Parent-Offspring Associations in Body Composition: Findings From the Southampton Women's Survey Prospective Cohort Study.

CONTEXT: Children born to parents who are overweight or obese have a high risk of adult obesity, but it is unclear if transgenerational associations relating to unfavorable body composition differ by parent. OBJECTIVE: To examine differential mother-offspring and father-offspring associations in body composition in early childhood. METHODS: A total of 240 mother-father-offspring trios from a prospective UK population-based pre-birth cohort (Southampton Women's Survey) were included for anthropometry and dual-energy x-ray absorptiometry assessment of whole-body-less-head body composition in the offspring at 3 different ages (4, 6-7, and 8-9 years) and in the mother and father at the 8- to 9-year offspring visit. Associations were assessed using linear regression adjusting for the other parent. RESULTS: Positive associations between mother-daughter body mass index (BMI) and fat mass were observed at ages 6 to 7 (BMI: ß = .29 SD/SD, 95% CI = .10, .48; fat mass ß = .27 SD/SD, 95% CI = .05, .48) and 8 to 9 years (BMI: ß = .33 SD/SD, 95% CI = .13, .54; fat mass ß = .31 SD/SD, 95% CI = .12, .49), with similar associations at age 4 years but bounding the 95% CI. The mother-son, father-son, and father-daughter associations for BMI and fat mass were weaker at each of the ages studied. CONCLUSION: A strong association between the fat mass of mothers and their daughters but not their sons was observed. In contrast, father-offspring body composition associations were not evident. The dimorphic parent-offspring effects suggest particular attention should be given to early prevention of unfavorable body composition in girls born to mothers with excess adiposity.

Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: a retrospective cohort study.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common. AIM: To determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine. DESIGN AND SETTING: Two-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK. METHOD: Patients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality. RESULTS: Of 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities. CONCLUSION: Persistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored.

Characterising risk of non-steroidal anti-inflammatory drug-related acute kidney injury: a retrospective cohort study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. AIM: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. DESIGN & SETTING: Retrospective 2-year closed-cohort study. METHOD: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. RESULTS: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. CONCLUSION: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered.

Lupus, vaccinations and COVID-19: What we know now.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services, with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Patients with systemic lupus erythematosus (SLE) are at increased risk of viral infections, and recent data suggests they may be at an increased risk of poor outcomes with COVID-19. This may be particularly true for those on rituximab or high dose steroids. A huge international effort from the scientific community has so far resulted in the temporary authorisation of three vaccines which offer protection against SARS-CoV-2, with over 30 other vaccines being evaluated in ongoing trials. Although there has historically been concern that vaccines may trigger disease flares of SLE, there is little convincing evidence to show this. In general lupus patients appear to gain good protection from vaccination, although there may be reduced efficacy in those with high disease activity or those on immunosuppressive therapies, such as rituximab or high dose steroids. Recent concerns have been raised regarding rare clotting events with the AstraZeneca/Oxford vaccine and it is currently unknown whether this risk is higher for those patients with secondary antiphospholipid syndrome. With the possibility of annual COVID vaccination programmes in the future, prospective data collection and registries looking at the effect of vaccination on SLE disease control, the incidence of COVID-19 in SLE patients and severity of COVID-19 disease course would all be useful. As mass vaccination programmes begin to roll out across the world, we assess the evidence of the use of vaccines in SLE patients and in particular vaccines targeting SARS-CoV-2.

Rheumatoid Arthritis: The Impact of Mental Health on Disease: A Narrative Review.

Over 60% of rheumatoid arthritis (RA) patients achieve a good response after 12 months of treatment when following the European league against rheumatism (EULAR) guidelines for treatment. However, almost half of patients still suffer from moderate to severe disease activity despite this. In addition, mental health problems may remain despite reduced measures of inflammation systemically and within joints. Depression is two times more common in RA patients than in the general population, and intriguingly a bi-directional relationship with RA has been shown in cross-sectional studies. Chronic inflammation impairs the physiological responses to stress including effective coping behaviours, resulting in depression, which leads to a worse long-term outcome in RA. In RA patients, the pain score is not always solely related to inflammatory arthritis and immunological disease activity by Bak et al. (Patient Prefer Adherence 13:223-231, [1]). Non-inflammatory pain secondary to anxiety, depression, sleep disturbance and the psychosocial situation needs to be considered whilst fibromyalgia, mechanical pain and neuropathic pain can also contribute to overall pain scores by Chancay et al. (Women's Midlife Health 5:3, [2]). Hence, the UK National Institute for Health and Care Excellence (NICE) guideline for the management of RA included psychological interventions for fatigue, low mood and social well-being (NICE NG100, 2018) [3], and the NICE clinical guidelines (CG91) [4] suggest managing mental health and depression in chronic medical conditions to improve treatment outcomes. This is a narrative review of the impact of mental health on RA disease activity in terms of patient-reported outcomes (PROs).

