An analysis of the efficacy of calcitonin gene-related peptide inhibitors on the treatment of migraine in adults

The CGRP monoclonal antibodies are the first class of medication developed specifically for migraine prevention, in contrast to previous preventative medications, that were in the anti-hypertensive, anti-epileptic and anti-depressant class. There are two notable divisions within the CGRP inhibitor class: the CGRP monoclonal antibodies (CGRP mAbs), and the small molecule CGRP antagonists (gepants). This thesis conducts a retrospective analysis of notable clinical trials such as the ACHIEVE I, ACHIEVE II, LIBERTY, ARISE, STRIVE, PREEMPT, and COMPEL studies to determine the efficacy of CGRP inhibitors. In ACHIEVE I, 38.6% of participants in the 50 mg ubrogepant group experienced pain freedom 2 hours post dose (p=0.002) and in ACHIEVE II trial in the 50 mg ubrogepant group, 21.8% reported pain freedom 2 hours. In participants that received Rimegepant at a 75mg dose, 21%of participants reported more freedom from pain at 2 hours than placebo (p<0.0001).^40 In another study, participants received placebo, 50 mg and 100 mg of sumatriptan.^43 Results of the study showed that more than half of participants, 57%, in the 100 mg Sumatriptan group and exactly half of participants in the 50 mg group had pain relief at 2 hours post-dose.^43 In the LIBERTY trial, at 12 weeks, 30% of individuals that received erenumab reported a fifty percent or more reduction in the monthly number of migraine days than individuals in the placebo group (p=0.002).^45 In the STRIVE trial, the average number of migraine days experienced by the participant at baseline was 8.3, and was assessed by the 4th month through the 6th month. This baseline decreased to 5.1 days (a 3.2 difference) in the participants that received an injection of 70 mg of erenumab (p<0.001).^46 The participants that received an injection of 140 mg erenumab, decreased from the baseline to 4.6 days of migraine (a 3.7 difference) (p<0.001) . 46 Participants that received placebo reported the least change from baseline, only a 1.8 day change (p<0.001).46 In the ARISE Trial patients receiving erenumab experienced a change of 2.9 monthly migraine days, a 1.1 increase from the reported change of 1.8 days reported by study participants for the monthly migraine days in the placebo group (p<0.001).^47 The PREEMPT1 trial did not meet statistical significance for their primary endpoint or study measure, which was to assess for a mean change in monthly mean headache episode frequency between baseline and week 24 of the trial (p=0.344)^48. Participants in the PREEMPT2 trial experienced a reduction by 9 days when compared to placebo for the primary end point, frequency of headache days per 28 days relative to baseline (p<0.001)^49. In the COMPEL study, participants experienced -10.7 day reduction in headache days by 108 weeks (p<0.0001).^50 There are several advantages to CGRP mAbs. Patients are more likely to adhere to CGRP mAbs medication and tolerate this medication than other medication options^17, CGRP mAbs do not give rise to toxicity in the liver because these medications do not interact with the liver^17, and CGRP mAbs have a long duration in the human body as they have a half-life of 20 to 30 days which provides patients with the opportunity to not take the medication as frequently.^51 Another reason why CGRP mAbs are advantageous compared to traditional treatment options is that they have a strong affinity and specificity for the CGRP receptor or CGRP molecule. This high specificity prevents the medication from causing undesirable effects on other receptors^51

