Individual neurophysiological signatures of spontaneous rhythm processing.

When sensory input conveys rhythmic regularity, we can form predictions about the timing of upcoming events. Although rhythm processing capacities differ considerably between individuals, these differences are often obscured by participant- and trial-level data averaging procedures in M/EEG research. Here, we systematically assessed neurophysiological variability displayed by individuals listening to isochronous (1.54 Hz) equitone sequences interspersed with unexpected (amplitude-attenuated) deviant tones. Our approach aimed at revealing time-varying adaptive neural mechanisms for sampling the acoustic environment at multiple timescales. Rhythm tracking analyses confirmed that individuals encode temporal regularities and form temporal expectations, as indicated in delta-band (1.54 Hz) power and its anticipatory phase alignment to expected tone onsets. Zooming into tone- and participant-level data, we further characterized intra- and inter-individual variabilities in phase-alignment across auditory sequences. Further, individual modeling of beta-band tone-locked responses showed that a subset of auditory sequences was sampled rhythmically by superimposing binary (strong-weak; S-w), ternary (S-w-w) and mixed accentuation patterns. In these sequences, neural responses to standard and deviant tones were modulated by a binary accentuation pattern, thus pointing towards a mechanism of dynamic attending. Altogether, the current results point toward complementary roles of delta- and beta-band activity in rhythm processing and further highlight diverse and adaptive mechanisms to track and sample the acoustic environment at multiple timescales, even in the absence of task-specific instructions.

Inefficient procurement processes undermine access to medicines in the Western Cape Province of South Africa.

BACKGROUND: South Africa (SA) has experienced several stock-outs of life-saving medicines for the treatment of major chronic infectious and non-communicable diseases in the public sector. OBJECTIVE: To identify the causes of stock-outs and to illustrate how they undermine access to medicines (ATM) in the Western Cape Province, SA. METHODS: This qualitative study was conducted with a sample of over 70 key informants (frontline health workers, sub-structure and provincial health service managers). We employed the critical incident technique to identify significant occurrences in our context, the consequences of which impacted on access to medicines during a defined period. Stock-outs were identified as one such incident, and we explored when, where and why they occurred, in order to inform policy and practice. RESULTS: Medicines procurement is a centralised function in SA. Health service managers unanimously agreed that stock-outs resulted from the following inefficiencies at the central level: (i) delays in awarding of pharmaceutical tenders; (ii) absence of contracts for certain medicines appearing on provincial code lists; and (iii) suppliers' inability to satisfy contractual agreements. The recurrence of stock-outs had implications at multiple levels: (i) health facility operations; (ii) the Chronic Dispensing Unit (CDU), which prepacks medicines for over 300 000 public sector patients; and (iii) community-based medicines distribution systems, which deliver the CDU's prepacked medicines to non-health facilities nearer to patient homes. For instance, stock-outs resulted in omission of certain medicines from CDU parcels that were delivered to health facilities. This increased workload and caused frustration for frontline health workers who were expected to dispense omitted medicines manually. According to frontline health workers, this translated into longer waiting times for patients and associated dissatisfaction. In some instances, patients were asked to return for undispensed medication at a later date, which could potentially affect adherence to treatment and therapeutic outcomes. Stock-outs therefore undermined the intended benefits of ATM strategies. CONCLUSION: Addressing the procurement challenges, most notably timeous tender awards and supplier performance management, is critical for successful implementation of ATM strategies.

Non-hip and non-vertebral fractures: the neglected fracture sites.

