Novel Local Anesthetics in Clinical Practice: Pharmacologic Considerations and Potential Roles for the Future.

The treatment of pain, both acute and chronic, has been a focus of medicine for generations. Physicians have tried to develop novel ways to effectively manage pain in surgical and post-surgical settings. One intervention demonstrating efficacy is nerve blocks. Single-injection peripheral nerve blocks (PNBs) are usually preferred over continuous PNBs, since they are not associated with longer lengths of stay. The challenge of single injection PNBs is their length of duration, which at present is a major limitation. Novel preparations of local anesthetics have also been studied, and these new preparations could allow for extended duration of action of anesthetics. An emerging preparation of bupivacaine, exparel, uses a multivesicular liposomal delivery system which releases medication in a steady, controlled manner. Another extended-release local anesthetic, HTX-011, consists of a combination of bupivacaine and low-dose meloxicam. Tetrodotoxin, a naturally occurring reversible site 1 sodium channel toxin derived from pufferfish and shellfish, has shown the potential to block conduction of isolated nerves. Neosaxitoxin is a more potent reversible site 1 sodium channel toxin also found in shellfish that can also block nerve conduction. These novel formulations show great promise in terms of the ability to prolong the duration of single injection PNBs. This field is still currently in development, and more researchers will need to be done to ensure the efficacy and safety of these novel formulations. These formulations could be the future of pain management if ongoing research continues to prove positive effects and low side effect profiles.

Opicapone for the Treatment of Parkinson's Disease "Off" Episodes: Pharmacology and Clinical Considerations.

Parkinson's disease (PD) is a common neurodegenerative disorder. It is also the fastest-growing neurodegenerative disorder and has more than doubled between 1990 and 2016. Parkinson's disease causes significant morbidity and disability from motor dysfunction, sleep disturbances, and cognitive and psychiatric symptoms. This paper reviews recent evidence in the treatment of PD "off" episodes with the novel drug opicapone, including its efficacy, safety, and clinical indications. Opicapone is a novel, peripherally acting catechol-O-methyl transferase (COMT) inhibitor used as adjunctive therapy to carbidopa/levodopa for treatment and prevention of "off" episodes. It has been approved for use as an adjunct to levodopa since 2016 in Europe and has recently (April 2020) gained FDA approval for use in the USA. By inhibiting COMT, opicapone slows levodopa metabolism and increases its availability. Several clinical studies demonstrated significant improvement in treatment efficacy and reduction in the duration of "off" episodes The main side effect demonstrated was dyskinesia, mostly with the 100 mg dose, which is higher than the approved, effective dose of 50 mg.

A Comprehensive Review of Novel Interventional Techniques for Chronic Pain: Spinal Stenosis and Degenerative Disc Disease-MILD Percutaneous Image Guided Lumbar Decompression, Vertiflex Interspinous Spacer, MinuteMan G3 Interspinous-Interlaminar Fusion.

Spinal stenosis is the compression of nerve roots by bone or soft tissue secondary to the narrowing of the spinal canal, lateral recesses, or intervertebral foramina. Spinal stenosis may have acquired or congenital origins. Most cases are acquired and caused by hypertrophy of the ligamentum flavum, enlarged osteophytes, degenerative arthritis, disk herniations, and various systemic illnesses. The ligamentum flavum (LF) is a highly specialized elastic ligament that connects the laminae of the spine and fuses them to the facet joint capsules. There are a number of treatment options available for spinal stenosis. Implants and surgical interventions have grown in popularity recently, and a number of these have been shown to have varying efficacy, including the minimally invasive lumbar decompression (MILD®), Vertiflex®, Coflex® Interlaminar Stabilization, and MinuteMan G3® procedures. Minimally invasive lumbar decompression (MILD®) is a minimally invasive outpatient procedure to treat spinal stenosis related to hypertrophied ligamentum flavum. The Superion® Interspinous Spacer, also known as Vertiflex®, is a titanium implant that is delivered percutaneously to relieve back pain caused by lumbar spinal stenosis. The MinuteMan® is a minimally invasive, interspinous-interlaminar fusion device planned for the temporary fixation of the thoracic, lumbar, and sacral spine, which eventually results in bony fusion. Based on our review of the available current scientific literature, the novel interventions for symptomatic lumbar spinal stenosis, such as the MILD® procedure and the Superion® interspinous spacer, generally appear to be safe and effective. There is a possibility in the future that these interventions could disrupt current treatment algorithms for lumbar spinal stenosis.

