Introduction Some levothyroxine unresponsive individuals with hypothyroidism are prescribed a Natural Desiccated Thyroid (NDT) preparation such as Armour Thyroid® or ERFA Thyroid®. These contain a mixture of levothyroxine and liothyronine in a fixed ratio. We evaluated the response to NDT in individuals at a single endocrine centre in terms of how the change from levothyroxine to NDT impacted on their lives in relation to quality of life (QOL) and thyroid symptoms. Methods The ThyPRO39 (thyroid symptomatology) and EQ-5D-5L-related QoL)/EQ5D5L (generic QOL) questionnaires were administered to 31 consecutive patients who had been initiated on NDT, before initiating treatment/6 months later. Results There were 28women/3men. The dose range of NDT was 60mg-180mg daily. Age range was 26-77 years with length of time since diagnosis with hypothyroidism ranging from 2-40 years. One person discontinued the NDT because of lack of response; 2 because of cardiac symptoms. EQ-5D-5L utility increased from a mean (SD) of 0.214 (0.338) at baseline, to 0.606 (0.248) after 6 months; corresponding to a difference of 0.392 (95% CI 0.241-0.542), t=6.82, p<0.001. EQ-VAS scores increased from 33.4 (17.2) to 71.1 (17.5), a difference of 37.7 (95%CI 25.2-50.2), t=-4.9, p<0.001. ThyPRO scores showed consistent fall across all domains with the composite QoL-impact Score improving from 68.3 (95%CI 60.9-75.7) to 25.2 (95%CI 18.7-31.7), a difference of 43.1 (95%CI 33. -53.2) (t=5.6, p<0.001). Conclusion Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism, suggesting the need for further evaluation of NDT in this context.

Introduction Type 2 diabetes mellitus (T2DM) frequently associates with increasing multi-morbidity/treatment complexity. Some headway has been made to identify genetic and non-genetic risk factors for T2DM. However longitudinal clinical histories of individuals both before and after diagnosis of T2DM are likely to provide additional insight into both diabetes aetiology/further complex trajectory of multi-morbidity. Methods This study utilised diabetes patients/controls enrolled in the DARE (Diabetes Alliance for Research in England) study where pre- and post-T2DM diagnosis longitudinal data was available for trajectory analysis. Longitudinal data of 281 individuals (T2DM n=237 vs matched non-T2DM controls n=44) were extracted, checked for errors and logical inconsistencies and then subjected to Trajectory Analysis over a period of up to 70 years based on calculations of the proportions of most prominent clinical conditions for each year. Results For individuals who eventually had a diagnosis of T2DM made, a number of clinical phenotypes were seen to increase consistently in the years leading up to diagnosis of T2DM. Of these documented phenotypes, the most striking were diagnosed hypertension (more than in the control group) and asthma. This trajectory over time was much less dramatic in the matched control group. Immediately prior to T2DM diagnosis a greater indication of ischaemic heart disease proportions was observed. Post-T2DM diagnosis, the proportions of T2DM patients exhibiting hypertension and infection continued to climb rapidly before plateauing. Ischaemic heart disease continued to increase in this group as well as retinopathy, impaired renal function and heart failure. Conclusion These observations provide an intriguing and novel insight into the onset and natural progression of T2DM. They suggest an early phase of potentially-related disease activity well before any clinical diagnosis of diabetes is made. Further studies on a larger cohort of DARE patients are underway to explore the utility of establishing predictive risk scores.

Introduction The COVID-19 vaccination programme is under way. Anecdotal evidence is increasing that some people with Type 1 Diabetes Mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before and after vaccination. Methods We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle® Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage(%) BG readings in the designated target range 3.9-10mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week -1) and the 7 days after the vaccination (week +1). Results There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ±se 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ±se 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1-13.9%/ ≥14%. There was no significant change in BG variability in the 7days post COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal bolus insulin (-23%) vs no oral hypoglycaemic agents (-4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (-18% vs -9%)). Conclusion In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may have consequences for patients with T2DM who are currently not supported by flash glucose monitoring.

