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2.
Pain Physician ; 24(2): E131-E152, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33740342

RESUMO

BACKGROUND: Peripheral nerve stimulation (PNS) has been increasingly used to manage acute and chronic pain. However, the level of clinical evidence to support its use is not clear. OBJECTIVES: To assess the clinical evidence of PNS in the treatment of acute or chronic pain. STUDY DESIGN: A systematic review of the efficacy and safety of PNS in managing acute or chronic pain. METHODS: Data sources were PubMed, Cochrane Library, Scopus, CINAHL Plus, Google Scholar, and reference lists. The literature search was performed up to December 2019. Study selection included randomized trials, observational studies, and case reports of PNS in acute or chronic pain. Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR). The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. Data syntheses: 227 studies met inclusion criteria and were included in qualitative synthesis. RESULTS: Evidence synthesis based on randomized controlled trials (RCTs) and observational studies showed Level I and II evidence of PNS in chronic migraine headache; Level II evidence in cluster headache, postamputation pain, chronic pelvic pain, chronic low back and lower extremity pain; and Level IV evidence in peripheral neuropathic pain, and postsurgical pain. Peripheral field stimulation has Level II evidence in chronic low back pain, and Level IV evidence in cranial pain. LIMITATIONS: Lack of high-quality RCTs. Meta-analysis was not possible due to wide variations in experimental design, research protocol, and heterogeneity of study population. CONCLUSIONS: The findings of this systematic review suggest that PNS may be effective in managing chronic headaches, postamputation pain, chronic pelvic pain, and chronic low back and lower extremity pain, with variable levels of evidence in favor of this technique.

3.
Pain Physician ; 24(2): E169-E176, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33740350

RESUMO

BACKGROUND: Chronic pain, especially low back pain and hip pain, has been a growing public health concern that affects over 100 million Americans annually. Radiofrequency ablation (RFA) has distinct advantages over other chronic pain management modalities and its use has been increasing over the past decade. Among the growing population with comorbid conduction disorders and persistent pain, RFA and its potential interference with implantable cardiac devices is of concern.RFA is becoming a foundational element of persistent pain management and has been shown to be effective in a multitude of chronic pain syndromes. Cardiac implantable electronic devices (CIED), such as cardiac pacemakers or implantable cardioverter defibrillators, have been used in the treatment of cardiac conduction diseases for a number of decades. With our aging population, these diseases have increased in both incidence and prevalence. Chronic pain and cardiac conduction diseases are both common in our increasingly aging population. OBJECTIVES: This study aims to determine if the literature supports the hypothesis that patients with CIEDs can safely use RFA with minimal to no interaction. STUDY DESIGN: Systematic assessment of literature with a modified approach with bipolar RFA. METHODS: A narrative review with systematic assessment of the literature was carried out. In this review, we included randomized controlled trials (RCTs), open non-randomized control studies, prospective studies, retrospective studies, case series, and case reports. All types of radiofrequency utilized for pain management including pulsed and conventional were included. Outcome measures included interactions between the cardiovascular implantable electronic device (CIED) and radiofrequency ablation (RFA), adverse events, RFA efficacy in treating the pain using pain scores, and other complications. RESULTS: Our search criteria yielded 4 studies for inclusion, with inclusion of 33 patients and 71 bipolar radiofrequency for treatments. No adverse events or interactions occurred between the bipolar radiofrequency device and the implanted cardiac devices in any of these patients. Bipolar radiofrequency was utilized in all patients (n = 33). Overall there were no complications or malfunctions. LIMITATIONS: Small sample size, narrative review. CONCLUSIONS: This study provides evidence that bipolar RFA can be safely used in patients with CIEDs for chronic pain provided that proper precautions are employed. Considerations for safe use are provided.

4.
Reg Anesth Pain Med ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33688037
5.
Neuromodulation ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33556220

