A small placental surface at birth has been shown to be associated with the development of hypertension in later life. In this study we extend this observation by looking at the relationship between the number of placental cotyledons and blood pressure in childhood. Because the number of cotyledons is correlated with the surface area, we hypothesized that fewer cotyledons would be associated with higher blood pressure.
The Alspac study is a longitudinal study of 13,971 children born in Bristol. Their placentas were stored in formalin. We photographed the placentas of a sample of the children and related the number of maternal cotyledons to their blood pressure levels at age 9 years.
Contrary to our hypothesis, a greater number of maternal cotyledons was associated with higher blood pressure. Among boys, a greater number of cotyledons was associated with higher systolic and diastolic pressure but not with higher pulse pressure. Diastolic pressure rose by 2.2 mmHg (95% CI 0.6 to 3.7, p =0.007) for every 10 additional cotyledons. Among girls, a greater number of cotyledons was associated with higher systolic pressure and pulse pressure but not with higher diastolic pressure. Pulse pressure rose by 2.7 mmHg (1.1 to 4.3, p<0.001) for every 10 additional cotyledons. These associations were little changed by adjustment for placental surface area.
Our study has shown that a large number of maternal cotyledons is associated with raised blood pressure in childhood. The associations differ in the two sexes.
Alspac; maternal cotyledons; blood pressure
The reduced muscle mass and impaired muscle performance that defines sarcopenia in older individuals is associated with increased risk of physical limitation and a variety of chronic diseases. It may also contribute to clinical frailty.
A gradual erosion of quality of life (QoL) has been evidenced in these individuals, although much of this research has been done using generic QoL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities.
This review and report of an expert meeting, presents the current definitions of these geriatric syndromes (sarcopenia and frailty). It then briefly summarises QoL concepts and specificities in older populations, examines the relevant domains of QoL and what is known concerning QoL decline with these conditions. It calls for a clearer definition of the construct of disability and argues that a disease-specific QoL instrument for sarcopenia/frailty would be an asset for future research and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade off study could be appropriate.
Age; aging; muscle weakness; quality of life; malnutrition
Little is known about preschool-aged children’s levels of physical activity (PA) over the course of the day. Using time-stamped data, we describe the levels and patterns of PA in a population-based sample of four-year-old British children.
Within the Southampton Women’s Survey the PA levels of 593 4-year-old children (51% female) were measured using (Actiheart) accelerometry for up to 7 days. Three outcome measures: minutes spent sedentary (<20 cpm); in light (LPA: ≥20 – 399 cpm) and in moderate-to-vigorous activity (MVPA: ≥400 cpm) were derived. Average daily activity levels were calculated and then segmented across the day (morning, afternoon and evening). MVPA was log-transformed. Two-level random intercept models were used to analyse associations between activity level and temporal and demographic factors.
Children were active for 67% (mean 568.5 SD 79.5 minutes) of their daily registered time on average, with 88% of active time spent in LPA. All children met current UK guidelines of 180 minutes of daily activity. There were no differences in children’s average daily levels of sedentary activity and LPA by temporal and demographic factors: differences did emerge when activity was segmented across the day. Sex differences were largest in the morning, with girls being more sedentary, spending fewer minutes in LPA and 18% less time in MVPA than boys. Children were more sedentary and less active (LPA and MVPA) in the morning if they attended childcare full-time compared to part-time, and on weekend mornings compared to weekdays. The reverse was true for weekend afternoons and evenings. Children with more educated mothers were less active in the evenings. Children were less sedentary and did more MVPA on summer evenings compared to winter evenings.
Preschool-aged children meet current physical activity guidelines, but with the majority of their active time spent in LPA, investigation of the importance of activity intensity in younger children is needed. Activity levels over the day differed by demographic and temporal factors, highlighting the need to consider temporality in future interventions. Increasing girls’ morning activity and providing opportunities for daytime activity in winter months may be worthwhile.
