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Globally, more than 5 million people have died from Covid-19 since the start of the pandemic. 1 This is certainly a grim number, but we are starting to see the lifesaving effect of vaccines. 2 From the global public health perspective, the initial primary objective of Covid-19 vaccination is to decrease the severe consequences of Covid-19, allowing for the earliest possible stabilization of health care systems, communities, and economies. The vaccines studied to date are highly effective against severe disease and death. 3 Although vaccine effectiveness against infection appears to decline with increasing time since vaccination, it is reassuring that vaccines continue to . . .

Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1–6 months after full vaccination. Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer–BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9–29·8) among people of all ages and 20·7 percentage points (10·2–36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4–41·6) in people of all ages and 32·0 percentage points (11·0–69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1–15·4) in people of all ages and 9·5 percentage points (5·7–14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20–30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. Coalition for Epidemic Preparedness Innovations.

The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant. For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case–control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605). 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1–83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4–35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4–99·2) at 12 months with primary series vaccination and 95·3% (81·9–98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5–52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0–57·3) at 6 months. All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected. WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.

Purpose of ReviewEven with insurance coverage increasing over time among the population with diabetes, a large proportion continues to have poorly controlled disease. The purpose of this narrative literature review is to describe the social determinants of poor management of type 2 diabetes among the insured population and illustrate drivers of poor outcomes beyond insurance coverage.Recent FindingsDespite the provision of health insurance, social determinants play a significant role in shaping diabetes outcomes, especially for economic instability (employment, out-of-pocket expenses associated with diabetes management), food insecurity, education and literacy, access to quality health care (health systems designed to effectively manage chronic disease), neighborhood and the built environment (segregated neighborhoods, socioeconomic conditions of communities, housing), and social and community context (discrimination, social support).SummaryMultiple social determinants shape poor diabetes outcomes among the insured. These determinants are now being further exacerbated by the COVID-19 pandemic, which has created the worst economic crisis for US families since the Great Depression. The evidence of this review points to the imperative need for more multilevel intervention approaches to address these determinants in the management of diabetes.

Severe trauma induces a widespread response of the immune system. This \"genomic storm\" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response.

Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later 1 – 3 . Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression. The evolution of myeloid malignancies is investigated using combined single-cell sequencing and immunophenotypic analysis.

BACKGROUND:Cost-related nonadherence (CRN) is prevalent among individuals with diabetes and can have significant negative health consequences. We examined health-related and non–health-related pressures and the use of cost-reducing strategies among the US adult population with and without diabetes that may impact CRN. METHODS:Data from the 2013 wave of National Health Interview Survey (n=34,557) were used to identify the independent impact of perceived financial stress, financial insecurity with health care, food insecurity, and cost-reducing strategies on CRN. RESULTS:Overall, 11% (n=4158) of adults reported diabetes; 14% with diabetes reported CRN, compared with 7% without diabetes. Greater perceived financial stress [prevalence ratio (PR)=1.07; 95% confidence interval (CI), 1.05–1.09], financial insecurity with health care (PR=1.6; 95% CI, 1.5–1.67), and food insecurity (PR=1.30; 95% CI, 1.2–1.4) were all associated with a greater likelihood of CRN. Asking the doctor for a lower cost medication was associated with a lower likelihood of CRN (PR=0.2; 95% CI, 0.2–0.3), and 27% with CRN reported this. Other cost-reducing behavioral strategies (using alternative therapies, buying prescriptions overseas) were associated with a greater likelihood of CRN. CONCLUSIONS:Half of the adults with diabetes perceived financial stress, and one fifth reported financial insecurity with health care and food insecurity. Talking to a health care provider about low-cost options may be protective against CRN in some situations. Improving screening and communication to identify CRN and increase transparency of low-cost options patients are pursuing may help safeguard from the health consequences of cutting back on treatment.

Financial hardship (including financial stress, financial strain, asset depletion, and financial toxicity) is a highly relevant construct among the 6.9 million people living with Alzheimer's disease and related dementias (ADRD) in the United States and their family networks. This scoping review will identify existing measures and approaches for capturing financial strain among these families. This scoping review will be reported in accordance with PRISMA-ScR guidelines. Searches will be conducted in Embase (Embase.com), Medline (Ovid), CINAHLComplete (EbscoHost), AgeLine (EbscoHost), APA PsycInfo (EbscoHost), Scopus, and Web of Science Core Collection databases to identify tools, measures, or approaches for measuring self-reported financial hardship among family members of people living with ADRD. Data elements from both the National Health and Aging Trends Study and the associated National Study of Caregiving will also be considered. Two independent raters will screen the search results and discrepancies with be resolved by a third rater. Extraction will include the use of artificial intelligence-based software and verification by an independent human rater; any changes that are made to the AI-generated extraction will be reviewed by a second independent rater. A frequency analysis will be conducted to analyze the data, and a summary of the psychometric properties of each of the identified measures will be presented. The findings from this review will be disseminated through peer-reviewed publications and conference presentations. Ultimately, this work will inform the development of a new patient-reported outcome measurement system designed to provide a comprehensive assessment of the different aspects of financial hardship for families of people living with ADRD. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P), the following protocol was registered via https://osf.io on March 14, 2025 (registration DOI: https://doi.org/10.17605/OSF.IO/J26KT).

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.