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory condition that affects 1% of the global population. RA can cause inflammation and damage to the joints. It can also present with extra-articular manifestations, affecting other major organs in the body. RA patients are more prone to have anxiety, depression and cognitive impairment compared to the general healthy population. Those mental health conditions contribute to less responsiveness to treatment and higher disease activity in RA mainly due to fatigue and bodily pain. Medications used in RA can improve anxiety and depression to a certain extent but not completely. Therefore, it is important to determine the most appropriate tool to monitor mental health well-being and quality of life (QoL) of RA patients in rheumatology outpatient clinics to optimise the care of the RA patients.

Identifying rheumatic disease patients at high risk and requiring shielding during the COVID-19 pandemic.

Rheumatology teams care for patients with diverse, systemic autoimmune diseases who are often immunosuppressed and at high risk of infections. The current COVID-19 pandemic has presented particular challenges in caring for and managing this patient group. The office of the chief medical officer (CMO) for England contacted the rheumatology community to provide expert advice on the identification of extremely vulnerable patients at very high risk during the COVID-19 pandemic who should be 'shielded'. This involves the patients being asked to strictly self-isolate for at least 12 weeks with additional funded support provided for them to remain at home. A group of rheumatologists (the authors) have devised a pragmatic guide to identifying the very highest risk group using a rapidly developed scoring system which went live simultaneous with the Government announcement on shielding and was cascaded to all rheumatologists working in England.

Rheumatoid arthritis in the elderly: Characteristics and treatment considerations.

The elderly rheumatoid arthritis (RA) population consists of both elderly-onset RA that manifests after the age of 60 and individuals diagnosed with RA early in life who age naturally to become members of this group. The elderly RA population is expanding due to both increased life expectancy and an increased incidence of elderly onset RA. Elderly onset RA seems to have a characteristic clinical pattern and perhaps biological profile different to that of early onset RA. The management of RA in elderly patients can be challenging, as robust treat-to-target approaches must be balanced against the adverse events due to increased comorbidities in old age. This produces a tendency to prefer less aggressive treatment in elderly RA patients in clinical practice. Despite the concerns about adverse events, there is limited evidence on the best way to approach RA in this population, as elderly patients are often not well presented in the clinical trials. Herein, we review the literature to assess the efficacy and safety of RA therapies in this age group. We then suggest a tailored approach that can be adopted in clinical practice, based on the disease severity and risk profiles of elderly RA patients.

Amongst patients taking biologic therapies for axial spondyloarthritis, which factors are associated with work non-participation?

BACKGROUND: Axial spondyloarthritis (axSpA) frequently presents during working age and therefore impacts work participation. Biologic therapies have demonstrated a positive impact on work-related outcomes in clinical trials but real world data are limited. Therefore, we investigated the prevalence and predictors of work impairment and disability among axSpA patients attending a biologic therapy clinic. METHODS: This was a single-centre, cross-sectional study of patients with axSpA treated with biologic therapy. Work participation was assessed with the Work Productivity and Activity Impairment (WPAI) Questionnaire. Work outcomes (presenteeism, absenteeism, health-related job loss) were compared for gender, time since diagnosis, smoking status and disease outcome measures. RESULTS: Data were available for 165 patients (mean age 47.6 years, 75% male, 21% current smokers). Mean time since diagnosis was 15.5 years and mean duration of biologic therapy 4.7 years; 19/165 (11.5%) were on a tapered-dose regimen. Occupational data were available for 144 patients amongst whom 101 (70.1%) were either currently employed or in full time education. Of those eligible to work, 17/118 (14.4%) reported inability to work due to their axSpA. Amongst those in employment, 10.8% reported absenteeism due to axSpA in the week prior to their clinic visit (mean hours missed = 13). The mean work productivity impairment was 23%. Higher disease activity (BASDAI) and markers of global health, quality of life and pain, (BAS-G, ASQoL and spinal pain VAS) were associated with axSpA related job loss, absenteeism and presenteeism. CONCLUSIONS: In this group of axSpA patients on biologic therapy (mean age 47.6 years), almost 1 in 6 (14.4%) reported axSpA related job loss. Poor work outcomes: axSpA-related work disability, absenteeism and presenteeism were associated with poorer scores for patient-reported disease outcome measures. Strategies for enhancing work productivity should be directed towards those patients at risk of poor work outcomes. More data are needed including details of the types of work that are most difficult with axSpA.

