Long-Term Cost Analysis of Third-Line Treatment Options for Overactive Bladder.

INTRODUCTION: We aimed to analyze the long-term cost of overactive bladder third-line treatments. METHODS: This insurance claims review analyzed the 2015 to 2020 MarketScan (MKS) claims data set subjects age ≥ 18, diagnosis of overactive bladder (OAB) using ICD-9/ICD-10 codes and receipt of treatment for percutaneous tibial nerve stimulation, sacral neuromodulation (SNM), or botulinum A. Age, gender, treatment types, and cost were extracted. Treatment costs were aggregated at the level of patient and treatment type for total payment and patient contribution by combining copay, coinsurance, and deductible. We used the Wilcoxon rank-sum test for continuous and chi-square test for categorical variables. SAS v9.4 was used for analyses. Significance was set at P < .05. RESULTS: We identified 17,755 patients from the commercial claims MKS and 10,912 patients from the Medicare supplemental (MDC) database with mean age 50.7±11.1 and 75.5±7.6 years, respectively, who underwent ≥ 1 third-line OAB treatment. Patients receiving third-line treatment were predominantly female (84.9%, MKS, 74.8%, MDC). Long-term costs over a 15-year period were estimated. Percutaneous tibial nerve stimulation is the most expensive in terms of total net payment ($105,337.50 MKS, $94,102.50 MDC) and patient contribution ($9177.60 MKS, $3921.00 MDC). Total net payment for botulinum A was $67,968 (MSK), $54,261 (MDC), and patient contribution cost was $2850 (MSK), $1110 (MDC). The most cost-effective option was SNM in terms of both total net payment ($5179.10 MKS, $6099.00 MDC) and patient contribution ($59.10 MKS, $60.00 MDC). CONCLUSIONS: SNM was the most cost-effective third-line treatment for OAB looking over a 15-year period in terms of both total net payment and patient contribution.

Pharmacological Management of Orofacial Pain.

Orofacial pain is a category of complex disorders, including musculoskeletal, neuropathic and neurovascular disorders, that greatly affect the quality of life of the patient. These disorders are within the fields of dentistry and medicine and management can be challenging, requiring a referral to an orofacial pain specialist, essential for adequate evaluation, diagnosis, and care. Management is specific to the diagnosis and a treatment plan is developed with diverse pharmacological and non-pharmacological modalities. The pharmacological management of orofacial pain encompasses a vast array of medication classes and approaches. This includes anti-inflammatory drugs, muscle relaxants, anticonvulsants, antidepressants, and anesthetics. In addition, as adjunct therapy, different injections can be integrated into the management plan depending on the diagnosis and needs. These include trigger point injections, temporomandibular joint (TMJ) injections, and neurotoxin injections with botulinum toxin and nerve blocks. Multidisciplinary management is key for optimal care. New and safer therapeutic targets exclusively for the management of orofacial pain disorders are needed to offer better care for this patient population.

The Value of Injection Therapy with Botulinum Toxin in Pain Treatment of Primary Chronic Anal Fissures Compared to Anal Dilation, and Local Nifedipine in Combination with Lidocaine.

Introduction: Anal fissure is a longitudinal tear of the mucosa of the anal canal extending from the outer anal orifice in the direction of the dentate line of the inner anal opening. Fissures are divided into primary and secondary, and acute or chronic. Besides minimal rectal bleeding, itching and soiling, primary chronic anal fissures (PCAF) manifest with anal pain as theirs main determinant. It is described as the most troubling symptom. Aim: To compare the effect of injection therapy with botulinum toxin A (ITBT) vs. anal dilation (AD), and local nifedipine with lidocaine (LNL) in pain treatment of PCAF. Materials and Methods: This controlled retrospective prospective longitudinal study covered 94 patients, divided in 3 groups. The first was treated with ITBT, the second with AD and third using LNL (31, 33 and 30 patients respectively). Clostridium botulinum toxin A was used, dissolved with saline to concentration of 200 U/ml. The solution was applied to both sides of PCAF at dose of 40U. Modified technique of AD was done using 3 fingers of a single hand, progressively introduced into the anal canal, followed by gradual lateral distraction during 1 min. LNL therapy was conducted using nifedipine (0.3%) with lidocaine (1.5%) ointment, applied twice daily for 3 weeks. To measure pain, a visual analog scale (VAS) was used. The follow-up period was 12 weeks with checkup at week 4. Results: The median age of participants was 46.6±13.9 years (50 males vs. 44 females). The type of therapy had a significantly different effect on pain at week 4 (p=0.0003). Severe pain was present in only 2 ITBT patients, 16 AD, and 6 LNL patients. Post hoc analyses showed different pain disappearance time by week 12 (p <0.0001). The mean time was shortest in ITBT group (6.1±1.5 weeks). Anal pain intensity significantly differed among the 3 groups (Fisher exact, p=0.002). Namely, 71% in ITBT group rated the pain as weakest (VAS score 1) compared to 18.2% in AD and 30% of patients in LNL group. The overall pain reduction significance was in favor of ITBT, due to the differences between the ITBT and AD groups (p=0.00024) and ITBT compared to LNL group (p=0.018). Conclusion: ITBT is superior to AD and LNL in reducing pain in PCAF.

