Posterior Tibial Nerve Research Articles

Transcutaneous posterior tibial nerve stimulation on demand during multichannel urodynamics: A new approach in the management of overactive bladder

Background:Overactive Bladder Syndrome (OAB) affects individuals across all ages and genders, reducing quality of life. Although Transcutaneous Posterior Tibial Nerve Stimulation (TTNS) is an effective treatment, its acute effects on OAB remain underexplored. Objectives:This study aimed to assess the acute effects of TTNS on OAB through invasive urodynamics (UDI), using an intermittent, on-demand approach; with a focus on urinary urgency as the central axis for its application. Methods:A proof-of-concept trial was conducted involving patients with OAB symptoms and no previous treatment. An initial urodynamic evaluation (UDI DG) identified patients with detrusor overactivity (DO) associated with urgency, who then received on-demand TTNS during a second urodynamic study (UDI TENS). Parameters measured included the number of involuntary detrusor contractions (IDC), episodes of urge urinary incontinence (UUI), and maximum cystometric capacity (MCC). Statistical significance was assessed using Student’s t-test and Wilcoxon test, with a p-value ≤ 0.05 chosen as significance threshold. Results:Of the initial twenty-nine participants, 12 completed the study. UDI DG measurements showed an average of 3.33 ± 1.3 IDCs, 0.67 ± 0.98 UUI episodes, and MCC of 235 ± 79 ml. During UDI TENS results demonstrated a significant reduction in IDCs to 0.08 ± 0.29 (p ≤ 0.001), an absence of UUI episodes, and an increase in MCC to 315 ± 83 ml (p = 0.00012). Conclusions:Our findings suggest that an acute, on-demand TTNS protocol is effective for managing OAB symptoms and improvement of UDI parameters. However, the limited number of participants and absence of a control group highlight the need for further research through larger, controlled studies.

Is posterior tibial nerve stimulation (PTNS) effective for the overactive bladder symptom complex? Reflections in a convoluted battlefield

Is posterior tibial nerve stimulation (PTNS) effective for the overactive bladder symptom complex? Reflections in a convoluted battlefield

Tarsal Tunnel Syndrome: A Narrative Review

Tarsal tunnel syndrome is a compressive neuropathy of the posterior tibial nerve beneath the flexor retinaculum on the medial ankle. Several intrinsic or extrinsic factors may contribute to pain over the medial plantar aspect of the foot that is aggravated by activities. In the presence of suggestive clinical features, appropriate use of radiographic and electrodiagnostic tests can be helpful. Surgical management is considered in patients who do not respond to non-operative treatment or those who have a space-occupying lesion within the tarsal tunnel. Along with surgical decompression of the posterior tibial nerve, complete removal of the causative space-occupying lesion is needed to prevent recurrence.

Cut-off value for a normal posterior tibial nerve to diagnose tarsal tunnel syndrome amongst people of different race in Pretoria, South Africa.

Posterior tibial nerve (PTN) cross-sectional area (CSA) reference values for the diagnosis of tarsal tunnel syndrome (TTS) using ultrasound imaging exist in several countries but not in South Africa (SA). Therefore, the objective was to measure the CSA reference values for PTN in SA. Ultrasound CSA measurements of PTN in both ankles on 112 participants were performed, the mean measurement was recorded, and the effect of race, age, gender, and body mass index (BMI) were recorded. In this study, the primary variables age and BMI affect the CSA measurement of the PTN. A positive correlation was found between PTN asymptomatic size and age (r = 0.196, P < 0.05), size and BMI (r = 0.200, P < 0.05). Age (categories) had a mean value of 3.17 for the age group 36-45 years (95% confidence interval (CI) 2.9-3.4). The mean BMI was 30.0 kg/m2 (CI 28.57-31.08). As for the asymptomatic PTN, a mean CSA reference value of 0.10 cm2 was obtained. With increase in age and BMI, a greater PTN measurement will occur. Race appears to be a contributing factor, but further research is needed in this regard. The reference CSA value for normal PTN should be set at 0.10 cm2 for all racial groups for a basic musculoskeletal ultrasound exam protocol in South Africa.

