COVID-19 is a current global pandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. Methods: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. Results: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI,), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. Conclusions: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.

Autologous bone grafting remains the gold standard for almost all bone void‐filling orthopedic surgery. However, autologous bone grafting has several limitations, thus scientists are trying to identify an ideal synthetic material as an alternative bone graft substitute. Magnesium‐doped biphasic calcium phosphate (Mg‐BCP) has recently been in the spotlight and is considered to be a potential bone substitute. The Mg‐BCP is a mixture of two bioceramics, that is, hydroxyapatite (HA) and β‐tricalcium phosphate (β‐TCP), doped with Mg2+, and can be synthesized through chemical wet‐precipitation, sol–gel, single diffusion gel, and solid state reactions. Regardless of the synthesis routes, it is found that the Mg2+ preferentially accommodates in β‐TCP lattice instead of the HA lattice. The addition of Mg2+ to BCP leads to desirable physicochemical properties and is found to enhance the apatite‐forming ability as compared to pristine BCP. In vitro results suggest that the Mg‐BCP is bioactive and not toxic to cells. Implantation of Mg‐BCP in in vivo models further affirmed its biocompatibility and efficacy as a bone substitute. However, like the other bioceramics, the optimum physicochemical properties of the Mg‐BCP scaffold have yet to be determined. Further investigations are required regarding Mg‐BCP applications in bone tissue engineering.

Cyclosporine is a primary drug in transplant immunosuppression regimens. It has a narrow therapeutic index and variable pharmacokinetic behavior. This study aimed to develop a population pharmacokinetic model of cyclosporine in Malaysian renal transplant recipients as well as to evaluate the performances of different methodsfor handling missing doses. A total of 2804 concentrationts predose and 2 hours after doses were collected retrospectively from 113 renal transplant patients on cyclosporine in Penang General Hospital. Model structure and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling software. Missing doses were handled using different methods to evaluate their performance. Covariate analysis was performed using stepwise forward addition (P < .05) followed by backward elimination (P < .001). Prediction-corrected visual predictive check and sampling-importance resampling methods were used to validate the final model. A 1-compartment model with first-order absorption and elimination best fitted the data. All methods to handle missing doses performed well with the missing dose method being superior to other methods and thus was applied in the final model. Cyclosporine clearance (CL/F) was estimated as 15.1 L/h, and volume of distribution (V/F) was 108 L. Postoperative time, sex, and calcium channel blockers were identified as significant covariates on CL/F, whereas sex and cholesterol level were identified as significant covariates on V/F. This is the first population pharmacokinetic model developed in Malaysian renal transplant patients using a large sample with an evaluation of different methods to handle missing doses in less informative conventional therapeutic drug-monitoring data.

It is well established that endogenously produced dynorphin 1-17 (DYN 1-17) is susceptible to enzymatic degradation, producing a variety of unique fragments in different tissue matrices and disease pathologies. DYN 1-17 and its major biotransformation fragments have significant roles in neurological and inflammatory disorders upon interacting with opioid and non-opioid receptors at both central and peripheral levels, thus highlighting their potential as drug candidates. Nevertheless, their development as promising therapeutics is challenged by several issues. This review aims to provide the latest and comprehensive updates on DYN 1-17 biotransformed peptides, including their pharmacological roles, pharmacokinetic studies and relevant clinical trials. Challenges in their development as potential therapeutics and proposed solutions to overcome these limitations are also discussed.

Supplemental Digital Content is Available in the Text.