We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of healthcare resources by decision-makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting, and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society with lifetime risks of any fracture of the hip, spine and forearm of around 40% for women and 13% for men. The economic impact is also large, for example, Europe’s six largest countries spent €31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision-makers in healthcare on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce healthcare resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision-makers efficiently allocate healthcare resources.
Burden of disease; cost-effectiveness; economic evaluation; health technology assessment; osteoporosis
We investigated relationships between early growth and proximal femoral geometry at age six years in a prospective population-based cohort, the Southampton Women’s Survey.
In 493 mother-offspring pairs we assessed linear size (individual measure dependent on developmental stage) using high-resolution ultrasound at 11, 19 and 34 weeks gestation (femur length) and at birth, 1, 2, 3, 4 and 6 years (crown-heel length/height). Standard deviation (SD)-scores were created and conditional regression modelling generated mutually independent growth variables. Children underwent hip DXA (Dual X-ray absorptiometry) at 6 years (Hologic Discovery, Hologic Inc., MA); hip structure analysis software yielded measures of geometry and strength.
There were strong associations between early linear growth and femoral neck section modulus (Z) at 6 years, with the strongest relationships observed for femur growth from 19-34 weeks gestation (β=0.26 cm3/SD, p<0.0001), and for height growth from birth to 1 year (β=0.25 cm3/SD, p<0.0001) and 1-2 years (β=0.33 cm3/SD, p<0.0001), with progressively weaker relationships over years 3 (β=0.23 cm3/SD, p=0.0002) and 4 (β=0.10 cm3/SD, p=0.18).
These results demonstrate that growth before age 3 years predicts proximal femoral geometry at six years old. The data suggest critical periods in which there is capacity for long term influence on the later skeletal growth trajectory.
To examine when, where and how fractures occur in postmenopausal women.
We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3.
Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68–86% of NHNV and 68–83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling.
In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.
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 and fibrinogen and risk of incident frailty in 2146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between C-reactive protein 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 increase in c-reactive protein 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 C-reactive protein 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
Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures.
Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis.
The ESCEO considers that the major challenges in DMOAD development are the absence of a precise definition of the disease, particularly in the early stages, and the lack of consensus on how to detect structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over time and should predict disease progression and outcomes such as joint replacement.
The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space narrowing >0.5 mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement. On-going research using techniques such as magnetic resonance imaging and biochemical markers may allow the identification of these patients earlier in the disease process.
magnetic resonance imaging; osteoarthritis; X-ray; responder; structure-modifying drug; pain
Against a backdrop of rising levels of obesity, we describe and estimate associations of body mass index (BMI), age and gender with time to revision for participants undergoing primary total hip (THR) or knee (TKR) replacement in the UK.
Population-based cohort study.
Routinely collected primary care data from a representative sample of general practices, including linked data on all secondary care events.
Population-based cohort study of 63 162 patients with THR and 54 276 with TKR in the UK General Practice Research Database between 1988 and 2011.
Primary and secondary outcomes
Risk of THR and TKR revision associated with BMI, age and gender, after adjusting for the competing risk of death.
The 5-year cumulative incidence rate for THR was 2.2% for men and 1.8% for women (TKR 2.3% for men, 1.6% for women). The adjusted overall subhazard ratio (SHR) for patients with THR undergoing subsequent hip revision surgery, with a competing risk of death, were estimated at 1.020 (95% CI 1.009 to 1.032) per additional unit (kg/m2) of BMI, 1.23 (95% CI 1.10 to 1.38) for men compared with women and 0.970 (95% CI 0.967 to 0.973) per additional year of age. For patients with TKR, the equivalent estimates were 1.015 (95% CI 1.002 to 1.028) for BMI; 1.51 (95% CI 1.32 to 1.73) for gender and 0.957 (95% CI 0.951 to 0.962) for age. Morbidly obese patients with THR had a 65.5% increase (95% CI 15.4% to 137.3%, p=0.006) in the subhazard of revision versus the normal BMI group (18.5–25). The effect for TKR was smaller (a 43.9% increase) and weaker (95% CI 2.6% to 103.9%, p=0.040).
