12 research outputs found
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Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008-2018.
OBJECTIVES: World Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process. STUDY DESIGN: We did a systematic, retrospective analysis of research questions identified in the published guidelines. METHODS: We analyzed guidelines published between January 1, 2008, and December 31, 2018, by the Communicable Diseases Cluster in five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs). Research questions were extracted independently by two researchers. We analyzed the distribution of research questions by disease and by topic category and did a qualitative assessment of optimum practice for research question generation during the guideline development process. RESULTS: A total of 48 guidelines were included: 26 on HIV, 1 on malaria, 11 on TB, 5 on TB/HIV, and 5 on NTDs. Overall, 36 (75%) guidelines encompassed a total of 360 explicit research questions; the remainder did not contain specific research questions. The number of research questions that focused on TB was 49, TB/HIV was 38, HIV was 250, and NTDs was 23. The number of research questions that focused on diagnosis was 43 (11.9%) of 360, prevention was 62 (17.2%), treatment was 103 (28.6%), good practice was 12 (3.3%), service delivery was 86 (23.8%), and other areas was 54 (15%). Research questions were often not formulated in a specific or actionable way and were hard to identify in the guideline. Examples of good practice identified by the review team involved the generation of specific and narrowly defined research questions, with accompanying recommendations for appropriate study design. CONCLUSIONS: The WHO must strengthen its approach to identifying and presenting research questions during the guideline development process. Ensuring access to research questions is a key next step in adding value to the guideline development process
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The immune status of migrant populations in Europe and implications for vaccine-preventable disease control: a systematic review and meta-analysis.
BACKGROUND: Ensuring vaccination coverage reaches established herd immunity thresholds (HIT) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPD) and outbreaks, yet it is not clear to what extent they are an under-immunised group. METHODS: We did a systematic review and meta-analysis to synthesise peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella, and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (January 1st 2000 to June 10th 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666). FINDINGS: Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n = 7, 57.4% [95% CI: 43.1-71.7%] I2 = 99% vs HIT 83-86%), measles (n = 21, 83.7% [95% CI: 79.2-88.2] I2 = 99% vs HIT 93-95%), and mumps (n = 8, 67.1% [95% CI: 50.6-83.6] I2 = 99% vs HIT 88-93%), and midway for rubella (n = 29, 85.6% [95% CI: 83.1-88.1%] I2 = 99% vs HIT 83-94%), with high heterogeneity across studies. INTERPRETATION: Migrants in Europe are an under-immunised group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents, and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses, and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life-course in under-immunised groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity
Relative contributions and mapping of ventral tegmental area dopamine and GABA neurons by projection target in the rat
The ventral tegmental area (VTA) is a heterogeneous midbrain structure that contains dopamine (DA), GABA, and glutamate neurons that project to many different brain regions. Here, we combined retrograde tracing with immunocytochemistry against tyrosine hydroxylase (TH) or glutamate decarboxylase (GAD) to systematically compare the proportion of dopaminergic and GABAergic VTA projections to 10 target nuclei: anterior cingulate, prelimbic, and infralimbic cortex; nucleus accumbens core, medial shell, and lateral shell; anterior and posterior basolateral amygdala; ventral pallidum; and periaqueductal gray. Overall, the non-dopaminergic component predominated VTA efferents, accounting for more than 50% of all projecting neurons to each region except the nucleus accumbens core. In addition, GABA neurons contributed no more than 20% to each projection, with the exception of the projection to the ventrolateral periaqueductal gray, where the GABAergic contribution approached 50%. Therefore, there is likely a significant glutamatergic component to many of the VTA's projections. We also found that VTA cell bodies retrogradely labeled from the various target brain regions had distinct distribution patterns within the VTA, including in the locations of DA and GABA neurons. Despite this patterned organization, VTA neurons comprising these different projections were intermingled and never limited to any one subregion. These anatomical results are consistent with the idea that VTA neurons participate in multiple distinct, parallel circuits that differentially contribute to motivation and reward. While attention has largely focused on VTA DA neurons, a better understanding of VTA subpopulations, especially the contribution of non-DA neurons to projections, will be critical for future work5275916941sem informaçãosem informaçã
Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis
Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined factors. R-spondin 3 (RSPO3) is one of the most potent enhancers of Wnt signaling and its expression is usually restricted to the stem cell niche where it provides localized enhancement of Wnt signaling to regulate stem cell expansion and differentiation. Disruption of this niche-confined expression can disturb proper tissue organization and lead to cancers. Here, we investigate the consequences of disrupting the niche restricted expression of RSPO3 in various tissues including the hematopoietic system. We show that normal Rspo3 expression is confined to the perivascular niche in the bone marrow. Induction of increased systemic levels of circulating RSPO3 outside of the niche results in prominent loss of early-B cell progenitors and anemia but surprisingly has no effect on hematopoietic stem cells (HSCs). Using molecular, pharmacological and genetic approaches, we demonstrate that these RSPO3-induced hematopoietic phenotypes are Wnt and RSPO3 dependent and mediated through non-canonical Wnt signaling. Our study highlights a distinct role for a Wnt/RSPO3 signaling axis in the regulation of hematopoiesis, as well as possible challenges related to therapeutic usage of R-spondins for regenerative medicine
Expectations Traps and Monetary Policy with Limited Commitment
We study the existence and uniqueness properties of monetary policy with limited commitment in LQ RE models. We use a New Keynesian model with debt accumulation in the spirit of Leeper (1991) as a 'lab', because this model generates multiple equilibria under pure discretion, and under full commitment there are two distinct determinate regimes. We study how these properties change over the continuum of intermediate cases between commitment and discretion. We find that although multiple equilibria exist for high degrees of precommitment, even a small degree of precommitment selects a unique equilibrium for a wide range of parameters. We discuss the stability properties of policy equilibria which can be used to design an equilibrium selection criterion. We also demonstrate very different welfare implications for different policy equilibria
The Interest Rate - Exchange Rate Nexus: Exchange Rate Regimes and Policy Equilibria
We study a credible Markov-perfect monetary policy in an open New Keynesian economy with incomplete financial markets. We demonstrate the existence of two discretionary equilibria. Following a shock the economy can be stabilised either 'quickly' or 'slow', both dynamic paths satisfy conditions of optimality and time-consistency. The model can help us to understand sudden change of the interest rate and exchange rate volatility in 'tranquil' and 'volatile' regimes even under a fully credible 'soft peg' of the nominal exchange rate in developing countries
Engineering Human Brain Organoids: From Basic Research to Tissue Regeneration
Background: Brain organoids are self-organized from human pluripotent stem cells and developed into various brain region following the developmental process of brain. Brain organoids provide promising approach for studying brain development process and neurological diseases and for tissue regeneration. Methods: In this review, we summarized the development of brain organoids technology, potential applications focusing on disease modeling for regeneration medicine, and multidisciplinary approaches to overcome current limitations of the technology. Results: Generations of brain organoids are categorized into two major classes by depending on the patterning method. In order to guide the differentiation into specific brain region, the extrinsic factors such as growth factors, small molecules, and biomaterials are actively studied. For better modelling of diseases with brain organoids and clinical application for tissue regeneration, improvement of the brain organoid maturation is one of the most important steps. Conclusion: Brain organoids have potential to develop into an innovative platform for pharmacological studies and tissue engineering. However, they are not identical replicas of their in vivo counterpart and there are still a lot of limitations to move forward to clinical applications