Evaluation of adverse effects with COVID-19 vaccination in Pakistan

Objectives: Vaccinations work with different mechanisms to offer protection against disease; however, process of immunity building can cause symptoms. Therefore, this study aimed to determine the immediate side effects of COVID–19 vaccination in the Pakistani Population. Methods: This cross-sectional analytical study was conducted at Foundation University College of Dentistry, Islamabad from February to April 2021. 0.5 mL per dose of the Covid-19 vaccine was administered to the candidates. These 205 candidates receiving vaccination were then interviewed investigating the adverse effects of the vaccine. Post-vaccination side effects were compared among categorical groups using the Chi-Square test, whereas post-vaccination side effects were compared with age using independent samples T-test. A p-value of ≤0.05 was statistically significant. Results: Among post-vaccination side effects, fever was reported by 69 participants, while 56 of 205 reported soreness, redness, and swelling at the injection site. It was reported by 42/205 participants to have felt chills and rigor, whereas gastrointestinal disturbance and flu-like symptoms were reported in 55/205 and 28/205 participants, respectively. Younger participants were more likely to develop gastrointestinal disturbance and flu-like symptoms following vaccination as compared to older participants. Conclusion: Malaise, headache, and fever were observed to be the most common side effects of the vaccine, moreover there was a linear relationship between manifestations of adverse effects and history of comorbidities. doi: https://doi.org/10.12669/pjms.37.7.4522 How to cite this:Abbas S, Abbas B, Amir S, Wajahat M. Evaluation of adverse effects with COVID-19 vaccination in Pakistan. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4522 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Characteristics of Plant Eating in Domestic Cats

Plant eating by domestic cats is of interest to veterinarians and cat owners, especially with the current trend to keep cats totally indoors. Feline grass gardens are commonly provided to such cats as a reflection of cat owners believing in the need or desire of cats for eating plants. Two surveys with 1000 to 2000 returns from cat owners were launched over 10 years to test different hypotheses regarding plant eating. These hypotheses are that plant eating: (1) is a response to the cat feeling ill; (2) induces vomiting; (3) is a means of expelling hair balls from consumed hair. Additionally, a perspective acquired from observations of wild felids is that plant eating reflects an innate predisposition acquired from the ancestral cat. In this study, very few cats showed signs of illness before eating plants. However, 27 to 37 percent of cats, respectively in the two surveys, frequently vomited after eating plants, indicating that gastrointestinal disturbance may be related to vomiting in some cats. Young cats consumed plants more frequently than older cats and appeared ill and vomited less frequently in association with plant eating. Short-haired cats ate plants as frequently as long-haired cats, arguing against the hairball expelling hypothesis. Some guidelines for cat owners with indoor cats are provided.

THU0219 FIRST-INHUMAN STUDY OF SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF IRAK1/4 INHIBITOR R835 IN HEALTHY SUBJECTS

Background:Toll-Like Receptors (TLR) and Interleukin-1 Receptors (IL-1R) play a critical role in the innate immune response as microbial and tissue damage sensors, providing a bridge between the innate and adaptive immunity. Interleukin receptor associated kinases (IRAK) 1 and 4 are serine/threonine kinases that are essential for signaling downstream of most TLRs and IL-1Rs and the resulting production of pro-inflammatory cytokines. Suppression of TLR and IL-1R signaling through inhibition of IRAK1/4 kinases is a promising therapeutic approach for the treatment of inflammatory and autoimmune diseases. We have identified a potent and selective IRAK1/4 inhibitor (R835) that showed dose-dependent inhibition of lipopolysaccharide (LPS, a TLR4 agonist), and IL-1β induced serum cytokines in mice. R835 prevented disease onset and progression in multiple rodent models of inflammatory diseases, including arthritis and lupus models.Objectives:The aim of this FIH study was to characterize the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of R835 after single or multiple dose oral administrations.Methods:This study was a randomized, placebo-controlled, double-blind Phase 1 study in healthy subjects in three parts: single ascending doses (20 mg-1920 mg, Part A) with food effect in a separate cohort (480 mg), multiple ascending doses (120 mg and 960 mg, BID, Part B) with a caffeine interaction (960 mg cohort), and an intravenous LPS challenge test at 240 mg oral dose of R835 (Part C).Results:Single doses of up to 480 mg R835 in organic solution, single doses of up to 1920 mg R835 as capsule, multiple doses of 120 mg R835 Q12H (organic solution), and 960 mg R835 Q12H (capsule) were safe and well tolerated. All R835 related adverse events (AEs) were mild in intensity and reversible, and mostly associated with the higher doses of R835 in the organic solution. The most common AEs were headache and gastrointestinal disturbance. The PK of R835 was linear and dose proportional in exposure over the dose range studied. A nominal level of accumulation in plasma achieved rapidly upon repeated BID administrations with steady-state essentially attained in 2 days. A high-fat meal with the capsule formulation resulted in slow rate of absorption but had no effect on the extent of absorption. There was no effect of R835 on metabolism of caffeine (P450 CYP1A2 prototype substrate). In the LPS challenge test, R835 profoundly inhibited the acute release of cytokines, including TNF-α, IL-6, IL-8, MIP1α and MIP1β, but had no impact on CRP release.Conclusion:R835 was well tolerated after single or multiple dose administrations. The most common AEs were headache and gastrointestinal disturbance. For both of the formulations tested, the PK of R835 was linear and exposure was dose proportional with rapid steady-state attainment following BID administration. There was no drug-drug interaction by use of caffeine as the protype substrate. R835 inhibited the LPS induced release of cytokines in the serum, including TNF-α, IL-6, IL-8, MIP1α and MIP1β, mirroring preclinical data in mice. The desirable PK and safety profile combined with proof of mechanism, as demonstrated by inhibition of cytokine release, support progression of R835 into Phase II clinical development as an agent for the treatment of inflammatory and autoimmune diseases.Disclosure of Interests: :Lucy Yan Shareholder of: Amgen, Rigel, Employee of: Amgen, Rigel, Sandra Tong Shareholder of: Rigel, Employee of: Rigel, Anthony Absalom: None declared, Izaak den Daas: None declared, Gary Park Shareholder of: Rigel Pharmaceuticals, Employee of: Rigel Pharmaceuticals, Vanessa Taylor Shareholder of: Rigel Pharmaceuticals, Employee of: Rigel Pharmaceuticals, Donna Chow Shareholder of: Rigel, Employee of: Rigel, Meng Lee Shareholder of: Rigel, Employee of: Rigel, Hanzhe Zheng Shareholder of: Rigel, Employee of: Rigel, Andrew Chow Shareholder of: Rigel, Employee of: Rigel

Optimization of dysbiosis prevention and correction in children with gastrointestinal disturbance

Dysbiosis prevention and correction in children with gastrointestinal disturbance is the most disputable and currently central problem of modern gastroenterology. In the article are summarized studding resultes of liquid probiotics “Bifidumbacterinum “Bifishka” and Narine-forte effectiveness for gastrointestinal disturbance remedial measures optimization.