Botulinum neurotoxin injection in the deltoid muscle: application to cosmetic shoulder contouring.

BACKGROUND AND OBJECTIVES: This study describes the intramuscular nerve branching of the deltoid muscle in relation to shoulder surface anatomy, with the aim of providing essential information regarding the most appropriate sites for botulinum neurotoxin injection during shoulder line contouring. METHODS: The modified Sihler's method was used to stain the deltoid muscles (16 specimens). The intramuscular arborization areas of the specimens were demarcated using the marginal line of the muscle origin and the line connecting the anterior and posterior upper edges of the axillary region. RESULTS: The intramuscular neural distribution of the deltoid muscle had the greatest arborization patterns in the area between the horizontal 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line in middle deltoid bellies. The greatest part of the posterior circumflex artery and axillary nerve ran below the areas with the highest aborizations. CONCLUSION: We propose that botulinum neurotoxin injections should be administered in the area between the 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line on middle deltoid bellies. Accordingly, clinicians will ensure minimal dose injections and fewer adverse effects of the botulinum neurotoxin injection. Deltoid intramuscular injections, such as vaccines and trigger point injections, should ideally be adapted according to our results.

Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Intra-Articular Injection of Botulinum Toxin for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials.

The purpose of the present paper was to review the available evidence on intra-articular botulinum toxin (BTX) injection in the treatment of knee osteoarthritis and to compare it to other conservative treatment options. A systematic review of the literature was performed on the PubMed, Scopus, Cochrane Library, Web of Science, Pedro and Research Gate databases with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in the English language, and (3) published on indexed journals in the last 20 years (2001-2021) dealing with the use of BTX intra-articular injection for the treatment of knee OA. The risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. Nine studies involving 811 patients in total were included. Patients in the control groups received different treatments: conventional physiotherapy, hyaluronic acid injection or prolotherapy or a combination thereof in 5 studies, steroid infiltrative therapy (triamcinolone) in 1 study, placebo in 2, and local anesthetic treatment in 1 study. Looking at the quality of the available literature, two of the included studies reached "Good quality" standard, three were ranked as "Fair", and the rest were considered "Poor". No major complications or serious adverse events were reported following intra-articular BTX, which provided encouraging pain relief, improved motor function, and quality of life. Based on the available data, no clear indication emerged from the comparison of BTX with other established treatments for knee OA. The analysis of the available RCTs on BTX intra-articular injection for the treatment of knee OA revealed modest methodological quality. However, based on the data retrieved, botulinum toxin has been proven to provide good short-term outcomes, especially in patients with pain sensitization, by modulating neurotransmitter release, peripheral nociceptive transduction, and acting on the control of chronic pain from central sensitization.

Botulinum Toxin Versus Dextrose Prolotherapy: Which is More Effective for Temporomandibular Joint Subluxation? A Randomized Clinical Trial.

