An extract of phase II and III trials on recent developments in managing neuropathic pain syndromes: diabetic peripheral neuropathy, trigeminal neuralgia, and postherpetic neuralgia.

INTRODUCTION: Neuropathic pain (NP) conditions involve lesions to the somatosensory nervous system leading to chronic and debilitating pain. Many patients suffering from NP utilize pharmacological treatments with various drugs that seek to reduce pathologic neuronal states. However, many of these drugs show poor efficacy as well as cause significant adverse effects. Because of this, there is a major need for the development of safer and more efficacious drugs to treat NP. AREAS COVERED: In this review, we analyzed current treatments being developed for a variety of NP conditions. Specifically, we sought drugs in phase II/III clinical trials with indications for NP conditions. Various databases were searched including Google Scholar, PubMed, and clinicaltrials.gov. EXPERT OPINION: All the mentioned targets for treatments of NP seem to be promising alternatives for existing treatments that often possess poor side effect profiles for patients. However, gene therapy potentially offers the unique ability to inject a plasmid containing growth factors leading to nerve growth and repair. Because of this, gene therapy appears to be the most intriguing new treatment for NP.

Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

Impulse control disorders in Parkinson's disease patients treated with pramipexole and ropinirole: a systematic review and meta-analysis.

BACKGROUND: This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX). This study compares the two oral DAs to a transdermal patch, rotigotine (RTG). METHODS: We performed an extensive systematic search for eligible studies from PubMed, Embase, Cochrane Library, and Google Scholar. The data was analyzed by various software, including EndNote, Rayyan, PRISM, and RevMan. Two studies incorporating 658 patients collectively were assessed. RESULTS: This meta-analysis shows a significant correlation between the usage of PRX (25.3%) or ROP (21.8%) and the development of ICD in PD patients. Compared to the transdermal patch, RTG, PRX was found to have a significant relative risk (P < 0.0001) of 3.46 (95% CI 2.07-5.76), and ROP was found to have a significant relative risk (P < 0.0001) of 2.98 (95% CI 1.77-5.02). The data collected shows RTG is approximately three times less likely to cause ICDs than oral PRX and ROP. CONCLUSION: The present investigation provides insight into ICD occurrences with PRX, ROP, and RTG to allow physicians to make more informed decisions on risk versus reward when deciding how to treat a PD patient with these drugs. However, related to various disclosed limitations, our conclusion cannot provide definitive practice protocols.

Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review.

PURPOSE OF REVIEW: Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens. RECENT FINDINGS: However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.

Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.

PURPOSE OF REVIEW: Chronic pain affects a significant portion of the population globally, making it a leading cause of disability. Understanding the multifaceted nature of chronic pain, its various types, and the intricate relationship it shares with risk factors, comorbidities, and mental health issues like depression and anxiety is critical for comprehensive patient care. Factors such as socioeconomic status (SES), age, gender, and obesity collectively add layers of complexity to chronic pain experiences and pose management challenges. RECENT FINDINGS: Low SES presents barriers to effective pain care, while gender differences and the prevalence of chronic pain in aging adults emphasize the need for tailored approaches. The association between chronic pain and physical comorbidities like cardiovascular disease, chronic obstructive pulmonary disease (COPD), and diabetes mellitus reveals shared risk factors and further highlights the importance of integrated treatment strategies. Chronic pain and mental health are intricately linked through biochemical mechanisms, profoundly affecting overall quality of life. This review explores pharmacologic treatment for chronic pain, particularly opioid analgesia, with attention to the risk of substance misuse and the ongoing opioid epidemic. We discuss the potential role of medical cannabis as an alternative treatment with a nuanced perspective on its impact on opioid use. Addressing the totality and complexity of pain states is crucial to individualizing chronic pain management. With different types of pain having different underlying mechanisms, considerations should be made when approaching their treatment. Moreover, the synergistic relationship that pain states can have with other comorbidities further complicates chronic pain conditions.

IPACK Block Efficacy for Acute Pain Management after Total Knee Replacement: A Review.