BMI is estimated to have a small but statistically significant association with the risk of hip and knee revision, but absolute numbers are small. Further studies are needed in order to distinguish between effects for specific revision surgery indications.
Natural experimental studies are often recommended as a way of understanding the health impact of policies and other large scale interventions. Although they have certain advantages over planned experiments, and may be the only option when it is impossible to manipulate exposure to the intervention, natural experimental studies are more susceptible to bias. This paper introduces new guidance from the Medical Research Council to help researchers and users, funders and publishers of research evidence make the best use of natural experimental approaches to evaluating population health interventions. The guidance emphasises that natural experiments can provide convincing evidence of impact even when effects are small or take time to appear. However, a good understanding is needed of the process determining exposure to the intervention, and careful choice and combination of methods, testing of assumptions and transparent reporting is vital. More could be learnt from natural experiments in future as experience of promising but lesser used methods accumulates.
We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks’ gestation from ultrasound measurements in participants in the Southampton Women’s Survey. A total of 380 of the offspring underwent dual-energy X-ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19- to 34-week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19- to 34-week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks’ gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density.
EPIDEMIOLOGY; OSTEOPOROSIS; PROGRAMMING; DEVELOPMENTAL ORIGINS
Factors associated with parental awareness of children’s physical activity (PA) levels have not been explored in preschool-aged children. This paper investigates maternal awareness of preschool-aged children’s PA levels and determined correlates associated with maternal overestimation of PA.
Data from the Southampton Women’s Survey, a UK population-based study, were collected March 2006 through June 2009. Daily minutes of moderate-to-vigorous PA (MVPA) were derived using accelerometry in 478 4-year-old children. Mothers who were realistic or overestimated their child’s PA were identified. Log-binomial regression was used to analyse correlates of maternal overestimation of PA levels in children whose mothers perceived them to be active (n = 438).
40.8% of children were classified as inactive: 89.7% of these were perceived to be active by their mothers (over-estimators). These mothers were more likely to think their child sometimes lacked skills required to be physically active (RR (95% CI) = 1.29(1.03-1.63)) and their child was more likely to attend nursery full-time (RR = 1.53(1.14-2.04)). They were less likely to have older children at home (RR = 0.71(0.56-0.90)).
Almost 90% of mothers of inactive preschool-aged children perceive their child to be active. Nursery-school attendance and having older siblings at home may be important to consider when designing behavioural interventions to increase PA in preschool children.
Physical activity; Awareness; Preschool children
Obesity and asthma have increased in westernised countries. Maternal obesity may increase childhood asthma risk. If this relation is causal it may be mediated through factors associated with maternal adiposity, such as fetal development, pregnancy complications or infant adiposity. We investigated the relationships of maternal BMI and fat mass with childhood wheeze and examined the influences of infant weight gain and childhood obesity.
Maternal pre-pregnancy BMI and estimated fat mass (from skinfold thicknesses) were related to asthma, wheeze and atopy in 940 children. Transient or persistent/late wheeze was classified using questionnaire data collected at ages 6, 12, 24 and 36 months and 6 years. At 6 years, skin prick testing was conducted and exhaled nitric oxide and spirometry measured. Infant adiposity gain was calculated from skinfold thickness at birth and 6 months.
Greater maternal BMI and fat mass were associated with increased childhood wheeze (RR 1.08 per 5 kg m−2, p=0.006; RR 1.09 per 10 kg, p=0.003); these reflected associations with transient wheeze (RR 1.11, p=0.003; RR 1.13, p=0.002, respectively) but not with persistent wheeze or asthma. Infant adiposity gain was associated with persistent wheeze but not significantly. Adjusting for infant adiposity gain or BMI at 3 or 6 years did not reduce the association between maternal adiposity and transient wheeze. Maternal adiposity was not associated with offspring atopy, exhaled nitric oxide, or spirometry.
Greater maternal adiposity is associated with transient wheeze but not asthma or atopy, suggesting effects upon airway structure/function but not allergic predisposition.
adiposity; body mass index; obesity; asthma; allergic sensitisation
Detailed associations between physical activity (PA) subcomponents, sedentary time, and body composition in preschoolers remain unclear.