Novel Interventional Techniques for Chronic Pain with Minimally Invasive Arthrodesis of the Sacroiliac Joint: (INSITE, iFuse, Tricor, Rialto, and others).

Acute and chronic pain are public health issues that clinicians have been battling for years. Opioid medications have been a treatment option for both chronic and acute pain; however, they can cause unwanted complications and are a major contributor to our present opioid epidemic. The sacroiliac (SI) joint is a common cause of both acute and chronic low back pain. It affects about 15-25% of patients with axial low back pain, and up to 40% of patients with ongoing pain following lumbar fusion. Recent advances in the treatment of SI joint pain have led to the development of a wide variety of SI joint fusion devices. These fusion devices seek to stabilize the joints themselves in order that they become immobile and, in theory, can no longer be a source for pain. This is a minimally invasive procedure aimed to address chronic pain without subjecting patients to lengthy surgery or medications, including opioids with the potential for addiction and abuse. Minimally invasive SI fusion can be performed by a lateral approach (i.e., iFuse, Tricor) or posterior approach (i.e., CornerLoc, LinQ, Rialto). The posterior approach requires the patient to be in the prone position but allows for less disruption of muscles with entry. More data are necessary to determine which fusion system may be best for a particular patient. SI fusion devices are a promising way of treating chronic lower back pain related to the SI joint. This narrative review will discuss various types of SI fusion devices, and their potential use in terms of their safety and efficacy.

Peripheral Nerve Stimulation: A Review of Techniques and Clinical Efficacy.

Chronic pain is a common source of morbidity in many patient populations worldwide. There are growing concerns about the potential side effects of currently prescribed medications and a continued need for effective treatment. Related to these concerns, peripheral nerve stimulation has been regaining popularity as a potential treatment modality. Peripheral nerve stimulation components include helically coiled electrical leads, which direct an applied current to afferent neurons providing sensory innervation to the painful area. In theory, the applied current to the peripheral nerve will alter the large-diameter myelinated afferent nerve fibers, which interfere with the central processing of pain signals through small-diameter afferent fibers at the level of the spinal cord. Multiple studies have shown success in the use of peripheral nerve stimulation for acute post-surgical pain for orthopedic surgery, including post total knee arthroplasty and anterior cruciate ligament surgery, and chronic knee pain. Many studies have investigated the utility of peripheral nerve stimulation for the management of chronic shoulder pain. Peripheral nerve stimulation also serves as one of the potential non-pharmacologic therapies to treat back pain along with physical therapy, application of transcutaneous electrical neurostimulation unit, radiofrequency ablation, epidural steroid injections, permanently implanted neurostimulators, and surgery. Studies regarding back pain treatment have shown that peripheral nerve stimulation led to significant improvement in all pain and quality-of-life measures and a reduction in the use of opioids. Further studies are needed as the long-term risks and benefits of peripheral nerve stimulation have not been well studied as most information available on the effectiveness of peripheral nerve stimulation is based on shorter-term improvements in chronic pain.

Ultra-small superparamagnetic iron oxide (USPIO) magnetic resonance imaging in benign mixed tumor of the parotid gland.

Historically USPIO has been used to help with nodal staging but not in primary tumors. The ability to concentrate USPIO may help to differentiate BMT from other types of parotid tumors.

Ozanimod to Treat Relapsing Forms of Multiple Sclerosis: A Comprehensive Review of Disease, Drug Efficacy and Side Effects.

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing-remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

Endovascular Therapy for Acute Ischemic Stroke With Occlusion of the Middle Cerebral Artery M2 Segment.

