Pharmacokinetic Analysis and Antiepileptic Activity of Tetra-Methylcyclopropane Analogues of Valpromide

Purpose. The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetra-methylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. Methods. The study was carried out by investigating the pharmacokinetics in dogs and pharmacodynamics (anticonvulsant activity and neurotoxicity) of the following three cyclopropane analogues of VPD: 2,2,3,3-tetramethylcyclopropane carboxamide (TMCD), N-methyl TMCD (M-TMCD) and N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycinamide (TMC-GLD). Results. The three investigated compounds showed a good anticonvulsant profile in mice and rats due to the fact that they were metabolically stable VPD analogues which were not biotransformed to their non-active acid, 2,2,3,3-tetramethylcyclopropane carboxylic acid (TMCA). M-TMCD was metabolized to TMCD and TMC-GLD underwent partial biotransformation to its glycine analogue N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycine (TMC-GLN). Unlike TMC-GLN, the above mentioned amides had low clearance and a relatively long half life. Conclusions. In contrast to VPD which is biotransformed to VPA, the aforementioned cyclopropane derivatives were found to be stable to amide-acid biotransformation. TMCD and M-TMCD show that cyclic analogues of VPD, like its aliphatic isomers, must have either two substitutions at the position to the carbonyl, such as in the case of TMCD, or a substitution in the and in the positions like in the VPD isomer, valnoctamide (VCD). This paper discusses the antiepileptic potential of tetramethylcyclopropane analogues of VPD which are in animal models more potent than VPA and may be non-teratogenic and non-hepatotoxic.     

Proportion and predictors of Hypogonadism Recovery in Men with Macroprolactinomas treated with dopamine agonists

Pituitary - Hypogonadism is the most common form of hypopituitarism in men with macroprolactinoma. However, evidence on factors related to hypogonadism recovery is limited. We estimated the...     

The Anticipated Future of Public Health Services Post COVID-19: Viewpoint

In March 2020, the World Health Organization declared COVID-19 as a global pandemic. The COVID-19 pandemic has affected various public health functions and essential services in different ways and magnitudes. Although all countries have witnessed the effect of COVID-19, the impact differed based on many factors including the integrity and resiliency of the countries’ health systems. This paper presents opinions and expectations of the authors about the anticipated changes in the future of public health at the global, regional, and national levels. The viewpoint is based on the current efforts and challenges that various stakeholders have carried out to control COVID-19 and the contribution from the literature on the future of public health. Numerous agencies and actors are involved in the fight against COVID-19 with variations in their effectiveness. The public health services showed weaknesses in most of the countries, in addition to the lack of adequate curative medicine settings. The pandemic highlighted the need for better governance and stronger and more resilient health systems and capacities. The COVID-19 experience has also emphasized the importance of coordination and collaboration among the countries and stakeholders. The COVID-19 pandemic might lead to a wide discussion to improve international and national approaches to prepare for and respond to similar events in terms of preparedness and response mechanisms and tools. Public health will not be the same as before COVID-19. New health priorities, approaches, and new agendas will be on the table of the global platforms and initiatives. More investment in research and technology to meet the demand for new vaccines and medicines, innovative methods like distance learning and working, more respect and remuneration to health professionals, and normalization of the public health and social measures that were induced during the COVID-19 pandemic are expected to be seen in future.     

Impact of clinical pharmacist intervention in anticoagulation clinic in Sudan

Background Many trials have compared anticoagulation management provided by a pharmacist led anticoagulation clinic versus usual physician care showing the role for clinical pharmacist in the management of anticoagulant therapy, and demonstrating excellent outcomes. In Sudan, there is no published research evaluating the role of pharmacist in providing pharmaceutical care for patients taking warfarin. Objective The objective of the study is to assess the role of clinical pharmacist intervention in warfarin patients compared to usual medical care. Setting This study was conducted in Ahmed Gasim cardiac surgery and renal transplant center warfarin clinic. Methods One hundred thirty-five patients were randomly selected from adult patients on warfarin therapy The history of INR records, and adverse effects for the past year, were recorded. Then patients’ warfarin dose adjustments according to INR, was done by the clinical pharmacist for one year. Patients received continuous verbal education and written information about warfarin. Main outcome measure The primary outcome for this study was the INR control, while the secondary outcomes were the bleeding events and hospitalization due to warfarin. Results After the clinical pharmacist intervention there was significant (P < 0.01) improvement in INR control and a significant (P < 0.05) reduction in incidence of bleeding after clinical pharmacist intervention. Hospitalization due to warfarin related complications (bleeding, high INR, low INR) was also significantly (P < 0.001) reduced. Conclusion Clinical pharmacists intervention in warfarin therapy improve INR control, reduce bleeding and hospitalization due to warfarin complications.     

