The use of botulinum toxin type a to prepare patients with large ventral hernias for laparoscopic hernioplasty: Our experience.

OBJECTIVE: Aim: To study the effectiveness of BTA in a total dose of 100 IU as the preparation for patients with primary and incisional ventral hernias (VH). PATIENTS AND METHODS: Materials and Methods: The prospective study included 59 patients with large VH (defect ³10 cm). All patients received 100 IU of BTA in abdominal wall muscles 4-5 weeks before surgery from June 2017 to December 2022. An average age of the patients was 59.13 ± 9.07 years, body mass index - 32.20 ± 4.95 kg/m2. RESULTS: Results: An average width of the hernia defect after BTA decreased by 4.5 ± 1.11 cm (p<0.001). An average length of the hernia defect after BTA also decreased, without clinical significance. A significant increase in the length of the abdominal wall and a decrease in its thickness were observed. The abdominal cavity volume after BTA increased by 4.04 ± 4.55% (p=0.008) and the hernial sac volume decreased by 21.43 ± 16.57% (p=0.005). All patients underwent surgery with hernia defect suturing and without component separation: laparoscopic IPOM hernioplasty - 50 (84.7%) patients, open IPOM hernia repair - 7 (11.9%) patients, open sublay hernioplasty - 2 (3.4%) patients. There was no recurrence of hernia during 12 months after surgery. CONCLUSION: Conclusions: The administration of 100 IU BTA allows to increase the length of the abdominal wall muscles and to perform laparoscopic IPOM hernioplasty for patients with large VH.

Long-Term Adherence to Onabotulinum Toxin-A Intradetrusor Injections for Neurogenic Dysfunction in Children-A Retrospective Single-Center Evaluation.

Onabotulinum Toxin-A (BTX-A) is a second-line treatment for neurogenic bladder (NB). It requires repeated injections over time, which is a possible limit for long-term adherence, especially in children, as general anesthesia is required. Almost 50% of adults discontinue therapy; few data on pediatric patients are present. The aim of this study is to share our long-term experience of BTX-A adherence in children. This study is a retrospective review of 230 refractory NB patients treated with BTX-A. The inclusion criteria were ≥3 treatments and the first injection performed ≥10 years before the study endpoint. Fifty-four patients were included. Mean follow-up was 10.2 years; mean treatment number was 6.4 for each patient. During follow-up, 7% did not need BTX-A anymore; 76% discontinued therapy, with a prevalence of acquired NB (64% acquired vs. 34% congenital; p = 0.03); sex-based and urodynamic findings did not influence the discontinuation rate (p = 0.6, p = 0.2, respectively). Considering those who withdrew from the therapy, 43% were lost to follow-up/died after a mean of 7.5 years (although 33% still experienced clinical efficacy); 33% changed therapy after a mean of 5.8 years (with reduced efficacy in 22%, persistent efficacy in 11%). BTX-A is a safe and effective therapy for pediatric patients. The treatment abandonment rate is higher for children than for adults; no specific reasons were highlighted. It is necessary to evaluate any age-specific factors to explain these data.

Onabotulinumtoxina in the Prevention of Migraine in Pediatric Population: A Systematic Review.

Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children older than 12 years of age, but there is conflicting evidence regarding its efficacy. OnabotulinumtoxinA is a known and approved treatment for the management of chronic migraine in people older than 18 years. Several studies examine its role in the pediatric population with positive results; however, the clear-cut benefit is still unclear. OnabotulinumtoxinA seems not only to improve disability scores (PedMIDAS) but also to improve the quality, characteristics, and frequency of migraines in the said population. This systematic review aims to summarize the evidence on the efficacy, dosing, administration, long-term outcomes, and safety of onabotulinumtoxinA in pediatric and adolescent migraine. Eighteen studies met the eligibility criteria and were included in this review. The mean monthly migraine days (MMDs), decreased from of 21.2 days per month to 10.7 after treatment. The reported treatment-related adverse effects were mild and primarily injection site related and ranged from 0% to 47.0%. Thus, this review provides compelling evidence suggesting that OnabotulinumtoxinA may represent a safe and effective preventive treatment option for pediatric migraine.

Treatment of Primary Axillary Hyperhidrosis with Two Doses of Botulinum Toxin A-Observational Study.

