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Key Points: Question: Is patient participation in cancer drug trials associated with a survival benefit? Findings: In this systematic review and meta-analysis of 39 studies (85 comparisons), participation in trials by patients with cancer was associated with greater survival benefit compared with routine care (hazard ratio [HR], 0.76). However, survival benefit was not significantly greater when only high-quality studies were pooled (HR, 0.9) or when the sample was adjusted for possible publication bias (HR, 0.94). Meaning: After accounting for biases and confounders, cancer clinical trial participation was not associated with a survival benefit. Importance: Many cancer clinical investigators view clinical trials as offering better care for patients than routine clinical care. However, definitive evidence of clinical benefit from trial participation (hereafter referred to as the participation effect) has yet to emerge. Objective: To conduct a systematic review and meta-analysis of the evidence examining whether patient participation in cancer trials was associated with greater survival benefit compared with routine care. Data Sources: Studies were found through PubMed and Embase (January 1, 2000, until August 31, 2022), as well as backward and forward citation searching. Study Selection: Studies were included that compared overall survival of trial participants and routine care patients. Data Extraction and Synthesis: Data extraction and methodological quality assessment were completed by 2 independent coders using Covidence software. Data were pooled using a random-effects model and analyzed based on the quality of the comparison between trial participants and routine care patients (ie, extent to which studies controlled for bias and confounders). Main Outcomes and Measures: The hazard ratio (HR) for overall survival of trial participants vs routine care patients. Results: Thirty-nine publications were included, comprising 85 comparisons of trial participants and routine care patients. The meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR, 0.76 [95% CI, 0.69-0.82]) when all studies were pooled, regardless of design or quality. However, survival benefits diminished in study subsets that matched trial participants and routine care patients for eligibility criteria (HR, 0.85 [95% CI, 0.75-0.97]) and disappeared when only high-quality studies were pooled (HR, 0.91 [95% CI, 0.80-1.05]). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94 [95% CI, 0.86-1.03]). Conclusions and Relevance: Many studies suggest a survival benefit for cancer trial participants. However, these benefits were not detected in studies using designs addressing important sources of bias and confounding. Pooled results of high-quality studies are not consistent with a beneficial effect of trial participation on its own. This systematic review and meta-analysis examines whether patient participation in cancer trials is associated with greater survival benefit compared with routine care. [ABSTRACT FROM AUTHOR]

Background: Influenza may contribute to coronary/cerebrovascular events and exacerbate underlying conditions. Methods: We used self‐controlled case series (SCCS) design to analyze data from US Veterans ≥18 years with coronary/cerebrovascular or exacerbation event +/−1 year of lab‐confirmed influenza (LCI) during 2010–2018. We estimated the incidence ratio (IR) (95% CI) of the event for risk interval (Days 1–7 post‐LCI) versus control interval (all other times +/−1 year of LCI) with fixed‐effects conditional Poisson regression. We included biomarker data for mediation analysis. Results: We identified 3439 episodes with coronary/cerebrovascular‐related hospitalizations. IRs (95% CI) for LCI risk versus control interval were STEMI 0.6 (0.1, 4.4), NSTEMI 7.3 (5.8, 9.2), ischemic stroke 4.0 (3.0, 5.4), hemorrhagic stroke 6.2 (3.4, 11.5), and coronary spasm 1.3 (0.5, 3.0). IR significantly increased for NSTEMI and ischemic stroke among those ≥ 65 years. IR for NSTEMI and ischemic stroke dropped 26% and 10%, respectively, when white blood cell (WBC) and platelet count were considered. LCI was significantly associated with exacerbation of preexisting asthma, chronic obstructive pulmonary disease, and congestive heart failure. Conclusions: We found significant association between LCI and hospitalization for NSTEMI, ischemic stroke, and hemorrhagic stroke, the latter possibly due to unaccounted time‐varying confounding in SCCS design. [ABSTRACT FROM AUTHOR]

BACKGROUND. Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA. METHODS. Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on [CD4.sup.+] T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters. RESULTS. Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-[DR.sup.+][CD38.sup.+]) [CD4.sup.+] T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination. CONCLUSION. This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine. TRIAL REGISTRATION. ClinicalTrials.gov NCT02514018. FUNDING. Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments., Introduction Previous phase IIb/III HIV vaccine trials attest to the challenges faced in human immunodeficiency virus (HIV) vaccine development. The use of adenovirus serotype 5 (Ad5) as a recombinant viral [...]