SUMMARY: Non-hip, non-vertebral fractures (NHNVF) were compared with hip, vertebral and controls. NHNVF were younger and heavier than controls and hip/vertebral fractures in both men and women, respectively. Falls and prior fractures were less common in NHNVF than hip fractures. Glucocorticoid use was lower in NHNVF compared to vertebral fracture (VF) in men. INTRODUCTION: Although hip fracture (HF) and vertebral fractures (VF) receive the most attention in the literature and are the targeted sites for fracture prevention, non-hip, non-vertebral fracture (NHNVF) sites account for a greater proportion of fractures than the hip or vertebrae. This study aimed to assess risk factors for NHNVF and compare them with those for HF, VF and controls. METHODS: Incident fractures during 2005-2007 for men and 1994-1996 for women were identified using computerised keyword searches of radiological reports, and controls were selected at random from electoral rolls for participation in the Geelong Osteoporosis Study. Participants aged 60+ years were included in this study. RESULTS: Compared to controls, men and women with NHNVF were younger (ORs, 0.90, 95% CI 0.86-0.94; and 0.96, 0.93-0.98, respectively) and had a lower femoral neck bone mineral density (BMD) T-score (age-adjusted; difference [men] 0.383, P = 0.002; [women] 0.287, P = 0.001). Compared to HF, men and women with NHNVF were heavier (difference [men] 9.0 kg, P = 0.01; [women] 7.6 kg, P < 0.001). Heavier weight was also a risk factor for women with NHNVF compared to VF (1.03, 1.01-1.06). In men with NHNVF, falls (0.37, 0.14-0.97) and prior fractures (0.38, 0.15-0.98) were less common compared to HF; and glucocorticoid use was less common for NHNVF (0.30, 0.11-0.85) compared to VF. CONCLUSIONS: Given the high numbers of NHNVF sustained by men and women in this study, fracture prevention strategies should focus on individuals with high risk of sustaining these types of fractures, as well as on individuals who are more likely to sustain a HF or VF.

Calcaneal ultrasound reference ranges for Australian men and women: the Geelong Osteoporosis Study.

UNLABELLED: Heel ultrasound is a more portable modality for assessing fracture risk than dual-energy X-ray absorptiometry and does not use ionising radiation. Fracture risk assessment requires appropriate reference data to enable comparisons. This study reports the first heel ultrasound reference ranges for the Australian population. INTRODUCTION: This study aimed to develop calcaneal (heel) ultrasound reference ranges for the Australian adult population using a population-based random sample. METHODS: Men and women aged≥20 years were randomly selected from the Barwon Statistical Division in 2001-2006 and 1993-1997, respectively, using the electoral roll. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were measured at the heel using a Lunar Achilles Ultrasonometer. Gender-specific means and standard deviations for BUA, SOS and SI were calculated for the entire sample (men 20-93 years, n=1,104; women 20-92 years, n=914) and for participants aged 20-29 years (men, n=157; women, n=151). Associations between ultrasound measures and age were examined using linear regression. RESULTS: For men, mean±standard deviation BUA, SOS and SI were 118.7±15.8 dB/MHz, 1,577.0±43.7 m/s and 100.5±20.7, respectively; values for women were consistently lower (111.0±16.4 dB/MHz, P<0.001; 1,571.0±39.0 m/s, P=0.001; and 93.7±20.3, P<0.001, respectively). BUA was higher in young men compared with young women (124.5±14.4 vs 121.0±15.1 dB/MHz), but SOS (1,590.1±43.1 vs 1,592.5±35.0 m/s) and SI (108.0±19.9 vs 106.3±17.7) were not. The relationships between age and each ultrasound measure were linear and negative across the age range in men; associations were also negative in women but non-linear. CONCLUSION: These data provide reference standards to facilitate the assessment of fracture risk in an Australian population using heel ultrasound.

Bone mineral density is cross sectionally associated with cartilage volume in healthy, asymptomatic adult females: Geelong Osteoporosis Study.