Hyperhidrosis (HH) is defined as the production of more sweat than is necessary for its thermoregulatory function, negatively affecting patients' quality of life and interfering with their social, work and family life. In this context, the aim of thisstudy was to evaluate the efficacy of two different doses of botulinum toxin type A (50 or 100 units) in each axilla in severe primary axillary hyperhidrosis. A descriptive, observational, cross-sectional and post-authorisation study was conducted onpatients referred to our department.Thirty-one patients with severe primary axillary hyperhidrosis were included, some of whom received more than one infiltration during the follow-up period, performing a total of 82 procedures. They were assigned by simple random sampling to two types of treatment: infiltration of 50 or 100 units (U) of botulinum toxin A per axilla.Hyperhidrosis severity was assessed using the Hyperhidrosis Disease Severity Scale (HDSS), and quality of life was assessed using the Dermatology Life Quality Index (DLQI) questionnaire. Onabotulinum toxin A infiltration reduced the severity of hyperhidrosis and improved the quality of life of the treated patients, with no significant differences between the two groups.

Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine.

OnabotulinumtoxinA (BT-A) is used in different medical fields for its beneficial effects. BT-A, a toxin originally produced by the bacterium Clostridium botulinum, is widely known for its ability to temporarily paralyze muscles by blocking the release of acetylcholine, a neurotransmitter involved in muscle contraction. The literature continually reports new hypotheses regarding potential applications that do not consider blockade of acetylcholine release at the neuromuscular junction as a common pathway. In this opinion article, it is our aim to investigate the different pathway targets of BT-A in different medical applications. First of all, the acetylcholine effect of BT-A is used to reduce wrinkles for cosmetic purposes, in the treatment of urological problems, excessive sweating, temporomandibular joint disorders, obesity, migraine, spasticity in neurological diseases, and in various cases of muscle overactivity such as cervical dystonia, blepharospasm, and essential head tremor. In another potential pathway, glutamate A, CGRP, and substance P are targeted for pain inhibition with BT-A application in conditions such as migraine, trigeminal neuralgia, neuropathic pain, and myofascial pain syndrome. On the other hand, as a mechanism different from acetylcholine and pain mediators, BT-A is used in the treatment of hair loss by increasing oxygenation and targeting transforming growth factor-beta 1 cells. In addition, the effect of BT-A on the apoptosis of cancer cells is also known and is being developed. The benefits of BT-A applied in different doses to different regions for different medical purposes are shown in literature studies, and it is also emphasized in those studies that repeating the applications increases the benefits in the long term. The use of BT-A continues to expand as researchers discover new potential therapeutic uses for this versatile toxin.

Gait Reconstruction Strategy Using Botulinum Toxin Therapy Combined with Rehabilitation.

Numerous studies have established a robust body of evidence for botulinum toxin A (BoNT-A) therapy as a treatment for upper motor neuron syndrome. These studies demonstrated improvements in spasticity, range of joint motion, and pain reduction. However, there are few studies that have focused on improvement of paralysis or functional enhancement as the primary outcome. This paper discusses the multifaceted aspects of spasticity assessment, administration, and rehabilitation with the goal of optimising the effects of BoNT-A on lower-limb spasticity and achieving functional improvement and gait reconstruction. This paper extracts studies on BoNT-A and rehabilitation for the lower limbs and provides new knowledge obtained from them. From these discussion,, key points in a walking reconstruction strategy through the combined use of BoNT-A and rehabilitation include: (1) injection techniques based on the identification of appropriate muscles through proper evaluation; (2) combined with rehabilitation; (3) effective spasticity control; (4) improvement in ankle joint range of motion; (5) promotion of a forward gait pattern; (6) adjustment of orthotics; and (7) maintenance of the effects through frequent BoNT-A administration. Based on these key points, the degree of muscle fibrosis and preintervention walking speed may serve as indicators for treatment strategies. With the accumulation of recent studies, a study focusing on walking functions is needed. As a result, it is suggested that BoNT-A treatment for lower limb spasticity should be established not just as a treatment for spasticity but also as a therapeutic strategy in the field of neurorehabilitation aimed at improving walking function.

Efficacy of type A botulinum toxin treatment for androgenetic alopecia using ultrasound combined with trichoscopy.