PURPOSE OF REVIEW: Patients often experience a significant degree of knee pain following total knee replacement (TKR). To alleviate this pain, nerve blocks may be performed such as the adductor canal block (ACB). However, ACBs are unable to relieve pain originating from the posterior region of the knee. A new type of nerve block known as the IPACK block may be used in conjunction with ACBs as it is designed to inhibit nerve branches innervating this area. In this article, we examine the rationale behind the IPACK procedure, how it is performed, and clinical trials examining its efficacy. RECENT FINDINGS: 5 of the 7 clinical trials examined in this article showed the IPACK + ACB block to show superior efficacy in treating pain following TKR compared to other blocks. These blocks included PMDI+ACB, SPANK+ACB, PAI+ACB, ACB alone, and SCAB. 2 of the 7 clinical trials showed the IPACK + ACB to be less effective in managing patients pain following TKR compared to other blocks which included the CACB and 4 in 1 block. In most instances, the IPACK + ACB showed superior efficacy in managing patients' pain following TKR when compared to other types of nerve blocks. This was determined by measuring usage of opioids, reported postoperative pain, and length of hospital stays following TKR. Thus, we suppose the IPACK block may be used in conjunction with the ACB to effectively reduce patient's pain following TKR.

Efficacy and Safety of Intrathecal Morphine for Cesarean Delivery: A Narrative Review.

PURPOSE OF REVIEW: Pain management is a critical aspect of care during and following a cesarean delivery. Without proper control of pain, individuals can experience poor mobility, increased thromboembolic events, and difficulty caring for the neonate in the postpartum period. There have been multiple methods for pain management for cesarean delivery and intrathecal morphine (ITM) has emerged as a prominent option for post-operative analgesia due to its efficacy, safety, and potential benefits over other treatments. This review analyzes data on efficacy, side effects, and safety of ITM and the pain control alternatives. RECENT FINDINGS: A comprehensive literature review was conducted to compare ITM with other analgesic techniques in post-cesarean patients. ITM was found to be as effective or better than other analgesic options, including bilateral quadratus lumborum block (QLB), opioid-free epidural analgesia (CSEA-EDA), and intravenous fentanyl. One study found that both ITM and oral analgesia were effective in pain control and that ITM caused fewer breakthrough pain events but had a longer duration and a greater rate of side effects than oral opioid analgesia. Commonly observed side effects of intrathecal opioids include nausea, vomiting, pruritus, and urinary retention, and it is thought that the adverse effects from intrathecal administration of opioids are short-lived. ITM may provide a decreased risk of DVT and coagulation by decreasing lower extremity weakness and numbness, thereby decreasing recovery time and increasing mobility. ITM is a safe and effective option for post-cesarean analgesia, with comparable pain relief to alternative forms of pain control, and side effects that are generally manageable. Further research is warranted to explore beneficial combinations with other methods of pain management and optimal dosing strategies.

Apomorphine for Parkinson's disease: pharmacologic and clinical considerations.

INTRODUCTION: In Parkinson's disease, dopamine depletion in the basal ganglia leads to symptoms including bradykinesia, gait abnormalities, and cognitive impairment. Even with treatment, the disease course leads to decreases in the amount of dopamine produced and released into the synapse. As dopamine production falls and the treatment course is insufficient to match the metabolic supply and demand, acute 'off' periods develop that cause reemergence of symptoms. Apomorphine is used to reverse these 'off' periods and restore function in patients with Parkinson's. This review will provide clinicians a concise article to read to learn more about apomorphine and its appropriate utilization. AREAS COVERED: The research discussed is focused on the history, pharmacokinetics, and mechanism of action of Apomorphine. Its utilization as a treatment for Parkinson's Disease and its comparison to currently utilized drugs is also discussed in this review. We focused on articles published on PubMed and Google Scholar within the last 10 years, but in some instances had to go as far back as 1951 to include early articles published about apomorphine. EXPERT OPINION: The expert opinion section focuses on the ways in which apomorphine could be administered in the future to better promote utilization and increase tolerability.

Update on Overactive Bladder Therapeutic Options.

