A Survey of Radiology Practices\u27 Use of After-hours Services

Purpose: To identify the characteristics of and the motives behind radiologists use, or lack thereof, of after-hours services. Methods: From August 2005 to June 2006, 300 non-specialty hospitals randomly selected from the 2005 American Hospital Association Directory of Hospitals were contacted by phone, email, and mail, with an attempt made to speak to the chief of radiology. We obtained 115 responses, a 38.3% response rate, including 64 from practices that used an external after-hours service. Responses were analyzed using descriptive statistical analyses. Results Practices gave convenience as the most important reason they use an after-hours services, with value for recruiting ranked second and shortage of radiologists for off-hours coverage third. Three-fourths of practices said they receive 5% or fewer of their reads from these services. Two-thirds of practices paid the service about as much as they collected or more. Approximately 40% of respondents utilized an after-hours service located internationally. Of these, 56% said that the radiologists reading internationally were either all Americans or mostly Americans and 40% did not know the proportion of foreigners. Regardless, in-state licensure of all interpreting teleradiologists is essentially universal. Conclusions: Most radiology groups using after-hours services do so for convenience rather than shortage of staff to provide coverage. Most practices send a very small percentage of their studies to the services. While overseas-located services are commonly used, there is little evidence of other than American radiologists or American-trained radiologists at these services

Opioid Antagonists: Will they Solve all of the Problems Associated with Opioid Agonists?

Physicians employed in operating and emergency rooms have utilized opioid antagonist for almost half a century for the treatment of opioid overdose. The prototype antagonist remains naloxone hydrochloride, which actually received FDA approval back in 1971. Why after so many years on the market is this medication now being formulated in the form of an easy to use “auto-injector” that was designed for non-medical professionals to be able to utilize at a moment\u27s notice? Could this wonder product, being hailed as the best possible safety tool available for life threatening opioid emergencies actual make heroes out of lay people? [1]. Will marketing and providing to the family and caregivers of chronic pain patients prevent the epidemic of opioid medication related deaths of people in our country? What else can be done by physicians and the U.S. Food and Drug Administration (FDA) to reduce the unbelievable statistic of a death every 36 minutes from an opioid overdose in the United States? With upwards of 17,000 Americans dying yearly from prescription opioid overdose, accidently or intentionally via suicide& deliberate misuse, and constantly consuming more and more of these powerful painkillers-the million dollar question remaining to be answered is: will a new drug formulation device in the hands of laypeople really make a dent in this crisis that in recent years has actually surpassed car accidents as the leading cause of accidental death? [2]

Arithmetic of the Asai L-function for Hilbert Modular Forms.

Arithmetic of the Asai L-function for Hilbert modular forms Adam Kaye Chair: Kartik Prassanna We prove two results on rationality of special values of the Asai L-function attached to Hilbert modular forms at critical points. Such L-functions only admit critical values when the Hilbert modular form has non-parallel weight. Our rationality results generalize previous work of Shimura on algebraicity. The first result uses a period defined by transferring the Hilbert modular form to a Shimura curve. The second result uses a period defined using rational structures on the coherent cohomology of Hilbert modular surfaces. We also give some partial results towards integrality of such L-values. Our results are motivated by the study of a p-adic analog of the Beilinson conjecture, which is a deep conjecture relating algebraic cycles (and motivic cohomology) to values of L-functions.PhDMathematicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120693/1/adamkaye_1.pd

Combination Olanzapine and Samidorphan for the Management of Schizophrenia and Bipolar 1 Disorder in Adults: A Narrative Review

Schizophrenia is a debilitating psychotic disorder characterized by positive symptoms such as delusions, hallucinations, and disorganized thoughts, and negative symptoms like lack of effect or motivation. Bipolar 1 disorder (B1D) is a psychiatric illness characterized by recurrent manic episodes in alternation with depressive episodes and interspersed periods of euthymia, ultimately resulting in psychological distress and impairment of daily functioning. Effective treatments are needed for both schizophrenia and B1D to reach the treatment goals of reducing the debilitating symptomology, improving social functioning and quality of life, and increasing the chances of recovery and more favorable long-term outcomes. To date, olanzapine is one of the most efficacious atypical antipsychotics (AAPs) for the treatment of both schizophrenia and B1D and is associated with fewer extrapyramidal effects compared to other treatments. However, compared to other AAPs, olanzapine is associated with a greater chance of metabolic syndrome, limiting its clinical use and affecting treatment compliance. Samidorphan mitigates the weight gain side effects of olanzapine by antagonizing μ-, κ-, and δ-opioid receptors. The use of combination drugs to treat psychiatric conditions is an emerging field with the goal of increasing therapeutic efficacy and decreasing undesirable side effects. Clinical trials have demonstrated combination on olanzapine and samidorphan (OLZ/SAM) treatment resulted in significantly less weight gain than olanzapine monotherapy. Clinical trial patients reported improvements in symptoms of psychosis, reduced weight gain, and overall satisfaction with their treatment. OLZ/SAM has been as shown to be a safe and effective pharmaceutical option for the clinical management of schizophrenia and B1D

Deutetrabenazine for the treatment of chorea associated with Huntington’s disease