OBJECTIVE: This study aimed to assess the efficacy of type A botulinum toxin treatment for androgenetic alopecia (AGA) using a combination of ultrasound and trichoscopy. METHODS: Ninety patients with AGA who visited the Department of Dermatology at the Second Affiliated Hospital of Soochow University from September 2021 to December 2022 were prospectively selected. These patients met the diagnostic criteria outlined in the Chinese Guidelines for the Diagnosis and Treatment of Androgenetic Alopecia. The alopecia severity in the male patients ranged between grades 2 and 4 on the Norwood-Hamilton Scale. The patients were randomly assigned to receive injections of the same type of biological agent in a double-blind manner, with injection sites being the vertex or bilateral temporal-frontal hairline. In this study, the botulinum toxin group comprised 72 patients who received a biological agent with 100 units of type A botulinum toxin. The control group included 18 patients, and the biological agent administered to them contained 0 units of type A botulinum toxin. The patients were observed using 22-MHz ultrasound and trichoscopy before treatment, and 1 month and 3 months after treatment to compare the differences in various parameters at the injection sites. The ultrasound parameters included average follicle width, length, and count. The trichoscopy parameters were the number of hairs within a 1-cm2 area on the counting scale. No artificial interventions were performed at the injection sites, and all examination conditions were consistent. RESULTS: The patients in the botulinum toxin group had wider and longer average follicle width and length at the vertex 1 month and 3 months after treatment (p < 0.05), and wider and longer average follicle width and length in the left frontal area 3 months after treatment (p < 0.05) compared with those in the control group. The average follicle width and length gradually increased after treatment in the botulinum toxin group (p < 0.05), but no statistically significant differences were found in the control group (p > 0.05). The patients in the botulinum toxin group exhibited greater average follicle lengths after treatment at the vertex compared with the left frontal area (p < 0.05). No statistically significant differences were found in follicle count (p > 0.05) or hair count (p > 0.05) between the botulinum toxin and control groups after injection treatment. CONCLUSIONS: The follicle width and length are effective parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA. Ultrasound revealed that the changes in follicles at the vertex occurred earlier than those in the left frontal area following treatment. Additionally, the changes in follicles were detected earlier than the changes in hair count using ultrasound. Ultrasound combined with trichoscopy provided more parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA, resulting in a more comprehensive evaluation.

Comparison of outcome of botulinum toxin injection with and without glyceryl trinitrate in chronic anal fissure in terms of post operative pain and healing.

Objectives: To compare the outcome of botulinum toxin injection with and without glyceryl trinitrate with respect to postoperative pain and healing in the treatment of anal fissures. METHODS: The prospective, comparative study was conducted at the Department of General Surgery, Mayo Hospital, Lahore, Pakistan, from September 1, 2021, to August 31, 2022, and comprised adult chronic anal fissure patients of either gender. They were randomised using the lottery method into group A which received botulinum toxin injection, and group B which received botulinum toxin injection plus 1g of 0.2% topical glyceryl trinitrate cream. Post-operative pain was measured 24 hours after the procedure using the visual analogue scale. Healing was assessed by examining the wound for the appearance of granulation tissue 4 weeks post-procedure. Data was analysed using SPSS 26. RESULTS: Of the 88 patients, 44(50%) were in group A; 32(72.7%) males and 12(27.3%) females with mean age 33.91±14.8 years. There were 44(50%) patients in group B; 35(79.5%) males and 9(20.5%) females with mean age range 36.33±14.9 years. The mean postoperative pain at 24 hours in group A was 4.67±1.16 and it was 3.06±0.65 in group B (p=0.009). In group A, 23(69.7%) patients showed complete healing at 4 weeks compared to 30(90.9%) in group B (p=0.030). CONCLUSIONS: Botulinum toxin injection with glyceryl trinitrate could be considered as first line of treatment for chronic anal fissure in patients who refuse surgery and with previous sphincter surgery.

[Treatment of bruxism with botulinum toxin: think twice!] / Behandeling van bruxisme met botulinetoxine: bezint eer ge begint!

A recent publication in the Nederlands Tijdschrift Voor Tandheelkunde (Dutch Journal of Dentistry) suggests botulinum toxin as a primary treatment for bruxism, especially for severe complaints of teeth grinding or jaw clenching. However, in the opinion of Lobbezoo et al., some outdated views on bruxism are used, and botulinum toxin is incorrectly classified as safe, according to them. In this Vision article, the authors describe the current insights into bruxism; they indicate how the presence of bruxism can be assessed in the clinic; when and how bruxism is treated; and finally, what the role of botulinum toxin is: an ultimum refugium. Therefore, regarding the use of botulinum toxin within the discipline of orofacial pain and dysfunction Lobbezoo et al. recommend: think twice!