Introduction: Women with gestational diabetes (GDM) are at greatly increased risk of type 2 diabetes (T2DM). The UK guidance recommends screening for T2DM at around 6 weeks post-partum and annually thereafter. We evaluated conformity to this guidance in two separate time periods. Methods: The proportion of tests performed within guidance was assessed using longitudinal plasma glucose and glycated haemoglobin data in two cohorts (1999-2007, n=251; 2015-2016, n=260) from hospital records on women previously diagnosed with GDM. Results: In the 1999-2007 and 2015-2016 cohorts, 59.8% and 35.0% of women had the recommended post-partum testing, respectively (p<0.001); just 13.5% and 14.2%, respectively, underwent the first annual test on time. During long-term follow-up of the 1999-2007 cohort (median follow-up: 12.3 years), the proportion of women tested in any given year averaged 34.2% over a 17-year period; there was a progressive decline in the proportion of women receiving a yearly test with time since delivery (p=0.002). Over the follow-up period, 85 women from the 1999-2007 cohort developed blood test results in the diabetic range with a median time to presumed DM diagnosis of 5.2 years (range 0.11-15.95 years). Kaplan-Meier analysis showed that 18.8% of women had blood test results in the diabetes range by 5 years and 37.8% by 10 years post-partum. Conclusions: Despite high profile guidelines and a clear clinical rationale to screen women with a past diagnosis of GDM, many women did not receive adequate screening for T2DM, both in the short- and long-term. This suggests alternative approaches are needed to ensure effective follow-up of this high-risk group. To have an impact, interventions need to be tailored to a young, generally healthy group in which traditional approaches to follow-up may not be best suited.

The Short Synacthen Test is the way that we most often determine whether people's adrenal glands are working. We here have shown that an extra blood sample taken at 60 minutes post Synacthen vs a 30 minute sample alone, may make the test more effective at excluding those people who do not need to go on hydrocortisone supplementation or need further evaluation.

Objectives One important group of people at higher risk from the COVID-19 pandemic are those with autoimmune conditions including rheumatoid arthritis/inflammatory bowel disease. To minimise infection risk, many people are now being switched from intravenous to subcutaneous biologics including biosimilars. A key question is how transition costs are viewed by clinicians. Design The survey was designed to understand the comparative economic issues related to the intravenous infusion vs subcutaneous biologic administration routes for infliximab. The survey focused on direct cost drivers/indirect cost drivers. Wider policy implications linked to the pandemic were also explored. Setting/Participants Semi structured telephone interviews were carried out with twenty key stakeholders across the NHS from clinical/pharmacy/commissioning roles. The interviews were undertaken virtually 5thApril-27thApril 2020 and included a semi-structured interview framework with questions across the two administration routes. Results From interview results a simple cost analysis was developed plus a qualitative analysis of reports on wider policy/patient impacts. Key findings included evidence of significant variation in infusion tariffs UK wide, with interviewees reporting that not all actual costs incurred are captured in published tariff costs. A cost analysis showed administration costs 50% that of infusion, with a most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times and reduced risk of COVID-19 infection plus reduced patient costs. However, this was to some extent offset by increased pressure on home-care and community/primary care services. Conclusions Switching from infusion to subcutaneous routes is currently being driven by the COVID-19 pandemic in many services. A case for biologics (infusion vs subcutaneous) must be made on accurate real-world economic analysis. In an analysis of direct/indirect costs, excluding medicine acquisition costs, subcutaneous administration appears to be the more cost saving option for many patients even without the benefit of industry funded home-care.

Background In order to address the COVID-19 pandemic, health systems have used all their resources, including health care workers in training. Knowing the insights of these workers is of the utmost importance to generate adequate educative/political /administrative strategies. Methods An anonymous cross-sectional online survey was made by the General Directorate of Quality and Health Education in Mexico, in a convenience sample of 6,020 participants who belong to personnel in training for the health area, which included practitioners and professional technologists, undergraduate doctors, nursing, and residents in several specialties. Results Different positive and negative feelings were identified by the health workers who participated in facing this health emergency; emphasizing elements such as the need for Personal Protection Equipment (PPE) that, when deficient or lacking, generate concerns that raise questions about the medical/epidemiological attention to the pandemic. Based on an analysis of feelings, 8 main feelings were identified, which by frequency of appearing were: distrust(24.83%), fear(21.97%), sadness(12.45%), anticipation(11.65%), anger(10.71%), disgust(9.69%), joy(4.97%) and surprise(3.72%) which influence health workers in training and their wrok performance day to day. Concerning their positive and negative evaluation of their experience facing this health emergency, 13.83% of participants had a positive perception about participating in this kind of health emergency to support the country, 49.94% showed a negative evaluation, and 36.23% kept a neutral evaluation about their participation. Conclusions The health workers in training in Mexico gave a negative evaluation of the management of the health emergency. Distrust as a response to the absence of timely information from the education/health institutions, as well as concern about lack of personal protection equipment/inputs, are the main conflicts reported. We must establish a credible globally relevant continuity plan for the education of health care personnel in training, facing emergencies and disasters, so that next time we are properly prepared.