INTRODUCTION: The association between osteoporosis and osteoarthritis (OA) is controversial. Although previous studies have shown total body, lower limb, spinal and knee BMD and knee cartilage volume to be positively associated, the relationship between other distant site-specific measures of BMD and other knee structures is unknown. The aim of this study was to determine the associations between BMD at eight skeletal sites, and knee structure in asymptomatic young to middle-aged females without any clinical signs of OA. METHODS: One hundred and sixty healthy, asymptomatic females (29-50 yr) underwent magnetic resonance imaging of the knee. BMD was measured at the spine, hip, total body and forearm by dual energy X-ray absorptiometry, and at the calcaneus by quantitative ultrasound. BMD was tested for an association with cartilage volume, defects, and bone marrow lesions (BMLs). RESULTS: Medial cartilage volume was positively associated with BMD at the spine, total body, femoral neck, and Ward's triangle (all p<0.05), with non-significant associations in the same direction at the trochanter (p=0.07). Findings in the lateral compartment were similar. The presence of medial cartilage knee defects were also associated with BMD at the spine; defects in the lateral compartment were associated with BMD at the forearm (both p=0.05). BMD was not associated with the presence of BMLs. No associations were observed with calcaneus BMD. CONCLUSIONS: Site-specific BMD is associated with cartilage volume at the knee in asymptomatic young to middle-aged adults, with the direction and effects trending in the same direction. The magnitude of changes correlates with clinically relevant changes. QUS defined calcaneus BMD, showed no associations with knee structure. Although systemic factors may underlie the association between knee cartilage volume and axial/lower limb BMD, these data suggest that common local, possibly biomechanical factors may also play a role.

Incident hip fracture and social disadvantage in an Australian population aged 50 years or greater.

AIMS: There is an inverse association between socioeconomic status (SES) and most causes of morbidity. Hip fractures pose a significant public health burden on society. However, the association between quintiles of area-based SES and incident hip fractures has not been examined in Australia. Using a comprehensive register of hip fractures for the entire Barwon Statistical Division (BSD), we assessed the association between area-based SES and incident hip fractures over a two-year period in residents aged ≥ 50years. METHODS: Incident hip fractures were identified using a computerized keyword search of all radiological reports from all the radiological centers serving the BSD. Pathological fractures were excluded. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and categorized in quintiles based upon the BSD reference range. Homogeneity of population at risk in each SES quintile was tested using chi square comparison. Hip fractures in each quintile and within each age strata for the entire BSD region were defined as rates per 1000 person-years. RESULTS: During 2006-2007, there were 495 hip fractures (336 female). An inverse pattern of association was observed between SES and hip fracture incidence, with a peak in fracture numbers observed in the second quintile of SES, with differences between SES quintiles observed for both females (p = 0.005) and males (p = 0.007). CONCLUSION: The association between incident hip fractures and quintiles of area-based SES provides evidence that those of greater social disadvantage should be a specific target population for intervention to reduce the burden of hip fracture within Australia.

Patterns of treatment in Australian men following fracture.

UNLABELLED: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated even after a subsequent fracture. INTRODUCTION: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. METHODS: The study was conducted as part of the Geelong Osteoporosis Study in south-eastern Australia. Men in the study area who had sustained an incident fracture in the period July 2006 to December 2007 were identified from hospital radiology reports. A self-report questionnaire was sent to eligible participants approximately 12 months after fracture. Respondents were asked for details of medications prescribed for 'osteoporosis/fracture/low bone mass' before and after fracture, and where applicable, reasons for cessation of treatment. We analysed the results for 109 men aged 50 years and older who had sustained fracture in the study period. RESULTS: Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated. Of the 87 men who were untreated, nine had osteoporosis at the hip and/or spine and 29 (26.6%) reported having sustained a low trauma prior fracture. CONCLUSIONS: Our findings are consistent with previously published data showing low rates of treatment initiation in men eligible for osteoporosis treatment. There appear to be barriers involving participants' and medical practitioners' knowledge, beliefs and attitudes regarding osteoporosis and treatment, as well as in the doctor-patient partnership in osteoporosis management. Establishment of clinical pathways for fracture management beyond orthopaedic care may be one of a range of appropriate responses.

Bone mineral density reference ranges for Australian men: Geelong Osteoporosis Study.