Clinical efficacy and safety analysis of type A botulinum toxin in the treatment of adolescents with refractory overactive bladder.

The objective of this study was to assess the clinical effectiveness and safety of type A botulinum toxin in the treatment of refractory overactive bladder in adolescents. We conducted a retrospective analysis of 37 adolescent patients with refractory overactive bladder who were treated at the Urology Department of Hangzhou Third People's Hospital between January 2018 and August 2023. These patients received intravesical injections of type A botulinum toxin at a concentration of 10 U/mL, with an average of 20 injection points. We recorded changes in urination diaries and urodynamic parameters both before and 1 month after treatment. After 1 month of treatment, significant improvements were observed in several parameters, when compared to the pretreatment values. These included daytime frequency of urination (11.13 ±â€…6.45), average single void volume (173.24 ±â€…36.48) mL, nighttime frequency of urination (2.43 ±â€…0.31), urgency episodes (3.12 ±â€…0.27), initial bladder capacity (149.82 ±â€…41.34) mL, and maximum bladder capacity (340.25 ±â€…57.12) mL (all P < .001). After the first treatment, 5 patients had mild hematuria, 4 patients had urinary tract infection, and 1 patient had urinary retention, which was relieved after catheterization. No serious complications or adverse reactions were observed in other patients. The follow-up period ranged from 6 to 18 months, and the duration of efficacy varied from 2 to 8 months. Eight patients who initially had treatment failure achieved symptom relief after reinjection. In adolescents with refractory overactive bladder who do not respond well to conventional drug therapy, type A botulinum toxin can be administered safely and effectively. It significantly improves lower urinary tract symptoms and enhances the quality of life for these patients.

Application of botulinum toxin in the repair of a complex ventral hernia. / Aplicación de toxina botulínica en la reparación de una hernia ventral compleja.

INTRODUCTION: Preoperative application of botulinum toxin type A has demonstrated to be safe and effective in the closure of complex ventral hernias in adults. However, its use in pediatrics has been little documented. CASE REPORT: We present the case of a 22-month-old girl with a complex abdominal wall ventral hernia secondary to multiple neonatal laparotomies. In a first procedure, botulinum toxin was administered using an intramuscular approach at six sites of the muscle layers surrounding the defect, under general anesthesia and ultrasound control. 4 weeks later, an open hernia repair was conducted, without complications. DISCUSSION: Botulinum toxin at low doses could facilitate the surgical treatment of complex ventral incisional hernias in children. Even though it is important to adjust dosage and anatomical reference points according to hernia type and patient age and weight, further studies are required to optimize these variables.

INTRODUCCION: La aplicación preoperatoria de toxina botulínica A ha demostrado ser segura y efectiva en el cierre de hernias ventrales complejas en adultos. Sin embargo, se ha documentado poco su uso en pediatría. CASO CLINICO: Se presenta el caso de una niña de 22 meses con una hernia de pared abdominal ventral compleja secundaria a múltiples laparotomías neonatales. En una primera intervención se administró por vía intramuscular toxina botulínica en seis puntos de las capas musculares alrededor del defecto bajo anestesia general y control ecográfico. Cuatro semanas después, se realizó una reparación abierta de la hernia, sin complicaciones. COMENTARIOS: La toxina botulínica a dosis bajas podría facilitar el tratamiento quirúrgico de hernias incisionales ventrales complejas en niños. Es importante ajustar la dosis y los puntos de referencia anatómicos según el tipo de hernia, la edad y el peso del paciente, aunque se requieren más estudios para optimizar estas variables.

