AbstractObjectiveTo evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition.DesignInstrumental variable meta-analysis.Setting14 ...randomized controlled trials of drugs for the prevention or treatment of Alzheimer’s disease that targeted an amyloid mechanism, identified from ClinicalTrials.gov.PopulationAdults enrolled in randomized controlled trials of amyloid targeting drugs. Inclusion criteria for trials vary, but typically include adults aged 50 years or older with a diagnosis of mild cognitive impairment or Alzheimer’s disease, and amyloid positivity at baseline.Main outcome measuresAnalyses included trials for which information could be obtained on both change in brain amyloid levels measured with amyloid positron emission tomography and change in at least one cognitive test score reported for each randomization arm.ResultsPooled results from the 14 randomized controlled trials were more precise than estimates from any single trial. The pooled estimate for the effect of reducing amyloid levels by 0.1 standardized uptake value ratio units was an improvement in the mini-mental state examination score of 0.03 (95% confidence interval −0.06 to 0.1) points. This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels.ConclusionsPooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.
The mortality burden in children aged 5–14 years in the WHO European Region has not been comprehensively studied. We assessed the distribution and trends of the main causes of death among children ...aged 5–9 years and 10–14 years from 1990 to 2016, for 51 countries in the WHO European Region.
We used data from vital registration systems, cancer registries, and police records from 1980 to 2016 to estimate cause-specific mortality using the Cause of Death Ensemble model.
For children aged 5–9 years, all-cause mortality rates (per 100 000 population) were estimated to be 46·3 (95% uncertainty interval UI 45·1–47·5) in 1990 and 19·5 (18·1–20·9) in 2016, reflecting a 58·0% (54·7–61·1) decline. For children aged 10–14 years, all-cause mortality rates (per 100 000 population) were 37·9 (37·3–38·6) in 1990 and 20·1 (18·8–21·3) in 2016, reflecting a 47·1% (43·8–50·4) decline. In 2016, we estimated 10 740 deaths (95% UI 9970–11 542) in children aged 5–9 years and 10 279 deaths (9652–10 897) in those aged 10–14 years in the WHO European Region. Injuries (road injuries, drowning, and other injuries) caused 4163 deaths (3820–4540; 38·7% of total deaths) in children aged 5–9 years and 4468 deaths (4162–4812; 43·5% of total) in those aged 10–14 years in 2016. Neoplasms caused 2161 deaths (1872–2406; 20·1% of total deaths) in children aged 5–9 years and 1943 deaths (1749–2101; 18·9% of total deaths) in those aged 10–14 years in 2016. Notable differences existed in cause-specific mortality rates between the European subregions, from a two-times difference for leukaemia to a 20-times difference for lower respiratory infections between the Commonwealth of Independent States (CIS) and EU15 (the 15 member states that had joined the European Union before May, 2004).
Marked progress has been made in reducing the mortality burden in children aged 5–14 years over the past 26 years in the WHO European Region. More deaths could be prevented, especially in CIS countries, through intervention and prevention efforts focusing on the leading causes of death, which are road injuries, drowning, and lower respiratory infections. The findings of our study could be used as a baseline to assess the effect of implementation of programmes and policies on child mortality burden.
WHO and Bill & Melinda Gates Foundation.
ObjectivesEvidence on adverse childhood experiences (ACEs) and late-life cognitive outcomes is inconsistent, with little research among diverse racial/ethnic groups. We investigated whether ACE ...exposures were associated with worse late-life cognition for all racial/ethnic groups and at different ages of exposure.DesignCovariate-adjusted mixed-effects linear regression models estimated associations of: (1) total number of ACEs experienced, (2) earliest age when ACE occurred and (3) type of ACE with overall cognition.SettingKaiser Permanente Northern California members aged 65 years and older, living in Northern California.ParticipantsKaiser Healthy Aging and Diverse Life Experiences study baseline participants, aged 65 years and older (n=1661; including 403 Asian-American, 338 Latino, 427 Black and 493 white participants).ResultsMost respondents (69%) reported one or more ACE, most frequently family illness (36%), domestic violence (23%) and parental divorce (22%). ACE count was not adversely associated with cognition overall (β=0.01; 95% CI −0.01 to 0.03), in any racial/ethnic group or for any age category of exposure. Pooling across all race/ethnicities, parent’s remarriage (β=−0.11; 95% CI −0.20 to −0.03), mother’s death (β=−0.18; 95% CI −0.30 to −0.07) and father’s death (β=−0.11; 95% CI −0.20 to −0.01) were associated with worse cognition.ConclusionAdverse childhood exposures overall were not associated with worse cognition in older adults in a diverse sample, although three ACEs were associated with worse cognitive outcomes.
Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American ...retinoblastoma patients and explore factors associated with survival and globe salvage.
Subanalysis of prospective cohort study data.
Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income LIC, lower-middle income LMIC, upper-middle income UMIC, and high income HIC) of 491 treatment-naïve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models.
Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%), and 190 (38.7%) were from LIC, LMIC, UMIC, and HIC groups, respectively. Three-year survival rates in LICs were 60.0% (95% confidence interval CI 12.6-88.2) compared with 99.2% (95% CI 94.6%-99.9%) in HICs. Death was less likely in patients >4 years of age (vs ≤4 years, HR = 0.45 95% CI 0.27-0.78, P = .048). Patients with more advanced tumors (eg, cT3 vs cT1, HR = 4.65 × 109 95% CI 1.25 × 109-1.72 × 1010, P < .001) and females (vs males, HR = 1.98 95% CI 1.27-3.10, P = .04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI 5.1%-25.6%) in LMICs and 46.2% (95% CI 38.8%-53.3%) in HICs. At 3 years, 70.1% of cT1 eyes (95% CI 54.5%-81.2%) vs 8.9% of cT3 eyes (95% CI 5.5%-13.3%) were salvaged. Advanced tumor stage was associated with higher enucleation risk (eg, cT3 vs cT1, subhazard ratio = 4.98 95% CI 2.36-10.5, P < .001).
Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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