SUMMARY: A large population-based random sample of Australian white men was used to provide normative bone mineral density (BMD) data at multiple anatomical sites. The femoral neck BMD data are very similar to those obtained in USA non-Hispanic white males participating in the National Health and Nutrition Examination Survey III (NHANES III). The reference ranges will be suitable for similar populations. INTRODUCTION: To provide normative BMD data for Australian men derived from a large population-based random sample. METHODS: An age-stratified random sample of men was recruited from the Australian electoral rolls (n = 1,467 aged 20-97 years). BMD was quantified at multiple sites using Lunar densitometers. RESULTS: Age-related differences in BMD were best predicted by linear relationships at the spine and hip and by quadratic functions at the whole body and forearm. At the spine, a small age-related increase in mean BMD was observed. Although in the subset with no spinal abnormalities, there was a decrease of 0.003 g/cm(2) per year from age 20. At the hip sites, mean BMD decreased at 0.001-0.006 g/cm(2) per year from age 20. At the forearm and whole body, BMD peaked at 41-47 years. Apart from a small difference in men greater than or equal to 80 years, the Australian femoral neck BMD data are not different to those obtained in USA non-Hispanic white males participating in NHANES III and were generally similar to those of large studies from Canada (CaMos) and Spain. CONCLUSIONS: These data supply BMD reference ranges at multiple anatomical sites that will be applicable to white Australian men and similar populations such as USA non-Hispanic white men.

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men.

UNLABELLED: The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry. INTRODUCTION: Vertebral fractures are sentinel events for osteoporosis. We aimed to compare quality of life and physical function in men with and without MVF. METHODS: Using morphometric X-ray absorptiometry (T10-L4), MVFs were identified in a random sample of men aged 20-93 years. Moderate and severe wedge, biconcave or compression deformities (>25% reduction in any vertebral height) were classified as MVFs. RESULTS: Of 1,147 men, MVFs were identified in 64. No MVFs were detected for men in their twenties. Prevalence was 1.5% for 30-39 years, 1.4% 40-49 years, 3.2% 50-59 years, 4.7% 60-69 years, 10.0% 70-79 years and 14.6% 80+ years. Among 555 men aged 60+ years, those with MVFs were twice as likely to have quality of life scores in the lowest tertile (age-adjusted OR = 2.35, 95%CI 1.24-4.45). MVFs were associated with lower mean age-adjusted physical activity scores [11.3 (95%CI 9.0-13.8) vs 14.0 (13.2-14.9), P = 0.04] and longer mean age-adjusted 'Up-&-Go' times [9.5 (8.9, 10.1) vs 8.9 (8.8, 9.1) s, P = 0.06]. CONCLUSION: Despite most men being unaware of their condition, MVFs were associated with poor quality of life and impaired physical function. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry because detection of MVFs has important implications for osteoporosis management in men.

The population burden of fractures originates in women with osteopenia, not osteoporosis.

INTRODUCTION: Osteoporosis is associated with increased risk for fracture. However, most postmenopausal women have bone mineral density (BMD) within the normal or osteopenic range. The aim of this study was to determine the proportion of the population burden of fragility fractures arising from women at modest risk for fracture. METHODS: We measured baseline BMD in a population-based random sample of 616 postmenopausal women aged 60-94 years and followed these individuals for a median of 5.6 years (IQR 3.9-6.5) to determine the incidence of fractures according to age, BMD and the presence of a prior fracture. RESULTS: Based on WHO criteria, 37.6% of the women had normal total hip BMD, 48.0% had osteopenia and 14.5% had osteoporosis. The incidence of fracture during follow-up was highest in women with osteoporosis, but only 26.9% of all fractures arose from this group; 73.1% occurred in women without osteoporosis (56.5% in women with osteopenia, 16.6% in women with normal BMD). Decreasing BMD, increasing age and prior fracture contributed independently to increased fracture risk; in a multivariate model, the relative risk for fracture increased 65% for each SD decrease in BMD (RR=1.65, 95%CI 1.32-2.05), increased 3% for every year of age (RR=1.03, 95%CI 1.01-1.06) and doubled with prevalent fracture (RR=2.01, 95% CI 1.40-2.88). A prevalent fracture increased the risk for fractures such that women with osteopenia and prevalent fracture had the same, if not greater, risk as women with osteoporosis alone. CONCLUSIONS: Reducing the population burden of fractures requires attention to women with osteopenia, as well as osteoporosis, because over half of the fragility fractures in the population arise in these individuals, and women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis.