RESUMO

OBJECTIVES: Chronic pain syndromes in children can carry significant threats to psychological well-being, opioid overuse, functional impairments, and severe disability. While several high-level studies, almost exclusively in adults, have demonstrated the utility of implantable electrical neuromodulation systems for treating various chronic pain syndromes, there exists a paucity of pediatric-specific evidence. Unfortunately, evidence and practice patterns established from adults may not be fully translatable to children given differences in disease manifestations and anatomical variances. MATERIALS AND METHODS: We performed a systematic review using conventional PRISMA methodology to identify studies reporting use of implantable electrical neuromodulation systems in children. The primary outcome parameters collected were analgesic relief and functional benefits. Additionally, previous interventions attempted, neuromodulation parameters, and limitations were collected as reported. RESULTS: A total of 11 studies was identified, which described 19 patients who were refractory to multidisciplinary pain management strategies. The cohort was mostly adolescent (18/19), suffered from CRPS (14/19), and received SCS (17/19). Nearly all patients, both those with CRPS (13/14) and non-CRPS conditions (4/4), reported significant pain relief and functional recovery following neuromodulation. There were no severe complications reported; limitations included suboptimal benefit or loss of analgesia (3/19), lead or device revision (3/19), and subcutaneous infection (1/19), all of which were congruent with adult outcomes. CONCLUSION: There exist children with chronic pain refractory to standard of care approaches who could be considered for neuromodulation interventions. The existing data, which was limited and from a low tier of evidence, suggest that these interventions are relatively safe and provide meaningful pain reduction and functional improvements. While not previously reported, we recommend careful consideration of the pubertal growth spurt prior to device lead placement-if reasonable and appropriate-given the possibility of inferior lead migration with physiologic growth in patients with SCS devices or foraminal extrusion in patients with dorsal root ganglion stimulation devices.

6.
Reg Anesth Pain Med ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574157
7.
Pain Res Manag ; 2021: 6639801, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613793

RESUMO

Background: Spinal cord stimulation (SCS) has been used over decades for pain management, but migration of percutaneous leads has been the most common complication. Better surgical techniques and newer SCS technologies likely reduced the incidence of lead migration requiring surgical revision, although data are sparse. This study aimed to retrospectively evaluate the incidence of clinically significant percutaneous lead migration in patients permanently implanted with a 10 kHz SCS system. Methods: Consecutive patients with chronic trunk and/or limb pain, permanently implanted between January 2016 and June 2019, were included in the analysis. Data were collected from the hospital's electronic medical records and the manufacturer's database. Clinically significant lead migration, defined as diminished pain relief followed by surgery to correct lead location, was assessed at the 6-month follow-up. Results: At the 6-month follow-up, there were no cases of clinically significant lead migration, average pain relief was 65.2%, 82% of patients had response (≥50% pain relief), improvement of function was noted in 72% of patients, and decrease of medication was observed in 42% of patients. Therapy efficacy was sustained in patients with >12 months follow-up; the average pain relief was 58.5%, and the response rate was 82%. Conclusions: The surgical techniques in use today are designed to minimise the risk of percutaneous lead migration and may have reduced its incidence. In addition, new SCS systems may give greater opportunity to mitigate cases of minor lead movement using alternative stimulation programs.

8.
Adv Ther ; 38(3): 1425-1446, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33570737

RESUMO

While radiation therapy is increasingly utilized in the treatment paradigm of many solid cancers, the chronic effects of radiation therapies are poorly characterized. Notably, understanding radiation-specific chronic pain syndromes is paramount given that the diagnosis and management of these conditions can serve to prevent long-standing functional impairments, optimize quality of life, and even allow for continued radiotherapy candidacy. These radiation-specific chronic pain phenomena include dermatitis, mucositis, enteritis, connective tissue fibrosis, lymphedema, and neuropathic pain syndromes. It is necessary to maintain a low threshold of suspicion for appropriately diagnosing these conditions as there exists a variance in when these symptoms arise after radiation. However, we present key epidemiological data delineating vulnerable cancer populations for each pain syndrome along with the available evidence for the management for each specific condition.

10.
Curr Pain Headache Rep ; 25(1): 6, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495883

RESUMO

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available. RECENT FINDINGS: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

11.
Neuromodulation ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449428

RESUMO

OBJECTIVES: To assist in assessment of therapy risks and benefits of targeted drug delivery (TDD) for chronic nonmalignant pain using registry data on product performance, adverse events, and elective device replacement. MATERIALS AND METHODS: The Product Surveillance Registry (PSR) (NCT01524276) is an ongoing prospective, long-term, multicenter registry enrolling consented patients implanted with an intrathecal drug delivery system. Patients are followed prospectively with participating investigators providing pump and catheter performance data for events related to the device, procedure, and therapy. Event descriptions include patient symptoms and outcomes. RESULTS: Registry data from the 4646 patients (59.7% female) treated with TDD for chronic, nonmalignant pain at 59 registry sites between August 2003 and October 2019, with over 17,000 patient-years (4646 patients with 44 months average follow-up), were analyzed. Registry discontinuation was largely (46.2% of discontinued patients) due to study site closure and patient death; exit due to an adverse or device event was limited to 10.2%. CONCLUSIONS: Treating chronic pain with escalating doses of strong systemic opioids often leads to inconsistent pain control, impaired function, untenable side effects, and reduced quality of life and this practice has contributed to the current opioid crisis in the United States. TDD has been an available therapy for these patients for greater than 30 years, and data from this real-world registry offer supporting evidence to the long-term safety of this therapy as an alternative to systemic opioids, as well as insights into patient acceptance and satisfaction.

