Sex differences in recovery of quality of life 12 months post-fracture in community-dwelling older adults: analyses of the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS).

In this study of 695 Australian older adults (aged ≥50 years), we found that men and women had a similar trajectory of health-related quality of life (HRQoL) recovery following fragility fracture at any skeletal site. These results provide us with critical knowledge that improves our understanding of health outcomes post-fracture. INTRODUCTION: Mortality is higher in men than that in women following a fragility fracture, but it is unclear whether recovery of patient-reported outcomes such as health-related quality of life (HRQoL) differs between sexes. This study aimed to identify sex differences in HRQoL recovery 12 months post-fracture. METHODS: Data were from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS). Participants recruited to AusICUROS were adults aged ≥50 years who sustained a fragility fracture. HRQoL was measured using the EQ-5D-3L at three time-points post-fracture: within 2 weeks (including pre-fracture recall) and at 4 and 12 months. Multivariate logistic regression analyses were undertaken, adjusting for confounders including age, education, income, and healthcare utilization post-fracture. RESULTS: Overall, 695 AusICUROS participants (536 women, 77.1%) were eligible for analysis with fractures at the hip (n = 150), distal forearm (n = 261), vertebrae (n = 61), humerus (n = 52), and other skeletal sites (n = 171). At the time of fracture, men were younger, reported a higher income, and were more likely to be employed, compared with women. For all fracture sites combined, there were no differences between men and women in recovery to pre-fracture HRQoL at 12-month follow-up (adjusted OR = 1.09; 95% CI: 0.75-1.61). When stratified by fracture site, no significant sex differences were seen for hip (OR = 1.02; 95% CI: 0.42-2.52), distal forearm (OR = 1.60; 95% CI: 0.68-3.78), vertebral (OR = 2.28; 95% CI: 0.61-8.48), humeral (OR = 1.62; 95% CI: 0.16-9.99), and other fractures (OR = 1.00; 95% CI: 0.44-2.26). CONCLUSION: Community-dwelling men and women who survived the 12 months following fragility fracture had a similar trajectory of HRQoL recovery at any skeletal site.

An outbreak of meticillin-resistant Staphylococcus aureus colonization in a neonatal intensive care unit: use of a case-control study to investigate and control it and lessons learnt.

AIM: To describe the investigation and management of a meticillin-resistant Staphylococcus aureus (MRSA) outbreak on a neonatal intensive care unit (NICU) and the lessons learnt. METHODS: This was an outbreak report and case-control study conducted in a 40-cot NICU in a tertiary referral hospital and included all infants colonized/infected with gentamicin-resistant MRSA. INTERVENTION: Standard infection-control measures including segregation of infants, barrier precautions, enhanced cleaning, assessment of staff practice including hand hygiene, and increased MRSA screening of infants were implemented. Continued MRSA acquisitions led to screening of all NICU staff. A case-control study was performed to assess staff contact with colonized babies and inform the management of the outbreak. FINDINGS: Eight infants were colonized with MRSA (spa type t2068), one of whom subsequently developed an MRSA bacteraemia. MRSA colonization was significantly associated with lower gestational age; lower birthweight and with being a twin. Three nurses were MRSA colonized but only one nurse (45) was colonized with MRSA spa type t2068. Multivariable logistic regression analysis identified being cared for by nurse 45 as an independent risk factor for MRSA colonization. CONCLUSIONS: Lack of accurate recording of which nurses looked after which infants (and when) made identification of the risk posed by being cared for by particular nurses difficult. If this had been clearer, it may have enabled earlier identification of the colonized nurse, avoiding subsequent cases. This study highlights the benefit of using a case-control study, which showed that most nurses had no association with colonized infants.

Diversity in fall characteristics hampers effective prevention: the precipitants, the environment, the fall and the injury.

