Calcitonin Gene-Related Peptide Antagonists as a Savior in Episodic and Chronic Migraine: A Review.

Headaches due to migraine are the second leading cause of disability in the world. Migraine can be classified as episodic migraine (EM) and chronic migraine (CM). The course of the disease starts from an aura followed by 4-72 hours of bouts of throbbing, mostly unilateral headache associated with nausea, photo/phonophobia with/without neurological deficit. The pathophysiology of migraine remains debatable and many drugs are used to help control migraine attacks with little or no benefit. However, patient compliance remains a reason for over and underdosing of these medications. The calcitonin gene-related peptide (CGRP), a vasoactive peptide is known to contribute to the disease course. Much work is done on antagonizing the receptor or the molecule itself. For this purpose, genetically engineered monoclonal antibodies are being utilized for long-term reduction in morbidity and prevention of migraine headaches. The four to name are: galcanezumab, fremanezumab, eptinezumab, and erenumab. The purpose of this review is to shed light on the use of these monoclonal antibodies, completed and recruiting trials, and the role of these medications in the prevention of not only EM and CM but also in medication overuse headaches.

Sensorineural Hearing Loss and Its Relationship with Duration of Chelation Among Major ß-Thalassemia Patients.

Introduction Thalassemia is a common genetic disorder worldwide, also occurring frequently in Karachi, Pakistan. Beta (ß)-thalassemia major patients need repeated transfusions which cause iron overload. Patients are treated with chelating agents to reduce the high serum ferritin level and to decrease morbidity and mortality due to increased iron levels. This combined therapy also leads to some complications. One of them is the sensorineural hearing loss (SNHL). To date, no data is available in Pakistan regarding SNHL among major ß-thalassemia patients on chelating therapy.  Methods A cross-sectional study was performed in collaboration with the Thalassemia Center and Dr. Ruth Pfau at the Department of Ear, Nose, and Throat, Civil Hospital, Karachi, Pakistan. The variable to detect hearing was pure tone air and bone conduction thresholds at the frequencies of 250 - 4,000 Hz. Clinical data, such as chelating agent dose, duration, and hearing status, were recorded. Demographic characteristics, like age, gender, height, and weight, were noted. The hemoglobin and serum ferritin levels of the subjects were also included. Results Forty-five percent of cases of thalassemia were suffering from SNHL. In the right ear, the Pearson correlation of chelating agent dose (mg) with SNHL was mildly positive and statistically significant (r = 0.261, p < 0.001), (r = 0.337, p < 0.001), (r = 0.198, p = 0.005), and (r = 0.207, p = 0.003) at the frequencies of 250, 500, 1,000, and 2,000 Hz, respectively, and the Pearson correlation of chelating agent used (in months) with SNHL was mildly positive and statistically significant (r = 0.232, p = 0.001), and (r = 0.301, p < 0.001) at frequencies 250 to 500 Hz, respectively. In the left ear, the Pearson correlation of chelating agent dose (mg) with SNHL was mildly positive and statistically significant, (r = 0.191, p = 0.007), (r = 0.202, p = 0.004), (r = 0.297, p < 0.001), (r = 0.183, p = 0.010) and (r = 0.221, p = 0.002) at frequencies 250, 500, 1,000, 2,000, and 4,000 Hz, respectively, and Pearson correlation of chelating agent used (months) with SNHL was mildly positive and statistically significant only at the frequency of 2,000 Hz (r = 140, p = 0.049).  Conclusion Chelation therapy and regular blood transfusions, apart from prolonging the life of thalassemic patients, also leads to some complications. With this survey, it was concluded that almost half of the patients had normal hearing, while the other half had sensorineural hearing loss after the use of deferasirox. It is inferred that the incidence of SNHL is not only dose-related but the duration of use of a chelating agent is also a contributing factor.

Ebola Holding Units at government hospitals in Sierra Leone: evidence for a flexible and effective model for safe isolation, early treatment initiation, hospital safety and health system functioning.

The 2014-2015 West African outbreak of Ebola Virus Disease (EVD) claimed the lives of more than 11,000 people and infected over 27,000 across seven countries. Traditional approaches to containing EVD proved inadequate and new approaches for controlling the outbreak were required. The Ministry of Health & Sanitation and King's Sierra Leone Partnership developed a model for Ebola Holding Units (EHUs) at Government Hospitals in the capital city Freetown. The EHUs isolated screened or referred suspect patients, provided initial clinical care, undertook laboratory testing to confirm EVD status, referred onward positive cases to an Ebola Treatment Centre or negative cases to the general wards, and safely stored corpses pending collection by burial teams. Between 29th May 2014 and 19th January 2015, our five units had isolated approximately 37% (1159) of the 3097 confirmed cases within Western Urban and Rural district. Nosocomial transmission of EVD within the units appears lower than previously documented at other facilities and staff infection rates were also low. We found that EHUs are a flexible and effective model of rapid diagnosis, safe isolation and early initial treatment. We also demonstrated that it is possible for international partners and government facilities to collaborate closely during a humanitarian crisis.

A review of polymeric refabrication techniques to modify polymer properties for biomedical and drug delivery applications.

Polymers are extensively used in the pharmaceutical and medical field because of their unique and phenomenal properties that they display. They are capable of demonstrating drug delivery properties that are smart and novel, such properties that are not achievable by employing the conventional excipients. Appropriately, polymeric refabrication remains at the forefront of process technology development in an endeavor to produce more useful pharmaceutical and medical products because of the multitudes of smart properties that can be attained through the alteration of polymers. Small alterations to a polymer by either addition, subtraction, self-reaction, or cross reaction with other entities have the capability of generating polymers with properties that are at the level to enable the creation of novel pharmaceutical and medical products. Properties such as stimuli-responsiveness, site targeting, and chronotherapeutics are no longer figures of imaginations but have become a reality through utilizing processes of polymer refabrication. This article has sought to review the different techniques that have been employed in polymeric refabrication to produce superior products in the pharmaceutical and medical disciplines. Techniques such as grafting, blending, interpenetrating polymers networks, and synthesis of polymer complexes will be viewed from a pharmaceutical and medical perspective along with their synthetic process required to attain these products. In addition to this, each process will be evaluated according to its salient features, impeding features, and the role they play in improving current medical devices and procedures.

Acyclovir-induced acute renal failure and the importance of an expanding waist line.

A 23-year-old gentleman with no significant medical history other than obesity was admitted with a history of balance problems, double vision and strange behaviour following a fall from bed. Systems examination was unremarkable. The patient was given intravenous acyclovir and intravenous ceftriaxone given the suspicion of encephalitis/meningitis. Investigations including routine bloods, CT/MRI Head and lumbar puncture were unremarkable. Within 48 h of commencing intravenous acyclovir, there was a marked deterioration in renal function. On stopping acyclovir therapy, renal function improved back to baseline. No other cause for deterioration in renal function was identified. The most likely cause for acute renal failure was secondary to acyclovir therapy. This has been well documented and is due to intratubular crystal precipitation. Moreover, in this case nephrotoxicity is likely secondary to the large boluses of intravenous acyclovir that had been given as prescribed according to the total body weight.