PURPOSE: Botulinum toxin type A (BTX-A) therapy or dextrose prolotherapy (DP) has been used to treat temporomandibular joint (TMJ) disorders. However, the superiority of one method over the other has not been studied in patients with TMJ subluxation. Therefore, this study aims to answer the following clinical question: among patients with TMJ subluxation, do those undergoing BTX-A injection into lateral pterygoid muscles, compared to those undergoing intra- and periarticular DP injections, have better outcomes in terms of locking episodes and patient satisfaction? METHODS: A randomized clinical trial was implemented in adult patients with TMJ subluxation. The sample was composed of patients with TMJ subluxation with painful open-locking during wide mouth opening and/or yawning at baseline. The subjects were treated randomly with one of two treatment techniques with equal numbers as follows: one-session BTX-A injection into lateral pterygoid muscles (BTX-A group) or three sessions of dextrose injections around TMJ (prolotherapy group). The predictor variable was the treatment technique (BTX-A or prolotherapy injections). The primary outcome variable was the frequency of locking episodes. The secondary outcome variable was patient satisfaction. The primary outcome variable was recorded at baseline and 8-12 months following the injections. The secondary outcome variable was recorded only 8-12 months following the injections. Descriptive and bivariate statistics were computed. The data were analyzed with the Wilcoxon and Mann-Whitney U tests. RESULTS: The baseline sample was composed of 30 patients with TMJ subluxation. However, the follow-up sample comprised 25 subjects: 11 (9 females, 2 males; 25.64 years) in the BTX-A group and 14 (10 females, 4 males; 32.37 years) in the prolotherapy group. Locking episodes decreased significantly in the two groups with no significant difference (P < .01). Seven patients in the BTX-A group (7 of 11 patients; 63.6 percent) and eight (8 of 14 patients; 57.1 percent) in the prolotherapy group reported no complaint of locking at the end of follow-up, with no significant difference between the groups (P > .05). Patient satisfaction showed no significant difference between the groups (P > .05). CONCLUSION: These findings suggested that BTX-A injection is no more effective than DP for any outcome variables of TMJ subluxation assessed.

Virtual Reality for Decreasing Procedural Pain during Botulinum Toxin Injection Related to Spasticity Treatment in Adults: A Pilot Study.

BACKGROUND AND OBJECTIVES: Botulinum toxin injections are commonly used for the treatment of spasticity. However, injection procedures are associated with pain and procedural anxiety. While pharmacological approaches are commonly used to reduce these, innovative technology might be considered as a potential non-pharmacological alternative. Given this context, immersive virtual reality (VR) has shown effectiveness in the management of procedural pain. Our retrospective pilot study aimed to assess the potential added value of virtual reality in the management of pain and anxiety during intramuscular injections of botulinum toxin. MATERIALS AND METHODS: Seventeen adult patients receiving botulinum toxin injections were included. A numerical rating scale was used to assess pain and anxiety during the injection procedure. The patients reported the pain experienced during previous injections without VR before injection and the pain experienced in the current procedure with VR after the end of the procedure. The level of satisfaction of VR experience, whether or not they agreed to reuse VR for the subsequent toxin botulinum injection, and whether or not they would recommend VR to other patients were assessed. RESULTS: The use of virtual reality led to a decrease of 1.8 pain-related points compared to the procedure without technology. No significant improvement in the level of anxiety was reported. Patients were very satisfied with their VR experiences (7.9 out of 10), and many would agree to reuse VR in their next injection procedure (88%) and to recommend the use of VR in other patients (100%). CONCLUSION: VR was useful for managing procedural pain related to botulinum toxin injection in adults, with a high level of satisfaction reported by the patients. VR should be considered as a valuable alternative to pharmacological approaches to manage procedural pain during botulinum toxin injection in adults.

Long term outcome of antegrade colonic enema (ACE) stoma for treatment of constipation and fecal incontinence in children.

AIM: To determine the long term outcome of antegrade colonic enema (ACE) stoma for treatment of chronic constipation and soiling in children. METHOD: We reviewed patients prospectively who underwent formation of ACE stoma after failure of maximum medical treatment of chronic constipation and soiling from September 2008 to October 2020. All patients had anorectal manometry, endosonography and colonic transit study. A validated symptom severity (SS) score questionnaire was used pre operatively and during follow up. The sum of SS score ranged between 0 (best) and 65 (worst). Data was expressed as median(range) and Wilcoxon rank sum test was used and p value < 0.05 was considered significant. RESULTS: 58 patients had formation of ACE stoma, laparoscopic appendicostomy 56, cecostomy 1, and open procedure 1. The main indications for the ACE stoma were chronic functional constipation (FC) 50(86%), anorectal malformations (ARM) 6(11%) and Hirschsprung disease (HD) 2(3%). 41(71%) of patients had previous intrasphincteric botulinum toxin (BT) treatment. Age at operation was 11(range 4-15) years and follow up was 36(3-84) months. 47(81%) patients were continent of stool within three months postoperatively. The preoperative SS score improved from 34/65 (26-47) to 8/65 (4-12) at 12 months and 5/65 (2-11) at 24 months follow up, p ≤ 0.05. OVERALL: complication rate was 15(26%), wound infection 5, granulation tissue 4, stoma prolapse 4, retraction 1, abscess formation and fistula 1. 15 (26%) adolescents had transition of their care to adult services. CONCLUSION: There is a significant improvement of constipation, soiling and general health of patients following formation of ACE stoma. Adolescents benefits an orderly transition of their care to adult services. LEVEL OF EVIDENCE: Level 2, Therapeutic study.

