Heterologous versus homologous COVID-19 booster vaccinations for adults: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials.

BACKGROUND: To combat coronavirus disease 2019 (COVID-19), booster vaccination strategies are important. However, the optimal administration of booster vaccine platforms remains unclear. Herein, we aimed to assess the benefits and harms of three or four heterologous versus homologous booster regimens. METHODS: From November 3 2022 to December 21, 2023, we searched five databases for randomised clinical trials (RCT). Reviewers screened, extracted data, and assessed bias risks independently with the Cochrane risk-of-bias 2 tool. We conducted meta-analyses and trial sequential analyses (TSA) on our primary (all-cause mortality; laboratory confirmed symptomatic and severe COVID-19; serious adverse events [SAE]) and secondary outcomes (quality of life [QoL]; adverse events [AE] considered non-serious). We assessed the evidence with the GRADE approach. Subgroup analyses were stratified for trials before and after 2023, three or four boosters, immunocompromised status, follow-up, risk of bias, heterologous booster vaccine platforms, and valency of booster. RESULTS: We included 29 RCTs with 43 comparisons (12,538 participants). Heterologous booster regimens may not reduce the relative risk (RR) of all-cause mortality (11 trials; RR 0.86; 95% CI 0.33 to 2.26; I2 0%; very low certainty evidence); laboratory-confirmed symptomatic COVID-19 (14 trials; RR 0.95; 95% CI 0.72 to 1.25; I2 0%; very low certainty); or severe COVID-19 (10 trials; RR 0.51; 95% CI 0.20 to 1.33; I2 0%; very low certainty). For safety outcomes, heterologous booster regimens may have no effect on SAE (27 trials; RR 1.15; 95% CI 0.68 to 1.95; I2 0%; very low certainty) but may raise AE considered non-serious (20 trials; RR 1.19; 95% CI 1.08 to 1.32; I2 64.4%; very low certainty). No data on QoL was available. Our TSAs showed that the cumulative Z curves did not reach futility for any outcome. CONCLUSIONS: With our current sample sizes, we were not able to infer differences of effects for any outcomes, but heterologous booster regimens seem to cause more non-serious AE. Furthermore, more robust data are instrumental to update this review.

Blood Pressure Control Following Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers: Insights from a Triple-Blind, Randomized, Clinical Trial.

Data on substituting one antihypertensive medication with the proper dose of another antihypertensive medication, in certain medical conditions, are scarce. Herein, we present the results of replacing angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) with the calcium channel blocker (CCB) amlodipine, with or without the alpha- and beta-blocker carvedilol, to control high blood pressure in patients with coronavirus disease 2019 (COVID-19). Iranian hypertensive patients with COVID-19 and a history of taking ACEI or ARB were randomized to "continue" and "change" groups. The continue group comprised patients who continued using their previous antihypertensive medication regimen as normal, whereas patients in the change group had their antihypertensive drugs changed to the CCB amlodipine, with or without the alpha- and beta-blocker carvedilol, based on their response to amlodipine. Patients' blood pressures were measured for 8 days following their recruitment. A total of 31 and 33 patients were randomly allocated to the ACEI/ARB continue and ACEI/ARB change groups, respectively. No significant deviations were seen in patients' systolic blood pressure by substituting an ACEI/ARB agent with the CCB amlodipine, with or without the alpha- and beta-blocker carvedilol. Moreover, the change group had a more balanced systolic blood pressure (ie, 110-130 mmHg) compared with the continue group (ie, 111.5-140.0 mmHg) throughout their hospitalization period. During their hospitalization, the blood pressure of the change group was well controlled with the proposed equivalent doses. Further investigations of the proposed equivalent doses in larger randomized clinical trials, populations other than Iranian COVID-19 patients, and extended duration are encouraged (clinical trial registration ID: IRCT20151113025025N3).

Investigating the effects of bark extract and volatile oil of Pinus eldarica against cisplatin-induced genotoxicity on HUVECs cell line.

Cisplatin is used for treating multiple types of cancers. Alongside its therapeutic effects, there are side effects, including cytotoxicity and genotoxicity for healthy cells, which are mainly related to radical oxygen species (ROS) production by the drug. These side effects could troublesome the treatment process. Previous studies have suggested that members of Pinaceae family are rich sources of antioxidant components. This article investigates the antioxidant activity (AA) of Pinus eldarica (Pinaceae) along with its cyto/genoprotective effects following cisplatin exposure on human umbilical vein endothelial cells (HUVECs) cell line. Pinus eldarica's hydroalcoholic bark extract (PEHABE) and P. eldarica's needle volatile oil (PENVO) were prepared using maceration and hydrodistillation methods, respectively. PENVO was analysed via gas chromatograph-mass spectrometry, and the total phenolic content of PEHBAE was measured by folin-ciocalteu reagent. AA of both PEHABE and PENVO were determined using DPPH assay. Moreover, MTT test was used to determine the cytoprotective effects of both agents. Comet and micronucleus (MN) tests were also performed to investigate the genoprotective effect of P. eldarica. Germacrene D (35.72%) was the main component of PENVO. PEHABE showed higher AA compared with PENVO, with the highest AA observed at 25 and 250 µg/ml, respectively. Both PENVO and PEHABE were cytoprotective, with the latter having mitogenic effects on cells at 75, 100, and 200 µg/ml concentrations (P < 0.01 and P < 0.001). Also, both PEHABE and PENVO showed genoprotective effects against cisplatin in comet assay (P < 0.001). As PEHABE's concentrations were increased, a reduced number of MN formation was observed after cisplatin's exposure (P < 0.001). In conclusion, PEHABE had higher AA compared with PENVO, and both agents had cyto/genoprotective effects on HUVECs.