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Despite a growing global commitment to universal health coverage, considerable vaccine coverage and uptake gaps persist in resource-constrained settings. One way of addressing the gaps is by ensuring product innovation is relevant and responsive to the needs of these contexts. Total Systems Effectiveness (TSE) framework has been developed to characterize preferred vaccine attributes from the perspective of country decision-makers to inform research and development (R&D) of products. A proof of concept pilot study took place in Thailand in 2018 to examine the feasibility and usefulness of the TSE approach using a rotavirus hypothetical test-case. The excel-based model used multiple-criteria decision analysis (MCDA) to compare and evaluate five hypothetical rotavirus vaccine products. The model was populated with local data and products were ranked against decision criteria identified by Thai stakeholders. A one-way sensitivity analysis was performed to identify criteria that influenced vaccine ranking. Self-assessment forms were distributed to R&D stakeholders on the usability of the approach and were subsequently analysed. The model identified significant parameters that impacted on MCDA rankings. Self-assessment forms revealed that TSE was perceived as being able to encourage closer collaboration between country decision makers and vaccine developers. The pilot study demonstrates that it is feasible to use an MCDA approach to elicit stakeholder preferences and determine influential parameters to help identify the preferred product characteristics for R&D from the perspective of country decision-makers. It found that TSE can help steer manufacturers to develop products that are better aligned with country need. Findings will guide further development of the TSE concept.

Wanrudee Isaranuwatchai and colleagues highlight the importance of local context in making decisions about implementing interventions for preventing non-communicable diseases

Background At the height of the COVID-19 pandemic, Thailand had almost depleted its critical care resources, particularly intensive care unit (ICU) beds and ventilators. This prompted the necessity to develop a national guideline for resource allocation. This paper describes the development process of a national guideline for critical resource allocation in Thailand during the COVID-19 pandemic. Methods The guideline development process consisted of three steps: (1) rapid review of existing rationing guidelines and literature; (2) interviews of Thai clinicians experienced in caring for COVID-19 cases; and (3) multi-stakeholder consultations. At steps 1 and 2, data was synthesized and categorized using a thematic and content analysis approach, and this guided the formulation of the draft guideline. Within step 3, the draft Thai critical care allocation guideline was debated and finalized before entering the policy-decision stage. Results Three-order prioritization criteria consisting of (1) clinical prognosis using four tools (Charlson Comorbidity Index, Sequential Organ Failure Assessment, frailty assessment and cognitive impairment assessment), (2) number of life-years saved and (3) social usefulness were proposed by the research team based on literature reviews and interviews. At consultations, stakeholders rejected using life-years as a criterion due to potential age and gender discrimination, as well as social utility due to a concern it would foster public distrust, as this judgement can be arbitrary. It was agreed that the attending physician is required to be the decision-maker in the Thai medico-legal context, while a patient review committee would play an advisory role. Allocation decisions are to be documented for transparency, and no appealing mechanism is to be applied. This guideline will be triggered only when demand exceeds supply after the utmost efforts to mobilize surge capacity. Once implemented, it is applicable to all patients, COVID-19 and non-COVID-19, requiring critical care resources prior to ICU admission and during ICU stay. Conclusions The guideline development process for the allocation of critical care resources in the context of the COVID-19 outbreak in Thailand was informed by scientific evidence, medico-legal context, existing norms and societal values to reduce risk of public distrust given the sensitive nature of the issue and ethical dilemmas of the guiding principle, though it was conducted at record speed. Our lessons can provide an insight for the development of similar prioritization guidelines, especially in other low- and middle-income countries.

As COVID-19 ravages the world, many countries are faced with the grim reality of not having enough critical-care resources to go around. Knowing what could be in store, the Thai Ministry of Public Health called for the creation of an explicit protocol to determine how these resources are to be rationed in the situation of demand exceeding supply. This paper shares the experience of developing triage criteria and a mechanism for prioritizing intensive care unit resources in a middle-income country with the potential to be applied to other low- and middle-income countries (LMICs) faced with a similar (if not more of a) challenge when responding to the global pandemic. To the best of our knowledge, this locally developed guideline would be among the first of its kind from an LMIC setting. In summary, the experience from the Thai protocol development highlights three important lessons. First, stakeholder consultation and public engagement are crucial steps to ensure the protocol reflects the priorities of society and to maintain public trust in the health system. Second, all bodies and actions proposed in the protocol must not conflict with existing laws to ensure smooth implementation and adherence by professionals. Last, all components of the protocol must be compatible with the local context including medical culture, physician–patient relationship, and religious and societal norms.

Background: The World Health Organization (WHO) has developed the Total System Effectiveness (TSE) framework to assist national policy-makers in prioritizing vaccines. The pilot was launched in Thailand to explore the potential use of TSE in a country with established governance structures and accountable decision-making processes for immunization policy. While the existing literature informs vaccine adoption decisions in GAVI-eligible countries, this study attempts to address a gap in the literature by examining the policy process of a non-GAVI eligible country. Methods: A rotavirus vaccine (RVV) test case was used to compare the decision criteria made by the existing processes (Expanded Program on Immunization [EPI], and National List of Essential Medicines [NLEM]) for vaccine prioritization and the TSE-pilot model, using Thailand specific data. Results: The existing decision-making processes in Thailand and TSE were found to offer similar recommendations on the selection of a RVV product. Conclusion: The authors believe that TSE can provide a well-reasoned and step by step approach for countries, especially low- and middle-income countries (LMICs), to develop a systematic and transparent decision-making process for immunization policy.

