxin. Recently, a therapeutic 30 mm hydrostatic balloon dilator (EsoFLIP, Medtronic, Minneapolis, MN, USA) has been introduced, which uses impedance planimetry technology like EndoFlip. We performed a systematic review to evaluate the safety and efficacy of EsoFLIP in the management of esophageal motility disorders. A systematic literature search was performed with Medline, Embase, Web of science, and Cochrane library databases from inception to November 2022 to identify studies utilizing EsoFLIP for management of esophageal motility disorders. Our primary outcome was clinical success, and secondary outcomes were adverse events. Eight observational studies including 222 patients met inclusion criteria. Diagnoses included achalasia (158), EGJOO (48), post-reflux surgery dysphagia (8), and achalasia-like disorder (8). All studies used 30 mm maximum balloon dilation except one which used 25 mm. The clinical success rate was 68.7%. Follow-up duration ranged from 1 week to a mean of 5.7 months. Perforation or tear occurred in four patients. EsoFLIP is a new therapeutic option for the management of achalasia and EGJOO and appears to be effective and safe. Future comparative studies with other therapeutic modalities are needed to understand its role in the management of esophageal motility disorders.

Endoscopic balloon dilatation for pediatric subglottic stenosis: a meta-analysis of successful outcomes.

OBJECTIVES: The primary goal of this study was to systematically identify all relevant published articles on the use of primary endoscopic balloon dilation for the management of pediatric patients with subglottic stenosis, critically assess the technique's success, and determine which patients are the best candidates for the procedure. METHODOLOGY: This was a systematic review and meta-analysis that aimed to investigate the use and success rate of EBD for treating pediatric SGS. An electronic systematic literature search of three major databases, PubMed, EBSCO, and Web of Science&MEDLINE through Clarivate, was conducted to include the eligible articles. RESULTS: A total of 14 unique studies were included in the final analysis, with 473 cases of pediatric SGS. The pooled success rate of EBD in treatment of pediatric SGS was 76% (k = 14 studies, 95% confidence interval [CI] = 0.65-0.86, P < 0.001, Q test for heterogeneity = 0.03, P < .001, I2 = 91%). CONCLUSIONS: We reported a high success rate of EBD in treating pediatric SGS. The reported complications were uncommon, although they can be serious and life threatening. The intensity of SGS may be related to the likelihood of therapy failure.

Randomized control trial comparing hygroscopic cervical dilators to cervical ripening balloon for outpatient cervical ripening.

BACKGROUND: Outpatient term preinduction cervical ripening with mechanical agents has been associated with reduced length of stay, decreased cesarean delivery rates, low maternal and neonatal complications, and increased incidence of vaginal delivery within 24 hours. OBJECTIVE: This study aimed to demonstrate equivalent efficacy between synthetic hygroscopic dilators and the single-balloon catheter for outpatient cervical ripening. STUDY DESIGN: This randomized control equivalence trial compared synthetic hygroscopic dilators with the 30-mL silicone single-balloon catheter in primiparous and multiparous patients undergoing labor induction. The primary outcome was time from admission to delivery, with a prespecified 3-hour margin of equivalence. The secondary objectives were patient outcomes and perspectives. RESULTS: Between March 1, 2019, and May 31, 2021, 1605 patients met the screening criteria, and 174 patients completed the study. The mean admission-to-delivery time was equivalent at 18.01 hours for the dilator group vs 17.55 hours for the balloon group (P=.04). The cesarean delivery rate of primiparous patients was similar at 28.1% with dilators vs 29.7% with the balloon. The groups had similar median cervical dilation and pain scores on insertion and admission. Overall patient satisfaction was high, 92.8% with dilators vs 96.2% with the balloon. The balloon group had significantly higher rates of early admission and device expulsion. CONCLUSION: Although the enrollment goal was not met, our study suggests that synthetic hygroscopic dilators and the single-balloon catheter for outpatient cervical ripening are both efficacious with similar time from admission to delivery, pain scores, and patient satisfaction with the procedure.

Comparing Simulation Training of Bronchoscopy-Guided Percutaneous Dilatational Tracheostomy Using Conventional Versus 3D Printed Simulators (TRAC-Sim Study).