Long-Term Outcome of Biofeedback versus Transcutaneous Posterior Tibial Nerve Stimulation in The Treatment of Functional Non-Retentive Fecal Incontinence

Long-Term Outcome of Biofeedback versus Transcutaneous Posterior Tibial Nerve Stimulation in The Treatment of Functional Non-Retentive Fecal Incontinence

Posterior Tibial Nerve Stimulation for the Treatment of Detrusor Overactivity in Multiple Sclerosis Patients: A Narrative Review.

Bladder dysfunction, particularly neurogenic detrusor overactivity (DO), poses a substantial challenge in multiple sclerosis (MS) patients, detrimentally impacting their quality of life (QoL). Conventional therapies often fall short, necessitating alternative approaches like posterior tibial nerve stimulation (PTNS) for effective management. This narrative review critically examines the application of PTNS in treating DO among MS patients, aiming to provide a comprehensive synthesis of its efficacy, underlying mechanisms, and clinical outcomes. By evaluating a spectrum of studies, including randomized controlled trials and long-term follow-up research, the review elucidates PTNS's role in enhancing bladder control and ameliorating symptoms of urgency and incontinence, thereby improving patient well-being. Despite its potential, the review acknowledges the limited scope of existing research specific to MS-induced neurogenic DO and calls for further investigation to optimize PTNS protocols and understand its long-term benefits. Highlighting PTNS's minimal invasiveness and favorable safety profile, the review advocates for its consideration as a viable third-line treatment option in MS-related bladder dysfunction management. Through this analysis, the review contributes to the broader narrative of seeking effective, patient-centered therapeutic strategies for MS-related complications, underscoring the importance of personalized care in improving patient outcomes.

Optimization of direct cortical stimulation using tibial versus median nerve sensory mapping during midline brain tumor resection: illustrative case.

During brain tumor resection, neurophysiological mapping and monitoring help surgeons locate, characterize, and functionally assess eloquent brain areas in real time. The selection of mapping and monitoring targets has implications for successful surgery. Here, the authors compare direct cortical stimulation (DCS) as suggested by median nerve (MN) with posterior tibial nerve (PTN) cortical sensory mapping (SM) during mesial lesion resection. Recordings from a 6-contact cortical strip served to generate an MN and a PTN sensory map, which indicated the strip was anterior to the central sulcus. Responses exhibited an amplitude gradient with no phase reversal (PR). DCS, elicited through a stimulus probe or contact(s) of the strip, yielded larger responses from the corresponding sensory mapped limb; that is, PTN SM resulted in larger lower limb muscle responses than those suggested by MN SM. SM of the MN and PTN is effective for localizing eloquent cortical areas wherein the PTN is favored in surgery for mesial cortical tumors. The recorded amplitude of the cortical somatosensory evoked potential is a valuable criterion for defining the optimal location for DCS, despite an absent PR. The pathway at risk dictates the specifics of SM, which subsequently defines the optimal location for DCS.

Updates in pelvic neuromodulation: the role of pelvic neuromodulation in pelvic disorders

Pelvic disorders affecting both male and female patients are major areas of concern for clinicians in cases where pharmacotherapy and behavioral therapy are not effective. In such cases, pelvic neuromodulation has become an alternative therapy that could relieve chronic pelvic pain and enhance the quality of life. The goal of this paper was to present a summary of the current therapeutic applications of various pelvic neuromodulation techniques and their efficacy in treating patients with a range of pelvic illnesses. Based on the available literature, this review assessed the validity and significance of the last 10 years’ advancements in the fields of sacral neuromodulation (SNM), posterior tibial nerve stimulation (PTNS), and pudendal neuromodulation (PNM), including meta-analyses, randomized controlled trials, and observational, prospective, and retrospective studies.

Clarifying practical aspects of posterior tibial nerve stimulation for neurogenic overactive bladder: A scoping review