Placental Size Is Associated Differentially With Postnatal Bone Size and Density.

We investigated relationships between placental size and offspring adolescent bone indices using a population-based, mother-offspring cohort. The Avon Longitudinal Study of Parents and Children (ALSPAC) recruited pregnant women from the southwest of England between 1991 and 1993. There were 12,942 singleton babies born at term who survived at least the first 12 months. From these, 8933 placentas were preserved in formaldehyde, with maternal permission for their use in research studies. At the approximate age of 15.5 years, the children underwent a dual-energy X-ray absorptiometry (DXA) scan (measurements taken of the whole body minus head bone area [BA], bone mineral content [BMC], and areal bone mineral density [aBMD]). A peripheral quantitative computed tomography (pQCT) scan (Stratec XCT2000L; Stratec, Pforzheim, Germany) at the 50% tibial site was performed at this visit and at approximately age 17.7 years. In 2010 a sample of 1680 placentas were measured and photographed. To enable comparison of effect size across different variables, predictor and outcome variables were standardized to Z-scores and therefore results may be interpreted as partial correlation coefficients. Complete placental, DXA, and pQCT data were available for 518 children at age 15.5 years. After adjustment for gender, gestational age at birth, and age at time of pQCT, the placental area was positively associated with endosteal circumference (ß [95% CI]: 0.21 [0.13, 0.30], p < 0.001), periosteal circumference (ß [95% CI]: 0.19 [0.10, 0.27], p < 0.001), and cortical area (ß [95% CI]: 0.10 [0.01, 0.18], p = 0.03), and was negatively associated with cortical density (ß [95% CI]: -0.11 [-0.20, -0.03], p = 0.01) at age 15.5 years. Similar relationships were observed for placental volume, and after adjustment for additional maternal and offspring covariates. These results suggest that previously observed associations between placental size and offspring bone development persist into older childhood, even during puberty, and that placental size is differentially related to bone size and volumetric density. © 2016 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

Are there dangers in biologic dose reduction strategies?

Biologic dose reduction strategies, for patients with inflammatory rheumatic diseases, have been assessed in multiple studies to assess outcomes compared to ongoing maintenance dosing. Whilst cessation in established disease usually leads to disease flare, dose tapering approaches for those achieving low disease activity often appear to be successful in the short term. However, tapering can be associated with a higher risk of losing disease control and rates of recapture of disease control using the original biologic dose vary between studies. Over relatively short periods of follow-up, a number of studies have shown no statistical difference in radiographic progression in patients tapering or discontinuing biologics. However, a Cochrane review found that radiographic and functional outcomes may be worse after TNF inhibitor discontinuation, and over long-term disease follow-up flares have been associated with radiographic progression and worse patient reported outcomes. To date, no studies of biological therapy dose reduction have specifically investigated the risk of increased immunogenicity or the effects on cardiovascular risk and other co-morbidities, although these remain important potential risks. In addition, whether there are greater dangers in certain dose reduction approaches such as a reduction in dose at the same frequency or a spacing of doses is not established.

Does combined clinical and ultrasound assessment allow selection of individuals with rheumatoid arthritis for sustained reduction of anti-tumor necrosis factor therapy?

