Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

BackgroundReliable information on the prevalence of hypertension is crucial in the development of health policies for prevention, control, and early diagnosis of this condition. This study describes the prevalence of hypertension among Costa Rican elderly, and identifies co-factors associated with its prevalence, unawareness and treatment.MethodsThe prevalence of hypertension is estimated for the Costa Rican elderly. Measurement error is assessed, and factors associated with high blood pressure are explored. Data for this study came from a nationally representative sample of about 2,800 individuals from CRELES (Costa Rica: Longevity and Healthy Aging Study). Two blood pressure measures were collected using digital monitors. Self reports of previous diagnosis, and medications taken were also recorded as part of the study.ResultsNo evidence of information bias was found among interviewers, or over time. Hypertension prevalence in elderly Costa Ricans was found to be 65% (Males = 60%, Females = 69%). Twenty-five percent of the studied population did not report previous diagnoses of hypertension, but according to our measurement they had high blood pressure. The proportion of unaware men is higher than the proportion of unaware women (32% vs. 20%). The main factors associated with hypertension are: age, being overweight or obese, and family history of hypertension. For men, current smokers are 3 times more likely to be unaware of their condition than non smokers. Both men and women are less likely to be unaware of their condition if they have a family history of hypertension. Those women who are obese, diabetic, have suffered heart disease or stroke, or have been home visited by community health workers are less likely to be unaware of their hypertension. The odds of being treated are higher in educated individuals, those with a family history of hypertension, elderly with diabetes or those who have had heart disease.ConclusionSex differences in terms of hypertension prevalence, unawareness, and treatment in elderly people have been found. Despite national programs for hypertension detection and education, unawareness of hypertension remains high, particularly among elderly men. Modifiable factors identified to be associated with prevalence such as obesity and alcohol intake could be used in educational programs aimed at the detection and treatment of those individuals who have the condition.

In myotonic dystrophy type 1 (DM1), somatic mosaicism of the (CTG)n repeat expansion is age-dependent, tissue-specific, and expansion-biased. These features contribute toward variation in disease severity and confound genotype to phenotype analyses. To investigate how the (CTG)n repeat expansion changes over time, we collected three longitudinal blood DNA samples separated by 8 to 15 years and used small pool and single molecule PCR in 43 DM1 patients. We used the lower boundary of the allele length distribution as the best estimate for the inherited progenitor allele length (ePAL), which is itself the best predictor of disease severity. Although in most patients the lower boundary of the allele length distribution was conserved over time, in many this estimate also increased with age, suggesting samples for research studies and clinical trials should be obtained as early as possible. As expected, the modal allele length increased over time, driven primarily by ePAL, age-at-sampling and the time interval. As expected, small expansions < 100 repeats, did not expand as rapidly as larger alleles. However, the rate of expansion of very large alleles was not obviously proportionally higher. This may, at least in part, be a result of the allele length-dependent increase in large contractions that we also observed. We also determined that individual-specific variation in the increase of modal allele length over time not accounted for by ePAL, age-at-sampling and time was inversely associated with individual-specific variation in age-at-onset not accounted for by ePAL, further highlighting somatic expansion as a therapeutic target in DM1.

Myotonic dystrophy type 1 (DM1) is a complex disease with a wide spectrum of symptoms. The exact relationship between mutant CTG repeat expansion size and clinical outcome remains unclear. DM1 congenital patients (CDM) inherit the largest expanded alleles, which are associated with abnormal and increased DNA methylation flanking the CTG repeat. However, DNA methylation at the DMPK locus remains understudied. Its relationship to DM1 clinical subtypes, expansion size and age-at-onset is not yet completely understood. Using pyrosequencing-based methylation analysis on 225 blood DNA samples from Costa Rican DM1 patients, we determined that the size of the estimated progenitor allele length (ePAL) is not only a good discriminator between CDM and non-CDM cases (with an estimated threshold at 653 CTG repeats), but also for all DM1 clinical subtypes. Secondly, increased methylation at both CTCF sites upstream and downstream of the expansion was almost exclusively present in CDM cases. Thirdly, levels of abnormal methylation were associated with clinical subtype, age and ePAL, with strong correlations between these variables. Fourthly, both ePAL and the intergenerational expansion size were significantly associated with methylation status. Finally, methylation status was associated with ePAL and maternal inheritance, with almost exclusively maternal transmission of CDM. In conclusion, increased DNA methylation at the CTCF sites flanking the DM1 expansion could be linked to ePAL, and both increased methylation and the ePAL could be considered biomarkers for the CDM phenotype.