AbstractPatients with neurological diseases often suffer from overactive bladder. Posterior tibial nerve stimulation is mentioned in guidelines as a treatment when antimuscarinics fail or cannot be tolerated by patients, but the evidence is scant. This article summarizes the evidence on the practical aspects of tibial nerve stimulation for neurogenic overactive bladder (NOAB), such as electrical parameters and treatment duration, and identifies areas requiring further investigation. Scoping review. Literature search on PubMed, CINAHL, and Cochrane Library, including studies from 2010 to 2024 regarding tibial nerve stimulation for NOAB. Sixteen papers were considered: seven on transcutaneous tibial nerve stimulation (TTNS), seven on percutaneous tibial nerve stimulation (PTNS) and two protocols. Most studies enrolled neurological and non‐neurological patients or studied non‐randomized samples of a few patients. Clinical outcomes, treatment duration, number of sessions, and follow‐up times showed considerable heterogeneity, but some practical recommendations could be drawn. For PTNS, most authors suggest using 20 Hz and 200 μs, but the amplitude is highly variable among studies. For TTNS, 10 Hz and 200 μs are suggested, with considerable variability in the number of sessions and overall treatment duration. Most papers propose similar criteria regarding the frequency and duration of the stimulation, and all of them support the efficacy of tibial nerve stimulation, except for one. The areas requiring research include long‐term results, allowing for shaping adequate maintenance programmes to avoid losing the results achieved.

Soleus H-reflex amplitude modulation during walking remains physiological during transspinal stimulation in humans.

The soleus H-reflex modulation pattern was investigated during stepping following transspinal stimulation over the thoracolumbar region at 15, 30, and 50Hz with 10kHz carry-over frequency above and below the paresthesia threshold. The soleus H-reflex was elicited by posterior tibial nerve stimulation with a single 1 ms pulse at an intensity that the M-wave amplitudes ranged from 0 to 15% of the maximal M-wave evoked 80ms after the test stimulus, and the soleus H-reflex was half the size of the maximal H-reflex evoked on the ascending portion of the recruitment curve. During treadmill walking, the soleus H-reflex was elicited every 2 or 3 steps, and stimuli were randomly dispersed across the step cycle which was divided in 16 equal bins. For each subject and condition, the soleus M-wave and H-reflex were normalized to the maximal M-wave. The soleus background electromyographic (EMG) activity was estimated as the linear envelope for 50ms duration starting at 100ms before posterior tibial nerve stimulation for each bin. The gain was determined as the slope of the relationship between the soleus H-reflex and the soleus background EMG activity. The soleus H-reflex phase-dependent amplitude modulation remained unaltered during transspinal stimulation, regardless frequency, or intensity. Similarly, the H-reflex slope and intercept remained the same for all transspinal stimulation conditions tested. Locomotor EMG activity was increased in knee extensor muscles during transspinal stimulation at 30 and 50Hz throughout the step cycle while no effects were observed in flexor muscles. These findings suggest that transspinal stimulation above and below the paresthesia threshold at 15, 30, and 50Hz does not block or impair spinal integration of proprioceptive inputs and increases activity of thigh muscles that affect both hip and knee joint movement. Transspinal stimulation may serve as a neurorecovery strategy to augment standing or walking ability in upper motoneuron lesions.

Pain Management of Sciatic Nerve Injury Induced by Intramuscular Injection Using Distal Nerve Block

Abstract Injury to the sciatic nerve from dorsogluteal intramuscular (IM) injection is not an uncommon iatrogenic cause. This case report discusses the successful management of a child with sciatic nerve injury due to an IM injection in the left gluteal region. The child experienced severe pain that was not responding to pharmacological therapy and was limiting physiotherapy, which forms an important step in the management of patients with peripheral nerve injuries. The case report outlines the use of a posterior tibial nerve block, which provided immediate relief of pain sensations in the sole of the foot, allowing the child to walk and eventually improving sleep and appetite. The report suggests that distal nerve blocks may be an effective treatment option for patients with severe neuropathic symptoms resulting from peripheral nerve injury.

Examining the Role of Frailty on Treatment Patterns and Complications Among Older Women Undergoing Procedure-Based Treatment for Urinary Incontinence.