Falls among the elderly are common and characteristics may differ between injurious and non-injurious falls. Among 887 older Australian women followed for 1.6 years, 32% fell annually. Only 8.5% resulted in fracture and/or hospital admission. The characteristics of those falls are indistinguishable from those not coming to medical attention. INTRODUCTION: The precipitants and environment of all falls occurring among a large cohort of older Caucasian women were categorised by injury status to determine if the characteristics differed between injurious and non-injurious falls. METHODS: Among 887 Australian women (70+ years), falls were ascertained using monthly postcard calendars and a questionnaire was administered for each fall. Hospital admissions and fractures were independently confirmed. RESULTS: All falls were reported for a mean observation time of 577 (IQR 546-607) days per participant, equating to a total 1400 person-years. Thirty-two percent fell at least once per year. The most common features of a fall were that the faller was walking (61%) at home (61%) during the day (88%) and lost balance (32%). Only 12% of all falls occurred at night. Despite no difference in the type of injury between day and night, the likelihood of being hospitalised from a fall at night was 4.5 times greater than that of a daytime fall with adjustment for injury type and participant age (OR 4.5, 95% CI 2.1, 9.5; p < 0.001). Of all falls, approximately one third were associated with no injury to the faller (31%), one third reported a single injury (37%) and one third reported more than one injury (32%). In 95% of falls, the faller was not admitted to hospital. Only 5% of falls resulted in fracture(s). CONCLUSIONS: Our findings demonstrate the significant diversity of precipitants and environment where falls commonly occur among older community-dwelling women. Falls resulting in fracture and/or hospital admission collectively represent 8.5% of all falls and their characteristics are indistinguishable from falls not coming to medical attention and incurring no apparent cost to the health system.

Physical health comorbidities in women with personality disorder: Data from the Geelong Osteoporosis Study.

BACKGROUND: Associations between common psychiatric disorders, psychotic disorders and physical health comorbidities are frequently investigated. The complex relationship between personality disorders (PDs) and physical health is less understood, and findings to date are varied. This study aims to investigate associations between PDs with a number of prevalent physical health conditions. METHODS: This study examined data collected from women (n=765;≥ 25 years) participating in a population-based study located in south-eastern Australia. Lifetime history of psychiatric disorders was assessed using the semi-structured clinical interviews (SCID-I/NP and SCID-II). The presence of physical health conditions (lifetime) were identified via a combination of self-report, medical records, medication use and clinical data. Socioeconomic status, and information regarding medication use, lifestyle behaviors, and sociodemographic information was collected via questionnaires. Logistic regression models were used to investigate associations. RESULTS: After adjustment for sociodemographic variables (age, socioeconomic status) and health-related factors (body mass index, physical activity, smoking, psychotropic medication use), PDs were consistently associated with a range of physical health conditions. Novel associations were observed between Cluster A PDs and gastro-oesophageal reflux disease (GORD); Cluster B PDs with syncope and seizures, as well as arthritis; and Cluster C PDs with GORD and recurrent headaches. CONCLUSIONS: PDs were associated with physical comorbidity. The current data contribute to a growing evidence base demonstrating associations between PDs and a number of physical health conditions independent of psychiatric comorbidity, sociodemographic and lifestyle factors. Longitudinal studies are now required to investigate causal pathways, as are studies determining pathological mechanisms.

The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men.

OBJECTIVE: Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men. METHODS: Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression. RESULTS: Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site). CONCLUSIONS: Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men.

Changes in quality of life associated with fragility fractures: Australian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (AusICUROS).

