Timeliness of childhood vaccination in England: A population-based cohort study.

INTRODUCTION: Vaccine surveillance for children in England focuses on coverage at ages 1, 2, and 5 years. Previous studies exploring vaccine timeliness have used different arbitrary categories to define whether vaccines were received 'late' or 'on time'. This paper aims to provide more detailed and holistic information on timing and patterns of vaccine uptake across the childhood immunisation schedule in England. METHODS: We included all children born in England between 2006 and 2014 and registered in the Clinical Practice Research Datalink (CPRD) Aurum, a primary care electronic health record. We described vaccine uptake for representative antigens (pertussis, pneumococcus, measles) by age in days and stratified by ethnicity, region and birth cohort. Alluvial diagrams were used to illustrate common journeys through the vaccination schedule, and we applied survival analysis using accelerated failure time models (AFT) to predict age of vaccine receipt based on timing of previous doses. RESULTS: 573,015 children were followed up until their fifth birthday, when they had 90.16 % coverage for two doses of measles, mumps, rubella (MMR) vaccine and 88.78% coverage for four doses of diphtheria, tetanus, pertussis (DTP) vaccine. Overall, the later the age at which a vaccine was due, the more delay in vaccination. Children of Black Ethnicity or from London showed deviating uptake patterns. If a child received their third DTP dose more than a year later than recommended, they would receive the next dose 2.7 times later than a child who was vaccinated on time. A smaller delay was found for children who did not receive first MMR dose on time. DISCUSSION: We showed that the risk of vaccination delay increased with the age of the child and significant delay of previous doses. Primary care data can help to promptly identify children at higher risk of delayed vaccination.

Association between vitamin D and incident herpes zoster: a UK Biobank study.

BACKGROUND: Vitamin D has immunomodulatory effects, but any association with herpes zoster (HZ) is unclear. AIM: To explore the association between vitamin D status and risk of incident HZ in adults in the UK. DESIGN AND SETTING: A cohort study involving participants of UK Biobank (a database containing the health information from half a million individuals) across England, Wales, and Scotland, who had at least one vitamin D testing result with linked primary care electronic health records. METHOD: The primary exposure was vitamin D status, categorised as deficient (<25 nmol/L), insufficient (25-49 nmol/L), or sufficient (≥50 nmol/L). The secondary exposures were self-reported vitamin D supplementation at baseline assessment and vitamin D prescription records. The outcome was diagnosed incident HZ, identified from linked primary care or hospital inpatient records. Weibull regression was used, adjusting for potential confounders, including demographic factors, comorbidities, and immunosuppression. RESULTS: In total, 177 572 eligible participants were included in the analysis, with a mean follow-up time of 10.1 years (standard deviation 1.9 years). No evidence showed that low vitamin D was associated with a higher incidence of HZ, compared with people with sufficient vitamin D (deficient: adjusted hazard ratio [HR] 0.99, 95% confidence interval [CI] = 0.90 to 1.10; insufficient: HR 1.03, 95% CI = 0.96 to 1.10). No evidence was found that supplementing vitamin D or receiving vitamin D prescription was associated with HZ incidence (supplementation: HR 0.88, 95% CI = 0.67 to 1.16; prescription: HR 1.11, 95% CI = 0.91 to 1.34). CONCLUSION: No association of vitamin D status, supplementation, or prescription with incident HZ was observed. No evidence supported vitamin D supplementation as a strategy to prevent HZ.

The association between vitamin D status and COVID-19 in England: A cohort study using UK Biobank.

BACKGROUND: Recent studies indicate that vitamin D supplementation may decrease respiratory tract infections, but the association between vitamin D and COVID-19 is still unclear. OBJECTIVE: To explore the association between vitamin D status and infections, hospitalisation, and mortality due to COVID-19. METHODS: We used UK Biobank, a nationwide cohort of 500,000 individuals aged between 40 and 69 years at recruitment between 2006 and 2010. We included people with at least one serum vitamin D test, living in England with linked primary care and inpatient records. The primary exposure was serum vitamin D status measured at recruitment, defined as deficiency at <25 nmol/L, insufficiency at 25-49 nmol/L and sufficiency at ≥ 50 nmol/L. Secondary exposures were self-reported or prescribed vitamin D supplements. The primary outcome was laboratory-confirmed or clinically diagnosed SARS-CoV-2 infections. The secondary outcomes included hospitalisation and mortality due to COVID-19. We used multivariable Cox regression models stratified by summertime months and non-summertime months, adjusting for demographic factors and underlying comorbidities. RESULTS: We included 307,512 participants (54.9% female, 55.9% over 70 years old) in our analysis. During summertime months, weak evidence existed that the vitamin D deficiency group had a lower hazard of being diagnosed with COVID-19 (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77-0.95). During non-summertime, the vitamin D deficiency group had a higher hazard of COVID-19 compared with the vitamin D sufficient group (HR = 1.14, 95% CI = 1.01-1.30). No evidence was found that vitamin D deficiency or insufficiency was associated with either hospitalisation or mortality due to COVID-19 in any time strata. CONCLUSION: We found no evidence of an association between historical vitamin D status and hospitalisation or mortality due to COVID-19, along with inconsistent results for any association between vitamin D and diagnosis of COVID-19. However, studies using more recent vitamin D measurements and systematic COVID-19 testing are needed.