Aging beyond 65 years is associated with increased prevalence of urinary incontinence (UI), frailty, and increased complication rate with UI treatments. To investigate this relationship, we examined frailty as a predictor of procedure-based UI treatment patterns and urologic complications in Medicare-eligible women. We identified women undergoing procedures for UI between 2011 and 2018 in the 5% limited Medicare data set. A claims-based frailty index (CFI) using data from the 12 months prior to the index procedure defined frailty (CFI ≥0.25). Urologic complications were assessed during the 12 months following the index procedure. We used unadjusted logistic regression models to calculate odds of having a specific type of UI procedure based on frailty status. Odds of postprocedure urologic complications were examined with logistic regression adjusted for age and race. We identified 21783 women who underwent a procedure-based intervention for UI, of whom 3826 (17.5%) were frail. Frail women with stress UI were 2.6 times more likely to receive periurethral bulking (95% confidence interval [CI] 2.26-2.95), compared to nonfrail. Conversely, frailty was associated with lower odds of receiving a Sling or Burch colposuspension. Among women with urgency UI or overactive bladder, compared to nonfrail, frailty was associated with higher odds of both sacral neuromodulation (odds ratio [OR] = 1.21, 95% CI: 1.11-1.33) and intravesical Botox (OR = 1.16, 95% CI: 1.06-1.28), but lower odds of receiving posterior tibial nerve stimulation. Frailty was associated with higher odds of postprocedure urologic complications (OR = 1.64, 95% CI: 1.47-1.81). Frailty status may influence treatment choice for treatment of stress or urgency UI symptoms and increase the odds of postprocedural complications in older women.

Sensory Stimulation of the Triceps Surae Muscle Complex Modulates Spinal Reflex Responses-A Comparison between Tapotement Massage and Repetitive Peripheral Magnetic Stimulation (rPMS).

The reduction of muscular hypertonia is important in the treatment of various diseases or rehabilitation. This study aims to test the efficacy of a 5 Hz mechanical muscle stimulation (tapotement massage) in comparison to a 5 Hz repetitive peripheral magnetic stimulation (rPMS) on the neuromuscular reflex response. In a randomized control trial, 15 healthy volunteers were administered with either 5 Hz rPMS, tapotement massage, or rPMS sham stimulation. The posterior tibial nerve was stimulated with rPMS and sham stimulation. The Achilles tendon was exposed to a mechanically applied high-amplitude 5 Hz repetitive tendon tapotement massage (rTTM). The tendon reflex (TR) was measured for the spinal response of the soleus muscle. After rPMS, there was a reduction of the TR response (-9.8%, p ≤ 0.034) with no significant changes after sham stimulation. Likewise, TR decreased significantly (-17.4%, p ≤ 0.002) after Achilles tendon tapotement intervention. These findings support the hypothesis that both afferent 5 Hz sensory stimulations contributed to a modulation within the spinal and/or supraspinal circuits, which resulted in a reduction of the spinal reflex excitability. The effects could be beneficial for patients with muscle hypertonia and could improve the functional results of rehabilitation programs.

Transcutaneous Posterior Tibial Nerve Stimulation: An Adjuvant Treatment for Intractable Constipation in Children.

Functional constipation can lead to painful defecations, fecal incontinence, and abdominal pain, significantly affecting a child's quality of life. Treatment options include non-pharmacological and pharmacological approaches, but some cases are intractable and require alternative interventions like neuromodulation. A subtype of neuromodulation, called Transcutaneous Posterior Tibial Nerve Stimulation (TPTNS), comprises electrical stimulation at the ankle level, by means of electrodes fixed to the skin. TPTNS is a minimally invasive, easy-to-apply technique that can potentially improve constipation symptoms in the pediatric population by stimulating the sacral nerves. To evaluate the clinical results and applicability of TPTNS as an adjuvant treatment for children and adolescents with functional constipation. Between April 2019 and October 2021, 36 patients diagnosed with functional constipation according to the Rome IV Criteria were invited to participate in the study. The study followed a single-center, uncontrolled, prospective cohort design. Patients received TPTNS for 4 or 8 weeks, with assessments conducted immediately after the periods of TPTNS and 4 weeks after the end of the intervention period. The data normality distribution was determined by the Shapiro-Wilk test. The Wilcoxon test and Student's t-test for paired samples were used to compare quantitative variables, and the McNemar test was used to compare categorical variables. Of the 36 enrolled patients, 28 children and adolescents with intractable function constipation completed the study, receiving TPTNS for 4 weeks. Sixteen patients (57.1%) extended the intervention period for 4 extra weeks, receiving 8 weeks of intervention. TPTNS led to significant improvements in stool consistency, frequency of defecation, and bowel function scores, with a reduction in abdominal pain. Quality of life across physical and psychosocial domains showed substantial enhancements. The quality of life-related to bowel habits also improved significantly, particularly in lifestyle, behavior, and embarrassment domains. The positive effects of this intervention are seen relatively early, detected after 4 weeks of intervention, and even 4 weeks after the end of the intervention. TPTNS was well-tolerated, with an adherence rate of approximately 78%, and no adverse effects were reported. TPTNS is an adjuvant treatment for intractable functional constipation, improving bowel function and quality of life. The effects of TPTNS were observed relatively early and sustained even after treatment cessation.