Cocaine-induced renal infarction: report of a case and review of the literature

BACKGROUND: Cocaine abuse has been known to have detrimental effects on the cardiovascular system. Its toxicity has been associated with myocardial ischemia, cerebrovascular accidents and mesenteric ischemia. The pathophysiology of cocaine-related renal injury is multifactorial and involves renal hemodynamic changes, alterations in glomerular matrix synthesis, degradation and oxidative stress, and possibly induction of renal atherogenesis. Renal infarction as a result of cocaine exposure, however, is rarely reported in the literature. CASE PRESENTATION: A 48 year-old male presented with a four-day history of severe right flank pain following cocaine use. On presentation, he was tachycardic, febrile and had severe right costovertebral angle tenderness. He had significant proteinuria, leukocytosis and elevated serum creatinine and lactate dehydrogenase. Radiographic imaging studies as well as other screening tests for thromboembolic events, hypercoagulability states, collagen vascular diseases and lipid disorders were suggestive of Cocaine-Induced Renal Infarction (CIRI) by exclusion. CONCLUSION: In a patient with a history of cocaine abuse presenting with fevers and flank pain suggestive of urinary tract infection or nephrolithiasis, cocaine-induced renal infarction must be considered in the differential diagnosis. In this article, we discuss the prior reported cases of CIRI and thoroughly review the literature available on this disorder. This is important for several reasons. First, it will allow us to discuss and elaborate on the mechanism of renal injury caused by cocaine. In addition, this review will demonstrate the importance of considering the diagnosis of CIRI in a patient with documented cocaine use and an atypical presentation of acute renal injury. Finally, we will emphasize the need for a consensus on optimal treatment of this disease, for which therapy is not yet standardized

Non-Chemical Stressors and Cumulative Risk Assessment: An Overview of Current Initiatives and Potential Air Pollutant Interactions

Regulatory agencies are under increased pressure to consider broader public health concerns that extend to multiple pollutant exposures, multiple exposure pathways, and vulnerable populations. Specifically, cumulative risk assessment initiatives have stressed the importance of considering both chemical and non-chemical stressors, such as socioeconomic status (SES) and related psychosocial stress, in evaluating health risks. The integration of non-chemical stressors into a cumulative risk assessment framework has been largely driven by evidence of health disparities across different segments of society that may also bear a disproportionate risk from chemical exposures. This review will discuss current efforts to advance the field of cumulative risk assessment, highlighting some of the major challenges, discussed within the construct of the traditional risk assessment paradigm. Additionally, we present a summary of studies of potential interactions between social stressors and air pollutants on health as an example of current research that supports the incorporation of non-chemical stressors into risk assessment. The results from these studies, while suggestive of possible interactions, are mixed and hindered by inconsistent application of social stress indicators. Overall, while there have been significant advances, further developments across all of the risk assessment stages (i.e., hazard identification, exposure assessment, dose-response, and risk characterization) are necessary to provide a scientific basis for regulatory actions and effective community interventions, particularly when considering non-chemical stressors. A better understanding of the biological underpinnings of social stress on disease and implications for chemical-based dose-response relationships is needed. Furthermore, when considering non-chemical stressors, an appropriate metric, or series of metrics, for risk characterization is also needed. Cumulative risk assessment research will benefit from coordination of information from several different scientific disciplines, including, for example, toxicology, epidemiology, nutrition, neurotoxicology, and the social sciences

New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children

Hyponatremia is the most common electrolyte abnormality encountered in children. In the past decade, new advances have been made in understanding the pathogenesis of hyponatremic encephalopathy and in its prevention and treatment. Recent data have determined that hyponatremia is a more serious condition than previously believed. It is a major comorbidity factor for a variety of illnesses, and subtle neurological findings are common. It has now become apparent that the majority of hospital-acquired hyponatremia in children is iatrogenic and due in large part to the administration of hypotonic fluids to patients with elevated arginine vasopressin levels. Recent prospective studies have demonstrated that administration of 0.9% sodium chloride in maintenance fluids can prevent the development of hyponatremia. Risk factors, such as hypoxia and central nervous system (CNS) involvement, have been identified for the development of hyponatremic encephalopathy, which can lead to neurologic injury at mildly hyponatremic values. It has also become apparent that both children and adult patients are dying from symptomatic hyponatremia due to inadequate therapy. We have proposed the use of intermittent intravenous bolus therapy with 3% sodium chloride, 2 cc/kg with a maximum of 100 cc, to rapidly reverse CNS symptoms and at the same time avoid the possibility of overcorrection of hyponatremia. In this review, we discuss how to recognize patients at risk for inadvertent overcorrection of hyponatremia and what measures should taken to prevent this, including the judicious use of 1-desamino-8d-arginine vasopressin (dDAVP)