Objective The effects of ω-3 fatty acids on endothelial function, fibrinolysis and platelet function are uncertain. We investigated the effects of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in healthy cigarette smokers; a group at increased risk of myocardial infarction. Design, setting, participants Twenty cigarette smokers were recruited into a randomised, double-blind, placebo-controlled, crossover trial of ω-3 fatty acid supplementation. Intervention ω-3 fatty acid supplements (2 g/day) or placebo for a 6-week period. Main outcome measures Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 smokers during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion. Results All vasodilators caused dose-dependent increases in FBF (p<0.0001). Compared with placebo, ω-3 fatty acid supplementation led to greater endothelium-dependent vasodilatation with acetylcholine and substance P (p=0.0032 and p=0.056). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001) that was greater after ω-3 fatty acid supplementation compared with placebo (8.8±2.3 IU ml−1 vs 3.6±1.1 IU ml−1; p=0.029). ω-3 fatty acids did not affect platelet-monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40. Conclusions We have demonstrated for the first time that ω-3 fatty acids augment acute endothelial t-PA release and improve endothelial vasomotor function in cigarette smokers. Improved endogenous fibrinolysis and endothelial function may represent important mechanisms through which ω-3 fatty acids confer potential cardiovascular benefits.

Philadelphia’s unique urban fabric provides the opportunity to create a more cohesive urban fabric hat provides opportunities for diverse communities within its neighborhoods. It’s historical hierarchical street system provided the city with the ability to create multi-income blocks for hundreds of years. Modern developers are threatening this cohesive system, with lack of interest in maintaining the housing system that has been present since the city’s origins. This project aims to re-establish the hierarchical system in modern development. Using the rowhouse typology as a base, this project provides a modernizing neighborhood with a new development that provides all residents opportunities for housing.

While COVID-19 vaccines were crucial in containing the pandemic, there is limited evidence on the cost of delivering them in low- and middle-income countries. We estimated the cost of delivering COVID-19 vaccines in Bangladesh, Côte d'Ivoire, the Democratic Republic of the Congo, Mozambique, the Philippines, Uganda, and Vietnam. We retrospectively estimated the financial and economic cost of COVID-19 vaccine delivery from a payer perspective, using a bottom-up approach. Cost data were collected from 290 sites, while qualitative interviews were conducted with 192 key informants. We estimated volume-weighted average costs per dose in 2022 USD, for introduction phases, delivery modalities, and strategies. The financial cost per dose ranged from $0·29-$2·18 across countries, driven by per diem and supplies. The economic cost per dose ranged from $1·14-$9·50, driven by the cost of labor. Newly hired health workers were a cost driver only in the Philippines. The economic delivery cost per dose was inversely correlated with daily vaccine volume delivered at vaccination sites. Similarly, delivering through campaigns came at a lower unit cost than continuous delivery, and when programs scaled up, the cost per dose decreased dramatically. Political prioritization, health workers' commitment, and volunteers were highlighted as success factors, while resource constraints at implementation level and health workers shortages were flagged as key challenges. Our findings demonstrate how under-resourced health systems managed to deliver massive amounts of vaccines with relatively few resources. However, they also expose significant gaps and inefficiencies, and underscores the need to invest in resilient health systems to improve future pandemic responses.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology, based upon the company’s submission to NICE. The evidence was derived mainly from GEMINI 1, a Phase 3, multicentre, randomised, double-blinded, placebo-controlled study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate-to-severe active UC with an inadequate response to, loss of response to or intolerance of conventional therapy or anti-tumour necrosis factor (TNF)-α. The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post hoc subgroup analyses in patients with or without prior anti-TNF-α therapy, vedolizumab performed better then placebo ( p  value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab, and the frequency and types of adverse events were similar in the vedolizumab and placebo groups, but the evidence was limited to short-term follow-up. There were a number of limitations and uncertainties in the clinical evidence base, which warrants caution in its interpretation—in particular, the post hoc subgroup analyses and high dropout rates in the maintenance phase of GEMINI 1. The company also presented a network meta-analysis of vedolizumab versus other biologic therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects, since fixed-effects models were used, despite clear evidence of heterogeneity among the trials included in the network. Results from the company’s economic evaluation (which included price reductions to reflect the proposed patient access scheme for vedolizumab) suggested that vedolizumab is the most effective option compared with surgery and conventional therapy in the following three populations: (1) a mixed intention-to-treat population, including patients who have previously received anti-TNF-α therapy and those who are anti-TNF-α naïve; (2) patients who are anti-TNF-α naïve only; and (3) patients who have previously failed anti-TNF-α therapy only. The ERG concluded that the results of the company’s economic evaluation could not be considered robust, because of errors in model implementation, omission of relevant comparators, deviations from the NICE reference case and questionable model assumptions. The ERG amended the company’s model and demonstrated that vedolizumab is expected to be dominated by surgery in all three populations.