BACKGROUND: Millions of Americans are burdened by overactive bladder (OAB) syndrome and the psychogenic and economic hardships that accompany it. Several theories attempt to explain OAB as a neurogenic dysfunction, myogenic dysfunction, urothelial dysfunction, or decreased expression of a channel protein secondary to bladder outlet obstruction. Given that the etiology of OAB is a working theory, the management of OAB is also an evolving subject matter in medicine. There are uncertainties surrounding the pathophysiology of OAB, the strength of a clinical diagnosis, and accurate reporting because of the disease's stigma and decreased use of health care. DATA SOURCES: This is a narrative review that used PubMed, Google Scholar, Medline, and ScienceDirect to review literature on current and future OAB therapies. RESULTS: Currently, first-line treatment for OAB is behavioral therapy that uses lifestyle modifications, bladder-control techniques, and psychotherapy. Second-line therapy includes antimuscarinic agents or beta 3 adrenergic agonists, and studies have shown that combination therapy with antimuscarinics and beta 3 adrenergic agonists provides even greater efficacy than monotherapy. Third-line therapies discussed include onabotulinumtoxinA, posterior tibial nerve stimulation, and sacral neuromodulation. OnabotulinumtoxinA has been FDA-approved as a nonpharmaceutical treatment option for refractory OAB with minimal side effects restricted to the urinary tract. Posterior tibial nerve modulation and sacral neuromodulation are successful in treating refractory OAB, but the costs and complication rates make them high-risk procedures. Therefore, surgical intervention should be a last resort. Estrogen therapy is effective in alleviating urinary incontinence in postmenopausal women, consistent with the association between estrogen deficiency and genitourinary syndrome. Potassium channel activators, voltage-gated calcium channel blockers, and phosphodiesterase inhibitors look to be promising options for the future of OAB management. As new therapies are developed, individuals with OAB can better personalize their treatment to maximize their quality of life and cost-effective care.

Non-CGRP Antagonist/Non-Triptan Options for Migraine Disease Treatment: Clinical Considerations.

PURPOSE OF REVIEW: Although the association between CGRP and migraine disease is well-known and studied, therapies can target other pathways to minimize migraine symptoms. It is important to understand the role of these medications as options for migraine treatment and the varied mechanisms by which symptoms can be addressed. In the present investigation, the role of non-CGRP antagonist/non-triptan options for migraine disease therapy is reviewed, including NSAIDs, ß-blockers, calcium channel blockers, antidepressants, and antiepileptics. Pharmacologic therapies for both acute symptoms and prophylaxis are evaluated, and their adverse effects are compared. RECENT FINDINGS: At present, the Food and Drug Association has approved the beta-blockers propranolol and timolol and the anti-epileptic drugs topiramate and divalproex sodium for migraine prevention. Clinicians have other options for evidence-based treatment of episodic migraine attacks. Treatment decisions should consider contraindications, the effectiveness of alternatives, and potential side effects. NSAIDs are effective for the acute treatment of migraine exacerbations with caution for adverse effects such as gastrointestinal upset and renal symptoms. Beta-blockers are effective for migraine attack prophylaxis but are associated with dizziness and fatigue and are contraindicated in patients with certain co-morbidities, including asthma, congestive heart failure, and abnormal cardiac rhythms. Calcium channel blockers do not show enough evidence to be recommended as migraine attack prophylactic therapy. The anti-epileptic drugs topiramate and divalproex sodium and antidepressants venlafaxine and amitriptyline are effective for migraine exacerbation prophylaxis but have associated side effects. The decision for pharmacologic management should ultimately be made following consideration of risk vs. benefit and discussion between patient and physician.

Multi-agent Systems and Cancer Pain Management.

PURPOSE: The present investigation explores multi-agent systems, their function in cancer pain management, and how they might enhance patient care. Since cancer is a complex disease, technology can help doctors and patients coordinate care and communicate effectively. Even when a patient has a dedicated team, treatment may be fragmented. Multi-agent systems (MAS) are one component of technology that is making progress for cancer patients. Wireless sensory networks (WSN) and body area sensory networks (BASN) are examples of MAS. RECENT FINDINGS: Technology is advancing the care of patients, not only in everyday clinical practice, but also in creating accessible communication between patients and provider. Many hospitals have utilized electronic medical records (EHR), but recent advancements allowed the pre-existing infrastructure to network with personal devices creating a more congruent form of communications. Better communication can better organize pain management, leading to better clinical outcomes for patients, integrating body sensors, such as smart watch, or using self-reporting apps. Certain software applications are also used to help providers in early detections of some cancers, having accurate results. The integration of technology in the field of cancer management helps create an organized structure for cancer patients trying to understand/manage their complex diagnosis. The systems for the various healthcare entities can receive and access frequently updated information that can better provide better coverage of the patient's pain and still be within the legalities as it pertains to opioid medications. The systems include the EHR communicating with the information provided by the patient's cellular devices and then communicating with the healthcare team to determine the next step in management. This all happens automatically with much physical input from the patient decreasing the amount of effort from the patient and hopefully decreasing the number of patients' loss to follow-up.

Electronic Health Record Recording of Patient Pain: Challenges and Discrepancies.