Guidance to trigger point injection for treating myofascial pain syndrome: Intramuscular neural distribution of the quadratus lumborum.

Postural habits and repetitive motion contribute toward the progress of myofascial pain by affecting overload on specific muscles, the quadratus lumborum (QL) muscle being the most frequently involved. The therapy of myofascial pain syndrome includes the release of myofascial pain syndrome using injective agents such as botulinum neurotoxin, lidocaine, steroids, and normal saline. However, an optimal injection point has not been established for the QL muscle. This study aimed to propose an optimal injection point for this muscle by studying its intramuscular neural distribution using the whole mount staining method. A modified Sihler's procedure was completed on 15 QL muscles to visualize the intramuscular arborization areas in terms of the inferior border of the 12th rib, the transverse processes of L1-L4, and the iliac crest. The intramuscular neural distribution of the QL had the densely arborized areas in the three lateral portions of L3-L4 and L4-L5 and the medial portion between L4 and L5.

The pharmacological treatment and management of hyperhidrosis.

INTRODUCTION: Idiopathic hyperhidrosis is a dysfunctional disorder involving eccrine sweat glands, and its impact on patients' daily quality of life is well known. Unlike some years ago, when only poor effective and safe therapeutic alternatives were available, nowadays, several emerging pharmacological active substances have gained significant space as treatment options. AREAS COVERED: The authors report on, in this narrative review, the emerging data from the literature focusing on the pharmacological treatments to draw up a drug treatment flow chart for patients with idiopathic hyperhidrosis, taking into consideration specific differences among axillary, palmoplantar, and craniofacial hyperhidrosis. EXPERT OPINION: Idiopathic hyperhidrosis, regardless of the site of involvement, remains a functional disorder that places a significant burden on patients. After balancing efficacy against adverse events, systemic therapy, although off-label for all forms of hyperhidrosis, can be an added therapeutic option for patients with insufficient response to topical treatment. Until the pathophysiological mechanisms underlying hyperhidrosis are clear and the etiological therapeutic approach becomes realistic, the greatest challenge in the therapeutic management of hyperhidrotic patients seems to be the search for the most convenient combination between different therapeutic modalities (topical and systemic agents, and botulinum toxins) to achieve long-term control of the disease symptoms.

Transoral radiofrequency of the terminal branches of the recurrent nerve in the treatment of adductor spasmodic dysphonia: our experience over 11 patients.

PURPOSE: Spasmodic dysphonia (SD) or laryngeal dystonia is as a rare vocal disorder characterized by involuntary action-induced endolaryngeal contraction. In the last decade, botulin toxin injection has become the standard treatment in adductor spasmodic dysphonia necessitating repetitive injections. The purpose of this study is to analyze retrospectively data from patients treated with the minimal-invasive transoral radiofrequency-induced thermotherapy (RFITT) of the terminal branches of the recurrent nerve. METHODS: Between 2009 and 2015, 11 patients (six females and five males aged from 32 to 91 years) with adductor SD were treated with RFITT. Pre-operative and post-operative vocal assessments (VHI-30, GRBASI, and acoustic-aerodynamics measurements), number of surgical revisions, delay between procedures, and post-operative complications were recorded. Statistical analyses were carried out on the first vocal assessment performed 2-8 weeks after the first procedure. RESULTS: Based on available data from ten patients, voice handicap index (VHI) showed improvement with a mean value of -17.7 points (p-value (pval) = 0.014, adjusted p-value (adj pval) = 0.21); instability has also revealed improvement in six patients (pval = 0.05, adj pval = 0.31). Four patients underwent only one procedure including one patient showing still long-term beneficial results after 5 years of follow-up. Other patients required one to three new procedures with an average time between procedures of 15.3 months. Over 24 surgeries performed on a total of 11 patients, one definitive treatment-related severe adverse event was reported. CONCLUSION: Thanks to long-lasting effect, repetitive treatments are less frequent compared to botulin toxin therapy. In our opinion, RFITT is a promising alternative to botulin toxin as a second-step procedure in case of toxin resistance or patient's lack of compliance.

