Lower blood folate levels have been associated with depression in cross-sectional surveys, but no studies have examined the relationship prospectively to determine whether the relationship is causal. We designed a follow-up study to examine whether lower blood folate predicts incident depressive symptoms.
Women aged 20 to 34 years registered in general practices in Southampton, UK were asked to participate. Baseline assessment included the general health questionnaire (GHQ-12) measure of anxiety and depression, and socioeconomic factors, diet, smoking, and alcohol intake. Two years later participants’ general practice (GP) records were examined for evidence of incident symptoms of depression.
At baseline 5051 women completed the GHQ-12 and had red cell folate levels measured, of whom 1588 (31.4%) scored above the threshold for case level symptoms of anxiety and depression on the GHQ-12. Two years later GP records for 3996 (79.1%) were examined, but 1264 with baseline evidence of depression were excluded from follow-up analysis. Incident depressive symptoms were recorded for 307 (11.2%) of the remaining 2732. Lower red cell folate levels were associated with caseness on the GHQ-12 (adjusted prevalence ratio 0.99 per 100nmol/l red cell folate, 95% CI 0.98 to 1.00). No relationship was found between red cell folate levels and incident depressive symptoms over two years (adjusted hazard ratio 0.99 (95%CI: 0.96 to 1.02).
Low folate levels were not associated with subsequent depressive symptoms. This suggests that lower red cell folate levels may be a consequence rather than a cause of depressive symptoms.
Investigators have suggested a link between birth weight and both hand and lumbar spine osteoarthritis (OA). In this study, we sought to extend these observations by investigating relationships between growth in early life, and clinical and radiological diagnoses of OA at the hand, knee and hip, among participants from the Hertfordshire Cohort Study (HCS).
Data were available for 222 men and 222 women. Clinical OA was defined based on American College of Rheumatology (ACR) criteria. Radiographs were taken of the knees and hips, and graded for the presence of osteophytes and overall Kellgren and Lawrence (KL) score.
Lower weight at year one was associated with higher rates of clinical hand OA (OR 1.396, 95% CI 1.05, 1.85, p=0.021). Individuals with lower birth weights were more likely to have hip osteophytes, (OR 1.512, 95% CI 1.14, 2.00, p=0.004) and this remained robust after adjustment for confounders. Furthermore, a low weight at one year was also associated with a higher osteophyte number in the lateral compartment of the knee, after adjustment for confounders (OR 1.388, 95% CI 1.01, 1.91 p=0.043).
We have found further evidence of a relationship between early life factors and adult OA. These findings accord with previous studies.
Osteoarthritis; Bone; Programming; Birth weight
Supplemental Digital Content is available in the text.
High blood pressure is a major contributor to the global burden of disease and discovering novel causal pathways of blood pressure regulation has been challenging. We tested blood pressure associations with 280 fasting blood metabolites in 3980 TwinsUK females. Survival analysis for all-cause mortality was performed on significant independent metabolites (P<8.9×10−5). Replication was conducted in 2 independent cohorts KORA (n=1494) and Hertfordshire (n=1515). Three independent animal experiments were performed to establish causality: (1) blood pressure change after increasing circulating metabolite levels in Wistar–Kyoto rats; (2) circulating metabolite change after salt-induced blood pressure elevation in spontaneously hypertensive stroke-prone rats; and (3) mesenteric artery response to noradrenaline and carbachol in metabolite treated and control rats. Of the15 metabolites that showed an independent significant association with blood pressure, only hexadecanedioate, a dicarboxylic acid, showed concordant association with blood pressure (systolic BP: β [95% confidence interval], 1.31 [0.83–1.78], P=6.81×10−8; diastolic BP: 0.81 [0.5–1.11], P=2.96×10−7) and mortality (hazard ratio [95% confidence interval], 1.49 [1.08–2.05]; P=0.02) in TwinsUK. The blood pressure association was replicated in KORA and Hertfordshire. In the animal experiments, we showed that oral hexadecanedioate increased both circulating hexadecanedioate and blood pressure in Wistar–Kyoto rats, whereas blood pressure elevation with oral sodium chloride in hypertensive rats did not affect hexadecanedioate levels. Vascular reactivity to noradrenaline was significantly increased in mesenteric resistance arteries from hexadecanedioate-treated rats compared with controls, indicated by the shift to the left of the concentration–response curve (P=0.013). Relaxation to carbachol did not show any difference. Our findings indicate that hexadecanedioate is causally associated with blood pressure regulation through a novel pathway that merits further investigation.
blood pressure; fatty acid synthases; hypertension; metabolomics; mortality
Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates.
Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10−8) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10−14). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10−6 also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
During growth, severe vitamin D deficiency in childhood can result in symptomatic hypocalcaemia and rickets. Despite the suggestion from some studies of a secular increase in the incidence of rickets, this observation may be driven more by changes in population demographics than a true alteration to age, sex and ethnicity-specific incidence rates; indeed rickets remains uncommon overall and is rarely seen in fair-skinned children. Additionally, the impact of less severe vitamin D deficiency and insufficiency has received much interest in recent years, and in this review we consider the evidence relating vitamin D status to fracture risk and bone mineral density (BMD) in childhood and adolescence. We conclude that there is insufficient evidence to support the suggestion that low serum 25-hydroxyvitamin D [25(OH)D] increases childhood fracture risk. Overall, the relationship between 25(OH)D and BMD is inconsistent across studies and across skeletal sites within the same study; however there is evidence to suggest that vitamin D supplementation in children with the lowest levels of 25(OH)D might improve BMD. High quality randomised trials are now required to confirm this benefit.
vitamin D; rickets; bone mineral density; fracture; childhood
The growing recognition of sarcopenia, the age-related loss of skeletal muscle mass and function, has highlighted the need to understand more about its etiology. Declines in muscle mass and strength are expected aspects of aging, but there is significant variability between individuals in rates of loss. Although some of these differences can be explained by fixed factors, such as sex, much of the remaining variation is unexplained. This has led to increasing interest in the influence of adult lifestyle, particularly in the effects of modifiable factors such as physical activity and diet, and in identifying intervention opportunities both to prevent and manage sarcopenia. A number of trials have examined the separate effects of increased exercise or dietary supplementation on muscle mass and physical performance of older adults, but less is known about the extent to which benefits of exercise training could be enhanced when these interventions are combined. In a comprehensive review of the literature, we consider 17 studies of older adults (≥65 years) in which combined nutrition and exercise interventions were used to increase muscle strength and/or mass, and achieve improvements in physical performance. The studies were diverse in terms of the participants included (nutritional status, degree of physical frailty), supplementation strategies (differences in nutrients, doses), exercise training (type, frequency), as well as design (duration, setting). The main message is that enhanced benefits of exercise training, when combined with dietary supplementation, have been shown in some trials – indicating potential for future interventions, but that existing evidence is inconsistent. Further studies are needed, particularly of exercise training combined with dietary strategies that increase intakes of a range of nutrients, as well as bioactive non-nutrients, to provide the evidence on which public health and clinical recommendations can be based.
sarcopenia; diet; exercise; intervention
Aims and objectives
To determine the feasibility and acceptability of using trained volunteers as mealtime assistants for older hospital inpatients.
Poor nutrition among hospitalised older patients is common in many countries and associated with poor outcomes. Competing time pressures on nursing staff may make it difficult to prioritise mealtime assistance especially on wards where many patients need help.
Mixed methods evaluation of the introduction of trained volunteer mealtime assistants on an acute female Medicine for Older People ward in a teaching hospital in England.
A training programme was developed for volunteers who assisted female inpatients aged 70 years and over on weekday lunchtimes. The feasibility of using volunteers was determined by the proportion recruited, trained, and their activity and retention over 1 year. The acceptability of the training and of the volunteers’ role was obtained through interviews and focus groups with 12 volunteers, 9 patients and 17 nursing staff.
59 potential volunteers were identified: 38 attended a training session of whom 29 delivered mealtime assistance, including feeding, to 3,911 (76%) ward patients during the year (mean duration of assistance 5.5 months). The volunteers were positive about the practical aspects of training and on-going support provided. They were highly valued by patients and ward staff and have continued to volunteer.
Volunteers can be recruited and trained to help acutely unwell older female inpatients at mealtimes, including feeding. This assistance is sustainable and is valued.