We examined the magnitude of associations between objectively measured PA subcomponents and sedentary time with body composition in 4-y-old children.
We conducted a cross-sectional study in 398 preschool children recruited from the Southampton Women’s Survey. PA was measured by using accelerometry, and body composition was measured by using dual-energy X-ray absorptiometry. Associations between light physical activity, moderate physical activity (MPA), vigorous physical activity (VPA), and moderate-to-vigorous physical activity (MVPA) intensity; sedentary time; and body composition were analyzed by using repeated-measures linear regression with adjustment for age, sex, birth weight, maternal education, maternal BMI, smoking during pregnancy, and sleep duration. Sedentary time and PA were also mutually adjusted for one another to determine whether they were independently related to adiposity.
VPA was the only intensity of PA to exhibit strong inverse associations with both total adiposity [P < 0.001 for percentage of body fat and fat mass index (FMI)] and abdominal adiposity (P = 0.002 for trunk FMI). MVPA was inversely associated with total adiposity (P = 0.018 for percentage of body fat; P = 0.022 for FMI) but only because of the contribution of VPA, because MPA was unrelated to fatness (P ≥ 0.077). No associations were shown between the time spent sedentary and body composition (P ≥ 0.11).
In preschoolers, the time spent in VPA is strongly and independently associated with lower adiposity. In contrast, the time spent sedentary and in low-to-moderate–intensity PA was unrelated to adiposity. These results indicate that efforts to challenge pediatric obesity may benefit from prioritizing VPA.
Previous studies suggest a link between depression, anxiety and cardiovascular disease (CVD). The aim of the study was to determine the relationship between depressive and anxiety symptoms and CVD in a population based cohort.
1,578 men and 1,417 women from the Hertfordshire Cohort Study were assessed for CVD at baseline and after 5.9±1.4 years. Depressive and anxiety symptoms were measured using the HADS Scale.
Baseline HAD-D score, but not HAD-A, was significantly associated with baseline plasma triglycerides, glucose and insulin resistance (men only) and HDL cholesterol (women only).
After adjustment for CVD risk factors, higher baseline HAD-D scores were associated with increased odds ratios for CVD (men: 1.162 [95% CI 1.096 - 1.231]; women: 1.107 [1.038 – 1.181]). Higher HAD-A scores associated with increased CVD in men only.
High HAD-D scores predicted incident CVD (adjusted OR 1.130 [1.034 - 1.235]), all-cause mortality (adjusted HR 1.081, [1.012 – 1.154]) and cardiovascular mortality (adjusted HR 1.109 [1.002 - 1.229]) in men but not in women.
The use of a self-report measure of depressive and anxiety symptoms, ‘healthy’ responder bias and the low number of cardiovascular events are all limitations.
Depressive and anxiety symptoms are commoner in people with CVD. These symptoms are independent predictors of CVD in men. Although HAD-D score was significantly associated with several cardiovascular risk factors, this did not fully explain the association between HAD-D and CVD.
Depression; anxiety; cardiovascular disease; epidemiology; population studies
To explore whether risk factors for neurophysiologically confirmed carpal tunnel syndrome (CTS) differ from those for sensory symptoms with normal median nerve conduction, and to test the validity and practical utility of a proposed definition for impaired median nerve conduction, we carried out a case–control study of patients referred for investigation of suspected CTS.
We compared 475 patients with neurophysiological abnormality (NP+ve) according to the definition, 409 patients investigated for CTS but classed as negative on neurophysiological testing (NP-ve), and 799 controls. Exposures to risk factors were ascertained by self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression.
NP+ve disease was associated with obesity, use of vibratory tools, repetitive movement of the wrist or fingers, poor mental health and workplace psychosocial stressors. NP-ve illness was also related to poor mental health and occupational psychosocial stressors, but differed from NP+ve disease in showing associations also with prolonged use of computer keyboards and tendency to somatise, and no relation to obesity. In direct comparison of NP+ve and NP-ve patients (the latter being taken as the reference category), the most notable differences were for obesity (OR 2.7, 95 % CI 1.9-3.9), somatising tendency (OR 0.6, 95% CI 0.4-0.9), diabetes (OR 1.6, 95% CI 0.9-3.1) and work with vibratory tools (OR 1.4, 95% CI 0.9-2.2).