The functional lumen imaging probe contractile response pattern is the best predictor of botulinum toxin response in esophagogastric junction outflow obstruction.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is a heterogenous disorder in which the correct management strategy is unclear. We assessed whether functional lumen imaging probe (FLIP) topography data could select EGJOO, which would benefit from lower esophageal sphincter Botulinum toxin (Botox) injection. METHODS: This was a single-center prospective study of adult patients meeting Chicago Classification (CC) v3.0 criteria for EGJOO. We assessed differences in pretreatment physiologic measurements on high-resolution manometry (HRM) and FLIP and other relevant clinical variables in predicting Botox response (>50% in BEDQ at 2 months). KEY RESULTS: Sixty-nine patients were included (ages 33-90, 73.9% female). Of these, 42 (61%) were Botox responders. Majority of physiologic measures on HRM and FLIP and esophageal emptying were not different based on Botox response. However, a spastic-reactive (SR) FLIP contractile response (CR) pattern predicted a Botox response with OR 25.6 (CI 2.9-229.6) when compared to antegrade FLIP CR; and OR for impaired-disordered/absent CR was 22.5 (CI 2.5-206.7). Logistic regression model using backward elimination (p value = 0.0001, AUC 0.79) showed that a SRCR or IDCR/absent response and the upright IRP predicted Botox response. Response rates in tiered diagnostic groups were: (i) CCv3.0 EGJOO (60.9%), (ii) CCv4.0 EGJOO (73.1%), (iii) CCv4.0 + FLIP REO (80%), (iv) CCv4.0, FLIP REO, and abnormal FLIP CR (84.2%), and (v) CCv4.0, FLIP REO, and SR FLIP CR (90%). CONCLUSIONS AND INFERENCES: FLIP helps identify patients with EGJOO who are likely to response to LES Botox therapy. An abnormal FLIP contractile response pattern is the single-most important predictor of a Botox response.

Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity.

INTRODUCTION: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting. METHODS AND ANALYSIS: The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality. ETHICS AND DISSEMINATION: This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05379413.

Botulinum Toxin-A for the Treatment of Myogenous Temporomandibular Disorders: An Umbrella Review of Systematic Reviews.

OBJECTIVE: Temporomandibular disorders (TMDs) encompass several conditions that cause pain and impair function of the masticatory muscles (M-TMDs) and temporomandibular joints. There is a large interest among clinicians and researchers in the use of botulinum toxin-A (BoNT-A) as a treatment for M-TMD. However, due to the lack of consistent evidence regarding the efficacy as well as adverse events of BoNT-A, clinical decision making is challenging. Therefore, this umbrella review aimed to systematically assess systematic reviews (SRs) evaluating BoNT-A treatment effects on pain intensity, mandibular movements, and adverse events in patients with M-TMDs. METHOD: An electronic search was undertaken in the databases MEDLINE, EMBASE, CINAHL, Cochrane Central Registry of Controlled Trials (CENTRAL), Web of Science, Epistemonikos, ClinicalTrials.gov, and ICTRP to identify SRs investigating BoNT-A effects on M-TMDs, published from the inception of each database until 6 December 2023. The quality of evidence was rated according to the critical appraisal checklist developed by the umbrella review methodology working group. Only high-quality SRs were included. RESULTS: In total, 18 SRs were included. BoNT-A was shown to be more effective than placebo to reduce pain intensity, but not compared to standard treatments. Additionally, BoNT-A was not superior to placebo or standard treatments regarding improvement of mandibular movements. BoNT-A was considered to have a higher risk for adverse events on muscle and bony tissue compared with other treatments. CONCLUSION: The synthesis in this umbrella review provides the highest level of evidence present. Taken together, there are indications of effectiveness of BoNT-A for treatment of M-TMDs, supported by moderate evidence. However, considering the risk of causing serious adverse events, treatment with BoNT-A is recommended to be the last treatment alternative.

Treatments for intractable constipation in childhood.

