Background Randomised controlled trials demonstrating improved longevity are needed to justify high-dose vitamin D supplementation for older populations. Objectives To demonstrate the feasibility of a large trial (n ≈ 20,000) of high-dose vitamin D in people aged 65–84 years through general practitioner (GP) practices, and to cluster randomise participating practices between open-label and double-blind randomisation to compare effects on recruitment, compliance and contamination. Design Twenty GP practices were randomised in matched pairs between open-label and double-blind allocation. Within each practice, patients were individually randomised to vitamin D or control (i.e. no treatment or placebo). Participants were invited to attend their GP practice to provide a blood sample and complete a lifestyle questionnaire at recruitment and again at 2 years. Randomisation by telephone followed receipt of a serum corrected calcium assay confirming eligibility (< 2.65 nmol/l). Treatment compliance was reported by quarterly follow-up forms sent and returned by e-mail or post (participant choice). GP visits and infections were abstracted from GP records. Hospital attendances, cancer diagnoses and deaths were ascertained by linkage to Hospital Episode Statistics and national registration through NHS Digital. Setting GP practices in England. Participants Recruitment opened in October 2013 and closed in January 2015. A total of 1615 registered patients aged 65–84 years were randomised: 407 to vitamin D and 421 to no treatment in open practices; 395 to vitamin D and 392 to placebo in blind practices. Interventions There was a 24-month treatment period: 12 monthly doses (100,000 IU of vitamin D3 or placebo as 5 ml oily solution) were posted after randomisation and at 1 year (100,000 IU per month corresponds to 3300 IU per day). Reminders were sent monthly by e-mail, text message or post. Main outcome measures Recruitment, compliance, contamination and change in circulating 25-hydroxyvitamin D [25(OH)D] from baseline to 2 years. Results Participation rates (randomised/invited) were 15.0% in open practices and 13.4% in double-blind practices (p = 0.7). The proportion still taking study medication at 2 years was 91.2% in open practices and 89.2% in double-blind practices (p = 0.4). The proportion of control participants taking > 400 IU vitamin D per day at 2 years was 5.0% in open practices and 4.8% in double-blind practices. Mean serum 25(OH)D concentration was 51.5 nmol/l [95% confidence interval (CI) 50.2 to 52.8 nmol/l] with 82.6% of participants < 75 nmol/l at baseline. At 2 years, this increased to 109.6 nmol/l (95% CI 107.1 to 112.1 nmol/l) with 12.0% < 75 nmol/l in those allocated to vitamin D and was unaltered at 51.8 nmol/l (95% CI 49.8 to 53.8 nmol/l) in those allocated to no vitamin D (no treatment or placebo). Conclusions A trial could recruit 20,000 participants aged 65–84 years through 200 GP practices over 2 years. Approximately 80% would be expected to adhere to allocated treatment (vitamin D or placebo) for 5 years. The trial could be conducted entirely by e-mail in participants aged < 80 years, but some participants aged 80–84 years would require postal follow-up. Recruitment and treatment compliance would be similar and contamination (self-administration of vitamin D) would be minimal, whether control participants are randomised openly to no treatment with no contact during the trial or randomised double-blind to placebo with monthly reminders. Trial registration Current Controlled Trials ISRCTN46328341 and EudraCT database 2011-003699-34. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 10. See the NIHR Journals Library website for further project information.

The risk of radiation effects in children of individuals exposed to ionising radiation remains an ongoing concern for aged veterans of the British nuclear testing programme. The genetic and cytogenetic family trio (GCFT) study is the first study to obtain blood samples from a group of British nuclear test veterans and their families for the purposes of identifying genetic alterations in offspring as a consequence of historical paternal exposure to ionising radiation. In this report, we describe the processes for recruitment and sampling, and provide a general description of the study population recruited. In total, blood samples were received from 91 (49 test and 42 control) families representing veteran servicemen from the army, Royal Air Force and Royal Navy. This translated to an overall response rate of 14% (49/353) for test veterans and 4% (42/992) for control veterans (excluding responders known to be ineligible). Due to the lack of dose information available, test veterans were allocated to a three-point exposure rank. Thirty (61%) test veterans were ranked in the lower group. Nineteen (39%) of the 49 test veterans were classified in the mid (5 veterans; 10%)/high (14 veterans; 29%) exposure ranks and included 12 veterans previously identified as belonging to the special groups or listed in health physics documents. An increased number of test veteran families (20%), compared with control families (5%), self-reported offspring with congenital abnormalities (p = 0.03). Whether this observation in this small group is reflective of the entire UK test veteran cohort or whether it is selection bias requires further work. The cohort described here represent an important and unique family trio grouping whose participation is enabling genetic studies, as part of the GCFT study, to be carried out. The outcomes of these studies will be published elsewhere. ISRCTN Registry: 17461668.

Introduction HIV treatment recommendations have evolved over time, reflecting both growing availability of new antiretrovirals and accumulating evidence on their safe and effective use. We analysed patterns of antiretroviral use among diagnosed pregnant women living with HIV delivering in the UK and Ireland between 2008 and 2018 using national surveillance data. Methods All singleton pregnancies with known outcomes and known timing of antiretroviral initiation reported to the National Surveillance of HIV in Pregnancy and Childhood were included. Every individual instance of specific antiretroviral use was the unit of analysis in generating a snapshot of antiretroviral use overall and over calendar time. The final analysis was restricted to the 14 most frequently prescribed antiretrovirals. Results There were 12 099 singleton pregnancies reported during 2008–2018 and a total of 38 214 individual uses of the 14 most commonly prescribed antiretrovirals, the majority of which were started before conception (70.9%). In 2008, 37.7% (482/1279) of pregnancies were conceived under treatment, reaching 80.9% (509/629) by 2018. Patterns of antiretroviral use have changed over time, particularly for third agents. Between 2008 and 2018 the most frequently used protease inhibitor shifted from lopinavir to darunavir, whereas use of integrase inhibitors increased steadily over time. Conclusions These national surveillance data enable investigation of the ‘real‐world’ use of antiretrovirals in pregnancy on a population level. Findings demonstrate mixed responsiveness of antiretroviral prescription to changes in pregnancy guideline recommendations and may also reflect changes in commissioning and in the characteristics of pregnant women living with HIV.

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