UNLABELLED: We investigated change in health-related quality of life due to fracture in Australian adults aged over 50 years. Fractures reduce quality of life with the loss sustained at least over 12 months. At a population level, the loss was equivalent to 65 days in full health per fracture. PURPOSE: We aimed to quantify the change in health-related quality of life (HRQoL) that occurred as a consequence of a fracture using the EQ-5D-3 L questionnaire. METHODS: Adults aged ≥50 years with a low to moderate energy fracture were recruited from eight study centres across Australia. This prospective study included an 18-month follow-up of participants recruited within 2 weeks of a fracture (hip, wrist, humerus, vertebral and ankle). Information collected at baseline and 4, 12 and 18 months included characteristics of participants such as income level, education and prior fracture status. At 12 months post-fracture, the cumulative loss of quality of life was estimated using multivariate regression analysis to identify the predictors of HRQoL loss. RESULTS: Mean HRQoL for all participants before fracture was 0.86, with wrist fracture having the highest pre-fracture HRQoL (0.90), while vertebral fracture had the lowest (0.80). HRQoL declined to 0.42 in the immediate post-fracture period. Only participants with a wrist, humerus or ankle fracture returned to their pre-fracture HRQoL after 18 months. An increased loss of HRQoL over 12 months was associated with HRQoL prior to the fracture, hospitalisation, education and fracture site. The multiple regression explained 30 % of the variation in the cumulative HRQoL loss at 12 months post-fracture for all fractures. CONCLUSION: Low to moderate energy fractures reduce HRQoL, and this loss is sustained for at least 12 months or, in the case of hip and spine fractures, at least 18 months. At a population level, this represents an average loss of 65 days in full health per fragility fracture. This significant burden reinforces the need for cost-effective fracture prevention strategies.

Validation of the continuous glucose monitoring sensor in preterm infants.

OBJECTIVE: Recent studies have highlighted the need for improved methods of monitoring glucose control in intensive care to reduce hyperglycaemia, without increasing the risk of hypoglycaemia. Continuous glucose monitoring is increasingly used in children with diabetes, but there are little data regarding its use in the preterm infant, particularly at extremes of glucose levels and over prolonged periods. This study aimed to assess the accuracy of the continuous glucose monitoring sensor (CGMS) across the glucose profile, and to determine whether there was any deterioration over a 7 day period. DESIGN: Prospectively collected CGMS data from the NIRTURE Trial was compared with the data obtained simultaneously using point of care glucose monitors. SETTING: An international multicentre randomised controlled trial. PATIENTS: One hundred and eighty-eight very low birth weight control infants. OUTCOME MEASURES: Optimal accuracy, performance goals (American Diabetes Association consensus), Bland Altman, Error Grid analyses and accuracy. RESULTS: The mean (SD) duration of CGMS recordings was 156.18 (29) h (6.5 days), with a total of 5207 paired glucose levels. CGMS data correlated well with point of care devices (r=0.94), with minimal bias. It met the Clarke Error Grid and Consensus Grid criteria for clinical significance. Accuracy of single readings to detect set thresholds of hypoglycaemia, or hyperglycaemia was poor. There was no deterioration over time from insertion. CONCLUSIONS: CGMS can provide information on trends in glucose control, and guidance on the need for blood glucose assessment. This highlights the potential use of CGMS in optimising glucose control in preterm infants.

Combining active farmer involvement with detailed farm data in Denmark: a promising method for achieving water framework directive targets?

The Water Framework Directive (WFD) encourages active involvement during its implementation, although no specific participatory methods are suggested, whilst implementing the target-oriented Directive will require detailed agri-environmental data at catchment and farm level. The paper is a case study of the Danish AGWAplan project, which actively involved farmers in the selection of measures to reduce diffuse nutrient pollution at farm and catchment level, thereby providing an example of how active involvement might be operationalised. Active involvement has been identified as being of central importance to the success of the WFD. The project also entailed the accumulation of extensive agri-environmental data. The aim of the paper is to evaluate AGWAplan to establish the extent to which its expected objectives have been achieved and how, and to determine whether the project approach might facilitate WFD goals if implemented in forthcoming river basin management plans (RBMPs). AGWAplan resulted in advantageous outcomes, including win-win solutions to reduce nutrient leaching and greater acceptance of policy, although the original reduction targets where not fully reached. The paper concludes that actively involving farmers in a similar manner in RBMPs may make an important contribution to the implementation of the WFD, although caveats regarding its potential for transfer to other areas are identified.

Management of hyperglycaemia in the preterm infant.