IMPORTANCE: Randomized clinical trials have shown the superiority of endovascular therapy (EVT) compared with best medical management for acute ischemic strokes with large vessel occlusion (LVO) in the anterior circulation. However, of 1287 patients enrolled in 5 trials, 94 with isolated second (M2) segment occlusions were randomized and 51 of these received EVT, thereby limiting evidence for treating isolated M2 segment occlusions as reflected in American Heart Association guidelines. OBJECTIVE: To evaluate EVT safety and effectiveness in M2 occlusions in a cohort of patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study pooled patients with acute ischemic strokes and LVO isolated to M2 segments from 10 US centers. Patients with acute ischemic strokes and LVO in M2 segments presenting within 8 hours from their last known normal clinical status (LKN) from January 1, 2012, to April 30, 2015, were divided based on their treatment into EVT and medical management groups. Logistic regression was used to compare the 2 groups. Univariate and multivariate analyses evaluated associations with good outcome in the EVT group. MAIN OUTCOMES AND MEASURES: The primary outcome was the 90-day modified Rankin Scale score (range, 0-6; scores of 0-2 indicate a good outcome); the secondary outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 522 patients (256 men [49%]; 266 women [51%]; mean [SD] age, 68 [14.3] years) were identified, of whom 288 received EVT and 234 received best medical management. Patients in the medical management group were older (median [interquartile range] age, 73 [60-81] vs 68 [56-78] years) and had higher rates of intravenous tissue plasminogen activator treatment (174 [74.4%] vs 172 [59.7%]); otherwise the 2 groups were balanced. The rate of good outcomes was higher for EVT (181 [62.8%]) than for medical management (83 [35.4%]). The EVT group had 3 times the odds of a good outcome as the medical management group (odds ratio [OR], 3.1; 95% CI, 2.1-4.4; P < .001) even after adjustment for age, National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomographic Score (ASPECTS), intravenous tissue plasminogen activator treatment, and time from LKN to arrival in the emergency department (OR, 3.2; 95% CI, 2-5.2; P < .001). No statistical difference in symptomatic intracerebral hemorrhage was found (5.6% vs 2.1% for the EVT group vs the medical management group; P = .10). The treatment effect did not change after adjusting for center (OR, 3.3; 95% CI, 1.9-5.8; P < .001). Age, NIHSS score, ASPECTS, time from LKN to reperfusion, and successful reperfusion score of at least 2b (range, 0 [no perfusion] to 3 [full perfusion with filling of all distal branches]) were independently associated with good outcome of EVT. A linear association was found between good outcome and time from LKN to reperfusion. CONCLUSIONS AND RELEVANCE: Although a randomized clinical trial is needed to confirm these findings, available data suggest that EVT is reasonable, safe, and effective for LVO of the M2 segment relative to best medical management.

Hematopoietic stem-cell transplantation in the developing world: experience from a center in Western India.

We describe our experience of first 50 consecutive hematopoietic stem-cell transplants (HSCT) done between 2007 and 2012 at the Apollo Hospital, Gandhinagar, 35 autologous HSCT and 15 allogeneic HSCT. Indications for autologous transplant were multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, and acute myeloid leukemia, and indications for allogeneic transplants were thalassemia major, aplastic anaemia, chronic myeloid leukemia, and acute lymphoblastic and myeloid leukaemia. The median age of autologous and allogeneic patient's cohort was 50 years and 21 years, respectively. Median follow-up period for all patients was 39 months. Major early complications were infections, mucositis, acute graft versus host disease, and venoocclusive disease. All of our allogeneic and autologous transplant patients survived during the first month of transplant. Transplant related mortality (TRM) was 20% (N = 3) in our allogeneic and 3% (N = 1) in autologous patients. Causes of these deaths were disease relapse, sepsis, hemorrhagic complications, and GVHD. 46% of our autologous and 47% of our allogeneic patients are in complete remission phase after a median follow-up of 39 months. 34% of our autologous patients and 13% of our allogeneic patients had disease relapse. Overall survival rate in our autologous and allogeneic patients is 65.7% and 57.1%, respectively. Our results are comparable to many national and international published reports.

A Qualitative Study of Psychosocial Problems among Parents of Children with Cerebral Palsy Attending Two Tertiary Care Hospitals in Western India.

Objective. To explore the psychosocial problems faced by the parents of children with cerebral palsy (CP) in rural and urban settings. Design. Qualitative research design using focus group discussions (FGDs) was used for the study. Setting. Two FGDs comprising one at a rural tertiary level care hospital and the other at an urban tertiary level care hospital were conducted. Participants. A total of thirteen parents participated in the two FGDs. Main Outcome Measured. Psychosocial problems experienced by the parents of children suffering from CP were measured. Results. The problems experienced by the mothers were associated with common themes such as disturbed social relationships, health problems, financial problems, moments of happiness, worries about future of the child, need for more support services, and lack of adequate number of trained physiotherapists. All the parents had children with problems since birth and most had approached various health care providers for a cure for their child. Conclusions. A wide range of psychosocial problems are experienced by the parents of children with CP. Studies like this can provide valuable information for designing a family centered care programme for children with CP.