Background A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021. Methods We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models. Results We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%–94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%–99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%–94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%–99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants. Conclusions Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes. [ABSTRACT FROM AUTHOR]

Observational seasonal influenza relative vaccine effectiveness (rVE) studies employ a variety of statistical methods to account for confounding and biases. To better understand the range of methods employed and implications for policy, we conducted a brief literature review. Across 37 included rVE studies, 10 different types of statistical methods were identified, and only eight studies reported methods to detect residual confounding, highlighting the heterogeneous state of the literature. To improve the comparability and credibility of future rVE research, researchers should clearly explain methods and design choices and implement methods to detect and quantify residual confounding. [ABSTRACT FROM AUTHOR]

The nature of the relationship between receipt of the 2008-09 seasonal inactivated trivalent influenza vaccine (TIV) and the risk for infection with the pandemic (H1N1) 2009 virus strain, hereafter referred [...]

Aim: To describe the nutritional status of children under-five years of age in Libya.Population and methods: A secondary analysis of data of 5348 children taken from a nationalrepresentative, two-stage, cluster-sample survey that was performed in 1995.Results: Prevalence rates of underweight, wasting, stunting, and overweight were determined usingstandard definitions in reference to newly established WHO growth charts. The study revealed that4.3% of children were underweight, 3.7% wasted, 20.7% stunted, and 16.2% overweight. Seventypercent of children had normal weight. Undernutrition was more likely to be found in males, in ruralareas, and in underprivileged groups. Overweight was more likely found in urban, privileged groups.Wasting was more common in arid regions; stunting was more common in mountainous regions of Al-Akhdar, Al-Gharbi, and in Sirt. Al-Akhdar had the highest prevalence of overweight.Conclusion: The country had a low prevalence of underweight and wasting, moderate prevalence ofstunting, and high prevalence of overweight. The country is in the early stages of transition withevidence of dual-burden in some regions. Similar surveys are needed to verify secular trends of thesenutritional problems, particularly overweight.

Background: The incidence of anogenital warts (AGW) decreased after the introduction of the quadrivalent human papillomavirus (qHPV) vaccine in multiple jurisdictions. We studied how comparing AGW incidence rates with different outcomes affects the interpretation of the qHPV vaccination program. To do this, we replicated multiple study designs within a single jurisdiction (Manitoba). Methods: We measured the incidence rates of AGW, AGW-related prescriptions, chlamydia, and gonorrhea (the latter two as sham outcomes) between 2001 and 2017 using several clinical and administrative health databases from Manitoba. We then used incidence rate ratios (IRRs) to compare, for each outcome, the rate for the 1997–1998 birth cohort (the first cohorts eligible for the publicly funded qHPV vaccination program) and the older 1995–1996 birth cohort. Results: AGW incidence in Manitoba dropped 72% (95% confidence interval 54–83%) among 16–18 year-old girls and 51% (14–72%) among boys after the introduction of the female-only qHPV vaccination program. Trends in AGW-related prescriptions were different from trends in AGW diagnoses as these prescriptions peaked shortly after the introduction of the publicly funded qHPV vaccine program. Chlamydia and gonorrhea incidence rates also decreased 12% (5–18%) and 16% (-1-30%), respectively, for 16–18 year-old girls. Conclusions: The publicly funded school-based qHPV vaccine program reduced AGW incidence in Manitoba by three-quarters in young females. AGW-related prescriptions are a poor proxy for medically attended AGW after the introduction of the publicly funded qHPV vaccination program. Different sexual habits in adolescents are, at most, responsible for a small portion of the reduction in AGW incidence. [ABSTRACT FROM AUTHOR]