In the fetus, the predominant energy supply is glucose transported across the placenta from the mother. As pregnancy progresses, the amount of glucose transported increases, with glycogen and fat stores being laid down, principally in the third trimester. In the well-term baby, there is hormonal and metabolic adaptation in the perinatal period to ensure adequate fuel supply to the brain and other vital organs after delivery, but in the preterm infant, abnormalities of glucose homeostasis are common. After initial hypoglycaemia, due to limited glycogen and fat stores, preterm babies often become hyperglycaemic because of a combination of insulin resistance and relative insulin deficiency. Hyperglycaemia is associated with increased morbidity and mortality in preterm infants, but what should be considered optimal glucose control, and how best to achieve it, has yet to be defined in these infants.

The continuous glucose monitoring sensor in neonatal intensive care.

OBJECTIVE: To determine the feasibility of continuous glucose monitoring in the very low birthweight baby requiring intensive care, as these infants are known to be at high risk of abnormalities of glucose control. METHOD: Sixteen babies were studied from within 24 hours of delivery and for up to seven days. RESULTS: The subcutaneous glucose sensors were well tolerated and readings were comparable to those on near patient whole blood monitoring devices. CONCLUSION: Continuous glucose monitoring is practical in neonates, giving detailed information about glucose control.

Neonatal thyroid disorders.

Hypothyroxinaemia, which is common in the preterm infant, and thyrotoxicosis, which is rare, are important neonatal thyroid disorders. Their causes and treatment are discussed.

Hypoglycemia and resistance to ketoacidosis in a subject without functional insulin receptors.

Humans with congenital absence of the islets of Langerhans and mice rendered null for the insulin receptor rapidly develop severe hyperglycemia and ketoacidosis and, if untreated, die in the early neonatal period. In contrast, children with homozygous or compound heterozygous mutations of the insulin receptor gene, although hyperglycemic postprandially, survive for many months without developing ketoacidosis. Paradoxically, they often develop hypoglycemia. The rarity of the condition and the difficulties of undertaking metabolic studies in ill infants have limited the physiological information that might explain the clinical features. We studied a boy with Donohue's syndrome who represents a further example of the null phenotype, with two different and novel nonsense mutations in the alpha-subunit of the receptor. He survived for 8 months without developing ketoacidosis, and fasting hypoglycemia was a frequent problem. Despite the complete absence of insulin receptors, evidence for persistent insulin-like effects on fat and liver was seen; fasting plasma beta-hydroxybutyrate and nonesterified fatty acid levels were low, fell further during the early postprandial period, and failed to rise in response to hypoglycemia. The inverse relationships between plasma insulin and insulin-like growth factor-binding protein-1 levels were maintained, suggesting persistent hepatic effects of insulin. GH levels measured over a 6.5-h period were low throughout. Thus, the differences between congenital insulin deficiency vs. insulin receptor deficiency in humans may be explained by persistent insulinomimetic activity of the grossly elevated plasma insulin presumably being mediated through the type 1 insulin-like growth factor receptor. As GH plays a critical role in the regulation of ketogenesis during insulinopenia in humans, but not in rodents, this may contribute to the distinct phenotype of human vs. mouse insulin receptor knockouts.

Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn.

The relationship between GH, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin may be critical to the understanding of variation in early growth, especially in the small for gestational age (SGA) baby. To investigate these relationships, we have undertaken 12-h hormone profiles in 26 babies (13 SGA) at a median of 4.5 days of age. GH levels were measured every 10 min; insulin and IGFBP-1 were measured every 20 min. Mean levels of these hormones and IGF-I levels (from a single sample) were related to size at birth. The GH data were analyzed by Pulsar and time series analysis to characterize hormone pulsatility and relationship with feeds. IGF-I levels correlated with birth weight and length (r2 = 0.47; P = 0.004, and r2 = 0.5; P = 0.0005, respectively, after allowing for gestation), whereas mean GH levels were negatively related to birth size (r2 = -0.18; P = 0.04 and r2 = -0.2; P = 0.03 for weight and length, respectively). No direct relationship between mean GH levels and IGF-I was identified. IGF-I levels were higher in appropriate for gestational age (AGA; mean +/- SD, 82+/-61 ng/mL) than in SGA (34+/-22 ng/mL; P = 0.03) babies. Baseline (mean +/- SD, 25.9+/-11.9), mean (33.9+/-14.0), and peak (45.0+/-18.1 microg/L) GH levels were higher in SGA than in AGA babies [17.1+/-8.2 (P = 0.04), 22.5+/-10.4 (P = 0.03), and 30.7+/-15.4 microg/L (P = 0.04), respectively]. Mean IGFBP-1 levels were also higher in SGA than AGA babies (157.4+/-90.7 vs. 62.7+/-43.8 ng/mL; P = 0.01). A positive correlation was identified between changes in insulin and coincident pulses of GH (r = 0.147; P < 0.01), whereas there was an inverse relationship between insulin and IGFBP-1, with a lag time 120 min (r = -0.33; P < 0.0001). In conclusion, these studies indicate that the GH-IGF-I axis is closely related to feeding in the newborn. In SGA babies, low IGF-I and elevated IGFBP-1 reflect the slow growth, but elevated GH and rapid GH pulsatility may be a signal for lipolysis.