This is a comprehensive review of the literature regarding the use of Deutetrabenazine in treating chorea associated with Huntington’s disease. Unfortunately, treatment has been limited for many aspects of this neurodegenerative disease. The present investigation presents the background, evidence, and indications for the use Deutetrabenazine in the setting of Huntington’s disease. Huntington’s disease is characterized by a variety of motor, psychiatric, and cognitive symptoms with chorea being one of the more notable ones. Chorea is a movement disorder present in multiple neurologic diseases that causes involuntary and irregular muscle movements theorized to be stemming from high dopamine levels. Deutetrabenazine is thought to function as an inhibitor of the VMAT2 vesicular monoamine transporter resulting in decreased monoamine release, including dopamine, in the synaptic cleft which has a therapeutic effect in management of chorea. This drug was approved by the FDA in 2017 with a specific indication for tardive dyskinesia and choreiform movement in Huntington’s disease. Currently, there is no definitive treatment for Huntington’s disease. Thus, management is primarily focused on symptom management with the use of a variety of pharmaceutical agents. Chorea is one of the many manifestations that significantly alter the quality of life of many patients. Deutetrabenazine is a promising new option for the treatment of chorea in the setting of Huntington’s disease. Although studies so far have displayed mixed results, further research, including head-to-head studies, is necessary to elucidate the true potential of this drug

Chronic pain treatment strategies in Parkinson’s disease

Neurological disorders, including Parkinson’s disease (PD), have increased in prevalence and are expected to further increase in the coming decades. In this regard, PD affects around 3% of the population by age 65 and up to 5% of people over the age of 85. PD is a widely described, physically and mentally disabling neurodegenerative disorder. One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain. Compared to the general population of similar age, PD patients suffer from a significantly higher level and prevalence of pain. The most common form of pain reported by Parkinson’s patients is of musculoskeletal origin. One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain. Other treatments that have shown efficacy in treating pain of diverse etiologies are acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD. The selective serotonin and noradrenaline reuptake inhibitors (SNRIs) also possess pain relieving and antidepressant properties, but carry less of the risk of anticholinergic side effects seen in TCAs. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown in multiple studies to be effective against various types of PD associated pain symptoms. Massage therapy (MT) is one of the most common forms of complementary and alternative medicine. Studies have shown that pressure applied during MT may stimulate vagal activity, promoting reduced anxiety and pain, as well as increasing levels of serotonin. In a survey study of PD patients, rehabilitative therapy and physical therapy were rated as the most effective for pain reduction, though with only temporary relief but these studies were uncontrolled. Yoga has been studied for patients with a wide array of neurological disorders. In summary, PD pathology is thought to have a modulating effect on pain sensation, which could amplify pain. This could help explain a portion of the higher incidence of chronic pain felt by PD patients. A treatment plan can be devised that may include dopaminergic agents, acetaminophen, NSAIDs, opioids, antidepressants, physical therapies, DBS and other options discussed in this review. A thorough assessment of patient history and physical examination should be made in patients with PD so chronic pain may be managed effectively

Aducanumab, a Novel Anti-Amyloid Monoclonal Antibody, for the Treatment of Alzheimer’s Disease: A Comprehensive Review

Alzheimer’s disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role as caregiver. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD, however, these drugs are not curative. This review discusses the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, aducanumab, in treatment of AD. Currently aducanumab is the only Food and Drug Administration (FDA) approved drug that acts to slow progression of this disease. Aducanumab is an anti-amyloid drug which functions by selectively binding amyloid aggregates in both the oligomeric and fibrillar states. Studies show aducanumab may help to restore neurological function in patients with AD by reducing beta-amyloid plaques and reestablishing neuronal calcium permeability. However, there is concern the magnitude of this drug’s benefit may only be statistically significant and not clinically significant. Despite this skepticism, aducanumab has proven to significantly decrease amyloid in all cortical brain regions examined. In summary, aducanumab has provided hope for those working toward the goal of providing patients a safe and viable treatment option in the management of AD

Chronic pain treatment strategies in Parkinson’s disease

Neurological disorders, including Parkinson’s disease (PD), have increased in prevalence and are expected to further increase in the coming decades. In this regard, PD affects around 3% of the population by age 65 and up to 5% of people over the age of 85. PD is a widely described, physically and mentally disabling neurodegenerative disorder. One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain. Compared to the general population of similar age, PD patients suffer from a significantly higher level and prevalence of pain. The most common form of pain reported by Parkinson’s patients is of musculoskeletal origin. One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain. Other treatments that have shown efficacy in treating pain of diverse etiologies are acetaminophen, Nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors. Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD. The selective serotonin and noradrenaline reuptake inhibitors (SNRIs) also possess pain relieving and antidepressant properties, but carry less of the risk of anticholinergic side effects seen in TCAs. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown in multiple studies to be effective against various types of PD associated pain symptoms. Massage therapy (MT) is one of the most common forms of complementary and alternative medicine. Studies have shown that pressure applied during MT may stimulate vagal activity, promoting reduced anxiety and pain, as well as increasing levels of serotonin. In a survey study of PD patients, rehabilitative therapy and physical therapy were rated as the most effective for pain reduction, though with only temporary relief but these studies were uncontrolled. Yoga has been studied for patients with a wide array of neurological disorders. In summary, PD pathology is thought to have a modulating effect on pain sensation, which could amplify pain. This could help explain a portion of the higher incidence of chronic pain felt by PD patients. A treatment plan can be devised that may include dopaminergic agents, acetaminophen, NSAIDs, opioids, antidepressants, physical therapies, DBS and other options discussed in this review. A thorough assessment of patient history and physical examination should be made in patients with PD so chronic pain may be managed effectively

Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling

Cellular activation in trans by interferons, cytokines and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and / or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation

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