Relevance to clinical practice
This paper describes a successful method for recruitment, training and retention of volunteer mealtime assistants. It includes a profile of those volunteers who provided the most assistance, details of the training programme and role of the volunteers, and could be replicated by nursing staff in other healthcare units.
Nutrition; older; hospital; volunteer; mealtime assistance; nurses; nursing
The publication outcomes of the abstracts presented during the ECCEO-IOF 2011 reflect a high research productivity, support the robustness of the selection process conducted by the Scientific Advisory Committee and suggest that IOF-ESCEO WCO is successful in its mission to promote and disseminate research.
Background and Objective
The European (now World) Congress on Osteoporosis, Osteoarthritis and Musculo-Skeletal Diseases (IOF-ESCEO WCO, formerly ECCEO-IOF) is the largest worldwide event fully dedicated to the clinical, epidemiological, translational and economic aspects of bone, joint and muscle diseases. The role of the Scientific Advisory Committee is to select abstracts for oral communication or poster presentation based on a short summary of the research. The aim of the present survey was to determine the publication rate in international peer reviewed journals of abstracts accepted at the IOF-ESCEO WCO 2011 Meeting (formerly ECCEO-IOF11), the relationship, if any, between the presentation format of the abstract and its subsequent full publication and the impact factor of the journal in which research was published.
Of 619 abstracts accepted at the 2011 ECCEO-IOF11 annual meeting, 45 were accepted for oral communication and 574 accepted for poster presentation. In the subsequent 3 years (2011–2014), 191 abstracts were published as a full-length manuscript (30.9 %). The publication rate was significantly higher for oral communications (75.6 %) than for poster presentations (27.4 %; p < 0.0001). Publications derived from oral communications were published in journals with a higher impact factor (8.3 ± 10.1) than those arising from poster presentations (4.0 ± 2.3; p < 0.0001), but there was no difference in the time to publication (OC 16.3 [IQR 8.4–23.3] months vs PP 11.3 [IQR 5.3–21.4]; p = 0.14).
These results indicate a high research productivity and an appropriate selection of oral communication by the Scientific Advisory Committee of ESCEO-IOF.
Publication outcomes; ECCEO-IOF Meeting; Oral communication; Poster; Presentation format
National and international guidance emphasizes the need for hospitals to have effective secondary fracture prevention services, to reduce the risk of future fractures in hip fracture patients. Variation exists in how hospitals organize these services, and there remain significant gaps in care. No research has systematically explored reasons for this to understand how to successfully implement these services. The objective of this study was to use extended Normalization Process Theory to understand how secondary fracture prevention services can be successfully implemented.
Forty-three semi-structured interviews were conducted with healthcare professionals involved in delivering secondary fracture prevention within 11 hospitals that receive patients with acute hip fracture in one region in England. These included orthogeriatricians, fracture prevention nurses and service managers. Extended Normalization Process Theory was used to inform study design and analysis.
Extended Normalization Process Theory specifies four constructs relating to collective action in service implementation: capacity, potential, capability and contribution. The capacity of healthcare professionals to co-operate and co-ordinate their actions was achieved using dedicated fracture prevention co-ordinators to organize important processes of care. However, participants described effective communication with GPs as challenging. Individual potential and commitment to operationalize services was generally high. Shared commitments were promoted through multi-disciplinary team working, facilitated by fracture prevention co-ordinators. Healthcare professionals had capacity to deliver multiple components of services when co-ordinators ‘freed up’ time. As key agents in its intervention, fracture prevention coordinators were therefore indispensable to effective implementation.
Aside from difficulty of co-ordination with primary care, the intervention was highly workable and easily integrated into practice. Nevertheless, implementation was threatened by under-staffed and under-resourced services, lack of capacity to administer scans and poor patient access. To ensure ongoing service delivery, the contributions of healthcare professionals were shaped by planning, in multi-disciplinary team meetings, the use of clinical databases to identify patients and define the composition of clinical work and monitoring to improve clinical practice.
Findings identify and describe elements needed to implement secondary fracture prevention services successfully. The study highlights the value of Normalization Process Theory to achieve comprehensive understanding of healthcare professionals’ experiences in enacting a complex intervention.
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-015-0243-z) contains supplementary material, which is available to authorized users.