Intramuscular Innervation of the Supraspinatus Muscle Assessed Using Sihler's Staining: Potential Application in Myofascial Pain Syndrome.

Despite the positive effects of botulinum neurotoxin (BoNT) injection into the neural arborized area, there is no anatomical evidence in the literature regarding the neural arborization of the supraspinatus muscle. The present study aimed to define the intramuscular neural arborized pattern of the supraspinatus muscle using the modified Sihler's staining method to facilitate the establishment of safe and effective injection sites in patients with myofascial pain in the supraspinatus muscle. Seventeen supraspinatus muscles from 15 embalmed cadavers were dissected. Precise suprascapular nerve entry locations were also observed. Intramuscular neural arborization was visualized by Sihler's staining. The supraspinatus muscle was divided into four portions named A, B, C, and D. The nerve entry points were observed in 88.2% (15 of 17 cases) of section B and 76.5% (13 of 17 cases) of section C of the supraspinatus muscle, respectively. The concentration of intramuscular neural arborization was highest in section B of the supraspinatus muscle, which was the center of the supraspinatus muscle. When the clinician performs a trigger point and a BoNT injection into the supraspinatus muscle, injection within the medial 25-75% of the supraspinatus muscle will lead to optimal results when using small amounts of BoNT and prevent undesirable paralysis.

Intramuscular Neural Distribution of the Serratus Anterior Muscle: Regarding Botulinum Neurotoxin Injection for Treating Myofascial Pain Syndrome.

The serratus anterior muscle is commonly involved in myofascial pain syndrome and is treated with many different injective methods. Currently, there is no definite injection point for the muscle. This study provides a suggestion for injection points for the serratus anterior muscle considering the intramuscular neural distribution using the whole-mount staining method. A modified Sihler method was applied to the serratus anterior muscles (15 specimens). The intramuscular arborization areas were identified in terms of the anterior (100%), middle (50%), and posterior axillary line (0%), and from the first to the ninth ribs. The intramuscular neural distribution for the serratus anterior muscle had the largest arborization patterns in the fifth to the ninth rib portion of between 50% and 70%, and the first to the fourth rib portion had between 20% and 40%. These intramuscular neural distribution-based injection sites are in relation to the external anatomical line for the frequently injected muscles to facilitate the efficiency of botulinum neurotoxin injections. Lastly, the intramuscular neural distribution of serratus anterior muscle should be considered in order to practice more accurately without the harmful side effects of trigger-point injections and botulinum neurotoxin injections.

Non-surgical interventions for the treatment of masticatory muscular spasticity in patients with cerebral palsy. Systematic review of randomized clinical trials.

INTRODUCTION: Muscle disorders caused by cerebral palsy (CP) can affect oral function. The treatment for masticatory muscle spasticity is important to minimize muscle hyperactivity and preclude oral damages. OBJECTIVES: To evaluate the efficacy and safety of non-surgical interventions for the treatment of masticatory muscle spasticity in CP patients. METHODS: A comprehensive search was performed in the following databases: MEDLINE, Embase, Cochrane Library, LILACS, BBO, PEDro, Clinicaltrials.gov and WHO/ICTRP, without date and language restrictions. Randomized controlled trials (RCT) evaluating non-surgical interventions were considered. Primary outcomes such as masticatory function and adverse events were planned to be assessed. The risk of bias assessment was performed using the Cochrane risk of bias tool. The certainty of the evidence was assessed using the GRADE approach. RESULTS: Three RCT assessing the effects of botulinum toxin, functional masticatory training and neuromuscular electrostimulation (NMES) were included. Evidence with a very low certainty showed: (i) no difference between botulinum toxin and placebo regarding maximum chewing strength, chewing efficiency and global oral health scale; (ii) improvement in masticatory function in favor of functional masticatory training versus conventional exercises, and (iii) in favor of strengthening exercises plus NMES versus placebo. CONCLUSIONS: There was insufficient evidence to support the use of botulinum toxin and masticatory muscle strengthening programs alone and associated with NMES for the treatment of masticatory muscle in patients with PC. The clinical decision must be individualized, and further studies are needed to support or refute the use of different non-surgical interventions for PC. PROSPERO register number CRD42020209761.