PURPOSE OF REVIEW: In the present review, various categories of pain, clinician-observed pain scales, and patient-reported pain scales are evaluated to better understand factors that impact patient pain perceptions. Additionally, the expansion of areas that require further research to determine the optimal way to evaluate pain scale data for treatment and management are discussed. RECENT FINDINGS: Electronic health record (EHR) data provides a starting point for evaluating whether patient predictors influence postoperative pain. There are several ways to assess pain and choosing the most effective form of pain treatment. Identifying individuals at high risk for severe postoperative pain enables more effective pain treatment. However, there are discrepancies in patient pain reporting dependent on instruments used to measure pain and their storage in the EHR. Additionally, whether administered by a physician or another healthcare practitioner, differences in patient pain perception occur. While each scale has distinct advantages and limitations, pain scale data is a valuable therapeutic tool for assisting clinicians in providing patients with optimal pain control. Accurate assessment of patient pain perceptions by data extraction from electronic health records provides a potential for pain alleviation improvement. Predicting high-risk postoperative pain syndromes is a difficult clinical challenge. Numerous studies have been conducted on factors that impact pain prediction. Postoperative pain is significantly predicted by the kind of operation, the existence of prior discomfort, patient anxiety, and age.

Algorithms to Identify Nonmedical Opioid Use.

The rise in nonmedical opioid overdoses over the last two decades necessitates improved detection technologies. Manual opioid screening exams can exhibit excellent sensitivity for identifying the risk of opioid misuse but can be time-consuming. Algorithms can help doctors identify at-risk people. In the past, electronic health record (EHR)-based neural networks outperformed Drug Abuse Manual Screenings in sparse studies; however, recent data shows that it may perform as well or less than manual screenings. Herein, a discussion of several different manual screenings and recommendations is contained, along with suggestions for practice. A multi-algorithm approach using EHR yielded strong predictive values of opioid use disorder (OUD) over a large sample size. A POR (Proove Opiate Risk) algorithm provided a high sensitivity for categorizing the risk of opioid abuse within a small sample size. All established screening methods and algorithms reflected high sensitivity and positive predictive values. Neural networks based on EHR also showed significant effectiveness when corroborated with Drug Abuse Manual Screenings. This review highlights the potential of algorithms for reducing provider costs and improving the quality of care by identifying nonmedical opioid use (NMOU) and OUD. These tools can be combined with traditional clinical interviewing, and neural networks can be further refined while expanding EHR.

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone.

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40 mL/min/1.73 m2 for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver-kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD-6 e-GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m2 , P=.002), higher 24-hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post-LTA, the e-GFR (mL/min/1.73 m2 ) increased in all nine patients, with mean e-GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre-LTA e-GFR (P≤.005 at all time points). One patient developed end-stage renal disease 9 years post-LTA and another patient expired 7 years post-LTA. The low e-GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.

Incidence and Risks of HIV Infection, Medication Options, and Adverse Effects in Accidental Needle Stick Injuries: A Narrative Review.

Accidental needle sticks can lead to infections, including HIV. As scientists have learned more about HIV and its replicative physiology, identification of target sites and novel medications have been developed. HIV is spread throughout the population through contact with blood, semen, and rectal or vaginal secretions of infected individuals. Therefore, it is important in general for healthcare workers to be aware of its transmission modes and ways to minimize exposure. In this regard, even with hospitals providing education, training, and safety protocols, there is a continued infection spread with HIV, especially by accidental needle sticks. There is also a wide variety of testing that can be used for HIV utilizing different methodologies, allowing for improved measurement of infection status. Any person with HIV should be tested to clarify infection status and be educated to minimize future virus spread. The current CDC recommendations for HIV infection treatment are antiretroviral therapies, such as an HIV postexposure prophylaxis regimen, which consists of a cocktail of antiretrovirals and postexposure prophylaxis immediately for occupational exposures, such as accidental needlestick exposure from an HIV infected patient. To decrease accidental HIV stick injuries, there are safety precautions in place, that if followed, would help reduce this incidence. HIV accidental needle stick injuries still happen in the hospital workplace, but with proper education and treatment, if exposed, there is hope to minimize the effects.

The Effectiveness of the Gnana Laryngeal Mask Airway II (GLA-II) With Novel Suction Tubing in Gastrointestinal (GI) Cases.