Distribution of vitamin D status in the UK: a cross-sectional analysis of UK Biobank.

OBJECTIVE: No recent large studies have described the distribution of vitamin D status in the UK. Understanding the epidemiology of vitamin D deficiency is important to inform targeted public health recommendations. This study aimed to investigate the distribution of factors associated with serum vitamin D status in a large national cohort. DESIGN: A cross-sectional study. SETTING: The UK Biobank, a prospective cohort study following the health and well-being of middle-aged and older adults recruited between 2006 and 2010. PARTICIPANTS: A total of 449 943 participants aged 40-69 years with measured serum vitamin D status were eligible for the analysis. Participants completed a questionnaire about sex, age, ethnic background, vitamin D supplementation, smoking, drinking and socioeconomic status. PRIMARY AND SECONDARY OUTCOME MEASURES: We investigated the distribution of serum vitamin D status and the association between demographic factors and vitamin D deficiency or insufficiency. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D level <25 nmol/L. Multivariable logistic regression was used to assess the association between demographic factors and vitamin D status. RESULTS: Asian (n=4297/8000, 53.7%) and black (n=2459/7046, 34.9%) participants had a higher proportion of vitamin D deficiency than white participants (n=50 920/422 907, 12%). During spring and winter, the proportion of vitamin D deficiency was higher across the UK and higher in the north than in the south. Male sex, abnormal body mass index, non-white ethnic backgrounds, smoking and being more socioeconomically deprived were associated with higher odds of vitamin D deficiency. Increasing age, taking vitamin D supplements and drinking alcohol were associated with lower odds of deficiency. CONCLUSIONS: Vitamin D status varied among different ethnic groups and by season and geographical area within the UK. Taking supplements was associated with a lower risk of vitamin D deficiency. These findings support the vitamin D supplementation recommendations of Public Health England.

Vitamin D Deficiency or Supplementation and the Risk of Human Herpesvirus Infections or Reactivation: A Systematic Review and Meta-analysis.

BACKGROUND: Vitamin D may protect against respiratory virus infections, but any association with herpesviruses is unclear. METHODS: We undertook a systematic review of vitamin D deficiency or supplementation and the risk of 8 human herpesviruses. Six databases and 4 gray literature databases were searched for relevant cohort studies, case-control studies, and clinical trials. RESULTS: Ten studies were included, all conducted among immunosuppressed patients. There was no evidence that vitamin D deficiency is associated with cytomegalovirus (CMV) disease (pooled risk ratio, 1.06; 95% CI, 0.66-1.7), herpes zoster after transplantation (1 study), or HHV-8 among HIV patients (1 study). Vitamin D supplementation may decrease herpes zoster among hemodialysis patients (1 study) or CMV disease after renal transplantation (1 study), but supplementation was not associated with reduced EBV viral load among multiple sclerosis patients (1 study). CONCLUSIONS: Any association between vitamin D and herpesviruses remains inconclusive. Further studies in the general population are needed.

Vitamin D deficiency or supplementation and the risk of human herpesvirus infections or reactivation: a systematic review protocol.

INTRODUCTION: Human herpesviruses induce lifelong latent infections and may reactivate as the immune system deteriorates. Recent studies have suggested that vitamin D, an essential element of bone health, may have some effect of protecting against infections, but investigations of its potential to prevent herpesvirus infection or reactivation are limited. We will review the current literature examining vitamin D and the risk of herpesvirus infections or reactivation. METHODS AND ANALYSIS: Our systematic review will address two research questions: (1) Do deficient/insufficient serum vitamin D levels increase the risk of herpesvirus infections and (2) Does vitamin D supplementation protect against herpesvirus infections? We will include only intervention studies with control groups, cohort studies and case-control studies. We will use subject headings and keywords to search for synonyms of 'vitamin D' and 'herpesviruses' (including herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus and human herpesviruses type 6, 7 and 8) in Medline, Embase, Global Health, Web of Science, Scopus and Cochrane Central Register of Controlled Trials, and the grey literature databases Open Grey, EThOS and BASE from inception to 31 August 2019. References to the included articles and relevant systematic reviews will also be examined. Two reviewers will independently screen the study titles and abstracts, and examine the full texts to decide the final eligibility. They will independently extract data from the studies and assess bias using the Cochrane Collaboration approach. A third researcher will solve any discrepancies. The results will be narratively synthesised; if an adequate number of studies is included and the homogeneity between studies is acceptable, a meta-analysis will be performed. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework, and display the results in a summary of findings table. ETHICS AND DISSEMINATION: Ethical review is not required for a systematic review. We will publish the results in a peer-review journal. Any amendments to the protocol will be recorded in the supplementary section. PROSPERO REGISTRATION NUMBER: CRD42019130153.