When viewed in the context of earlier research, our findings suggest that obesity, diabetes, use of hand-held vibratory tools, and repeated forceful movements of the wrist and hand are causes of impaired median nerve function. In addition, sensory symptoms in the hand, whether from identifiable pathology or non-specific in origin, may be rendered more prominent and distressing by hand activity, low mood, tendency to somatise, and psychosocial stressors at work. These differences in associations with risk factors support the validity of our definition of impaired median nerve conduction.
Carpal tunnel syndrome; Nerve conduction; Case–control; Obesity; Vibration; Occupation; Psychosocial; Somatising tendency; Upper limb disorders
We have previously proposed that sensory nerve conduction (SNC) in the median nerve should be classed as abnormal when the difference between conduction velocities in the little and index fingers is > 8 m/s. In a prospective longitudinal study, we investigated whether this case definition distinguished patients who were more likely to benefit from surgical treatment.
We followed up 394 patients (response rate 56%), who were investigated by a neurophysiology service for suspected carpal tunnel syndrome. Information about symptoms, treatment and other possible determinants of outcome was obtained through questionnaires at baseline and after follow-up for a mean of 19.2 months. Analysis focused on 656 hands with numbness, tingling or pain at baseline. Associations of surgical treatment with resolution of symptoms were assessed by Poisson regression, and summarised by prevalence rate ratios (PRRs) and associated 95% confidence intervals (95% CIs).
During follow-up, 154 hands (23%) were treated surgically, and sensory symptoms resolved in 241 hands (37%). In hands with abnormal median SNC, surgery was associated with resolution of numbness, tingling and pain (PRR 1.5, 95% CI 1.0-2.2), and of numbness and tingling specifically (PRR 1.8, 95% CI 1.3-2.6). In contrast, no association was apparent for either outcome when median SNC was classed as normal.
Our definition of abnormal median SNC distinguished a subset of patients who appeared to benefit from surgical treatment. This predictive capacity gives further support to its validity as a diagnostic criterion in epidemiological research.
Carpal tunnel syndrome; Neurophysiology; Case definition; Validity; Surgery; Outcome
To inform the clinical management of patients with suspected carpal tunnel syndrome (CTS) and case definition for CTS in epidemiological research, we explored the relation of symptoms and signs to sensory nerve conduction (SNC) measurements.
Patients aged 20–64 years who were referred to a neurophysiology service for investigation of suspected CTS, completed a symptom questionnaire (including hand diagrams) and physical examination (including Tinel’s and Phalen’s tests). Differences in SNC velocity between the little and index finger were compared according to the anatomical distribution of symptoms in the hand and findings on physical examination.
Analysis was based on 1806 hands in 908 patients (response rate 73%). In hands with numbness or tingling but negative on both Tinel’s and Phalen’s tests, the mean difference in SNC velocities was no higher than in hands with no numbness or tingling. The largest differences in SNC velocities occurred in hands with extensive numbness or tingling in the median nerve sensory distribution and both Tinel’s and Phalen’s tests positive (mean 13.8, 95% confidence interval (CI) 12.6-15.0 m/s). Hand pain and thumb weakness were unrelated to SNC velocity.
Our findings suggest that in the absence of other objective evidence of median nerve dysfunction, there is little value in referring patients of working age with suspected CTS for nerve conduction studies if they are negative on both Tinel’s and Phalen’s tests. Alternative case definitions for CTS in epidemiological research are proposed according to the extent of diagnostic information available and the relative importance of sensitivity and specificity.
Epidemiology; Evidence-based medicine; Hand; Nerve compression syndromes; Wrist
Use of psychotropic drugs has been linked with an increased risk of fracture in older people, but there are indications that the conditions for which these drugs were prescribed may themselves influence fracture risk.
To investigate the relation between symptoms of anxiety and depression and risk of fracture in older people.