OBJECTIVE: To investigate whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti-tumor necrosis factor (anti-TNF) therapies. METHODS: As part of a real-world approach, patients with RA receiving anti-TNF therapies were reviewed in a dedicated biologic therapy clinic. Patients not taking oral corticosteroids with both Disease Activity Score in 28 joints (DAS28) remission (≤2.6) and absent synovitis on power Doppler US (PDUS 0) for >6 months were invited to reduce their anti-TNF therapy dose by one-third. RESULTS: Between January 2012 and February 2014, a total of 70 patients underwent anti-TNF dose reduction. Combined DAS28 and PDUS remission was maintained by 96% of patients at 3 months followup, 63% at 6 months, 37% at 9 months, and 34% at 18 months followup. However, 88% of patients maintained at least low disease activity (LDA) with DAS28 <3.2 and PDUS ≤1 at 6 months. The addition of PDUS identified 8 patients (25% of those that flared) in DAS28 remission, with subclinically active disease. Those who maintained dose reduction were more likely to be rheumatoid factor (RF) negative (46% versus 17%; P = 0.03) and have lower DAS28 scores at biologic therapy initiation (5.58 versus 5.96; P = 0.038). CONCLUSION: Combined clinical and US assessment identifies individuals in remission who may be suitable for anti-TNF dose reduction and enhances safe monitoring for subclinical disease flares. Despite longstanding severe RA, a subset of our cohort sustained prolonged DAS28 and PDUS remission. LDA at biologic therapy initiation and RF status appeared predictive of sustained remission.

Vitamin D supplementation in pregnancy: a systematic review.

BACKGROUND: It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved. OBJECTIVES: To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective? METHODS: We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers. SUBJECTS: pregnant women or pregnant women and their offspring. EXPOSURE: either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). OUTCOMES: offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis. RESULTS: Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5. LIMITATIONS: Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition. CONCLUSIONS: The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001426. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Vitamin D and the postmenopausal population.

Vitamin D, a hormone critical to the body's maintenance of serum calcium and phosphorus concentrations, is currently the subject of much scientific interest. Low levels of vitamin D have been observed in many populations and epidemiological studies have suggested a link between this biochemical state and a range of diseases, such as cancer, diabetes and multiple sclerosis. While the consequence of vitamin D deficiency is well documented for bone (rickets and osteomalacia), with mixed findings relating to falls and fractures, a causal link between vitamin D deficiency and these wider health outcomes has not been established. If these relationships were found to be causal, the morbidity and mortality resulting from low levels of vitamin D could be substantial; the current evidence base, however, most robustly supports the assessment of serum 25(OH)-vitamin D in the context of specific symptoms, low bone mineral density or biochemical abnormalities, rather than as an entity to treat in its own right or as the basis for a population-wide screening programme.

Session 2: Other diseases: Dietary management of osteoporosis throughout the life course.

Osteoporosis-related fractures have a major impact on health at the individual and societal levels, through associated morbidity and increased mortality. Up to 50% of women and 20% of men at age 50 years may have a fragility fracture in their remaining lifetimes. Nutrition is important throughout the life course. Thus, adequate Ca and vitamin D intake has been shown to reduce risk of fracture in old age. Other factors such as protein and vitamin K may also be important, although the evidence here is less strong. In childhood Ca or vitamin D supplementation trials have demonstrated modest short-term increases in bone mass, but the long-term implications have not been established. Over recent years it has become apparent that maternal nutrition may have critical and far-reaching persistent consequences for offspring health. Thus, reduced maternal fat stores and low levels of circulating 25-hydroxyvitamin D in pregnancy are associated with reduced bone mass in the offspring; placental Ca transport may be key to these relationships. Wider maternal dietary patterns have also been shown to predict offspring bone mass. These data suggest that an interventional approach aimed at specific micronutrients, such as vitamin D, should be complemented by general optimisation of the mother's diet and lifestyle in order to maximise intrauterine bone mineral accrual and postnatal skeletal growth and thus reduce the burden of osteoporotic fractures in future generations.

Epidemiology of osteoporosis.

Osteoporosis represents a major public health problem through its association with fragility fractures. All osteoporotic fractures increase patient morbidity; however, fractures of the hip and vertebrae are also linked with significant mortality. The public health burden of osteoporotic fracture is likely to rise in future generations, due in part to an increase in life expectancy. Understanding the epidemiology of this disease is therefore essential in trying to develop strategies to help reduce this load. This chapter will review the epidemiology of osteoporosis, including the relationship between low bone mass and fracture. It will review the epidemiology of fractures, concentrating on the sites where the majority of age-related fractures occur. Finally it will discuss new developments in the assessment of fracture risk.