BACKGROUND: Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation is challenging, involving pharmacological or non-pharmacological therapies, as well as surgical approaches. Unresolved constipation can negatively impact quality of life, with additional implications for health systems. Consequently, there is an urgent need to identify treatments that are efficacious and safe. OBJECTIVES: To evaluate the efficacy and safety of treatments used for intractable constipation in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers up to 23 June 2023. We also searched reference lists of included studies for relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any pharmacological, non-pharmacological, or surgical treatment to placebo or another active comparator, in participants aged between 0 and 18 years with functional constipation who had not responded to conventional medical therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were symptom resolution, frequency of defecation, treatment success, and adverse events; secondary outcomes were stool consistency, painful defecation, quality of life, faecal incontinence frequency, abdominal pain, hospital admission for disimpaction, and school absence. We used GRADE to assess the certainty of evidence for each primary outcome. MAIN RESULTS: This review included 10 RCTs with 1278 children who had intractable constipation. We assessed one study as at low risk of bias across all domains. There were serious concerns about risk of bias in six studies. One study compared the injection of 160 units botulinum toxin A (n = 44) to unspecified oral stool softeners (n = 44). We are very uncertain whether botulinum toxin A injection improves treatment success (risk ratio (RR) 37.00, 95% confidence interval (CI) 5.31 to 257.94; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Frequency of defecation was reported only for the botulinum toxin A injection group (mean interval of 2.6 days). The study reported no data for the other primary outcomes. One study compared erythromycin estolate (n = 6) to placebo (n = 8). The only primary outcome reported was adverse events, which were 0 in both groups. The evidence is of very low certainty due to concerns with risk of bias and serious imprecision. One study compared 12 or 24 µg oral lubiprostone (n = 404) twice a day to placebo (n = 202) over 12 weeks. There may be little to no difference in treatment success (RR 1.29, 95% CI 0.87 to 1.92; low certainty evidence). We also found that lubiprostone probably results in little to no difference in adverse events (RR 1.05, 95% CI 0.91 to 1.21; moderate certainty evidence). The study reported no data for the other primary outcomes. One study compared three-weekly rectal sodium dioctyl sulfosuccinate and sorbitol enemas (n = 51) to 0.5 g/kg/day polyethylene glycol laxatives (n = 51) over a 52-week period. We are very uncertain whether rectal sodium dioctyl sulfosuccinate and sorbitol enemas improve treatment success (RR 1.33, 95% CI 0.83 to 2.14; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Results of defecation frequency per week was reported only as modelled means using a linear mixed model. The study reported no data for the other primary outcomes. One study compared biofeedback therapy (n = 12) to no intervention (n = 12). We are very uncertain whether biofeedback therapy improves symptom resolution (RR 2.50, 95% CI 1.08 to 5.79; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). The study reported no data for the other primary outcomes. One study compared 20 minutes of intrarectal electromotive botulinum toxin A using 2800 Hz frequency and botulinum toxin A dose 10 international units/kg (n = 30) to 10 international units/kg botulinum toxin A injection (n = 30). We are very uncertain whether intrarectal electromotive botulinum toxin A improves symptom resolution (RR 0.96, 95% CI 0.76 to 1.22; very low certainty evidence) or if it increases the frequency of defecation (mean difference (MD) 0.00, 95% CI -1.87 to 1.87; very low certainty evidence). We are also very uncertain whether intrarectal electromotive botulinum toxin A has an improved safety profile (RR 0.20, 95% CI 0.01 to 4.00; very low certainty evidence). The evidence for these results is of very low certainty due to serious concerns with risk of bias and imprecision. The study did not report data on treatment success. One study compared the injection of 60 units botulinum toxin A (n = 21) to myectomy of the internal anal sphincter (n = 21). We are very uncertain whether botulinum toxin A injection improves treatment success (RR 1.00, 95% CI 0.75 to 1.34; very low certainty evidence). No adverse events were recorded. The study reported no data for the other primary outcomes. One study compared 0.04 mg/kg oral prucalopride (n = 107) once daily to placebo (n = 108) over eight weeks. Oral prucalopride probably results in little or no difference in defecation frequency (MD 0.50, 95% CI -0.06 to 1.06; moderate certainty evidence); treatment success (RR 0.96, 95% CI 0.53 to 1.72; moderate certainty evidence); and adverse events (RR 1.15, 95% CI 0.94 to 1.39; moderate certainty evidence). The study did not report data on symptom resolution. One study compared transcutaneous electrical stimulation to sham stimulation, and another study compared dietitian-prescribed Mediterranean diet with written instructions versus written instructions. These studies did not report any of our predefined primary outcomes. AUTHORS' CONCLUSIONS: We identified low to moderate certainty evidence that oral lubiprostone may result in little to no difference in treatment success and adverse events compared to placebo. Based on moderate certainty evidence, there is probably little or no difference between oral prucalopride and placebo in defecation frequency, treatment success, or adverse events. For all other comparisons, the certainty of the evidence for our predefined primary outcomes is very low due to serious concerns with study limitations and imprecision. Consequently, no robust conclusions could be drawn.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.