A importância da intervenção fisioterapêutica no vaginismo: uma revisão sistemática / The importance of physiotherapeutic intervention in vaginism: a systematic review

Objetivo: Descrever a importância da intervenção fisioterapêutica para mulheres com vaginismo. Fonte de dados: Foram utilizadas as bases de dados SciELO, PubMed, Biblioteca Virtual de Saúde (BVS) e Literatura Cinza, incluindo artigos nacionais e internacionais, sem delimitação temporal. Foram propostas para as buscas as seguintes palavras-chave e operadores boleanos: [("vaginismus") AND ("physiotherapy" OR "intervention" OR "efficiency")], sendo esses posteriormente adequados para as demais bases que foram utilizadas nesta revisão sistemática. Seleção dos estudos: A seleção dos estudos foi realizada por três examinadores independentes. Coleta de dados: Inicialmente foram excluídos estudos com base no título, em seguida os resumos foram analisados e, dos 353 artigos encontrados inicialmente, quatro foram elegíveis para esta revisão. Síntese dos dados: Os artigos incluídos descreveram que o tratamento fisioterapêutico é de extrema importância para as mulheres com vaginismo, pois aumenta a força e o controle sobre a musculatura do assoalho pélvico, diminuindo os sintomas do vaginismo e promovendo o incremento da satisfação sexual. Conclusão: A intervenção fisioterapêutica é imprescindível para mulheres que apresentam vaginismo, tendo em vista que suas técnicas têm efetividade na prevenção e tratamento do vaginismo, além de promover melhora importante na qualidade de vida e na satisfação sexual das mulheres.(AU)

Objective: To describe the importance of physical therapy intervention for women with vaginismus. Data source: The SciELO, PubMed, Virtual Health Library (BVS) and Gray Literature databases were used, including national and international articles, without temporal delimitation. The following keywords and Boolean operators were proposed for the searches: [("vaginismus") AND ("physiotherapy" OR "intervention" OR "efficiency")], which were later suitable for the other bases that were used in this systematic review. Study selection: Study selection was performed by three independent examiners. Data collection: Initially, studies were excluded based on the title, then the abstracts were analyzed and of the 353 articles found initially, 4 were eligible for this review. Data synthesis: The articles included described that physical therapy treatment is extremely important for women with vaginismus, as it increases strength and control over the pelvic floor muscles, decreasing the symptoms of vaginismus and promoting increased sexual satisfaction. Conclusion: Physical therapy intervention is essential for women who have vaginismus, considering that its techniques are effective in preventing and treating vaginismus, in addition to promoting an important improvement in women's quality of life and sexual satisfaction.(AU)

Botulinum Toxin Therapy in Writer's Cramp and Musician's Dystonia.

Task-specific focal dystonia is characterized by muscle contraction(s) during a specific task, resulting in abnormal postures or movements. Specifically, writer's cramp involves the upper extremity during the act of writing. Musician's dystonia has a highly variable presentation, and thus makes therapeutic options more limited. Treatments include oral pharmacologic agents, neuromodulation, surgery and, most often, botulinum toxin (BoNT) injection. Selection of target muscles for toxin injection continues to be an area of active research for these task-specific movements. We present a review of the literature selected from a predefined search of the MEDLINE and ClinicalTrials.gov databases. We include six controlled studies of botulinum toxin for the management of writer's cramp and focal task-specific dystonia (FTSD), including musician's dystonia. Overall, 139 patients were included across all studies, with 99 individuals injected for writer's cramp and the remaining 40 individuals with FTSD. The age range of all patients was 18-80 years old. We included studies that utilized only the BoNT-A serotype. These studies utilized various severity scales to quantify response to toxin injection, with ratings of instrument or pen control included as subjective ratings. Of the included 139 patients in this review, pooled data for toxin response show that 73% of patients who received the drug demonstrated improvement. Specific techniques for muscle localization and targeting were difficult to study as variable methods were employed. This remains an area of ongoing exploration.

The auditory startle response in relation to outcome in functional movement disorders.