Introduction: The approach to thyroid hormone replacement varies across centres but the extent and determinants of variation is unclear. We evaluated geographical variation in levothyroxine (LT4) and liothyronine (LT3) prescribing across General Practices in England and analysed the relationship of prescribing patterns to clinical and socioeconomic factors. Methods: Data was downloaded from the NHS monthly General Practice Prescribing Data in England for the period 2011-2020. Results Overall, 0.5% of levothyroxine treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019-20. Factors strongly influencing more levothyroxine prescribing (model accounted for 62% of variance) were the CCG to which the practice belonged and the proportion of people with diabetes registered on the practice list plus antidepressant prescribing, with socioeconomic disadvantage associated with less levothyroxine prescribing. For liothyronine prescribing (model accounted for 17% of variance), factors that were associated with increased levels of liothyronine prescribing were antidepressant prescribing and % of type 2 diabetes mellitus individuals achieving HbA1c control of 58mmol/mol or less. Factors that were associated with reduced levels of liothyronine prescribing included smoking and higher obesity rates. Conclusion: In spite of strenuous attempts to limit prescribing of liothyronine in general practice a significant number of patients continue to receive this therapy, although there is significant geographical variation in the prescribing of this as for levothyroxine, with specific general practice and CCG related factors influencing prescribing of both levothyroxine and liothyronine.

Vaccination against the COVID-19 virus began in December 2020 in the UK and is now running at 5% population/week. High Levels of social restrictions were implemented for the third time in January 2021 to control the second wave and resulting increases in hospitalisations and deaths. Easing those restrictions must balance multiple challenging priorities, weighing the risk of more deaths and hospitalisations against damage done to mental health, incomes and standards of living, education outcomes and provision of non-Covid-19 healthcare. Weekly and monthly officially published values in 2020/21 were used to estimate the impact of seasonality and social restrictions on the spread of COVID-19 by age group, on the economy and healthcare services. These factors were combined with the estimated impact of vaccinations and immunity from past infections into a model that retrospectively reflected the actual numbers of reported deaths closely both in 2020 and early 2021. It was applied prospectively to the next 6 months to evaluate the impact of different speeds of easing social restrictions. The results show vaccinations are significantly reducing the number of hospitalisations and deaths. The central estimate is that relative to a rapid easing, the avoided loss of 57,000 life years from a strategy of relatively slow easing over the next 4 months comes at a cost in terms of GDP reduction of around £0.4 million/life-year loss avoided. This is over 10 times higher than the usual limit the NHS uses for spending against Quality Adjusted Life Years (QALYs) saved. Alternative assumptions for key factors affecting give significantly different trade-offs between costs and benefits of different speeds of easing. Disruption of non-Covid-19 Healthcare provision also increases in times of higher levels of social restrictions. In most cases, the results favour a somewhat faster easing of restrictions in England than current policy implies.

Our analysis as described in this research letter highlights the fact that age outweighs many other factors in people with T2DM in relation to mortality from SARS-CoV-2 virus, once infected. This fact should be taken into account in relation to the vaccination programme against coronavirus-19 in people with T2DM in the UK and elsewhere.

Our findings illustrate the widespread collateral impact of implementing measures to mitigate the impact of COVID-19 in people with, or being investigated for diabetes mellitus (DM). Ironically, failure to focus of the wider implications for people with DM and other groups with long-term conditions, may place them at increased risk of poor outcomes from SARS-CoV-2 infection itself, irrespective of the implications for their longer-term health prospects.

Introduction The rapid spread of the pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)(COVID-19) virus resulted in governments around the world instigating a range of measures, including mandating the wearing of face coverings on public transport/in retail outlets. Methods We developed a sequential assessment of risk reduction provided by face coverings using a step-by-step approach. The United Kingdom Office of National Statistics(ONS) Population Survey data was utilised to determine the baseline total number of community-derived infections. These were linked to reported hospital admissions/hospital deaths to create case admission risk ratio/admission-related fatality rate. Results Overall, we show that only 7.3% of all community-based infection risk associates with public transport/retail outlets. The reported weekly community infection rate was 29,400 new cases at the start (24th July). The rate of growth in hospital admissions and deaths for England was around -15%/week, suggesting the infection rate, R, in the most vulnerable populations was just above 0.8. In this situation, average infections over the evaluated 13week follow-up period was 9,517/week. With face covering of 40% effectiveness, this reduced average infections by 844/week, hospital admissions by 8/week and deaths by 0.6/week; a fall of 9% over the period total. If, however, the R-value rises to 1.0, then average community infections would stay at 29,400/week and face coverings could reduce average weekly infections by 3,930, hospital admissions by 36 and deaths by 2.9/week; a 13% reduction. These reductions should be seen in the context of 102,000/week all-cause hospital emergency admissions in England and 8,900 reported deaths in the week ending 7thAugust 2020. Conclusion We have illustrated that the policy on mandation of face coverings in retail outlets/on public transport may have limited value in reducing hospital admissions/deaths. Impact appears small compared to all other sources of risk, thereby raising questions regarding effectiveness of the policy.