Comparing Pelvic Interferential Therapy and Posterior Tibial Nerve Stimulation for Neurogenic Detrusor Over Activity in Spinal Cord Injury.

Comparing Pelvic Interferential Therapy and Posterior Tibial Nerve Stimulation for Neurogenic Detrusor Over Activity in Spinal Cord Injury.

Evolving types of pudendal neuromodulation for lower urinary tract dysfunction.

Sacral neuromodulation and posterior tibial nerve stimulation for lower urinary tract dysfunction (LUTD) and overactive bladder yield good and reliable results. However, neuromodulation research is continuously evolving because there is still need for more patient-friendly treatment options in the therapeutic management of LUTD. Pudendal neuromodulation (PNM) has been emerging as a promising alternative treatment option for the last few decades. The aim of this study is to review the current state of the art of PNM. A wide literature search was conducted in the field of PNM using Medline through the PubMed database and Elsevier using the Scopus database; a critical review of the results was then carried out. PNM has been studied in its various possible aspects: percutaneous PNM, transrectal/transvaginal PNM, and both percutaneous and transcutaneous dorsal genital nerve stimulation. Each technique was found to result in promising improvements in different clinical outcomes, with some trials reporting even better results than sacral neuromodulation. As a result of a comparison between the various PNM techniques with both sacral neuromodulation and posterior tibial nerve stimulation, we think that PNM should be seen as seriously promising, and we believe it will expand the treatment options for overactive bladder. Even though several studies accordingly showed PNM to be safe and effective, a systematic review and meta-analysis were not feasible. PNM in its various techniques is a promising treatment for LUTD. Nevertheless, further research is needed to include it in treatment algorithms.

Posterior tibial nerve electrical stimulation in chronic constipation: a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to investigate posterior tibial nerve electrical stimulation application methods in patients with chronic constipation. Posterior tibial nerve electrical stimulation is a management procedure for chronic constipation. A comprehensive search was conducted on Ovid, PubMed, Scopus, ProQuest, Web of Science, and The Cochrane Library based on the PICO formation of the study. All randomized controlled trials and quasi-experimental studies in which patients with chronic constipation were treated with transcutaneous tibial nerve stimulation (TTNS) or percutaneous tibial nerve stimulation (PTNS) were included in this study. Two independent reviewers screened all titles, abstracts, and full texts. The selected studies' quality was assessed critically using the Joanna Briggs Institute checklists. The data synthesis was conducted using Review Manager Software. Out of 1016 records, 11 studies were included in this study. The results showed that TTNS was effective in improving constipation symptoms (SMD: -1.52, CI 95%: -2.81 to -0.22, p< 0.0001) and reducing defecation time of patients with chronic constipation (SMD: -0.86, CI 95%: -1.60 to -0.13, p= 0.17). Additionally, PTNS was found to improve the quality of life of these patients (SMD: -1.32, CI 95%: -2.05 to -0.59, p< 0.00001). Both TTNS and PTNS can be effective interventions for chronic constipation. To suggest a definitive and standard treatment plan, further research is needed to determine optimal parameters for TTNS and PTNS applications.

Midterm Outcomes after Operative Management of Hawkins Type III Talar Neck Fractures.