13.
Neuromodulation ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33501749

RESUMO

BACKGROUND: While the majority of indications and approvals for dorsal root ganglion stimulation (DRGS) are for the refractory management of complex regional pain syndrome (CRPS), emerging evidence has suggested that DRGS may be favorably used for a plethora of other chronic pain phenomena. Consequently, we aimed to characterize the use and efficacy of DRGS for these non-CRPS-related chronic pain syndromes. MATERIALS AND METHODS: A systematic review of clinical studies demonstrating the use of DRGS for non-CRPS-related chronic pain syndromes. The literature search was performed using PubMed, Cochrane Library, and CINAHL plus across August and September 2020. RESULTS: A total of 28 reports comprising 354 total patients were included in the analysis. Of the chronic pain syndromes presented, axial low back pain, chronic pelvic and groin pain, other peripheral neuropathies, and studies with multiple concomitant pain syndromes, a majority demonstrated >50% mean pain reduction at the time of last follow-up following DRGS. Physical function, quality of life (QOL), and lesser pain medication usage also were repeatedly reported to be significantly improved. CONCLUSIONS: DRGS continues to lack supportive evidence from well designed, high level studies and recommendations from consensus committee experts. However, we present repeated and consistent evidence from lower level studies showing success with the use of DRGS for various non-CRPS chronic pain syndromes in reducing pain along with increasing function and QOL from one week to three years. Due to such low-level, high bias evidence, we strongly encourage the continuation of high-level studies in order to provide a stronger foundation for the use of DRGS in non-CRPS chronic pain patients. However, it may be reasonable and appropriate to evaluate patients for DRGS candidacy on a case-by-case basis particularly if they manifest focal pain syndromes refractory to noninterventional measures and may not be ideal candidates for other forms of neuromodulation.

14.
Pain Physician ; 24(S1): S209-S232, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492919

RESUMO

BACKGROUND: Transforaminal epidural injections have been used since the late 1990s to treat lumbar radicular pain. They have been the subject of considerable attention, with varying conclusions from systematic reviews as to their efficacy. Transforaminal injections have been associated with rare but major complications. Further, the use of transforaminal injections has increased since the passage of the Affordable Care Act. Finally, with the SARS-CoV-2 pandemic, there has been heightened concern regarding the risk associated with steroid injections. OBJECTIVES: To evaluate and update the effectiveness of transforaminal injections for 4 indications: radicular pain; from spinal stenosis; from failed back surgery syndrome; and for axial low back pain; and to evaluate the safety of the procedure. STUDY DESIGN: A systematic review and meta-analysis of the efficacy of transforaminal injections. METHODS: The available literature on transforaminal injections was reviewed and the quality assessed. The level of evidence was classified on a 5-point scale based on the quality of evidence developed by the US Preventive Services Task Force (USPSTF) and modified by the American Society of Interventional Pain Physicians (ASIPP). Data sources included relevant literature from 1966 to April 2020, and manual searches of the bibliographies of known primary and review articles. Pain relief and functional improvement were the primary outcome measures. A minimum of 6 months pain relief follow-up was required. RESULTS: For this systematic review, 66 studies were identified. Eighteen randomized controlled trials met the inclusion criteria. No observational studies were included. Eleven randomized controlled trials dealt with various aspects of transforaminal injections for radicular pain owing to disc herniation. Based on these studies, there is Level 1 evidence supporting the use of transforaminal injections for radicular pain owing to disc herniation. A meta-analysis showed that at both 3 and 6 months, there was highly statistically significant improvement in both pain and function with both particulate and nonparticulate steroids. For radicular pain from central stenosis there is one moderate quality study, with Level IV evidence. For radicular pain caused by failed back surgery syndrome there is one moderate quality study, with Level IV evidence. For radicular pain from foraminal stenosis and for axial pain there is Level V evidence, opinion-based/consensus, supporting the use of transforaminal injections. Transforaminal injections are generally safe. However, they have been associated with major neurologic complications related to cord infarct. Causes other than intraluminal injection of particulates appear to be at play. The use of an infraneural approach and of blunt needles appear to offer the greatest patient safety. Because of concern over the role of particulate steroids, multiple other injectates have been evaluated, including nonparticulate steroids, tumor necrosis factor alpha (TNF-a) inhibitors, and local anesthetics without steroids. No injectate has been proven superior. If there is concern about immunosuppression because of risk of COVID-19 infection, either the lowest possible dose of steroid or no steroid should be used. LIMITATIONS: The study was limited by the paucity of literature for some indications. CONCLUSIONS: There is Level I evidence for the use of transforaminal injections for radicular pain from disc herniations.