Background: Individual implementation rate of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) varies among intensivists. Simulation training (ST) can increase the safety of medical procedures by reducing stress levels of the performing team. The aim of this study was to evaluate the benefit of ST in PDT regarding procedural time, quality of performance, and percepted feelings of safety of the proceduralist and to compare conventional simulators (CSIM) with simulators generated from 3D printers (3DSIM). Methods: We conducted a prospective, single-center, randomized, blinded cross-over study comparing the benefit of CSIM versus 3DSIM for ST of PDT. Participants underwent a standardized theoretical training and were randomized to ST with CSIM (group A) or 3DSIM (group B). After ST, participants' performance was assessed by two blinded examiners on a porcine trachea regarding time required for successful completion of PDT and correct performance (assessed by a performance score). Percepted feelings of safety were assessed before and after ST. This was followed by a second training and second assessment of the same aspects with crossed groups. Results: 44 participants were included: 24 initially trained with CSIM (group A) and 20 with 3DSIM (group B). Correctness of the PDT performance increased significantly in group B (p < .01) and not significantly in group A (p = .14). Mean procedural time required for performing a PDT after their second ST compared to the first assessment (p < .01) was lower with no difference between group A and group B and irrespective of the participants' previous experience regarding PDT, age, and sex. Moreover, percepted feelings of safety increased after the first ST in both groups (p < .001). Conclusions: ST can improve procedural skills, procedural time, and percepted feelings of safety of the proceduralist in simulated PDT.

A novel technique for one-step dilation followed by bile aspiration using an ultra-tapered bougie dilator with side holes to minimize bile leakage during EUS-guided hepaticogastrostomy.

Bile aspiration during endoscopic ultrasound-guided hepaticogastrostomy reduces the risk of bile leakage. Mukai and colleagues devised a method in which side holes for bile aspiration are created using a biopsy punch in a hard type ultra-tapered bougie dilator. Effective bile aspiration was achieved in all four cases attempted.

Long-term efficacy of balloon dilation of the pediatric Eustachian tube: A six-year matched cohort study.

PURPOSE: Balloon dilation of the Eustachian tube (BDET) has not been evaluated extensively in children outside of retrospective case series. The purpose of this study is to report the long-term safety and efficacy of this procedure in children with matched controls. MATERIALS AND METHODS: This is a two-center retrospective matched cohort study. Children having undergone tympanostomy tube (TT) placement and adenoidectomy with recurrence of symptoms underwent BDET at an academic affiliated multi-specialty practice. Comparison was made with children receiving TT at a tertiary medical center, matching for number of prior TT, prior adenoidectomy, age, and sex. Outcome measures were risk of failure and the need for additional surgery. Kaplan-Meier survival plots were used to compare risk of failure. RESULTS: Thirty-three Eustachian tubes were dilated in 20 patients, aged 14 months-14 years. All patients had previously undergone TT insertion and adenoidectomy. Patients undergoing BDET had normal post-operative tympanograms in 80 % of cases. Mean follow up was 6.7 years with 2 patients failing in the BDET group and 8 in the TT insertion group. Dilated patients had a significantly lower risk of failure than those who underwent TT insertion (adjusted HR: 0.18; 95 % CI: 0.04, 0.81; p = 0.03). The probability of being failure free at six years was 88 % (95 % CI: 71, 95 %) in the BDET cohort and 53 % (95 % CI: 33, 70 %) in the TT insertion cohort. There were no complications. CONCLUSIONS: BDET appears to be safe and possibly superior to TT placement in children with refractory Eustachian tube dysfunction. LEVEL OF EVIDENCE: 2b.