The use of an automated microsampling system for the characterization of growth hormone pulsatility in newborn babies.

To overcome the difficulties of studying hormone pulsatility in the newborn, we have developed an automated microsampling system that permits the measurement of hormones in small prediluted samples of blood (40 microL) taken at 10-min intervals over 12 h. The system has been validated in adult volunteers, and the error attributable to the dilution was <4%. Using this method in 10 preterm babies, we have been able to describe pulsatile changes in GH and have demonstrated a clear postprandial elevation in GH levels peaking 60 min after a feed. Fourier transform analysis indicated a pulse periodicity of 180 min in babies who were appropriate for gestational age (n = 6), but faster, co-dominant pulse periodicities of 90-100 and 140 min in babies who were small for gestational age (weight and length below the 10th centile) (n = 4). There was no significant difference between mean, peak, and baseline GH levels between the two groups.

Treatment of radiation-induced growth hormone deficiency with growth hormone-releasing hormone.

UNLABELLED: In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth. OBJECTIVE: We have aimed to determine the efficacy and safety of growth hormone-releasing hormone (GHRH) (1-29)-NH2 given as a twice daily subcutaneous injection in the treatment of growth failure in children with radiation-induced GH deficiency. DESIGN: A multicentre study comparing growth before and after 1 year of treatment with GHRH (1-29)-NH2, 15 micrograms/kg twice daily, by subcutaneous injection in children with radiation-induced GH deficiency. On completion of the study year all children were treated with GH (0.5 U/kg/week) and growth parameters were documented over the next year. PATIENTS: Nine children (six boys) with radiation-induced GH deficiency following cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant from the hypothalamic-pituitary axis (n = 8) or prophylaxis against central nervous system leukaemia (n = 1) were studied. All were prepubertal when the study commenced, which was at least 2 years from radiotherapy. MEASUREMENTS: Anthropometry and pubertal staging were carried out at 3-monthly intervals and bone age estimations at 6-monthly intervals (TW2 method). Pretreatment standing height velocities were compared with values during the year of GHRH treatment and then after the first year of GH therapy. In those that had received craniospinal irradiation, a change in leg-length Standard deviation score (SDS) was noted before and after GHRH therapy. Changes in skin-fold thickness and bone age during the GHRH study year were documented. Adverse events and 3-monthly measurements of clinical chemistry, haematology, lipid profile and thyroid function were recorded. RESULTS: There was a significant increase in height velocity from 3.3 (SD 1.1) cm/year before treatment, to 6.0 (SDS 1.5) cm/year after 1 year of GHRH treatment (P = 0.004). GHRH maintained or improved the leg length SDS in children who had received craniospinal irradiation. Bone age increased by a mean of 1.1 years/chronological year during treatment with GHRH. Subsequent height velocity during 1 year of GH therapy was 7.5 (SD 1.5)cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse events that could be attributed to GHRH therapy. One child went into puberty during the GHRH study year and three were pubertal during the first year of GH therapy. CONCLUSION: In cranially irradiated children, GHRH was effective in increasing growth velocity but this was less than that seen in response to GH therapy, although it matched that in children with isolated idiopathic GH deficiency treated with the same dose and schedule of GHRH administration.