Implementation; Normalization Process Theory; Qualitative research; Osteoporosis; Fragility fracture; Hip fracture
Epidemiological studies of knee osteoarthritis (OA) have often used a radiographic definition. However, the clinical syndrome of OA is influenced by a broad range of factors in addition to the structural changes required for radiographic OA. Hence more recently several studies have adopted a clinical or self-reported approach to OA diagnosis rather than a radiographic approach. The aim of this study was to investigate agreement between radiographic OA and the clinical and self-reported diagnoses of OA.
Data were available for 199 men and 196 women in the Hertfordshire Cohort Study (HCS), UK. Participants completed a questionnaire detailing self-reported OA. Clinical OA was defined based on American College of Rheumatology (ACR) criteria. Knee radiographs were taken and graded for overall Kellgren and Lawrence (K&L) score.
The mean (standard deviation (SD)) age of study participants was 75.2 (2.6) years and almost identical proportions of men and women. The prevalence of knee OA differed depending on the method employed for diagnosis; 21% of the study participants self-reported knee OA, 18% of the participants had clinical knee OA and 42% of the participants had radiographic OA. Of those 72 study participants with a self-reported diagnosis of knee OA 52 (72%) had a radiographic diagnosis of knee OA, while 66% (39 out of 59) of study participants with clinical knee OA had a diagnosis of radiographic knee OA. However 58% of those participants diagnosed with radiographic OA did not have either self-reported knee OA or a diagnosis of clinical OA. Therefore in comparison with the radiographic definition of OA, both the clinical and self-report definitions had high specificity (91.5% & 91.5% respectively) and low sensitivity (24.5% and 32.7% respectively).
There is modest agreement between the radiographic, clinical and self-report methods of diagnosis of knee OA.
Osteoarthritis; Epidemiology; Agreement; Radiographic; Definition
Background and objectives
Chronic widespread pain (CWP) is a common disorder affecting ∼10% of the general population and has an estimated heritability of 48–52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP.
We conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain.
The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10−8). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7×10−7) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4×10−8, I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (p>7.7×10−4).
We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.
Gene Polymorphism; Fibromyalgis/Pain Syndromes; Epidemiology
Hip fractures are usually the result of low impact falls and underlying osteoporosis. Since the risk of further fractures in osteoporotic patients can be reduced by between 20 - 70% with bone protection therapy, the NHS is under an obligation to provide effective fracture prevention services for hip fracture patients to reduce risk of further fractures. Evidence suggests there is variation in service organisation. The objective of the study was to explore this variation in more detail by looking at the services provided in one region in England.
A questionnaire was designed which included questions around staffing, models of care and how the four components of fracture prevention (case finding, osteoporosis assessment, treatment initiation and adherence (monitoring) were undertaken. We also examined falls prevention services. Clinicians involved in the delivery of osteoporosis services at 11 hospitals in one region in England completed the questionnaire.
The service overview showed significant variation in service organisation across all aspects of care examined. All sites provided some form of case finding and assessment. However, interesting differences arose when we examined how these components were structured. Eight sites generally initiated treatment in an inpatient setting, two in outpatients and one in primary care. Monitoring was undertaken by secondary care at seven sites and the remainder conducted by GPs.
The variability in service provision was not explained by local variations in care need. Further work is now needed to establish how the variability in service provision affects key patient, clinical and health economic outcomes.
Epidemiology; Osteoporosis; fracture; hip; femur; fragility
Data on the incidence of symptomatic osteoarthritis (OA) are scarce. We estimated incidence of clinical hip, knee and hand osteoarthritis, and studied the effect of prevalent OA on joint-specific incident OA.
SIDIAP contains primary care records for >5 million people from Catalonia (Spain). Participants aged ≥40 years with an incident diagnosis of knee, hip or hand OA between 2006 and 2010 were identified using ICD-10 codes. Incidence rates and female-to-male Rate Ratios (RR) for each joint site were calculated. Age, gender and body mass index-adjusted Hazard Ratios (HR) for future joint-specific OA according to prevalent OA at other sites were estimated using Cox regression.
3,266,826 participants were studied for a median of 4.45 years. Knee and hip OA rates increased continuously with age, and female-to-male RRs were highest at age 70-75 years. In contrast, female hand OA risk peaked at age 60-64 years, and corresponding female-to-male RR was highest at age 50-55.