INTRODUCTION: The Gnana laryngeal mask airway II (GLA-II) is a supraglottic airway device similar to the classic laryngeal mask airway, except it has an additional suction port. This suction port allows for the removal of secretions and saliva. A previous version of the Gnana laryngeal airway 4 was made of silicone, while this newer version is made of polyvinyl chloride (PVC), which is more affordable. This study aimed to demonstrate the effectiveness and tolerability of this PVC-designed GLA-II and evaluate its ability to suction secretions. METHODS: The prospective cohort study included 100 gastrointestinal (GI) cases to determine the effectiveness and toleration of the GLA-II. The American Society of Anesthesiologists (ASA) class 1-3 patients were evaluated with a Mallampati airway score for GI-related procedures. After anesthesia induction with propofol, the GLA-II was inserted, and the time for successful insertion was recorded. All cases were completed within 62 minutes. During this time, the secretion volumes were also measured. RESULTS: One hundred patients were included in the study: 52% were males and 48% were females. Thirty-four patients were scored as ASA class 1 or 2, while 66 were scored as ASA class 3. The GLA-II insertion was successful on the first attempt in 92 patients, and a second attempt was necessary for six patients. It was unsuccessful in two patients. The average time for successful insertion was 28.3 ± 4.3 seconds. The average amount of saliva suctioned was 9.3 ± 2.6 mL. There were no intraoperative or postoperative complications during these cases. CONCLUSION: The PVC GLA-II device is distinguished by its ability to allow suctioning during placement. With an adequate epiglottic seal, it can be safely and successfully inserted in a short period of time. More research should be conducted to explore the use of GLA-II devices in other settings, such as emergencies and life-saving scenarios.

An overview of the safety and efficacy of LX-9211 in treating neuropathic pain conditions.

INTRODUCTION: LX-9211 is a drug designed to treat neuropathic pain conditions. It functions by inhibiting the adaptor-associated kinase 1 (AAK1) enzyme which promotes clathrin-dependent endocytosis. Preclinical studies have shown that LX-9211 does produce a reduction in nociceptive related behaviors and produces no major adverse effects in rats. Thus, LX-9211 has advanced to clinical trials to assess its safety and efficacy in humans. So far, phase 1 and phase 2 clinical trials involving patients with postherpetic neuralgia and diabetic peripheral neuropathic pain have been conducted with phase 3 trials planned in the future. AREAS COVERED: This paper highlights preclinical studies involving LX-9211 in rodents. Additionally, phase 1 clinical trials examining the safety of LX-9211 in healthy subjects as well as phase 2 studies looking at the safety and efficacy of LX-9211 compared to placebo in patients with diabetic peripheral neuropathic pain and postherpetic neuralgia are also discussed. EXPERT OPINION: In phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety.

Clinical Considerations and Outcomes of Robotic Urologic Surgery in Obese Patients.

Obesity is associated with many significant physiological changes. These considerations are important to surgery, especially in urological procedures. Obese patients often undergo surgical procedures and are at higher risk of complications. This investigation reviews physiological and anaesthesia considerations for obese and morbidly obese patients. In addition, urological surgeries and procedures should be considered for these higher risk patients. Clinical anaesthesiologists must use detailed assessment and, when appropriate, consultation in developing safe anaesthesia plans for these patients. Newer technologies have improved safety related to airway management, advanced airway devices, and regional anaesthesia with ultrasound-guided nerve blocks, which can reduce the need for opioids postoperatively. Recent developments in drug and monitoring technologies have also been developed and can be effective for obese and morbidly obese patients undergoing urological procedures and perioperative surgery, thus improving the likelihood of safety in this higher risk population.

Testosterone replacement therapy: clinical considerations.

INTRODUCTION: As an increasingly popular therapeutic option, testosterone replacement therapy (TRT) has gained significant notoriety for its health benefits in indicated populations, such as those suffering from hypogonadism. AREAS COVERED: Benefits such as improved libido, muscle mass, cognition, and quality of life have led to widened public interest in testosterone as a health supplement. No therapy exists without side effects; testosterone replacement therapy has been associated with side effects such as an increased risk of polycythemia, benign prostate hypertrophy (BPH), prostate cancer, gynecomastia, testicular atrophy, and infertility. Testosterone replacement therapy is often accompanied by several prophylactic co-therapies aimed at reducing the prevalence of these side effects. Literature searches for sections on the clinical benefits and risks associated with TRT were performed to include clinical trials, meta-analyses, and systematic reviews from the last 10 years. EXPERT OPINION: Data from clinical studies over the last decade suggest that the benefits of this therapy outweigh the risks and result in overall increased quality of life and remission of symptoms related to hypogonadism. With this in mind, the authors of this review suggest that carefully designed clinical trials are warranted for the investigation of TRT in symptomatic age-related hypogonadism.