Significado do uso da prótese peniana de silicone no seguimento da braquiterapia pélvica / Significado do uso da prótese peniana de silicone no seguimento da braquiterapia pélvica / Meaning of the use of silicone penile prosthesis in the follow-up of pelvic brachytherapy

Objetivo: descrever o significado do uso da prótese peniana de silicone para dilatação vaginal no seguimento da braquiterapia em mulheres com câncer ginecológico. Método: pesquisa narrativa, realizada no Centro de Pesquisas Oncológicas, Brasil, com 34 mulheres, após braquiterapia pélvica, em seguimento no serviço de fisioterapia. Coleta de dados por entrevistas semiestruturadas, incluindo dados sociodemográficos, clínicos e o significado do uso da prótese peniana na dilatação vaginal, submetidas à análise de conteúdo e discutidas à luz do estudo From 'sex toy' to intrusive imposition. Resultados: o significado perpassa o exercício de dilatação vaginal; as dificuldades relacionadas às condições vaginais, doença, tratamento, dor, sexo, constrangimentos, preconceitos, falhas na educação em saúde; as motivações relacionam-se à busca por qualidade de vida, apoio dos companheiros e profissionais. Conclusão: a abordagem de possíveis barreiras emocionais, psicológicas, sociais e físicas deve ser planejada e executada para prevenção da estenose vaginal e melhor acolhimento.

Objective: to describe the meaning of the use of silicone penile prosthesis for vaginal dilation in the follow-up of brachytherapy in women with gynecological cancer. Method: narrative research conducted at the Centro de Pesquisas Oncológicas, Brazil, with 34 women after pelvic brachytherapy, under follow-up at the physical therapy service. Data collection through semi-structured interviews, including sociodemographic and clinical data and the significance of the use of penile prosthesis in vaginal dilation, submitted to content analysis and discussed in the light of the study From 'sex toy' to intrusive imposition. Results: the meaning permeates the vaginal dilation exercise; difficulties related to vaginal conditions, disease, treatment, pain, sex, constraints, prejudices, failures in health education; motivations are related to the search for quality of life, support of partners and professionals. Conclusion: the approach of possible emotional, psychological, social and physical barriers should be planned and executed for prevention of vaginal stenosis and better reception.

Objetivo: describir el significado del uso de una prótesis peneana de silicona para la dilatación vaginal posterior a la braquiterapia en mujeres con cáncer ginecológico. Método: investigación narrativa, realizada en el Centro de Pesquisas Oncológicas, Brasil, con 34 mujeres, después de braquiterapia pélvica, en seguimiento en el servicio de fisioterapia. Recopilación de datos a través de entrevistas semiestructuradas, incluyendo datos sociodemográficos y clínicos y el significado del uso de prótesis peneana en la dilatación vaginal, sometidos a análisis de contenido y discutidos a la luz del estudio From 'sex toy' to intrusive imposition. Resultados: el significado impregna el ejercicio de dilatación vaginal; dificultades relacionadas con condiciones vaginales, enfermedad, tratamiento, dolor, sexo, vergüenza, prejuicios, fallas en la educación para la salud; las motivaciones están relacionadas con la búsqueda de calidad de vida, apoyo de la pareja y profesionales. Conclusión: se debe planificar y ejecutar el abordaje de las posibles barreras emocionales, psicológicas, sociales y físicas para prevenir la estenosis vaginal y una mejor recepción.

Nasal dilator and physiological parameters associated to running performance: A systematic review and meta-analysis.

Nasal dilators were created to expand the nasal valve area. The aim of this systematic review was to verify physiological parameters associated to running performance with the use of nasal dilators. This study was registered in PROSPERO (CRD42021225795). According to the PICOS framework studies were included: Population: healthy subjects; Intervention: nasal dilators; Comparison: control group, placebo, minimal intervention, health education or other intervention; Outcomes: cardiorespiratory parameters and subjective perceptions; Study: randomized controlled trials, repeated measures or within-subjects design. The databases searched were MEDLINE, EMBASE, CENTRAL The Cochrane Library, CINAHL, SPORTDiscus, Web of Science, PEDro and Scopus. The descriptors "Running", "Nasal Dilator", "Randomized Controlled Trial", and synonyms were used. The risk of bias was assessed using the PEDro scale. Random effects Der Simonian and Laird model were used. The assessment of the certainty of the evidence was carried out using the GRADE approach. Eleven articles were included. There was a difference in favour of the nasal dilator when compared to placebo for maximal oxygen uptake and rating of perceived exertion. The certainty of the evidence was very low. Future studies will probably have an impact on estimation of the effect.