Assuntos
Dexmedetomidina , Bupivacaína , Humanos , Injeções Epidurais , Patient Protection and Affordable Care Act , Esteroides , Ultrassonografia de Intervenção , Estados Unidos
16.
Pain Physician ; 24(S1): S1-S26, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33492917

RESUMO

BACKGROUND: The re-engineered definition of clinical guidelines in 2011 from the IOM (Institute of Medicine) states, "clinical practice guidelines are statements that include recommendations intended to optimize patient care that is informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options." The revised definition distinguishes between the term "clinical practice guideline" and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria. OBJECTIVE: To assess the literature and develop methodology for evidence synthesis and development of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. METHODS: A systematic review of the literature including methodology of guideline development encompassing GRADE approach for guidance on evidence synthesis with recommendations. RESULTS: Some of the many factors described in 2011 continue as of 2020 and impede the development of clinical practice guidelines. These impediments include biases due to a variety of conflicts and confluence of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with the elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Thus, ideally, a knowledgeable, multidisciplinary panel of experts with true lack of bias and confluence of interest must develop guidelines based on a systematic review of the existing evidence. This manuscript describes evidence synthesis from observational studies, various types of randomized controlled trials (RCTs), and, finally, methodological and reporting quality of systematic reviews. The manuscript also describes various methods utilized in the assessment of the quality of observational studies, diagnostic accuracy studies, RCTs, and systematic reviews. LIMITATIONS: Paucity of publications with appropriate evidence synthesis methodology in reference to interventional techniques. CONCLUSION: This review described comprehensive evidence synthesis derived from systematic reviews, including methodologic quality and bias measurement. The manuscript described various methods utilized in the assessment of the quality of the systematic reviews, RCTs, diagnostic accuracy studies, and observational studies.

17.
Pain Physician ; 24(S1): S27-S208, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33492918

RESUMO

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and  recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations.

19.
Pain Ther ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433856

RESUMO

INTRODUCTION: Interventional techniques such as radiofrequency (RF) treatment can be used to interrupt pain signals transmitted through the sympathetic nervous system (SNS). RF treatments including the pulsed (PRF) and continuous (CRF) modalities show enhanced control over lesion size and enhanced ability to confirm accurate positioning compared to other interventional methods. PRF also acts to reduce the area of the lesion. In this article, we characterize the currently available evidence supporting the use and efficacy of RF treatments in sympathetically mediated pain (SMP) conditions. STUDY DESIGN: A comprehensive literature review. METHODS: A PubMed and Cochrane Library database search was performed for human studies applying RF treatment at sympathetic sites (sphenopalatine ganglion, stellate ganglion, cervical, thoracic, or lumbar sympathetic ganglia, celiac plexus, splanchnic nerves, superior hypogastric plexus, and ganglion impar) between January 1970 to May 2020. Data were extracted, summarized into tables, and qualitatively analyzed. RESULTS: PRF and CRF both show promise in relieving SMP conditions, such as complex regional pain syndrome (CRPS), pain in the perineal region, headache and facial pain, and oncologic and non-oncologic abdominal pain, in addition to other types of pain, with minimal complications. Furthermore, in most comparative studies, outcomes using RF treatments exceeded other interventional techniques, such as anesthetic block and chemical neurolysis. CONCLUSIONS: RF treatments can be effective in carefully selected patients who are refractory to conservative management. However, further randomized controlled studies are needed prior to implementing it into common practice.

20.
Adv Ther ; 38(2): 904-924, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33337537

RESUMO

BACKGROUND: Naltrexone (NTX) is an opioid antagonist traditionally used as a treatment for alcohol and opioid use disorders, but various studies have documented its involvement in cancer progression, exploring possible anticancer potential, when administered at high doses or as low dose naltrexone (LDN). Herein we present a systematic review of cancer-related outcomes from case reports, clinical trials, and retrospective and prospective studies conducted using cell cultures, animal models, and human subjects receiving NTX/LDN. METHODS: A systematic search of NTX in cancer therapy was conducted. Outcomes including tumor size and number, latency to tumor development, survival duration, progression of disease, and scan results were assessed in clinical and animal studies, and cell number was used as the outcome measure of culture studies. RESULTS: Several case reports demonstrate notable survival durations and metastatic resolutions in patients with late stage cancer when administered an average LDN dose of 3-5 mg/day. Animal and cell culture studies suggest an overarching principle of NTX involvement in cancer pharmacophysiology, suggesting that high doses and continuous administration can foster cancer progression, whereas low doses and intermittent treatment may hinder cell proliferation, impede tumorigenesis, and have potential anticancer efficacy. CONCLUSION: This review emphasizes the value of potential future research on NTX in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy.

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