Prospective cohort study.
1087 men and 1050 women aged 59-73 years completed the Hospital Anxiety and Depression Scale (HADS). Data on incident fracture during an average follow-up period of 5.6 years was collected through interview and a postal questionnaire.
Compared to men with no or few symptoms of anxiety (score ≤7 on the HADS anxiety subscale), men with probable anxiety (score ≥11) had an increased risk of fracture: after adjustment for age and potential confounding factors, the odds ratio (OR) (95% confidence interval) was 4.03 (1.55, 10.5). Men with possible anxiety (score 8-10) did not have an increased risk of fracture: multivariate-adjusted OR was 1.04 (0.36, 3.03). There were no associations between levels of anxiety and fracture risk in women. Few men or women had probable depression at baseline (score ≥11 on the HADS depression subscale). Among men with possible depression (score 8-10) there was an increased risk of fracture that was of borderline significance: multivariate-adjusted OR 3.57 (0.99, 12.9). There was no association between possible depression and fracture risk in women.
High levels of anxiety in older men may increase their risk of fracture. Future research needs to replicate this finding in other populations and investigate the underlying mechanisms.
anxiety; depression; fracture
Osteoporotic fracture is associated with considerable morbidity and mortality in women throughout the world. However, significant variation in hip fracture rates among women from different nations have been observed, and are likely to represent a combination of real and apparent differences due to ascertainment bias. Higher rates are observed in Caucasian women, with lowest rates observed in black women and intermediate rates among Asian women. These differences are likely to represent a combination of genetic and environmental differences; for example, among European women, the highest fracture rates are observed in Scandinavian women where vitamin D insufficiency is common. In all groups, an expansion in absolute fracture numbers is anticipated due to demographic changes.
Osteoporosis; Fracture; Geographic; Variation; Women; Epidemiology
Systematic review is a powerful research tool which aims to identify and synthesize all evidence relevant to a research question. The approach taken is much like that used in a scientific experiment, with high priority given to the transparency and reproducibility of the methods used and to handling all evidence in a consistent manner.
Early career researchers may find themselves in a position where they decide to undertake a systematic review, for example it may form part or all of a PhD thesis. Those with no prior experience of systematic review may need considerable support and direction getting started with such a project. Here we set out in simple terms how to get started with a systematic review.
Advice is given on matters such as developing a review protocol, searching using databases and other methods, data extraction, risk of bias assessment and data synthesis including meta-analysis. Signposts to further information and useful resources are also given.
A well-conducted systematic review benefits the scientific field by providing a summary of existing evidence and highlighting unanswered questions. For the individual, undertaking a systematic review is also a great opportunity to improve skills in critical appraisal and in synthesising evidence.
Systematic review; Systematic review methods; Meta-analysis; Early career researchers; Evidence synthesis; Observational studies
To study the effects of age and dose of selective serotonin reuptake inhibitors (SSRI), trycyclic antidepressants (TCA) and anxiolytics/sedatives on fracture risk.
Subjects and methods
Case control study. From the Danish National Health Service, we identified 124,655 fracture cases and 373,962 age- and gender-matched controls. Crude odds ratios (OR) were estimated, and propensity score adjustment was used to minimize confounding by indication.
A higher risk of fractures was associated with an increasing dose of anxiolytics and sedatives; the highest excess risk was present in the age stratum below 40 years of age (p<0.01), and thereafter the excess risk of fractures declined with age. For SSRI, a growing excess risk of fractures was seen with both increasing dose and age. Regarding TCA, no particular trend with age was present. However, an increasing risk of fractures was associated with increasing TCA dose in the age group above 60 years. Finally, for other antidepressants no particular trend with age or dose was observed. In our data, a hospital diagnosis of depression or manic-depression was associated with fewer fractures.
Caution should be shown upon prescription of SSRI to older subjects. A hospital diagnosis of depression or manic-depression and thus potentially more severe disease was not a risk factor for fractures.
Selective serotonin reuptake inhibitors; tricyclic antidepressants; antidepressant; fracture