Effect of low-level laser therapy in patients with chronic knee osteoarthritis: a single-blinded randomized clinical study

The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on pain relief and functional performance in patients with chronic knee osteoarthritis (OA). Forty patients with knee OA were randomly assigned into active laser group (n?=?20) and placebo laser group (n?=?20). The LLLT device used was a Ga–As diode laser with a power output of 50 mW, a wavelength of 850 nm, and a diameter beam of 1 mm. Eight points were irradiated and received dosage of 6 J/point for 60 s, with a total dosage of 48 J/cm² in each session. The placebo group was identical but treated without emission of energy. LLLT was applied two times per week over the period of 4 weeks. Outcome measurements included pain intensity at rest and at movement on visual analog scale, knee function using Western Ontario McMaster Universities Osteoarthritis Index scale, and ambulation duration. These measurements were collected at baseline and post-intervention. The results showed significant improvements in all assessment parameters in both groups compared to baseline. Active laser group showed significant differences in pain intensity at rest and movement, knee function, and ambulation duration when compared with the placebo group. Therefore, LLLT seemed to be an effective modality for short-term pain relief and function improvement in patients with chronic knee OA.     

Neurological Manifestation of Recreational Fatal and Near-Fatal Diethylene Glycol Poisonings: Case Series and Review of Literature

Diethylene glycol is a common industrial solvent which is responsible for accidental and epidemic poisoning as early as the 1930s. Due to the unavailability and unaffordability of ethanol, people in Qatar among the low income group are consuming household chemicals, some of which contain diethylene glycol, for recreational purposes.The history of ingestion is usually not volunteered and the initial clinical presentation is usually nonspecific, making it difficult to diagnose from the clinical presentation. Moreover, the biochemical profile varies with time, making the diagnosis more difficult. The neurological course and toxicity is less well characterized than its renal counterpart. Moreover, reports in the literature of such recreational poisoning is lacking particularly in the region.Three cases of recreational diethylene glycol poisoning seen in Hamad General Hospital, Doha, Qatar from 2009 to 2012 are detailed here.These illustrate the clinical course with emphasis on the neurological sequelae that include encephalopathy and multiple cranial and peripheral neuropathies with fatal and near-fatal outcomes. Neuroimaging in 2 were initially normal, but follow-up imaging showed brain atrophy. The third patient’s neuroimaging showed diffuse brain edema with evidence of transtentorial herniation. Nerve conduction studies were performed in 2 of the 3 cases and showed evidence of mixed sensorimotor neuropathy. The outcomes were death in 1 and severe neurological morbidity and disability in 2 cases.Diethylene glycol is a dangerous substance when ingested and can result in mortality and severe morbidity, particularly from the renal and neurological manifestations. Whereas the mechanism of damage is less well known, the damage is likely dose related. The typical clinical pattern of evolution of the poisoning in the absence of cost-effective ways to detect it in the serum can help clinicians in making the diagnosis.Neurological manifestations may include encephalopathy and multiple cranial and peripheral neuropathies with subsequent brain atrophy. Public awareness of the danger of such recreational use should be raised.     

Should metformin still be the first-line of treatment in type 2 diabetes mellitus? A comprehensive review and suggested algorithm

For more than a century, the high occurrences of coronary and peripheral artery diseases in diabetes mellitus patients has been well recognised; despite that, the ability to improve CV event rates by optimizing glycaemic control has remained elusive. Nevertheless, the last decade has seen several cardiovascular outcome clinical trials (CVOTs) of many antihyperglycemic agents that reported promising results for cardiovascular and renal outcomes. This leads to a hot debate on the ideal drug choice for first-line treatment in T2DM. The purpose of this paper is to review the evidence supporting the use of metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies for the management of individuals with T2DM and, discuss the rationale for selection.