This study aims to report the midterm outcomes after surgical treatment of Hawkins Classification III Talar neck fractures. From March 2010 to April 2022, among a total of 155 patients who visited our hospital with talus fractures, 31 patients underwent surgical treatment for Hawkins classification III talar neck fractures. The inclusion criteria comprised patients with a symptom duration of over 1 year who were available for outpatient follow-up and underwent magnetic resonance imaging (MRI) follow-up 2 months after surgery. Exclusion criteria included patients without preoperative ankle periarticular arthritis, and a total of 27 patients were enrolled. Traffic accidents and falls accounted for 86% of 23 cases, open fractures were 8 cases, and the mean follow-up period was 34.10 months (range, 12-80 months). Clinical outcomes were measured by American Orthopaedic Foot and Ankle Society (AOFAS) score and Foot function index (FFI), and radiological results were obtained using simple radiographs before and after surgery and MRI at 2 months postoperatively to confirm bone union and complications. Complete bone union was achieved in all cases, and the mean duration of union was 4.9 months (range, 4-6 months) and there were no nonunion and varus malunion. At the final follow-up, the mean AOFAS score was 80.18 points (range, 36-90 points) and the mean FFI score was 31.43 points (range, 10-68 points), showing relatively good clinical outcomes. There were 15 cases of avascular necrosis, 6 cases of traumatic arthritis of the ankle joint, 6 cases of irritation of the posterior tibial nerve, and 4 cases of wound problems. Hawkins classification III talar neck fractures are mostly caused by high-energy injuries and have a relatively poor prognosis due to the high incidence of complications such as avascular necrosis or posttraumatic arthritis. However, if correct anatomical reduction and rigid internal fixation are performed within a short time after the injury, good results can be expected.

Peripheral Nerve Stimulation With High-Frequency Electromagnetic Coupling at the Sural and Posterior Tibial Nerves for the Treatment of Complex Regional Pain Syndrome in Lower Extremities: Case Report

BACKGROUND: Complex regional pain syndrome (CRPS) type 1 is a debilitating condition that is notoriously difficult to treat due to its various manifestations. Peripheral nerve stimulation (PNS) is generally recommended when a patient’s symptoms are refractory to conservative measures, as CRPS often is. We present one case of CRPS with intractable lower extremity pain managed effectively with PNS. CASE REPORT: A 32-year-old man developed CRPS after a work-related accident that resulted in multiple injuries, including a crushed pelvis, injured left lower extremity, and a fractured face and skull. After pelvic and hip reconstruction, the patient was left with numbness, tingling, and pain in the left foot affecting functional activities and sleep. Previous therapies, including nerve blocks, physical therapy, narcotics, opioids, anticonvulsants, antidepressants, and nonsteroidal anti-inflammatory drugs, did not alleviate symptoms. The placement of a PNS device, however, led to significant improvement. RESULTS: Pain scores at baseline compared to 12-month follow-up decreased from 6/10 to 2/10 at rest and from 8/10 to 4/10 with activity. Average hours of sleep per night increased from 4 to 8 hours (an improvement of 100%). Antidepressants have been discontinued and opioids reduced to an as-needed basis (once every few days). The patient reports decreased sensitivity to cold, reduced swelling, and improved color changes in the foot. In addition, the patient has been able to increase activity, such as walking, standing, and wearing closed-toed shoes, from 20 minutes to now 4 hours at a time with pain levels maintained at a 4/10. CONCLUSIONS: Subthreshold PNS utilizing high-frequency electromagnetic coupling at the posterior tibial and sural nerves successfully relieved the patient’s chronic, debilitating pain in the lower extremity as a result of CRPS. KEY WORDS: Peripheral nerve stimulation, chronic pain, posterior tibial, sural, CRPS, lower extremity, foot

Effects of posterior tibial nerve stimulation (PTNS) on lower urinary tract dysfunction: An umbrella review.

Lower urinary tract dysfunction (LUTD) is a common, troublesome condition that often negatively affects patients' quality of life. Current literature has long been interested in how posterior tibial nerve stimulation (PTNS) can affect this condition. To extensively and systematically explore how PTNS affects LUTD based on the most recent systematic reviews. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All the systematic reviews, with or without meta-analysis that assessed the effects of PTNS on LUTD were retrieved. The quality of the included studies was assessed using the Joanna Briggs Institute tool, and analysis was conducted using the Comprehensive Meta-Analysis version 3 tool. From a total of 3077 citations, 20 systematic reviews entered this study, and 13 of them included meta-analysis. The population of studies varied vastly, for instance, some studies included only children or women while other focused on a specific pathology like multiple sclerosis-induced neurogenic LUTD. The majority of included studies reported an overall improvement in LUTD following percutaneousPTNS, although admitting that these results were derived from moderate to low-quality evidence. The findings of this thorough umbrella review showed that the positive benefits of PTNS in treating LUTD are currently supported by low-quality evidence, and it is crucial to interpret them with great care.