Adjusted HR for prevalent knee OA on risk of hip OA was 1.35 (99%CI 1.28-1.43); prevalent hip OA on incident knee OA 1.15 (1.08-1.23). Prevalent hand OA predicted both incident knee and hip OA: HR 1.20 (1.14-1.26) and 1.23 (1.13-1.34) respectively.
The effect of age is greatest in the elderly for knee and hip OA, but around the menopause for hand OA. OA clusters within individuals, with higher risk of incident knee and hip disease from prevalent lower limb and hand OA.
Concern over the sustainability of the National Health Service is often focussed on rising numbers of hospital admissions, particularly among older people. Hospital admissions are enumerated routinely by the Hospital Episode Statistics (HES) Service, but published data do not allow individual level service use to be explored. This study linked information on Hertfordshire Cohort Study (HCS) participants with HES inpatient data. with the objective of describing patterns and predictors of admissions among individuals.
2997 community-dwelling men and women aged 59-73 years completed a baseline HCS assessment between 1998 and 2004; HES and mortality data to 31/03/2010 were linked with the HCS database. This paper describes patterns of hospital use among the cohort at both the admission and individual person level.
The cohort experienced 8741 admissions; rates were 391 per 1000 person-years among men (95%CI 380, 402) and 327 among women (95%CI 316,338), p<0.0001 for gender difference. 1187 men (75%) and 981 women (69%) were admitted to hospital at least once; among these, median numbers of admissions were 3 in men (IQR 1,6) and 2 in women (IQR 1,5). 48% of those ever admitted had experienced an emergency admission and 70% had been admitted overnight.
It is possible to link routinely collected HES data with detailed information from a cohort study. Hospital admission is common among community dwelling ‘young-old’ men and women. These linked datasets will facilitate research into lifecourse determinants of hospital admission and inform strategies to manage demand on the National Health Service.
hospital admissions; older people; hospital episode statistics; data linkage; healthcare burden
Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.
Cross-sectional studies show that frailty is common in older people with cardiovascular disease. Whether older people at higher risk of developing cardiovascular disease are more likely to become frail is unclear. We used multinomial logistic regression to examine the prospective relation between Framingham cardiovascular disease risk scores and incidence of physical frailty or pre-frailty, defined according to the Fried criteria, in 1726 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing who had no history of cardiovascular disease at baseline. Men and women with higher Framingham cardiovascular risk scores were more likely to become frail over the 4-year follow-up period. For a standard deviation higher score at baseline, the relative risk ratio (95% confidence interval) for incident frailty, adjusted for sex and baseline frailty status, was 2.76 (2.18, 3.49). There was a significant association between Framingham cardiovascular risk score and risk of pre-frailty: 1.69 (1.46, 1.95). After further adjustment for other potential confounding factors the relative risk ratios for frailty and pre-frailty were 2.15 (1.68, 2.75) and 1.50 (1.29, 1.74) respectively. The associations were unchanged after excluding incident cases of cardiovascular disease. Separate adjustment for each component of the risk score suggested that no single component was driving the associations between cardiovascular risk score and incident pre-frailty or frailty. Framingham cardiovascular risk scores may be useful for predicting the development of physical frailty in older people. We now need to understand the biological mechanisms whereby cardiovascular risk increases the risk of frailty.
frailty; cardiovascular risk; cohort; longitudinal study
The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100 000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990–2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.
292 982 (95% UI 261 017–327 792) maternal deaths occurred in 2013, compared with 376 034 (343 483–407 574) in 1990. The global annual rate of change in the MMR was −0·3% (−1·1 to 0·6) from 1990 to 2003, and −2·7% (−3·9 to −1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290–2866) maternal deaths were related to HIV in 2013, 0·4% (0·2–0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1–1262·8) in South Sudan to 2·4 (1·6–3·6) in Iceland.
Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.
Bill & Melinda Gates Foundation.
Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol.
We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing).
Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males’ peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position.
This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.
Background: Early life may be a “critical period” when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects.
Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey).
Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m2) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry–assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003.
Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001).
Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.
adiposity; childhood obesity; early life; obesity; lifecourse; prevention
Cross-sectional studies show that higher blood concentrations of inflammatory markers tend to be more common in frail older people, but longitudinal evidence that these inflammatory markers are risk factors for frailty is sparse and inconsistent. We investigated the prospective relation between baseline concentrations of the inflammatory markers C-reactive protein (CRP) and fibrinogen and risk of incident frailty in 2,146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between CRP and fibrinogen and risk of incident frailty differed significantly by sex (p for interaction terms <0.05). In age-adjusted logistic regression analyses, for a standard deviation (SD) increase in CRP or fibrinogen, odds ratios (95 % confidence intervals) for incident frailty in women were 1.69 (1.32, 2.17) and 1.39 (1.12, 1.72), respectively. Further adjustment for other potential confounding factors attenuated both these estimates. For an SD increase in CRP and fibrinogen, the fully-adjusted odds ratio (95 % confidence interval) for incident frailty in women was 1.27 (0.96, 1.69) and 1.31 (1.04, 1.67), respectively. Having a high concentration of both inflammatory markers was more strongly predictive of incident frailty than having a high concentration of either marker alone. In men, there were no significant associations between any of the inflammatory markers and risk of incident frailty. High concentrations of the inflammatory markers CRP and fibrinogen are more strongly predictive of incident frailty in women than in men. Further research is needed to understand the mechanisms underlying this sex difference.
Frailty; Inflammation; C-reactive protein; Fibrinogen; Longitudinal study
To evaluate the use of an administered 80-item food frequency questionnaire (FFQ) to assess nutrient intake and diet quality in 3 year old children.
Frequency of consumption and portion size of the foods listed on the FFQ during the 3 months preceding the interview were reported by the child’s main caregiver; after the interview a 2-day prospective food diary (FD) was completed on behalf of the child. Nutrient intakes from FFQ and FD were estimated using UK food composition data. Diet quality was assessed from the FFQ and FD, according to the child’s scores for a principal component analysis-defined dietary pattern (‘prudent’ pattern), characterised by high consumption of fruit, vegetables, water and wholemeal cereals.
892 children aged 3 years in the Southampton Women’s Survey
Intakes of all nutrients assessed by FFQ were higher than FD estimates, but there was reasonable agreement in terms of ranking of children (range for Spearman rank correlations for energy-adjusted nutrient intakes, rs=0.41 to 0.59). Prudent diet scores estimated from the FFQ and FD were highly correlated (r=0.72). Some family and child characteristics appeared to influence the ability of the FFQ to rank children, most notably the number of child’s meals eaten away from home.
The FFQ provides useful information to allow ranking of children at this age with respect to nutrient intake and quality of diet, but may overestimate absolute intakes. Dietary studies of young children need to consider family and child characteristics that may impact on reporting error associated with an FFQ.
dietary assessment; young children; food frequency questionnaire
The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occurred since the Millennium Declaration.
To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bednets.
Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.
Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS’s estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.
Bill & Melinda Gates Foundation.
The relation between Dupuytren’s contracture and occupational exposure to hand-transmitted vibration (HTV) has frequently been debated. We explored associations in a representative national sample of workers with well-characterised exposure to HTV.
We mailed a questionnaire to 21,201 subjects aged 16 – 64 years, selected at random from the age-sex registers of 34 general practices in Great Britain and to 993 subjects chosen randomly from military pay records, asking about occupational exposure to 39 sources of HTV and about fixed flexion contracture of the little or ring finger. Analysis was restricted to men at work in the previous week. Estimates were made of average daily vibration dose (A(8) r.m.s.) over that week. Associations with Dupuytren’s contracture were estimated by Poisson regression, both for lifetime exposure to HTV and for exposures in the past week >A(8) of 2.8 ms−2 r.m.s.. Estimates of relative risk (Prevalence Ratio (PR)) were adjusted for age, smoking status, social class and certain manual activities at work.
In all 4,969 eligible male respondents supplied full information on the study variables. These included 72 men with Dupuytren’s contracture, 2,287 with occupational exposure to HTV, and 409 with A(8)>2.8 ms−2 in the past week. PRs for occupational exposure to HTV were elevated 1.5-fold. For men with an A(8)>2.8 ms−2 in the past week, the adjusted PR was 2.85 (95% confidence interval 1.37 to 5.97).
Our findings suggest that risk of Dupuytren’s contracture is more than doubled in men with high levels of weekly exposure to HTV.