BACKGROUND: The auditory startle reflex (ASR) is enlarged in patients with functional movement disorders (FMD). OBJECTIVES: To study whether the ASR relates to symptom reduction in FMD patients, who participated in a placebo controlled double blind treatment trial with Botulinum Neurotoxin (BoNT). METHODS: Response to treatment in the BoNT study was assessed using the Clinical Global Impression - Improvement scale (CGI-I). The electromyography (EMG) muscle activity of 7 muscles following 110 dB tones was measured in 14 FMD patients before and after one-year treatment and compared to 11 matched controls. The early and a late (behaviorally affected) component of the ASR and the sympathetic skin response (SSR) were assessed. RESULTS: 10 of 14 patients (71.4%) showed symptom improvement, which was believed to be mainly caused by placebo effects. The early total response probability of the ASR at baseline tended to be larger in patients compared to controls (p = 0.08), but normalized at follow-up (p = 0.84). The late total response probability was larger in patients vs. controls at baseline (p < 0.05), a trend that still was present at follow-up (p = 0.08). The SSR was higher in patients vs. controls at baseline (p < 0.01), and normalized at follow-up (p = 0.71). CONCLUSIONS: On a group level 71.4% of the patients showed clinical symptom improvement after treatment. The early part of the ASR, most likely reflecting anxiety and hyperarousal, normalized in line with the clinical improvement. Interestingly, the augmented late component of the ASR remained enlarged suggesting persistent altered behavioral processing in functional patients despite motor improvement.

Electrical Stimulation of Injected Muscles to Boost Botulinum Toxin Effect on Spasticity: Rationale, Systematic Review and State of the Art.

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has been proposed in the literature. We conducted a systematic review of current literature on the protocols of electrical stimulation to boost the effect of BoNT-A injection in patients with spasticity. A systematic search using the MeSH terms "electric stimulation", "muscle spasticity" and "botulinum toxins" and strings "electric stimulation [mh] OR electrical stimulation AND muscle spasticity [mh] OR spasticity AND botulinum toxins [mh] OR botulinum toxin type A" was conducted on PubMed, Scopus, PEDro and Cochrane library electronic databases. Full-text articles written in English and published from database inception to March 2021 were included. Data on patient characteristics, electrical stimulation protocols and outcome measures were collected. This systematic review provides a complete overview of current literature on the role of electrical stimulation to boost the effect of BoNT-A injection for spasticity, together with a critical discussion on its rationale based on the neurobiology of BoNT-A uptake.

Lentiviral vector-mediated expression of C3 transferase attenuates retinal ischemia and reperfusion injury in rats.

AIMS: Our previous study showed that intravitreal delivery of self-complementary AAV2 (scAAV2)-mediated exoenzyme C3 transferase (C3) can attenuate retinal ischemia/reperfusion (I/R) injury. The current study investigated the neuroprotective effects of lentivirus (LV)-mediated C3 transgene expression on rat retinal I/R injury. MAIN METHODS: The LV encoding C3 and green fluorescent protein (GFP) together (LV-C3-GFP) or GFP only (LV-GFP) was intravitreally injected to SPRAGUE-DAWLEY rats. On day 5 post-intravitreal injection, eyes were evaluated by slit-lamp examination. The GFP expression on retina was confirmed by in vivo and ex vivo assessments. RhoA GTPase expression in retina was examined by western blot. Retinal I/R injury was generated by transiently increasing intraocular pressure (110 mmHg, 90 min). Eyes were then enucleated, and retinas processed for morphological analysis and TdT-dUTP terminal nick-end labeling (TUNEL) assay. KEY FINDINGS: No obvious inflammatory reactions or surgical complications were observed after intravitreal injection of LV vectors. There was a significant decrease of total RhoA GTPase level in the retina treated with LV-C3-GFP. Compared to the blank control group, LV-C3-GFP and LV-GFP did not affect the retinal thickness, cell density in ganglion cell layer (GCL), or numbers of apoptotic cells in retinal flat-mounts. In the LV-GFP-treated retinas, I/R decreased the retinal thickness and GCL cell density and increased apoptotic retinal cell numbers. LV-C3-GFP significantly protected against all these degenerative effects of I/R. SIGNIFICANCE: This study indicated that LV-mediated C3 transgene expression exhibits neuroprotective effects on the retinal I/R injury and holds potential as a novel neuroprotective approach targeting certain retinopathies.