Background: Countries in Sub-Saharan Africa (SSA) are moving towards universal health coverage. The process of Health Technology Assessment (HTA) can support decisions relating to benefit package design and service coverage. HTA involves institutional cooperation with agreed methods and procedural standards. We systematically reviewed the literature on policies and capacity building to support HTA institutionalisation in SSA. Methods: We systematically reviewed the literature by searching major databases (PubMed, Embase, etc.) until June 2019 using terms considering three aspects: HTA; health policy, decision making; and SSA. We quantitatively extracted and descriptively analysed content and conducted a narrative synthesis eliciting themes from the selected literature, which varied in study type and apporach. Results: Half of the 49 papers identified were primary research studies and mostly qualitative. Five countries were represented in six of ten studies; South Africa, Ghana, Uganda, Cameroon, and Ethiopia. Half of first authors were from SSA. Most informants were policy makers. Five themes emerged: (1) use of HTA; (2) decision-making in HTA; (3) values and criteria for setting priority areas in HTA; (4) involving stakeholders in HTA; and (5) specific examples of progress in HTA in SSA. The first one was the main theme where there was little use of evidence and research in making policy. The awareness of HTA and economic evaluation was low, with inadequate expertise and a lack of local data and tools. Conclusions: Despite growing interest in HTA in SSA countries, awareness remains low and HTA-related activities are uncoordinated and often disconnected from policy. Further training and skills development are needed, firmly linked to a strategy focusing on strengthening within-country partnerships, particularly among researchers and policy makers. The international community has an important role here by supporting policy- relevant technical assistance, highlighting that sustainable financing demands evidence-based processes for effective resource allocation, and catalysing knowledge-sharing opportunities among countries facing similar challenges.

This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82–0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71–0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81–0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70–0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71–0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89–1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events. Trial registration: PROSPERO: registration number CRD42021294120.

In rats with acute renal failure induced by uranyl nitrate, the hepatic microsomal cytochrome P450 (CYP) 2E1 and CYP3A23 increased 2–4- and 4-times, respectively, CYP2C11 decreased to 80% of control, but the levels of CYP1A2 and CYP2B1/2 were not changed. It has been reported that theophylline was metabolized to 1,3-dimethyluric acid by CYP1A2 and CYP2E1 and 1-methylxanthine via CYP1A2, which was metabolized further to 1-methyluric acid via xanthine oxidase in rats. Hence, it was expected that the formation of 1,3-dimethyluric acid would show an increase in rats with renal failure as a result of induction of CYP2E1. The pharmacokinetics of theophylline were compared in control rats and rats with renal failure after intravenous administration of aminophylline, 5 mg kg−1 as theophylline. In rats with renal failure, the plasma concentrations of theophylline were considerably lower and the resultant total area under the plasma concentration-time curve from time zero to time infinity (AUC0-∞) of theophylline was significantly smaller (2200 vs 1550 μg min mL−1) compared with control rats. In rats with renal failure, the plasma concentrations of 1,3-dimethyluric acid were considerably higher and the resultant AUC0–6 h of 1,3-dimethyluric acid was significantly greater (44.4 vs 456 μg min mL−1) compared with control rats. Moreover, the AUC0–6 h, 1,3-dimethyluric acid/ AUC0–∞, theophylline ratio increased from 2.02% in control rats to 29.4% in rats with renal failure. The in-vitro intrinsic 1,3-dimethyluric acid formation clearance was significantly faster in rats with renal failure (734 vs 529 10−6 mL min−1) compared with control rats using hepatic microsomal fraction. The results led us to conclude that in rats with uranyl nitrate-induced renal failure after the administration of aminophylline, 5 mg kg−1 as theophylline, there was an increase in the formation of 1,3-dimethyluric acid as a result of an increase in CYP2E1 expression.

Interferon (IFN) has been highlighted in several randomized controlled trials as an attractive therapeutic candidate based plausible mode of action, suppressed response in severe COVID-19, and inhibition of SARS-CoV-2 replication. This study investigated the efficacy and safety of IFN in patients with COVID-19 according to clinical severity. Randomized controlled trials evaluating the efficacy and safety of IFN (systemic or inhaled IFN-α, -β, and -λ) treatment in adult patients with COVID-19 were identified by systematically searching electronic databases until January 2023. Risk of bias were assessed using the Cochrane risk of bias tool, meta-analysis, and certainty of evidence grading were followed for the systematic review. We included 11 trials comprising 6,124 patients. Compared with exclusive standard care or placebo, IFN therapy did not provide significant clinical benefits for mortality at day 28 (pooled risk ratio [RR] = 0.86, 95% confidence interval [CI]: 0.62–1.18, 9 studies, low-certainty evidence) and progression to mechanical ventilation (pooled RR = 1.08, 95% CI: 0.81–1.43, 6 studies, low-certainty evidence) in patients with COVID-19. IFN therapy resulted in significantly increased hospital discharge on day 14 relative to the control arm (pooled RR = 1.29, 95% CI: 1.04–1.59). These results were inconsistent compared to other comparable outcomes such as recovery at day 14 and time to clinical improvement. The IFN-treated arm was as safe as the control arm, regardless of clinical severity (pooled RR = 0.87, 95% CI: 0.64–1.19, 9 studies, low-certainty evidence). In conclusion, IFN therapy was safe but did not demonstrate favorable outcomes for major clinical indices in patients with COVID-19, particularly those with higher than moderate severity. IFN therapy was not associated with worsening outcomes in patients with severe COVID-19. Future clinical trials should evaluate the clinical efficacy of IFN therapy in patients with mild COVID-19 or at an earlier stage. Trial registration: The protocol for this review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022301413.

Kim SB, et al. Infect Chemother. 2021 Mar;53(1):166-219. https://doi.org/10.3947/ic.2021.0303

Kim J, et al. Infect Chemother. 2023 Nov;55:e50. https://doi.org/10.3947/ic.2023.0064