Femoral neck geometry and hip fracture risk: the Geelong osteoporosis study.

To determine the relationship between femoral neck geometry and the risk of hip fracture in post-menopausal Caucasian women, we conducted a retrospective study comparing the femoral neck dimensions of 62 hip fracture cases to those of 608 randomly selected controls. Measurements were made from dual-energy X-ray absorptiometry scans (Lunar DPX-L), using the manufacturer's ruler function, and included: hip axis length (HAL), femoral neck axis length (FNAL), femoral neck width (FNW), femoral shaft width (FSW), medial femoral shaft cortical thickness (FSCT(med)), and lateral femoral shaft cortical thickness (FSCT(lat)). The fracture group was older (median age 78.3 years vs 73.8 years), lighter (median weight 59.9 kg vs 64.5 kg), and, after adjustment for age, taller (mean height 158.7+/-0.8 cm vs 156.7+/-0.2 cm) than the controls. Furthermore, bone mineral density was lower in this group (0.682+/-0.016 g/cm(2) vs 0.791+/-0.006 g/cm(2)). After adjustment for age, bone mineral content (BMC) or height, hip fracture patients had greater FNW (up to 6.6%) and FSW (up to 6.3%) than did the controls. Each standard deviation increase in FNW and FSW was associated with a 1.7-fold (95% CI 1.3-2.3) and a 2.4-fold (95% CI 1.8-3.2) increase in the fracture risk, respectively. BMC-adjusted FNAL was greater in the fracture group (+2.1%) than in the controls, while the age-adjusted FSCT(med) was reduced (-7.2%). There was a trend towards longer HAL (up to 2.1%) after adjustment for age or BMC, and thinner age-adjusted FSCT(lat) (-1.7%) in fracture patients that did not reach statistical significance. In multivariate analysis, the risk of hip fracture was predicted by the combination of age, FNW, FSW, BMC and FSCT(med). HAL was not analyzed because of the small number of HAL measurements among fracture cases. We conclude that post-menopausal women with hip fractures have wider femoral necks and shafts, thinner femoral cortices and longer femoral neck axis lengths than do women with no fractures. Alteration in hip geometry is associated with the risk of hip fracture.

How doctors discuss major interventions with high risk patients: an observational study.

OBJECTIVE: To investigate the difficulties doctors face in discussing treatment options with patients with acute, life threatening illness and major comorbidities. DESIGN: Observational study of doctor-patient interviews based on a standardised clinical scenario involving high risk surgery in a hypothetical patient (played by an actor) with serious comorbidities. PARTICIPANTS: 30 trainee doctors 3-5 years after graduation. MAIN OUTCOME MEASURES: Adequacy of coverage of various aspects was scored from 3 (good) to 0 (not discussed). RESULTS: The medical situation was considered to be well described (median score 2.7 (interquartile range 2.1-3.0)), whereas the patient's functional status, values, and fears were poorly or minimally addressed (scores 0.5 (0.0-1.0), 0.5 (0.0-1.0), and 0.0 (0.0-1.5), respectively; all P < 0.001 v score for describing the medical situation). Twenty nine of the doctors indicated that they wished to include the patient's family in the discussion, but none identified a preferred surrogate decision maker. Six doctors suggested that the patient alone should speak with his family to reach a decision without the doctor being present. The doctors were reluctant to give advice, despite it being directly requested: two doctors stated that a doctor could not give advice, while 17 simply restated the medical risks, without advocating any particular course. Of the 11 who did offer advice, eight advocated intervention. CONCLUSIONS: Doctors focused on technical medical issues and placed much less emphasis on patient issues such as functional status, values, wishes, and fears. This limits doctors' ability to offer suitable advice about treatment options. Doctors need to improve their communication skills in this difficult but common clinical situation.

Reference ranges for bone densitometers adopted Australia-wide: Geelong osteoporosis study.

Bone densitometry reports a measure of fracture risk in comparison with young adults (T-scores) and age-matched peers (Z-scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia-wide. The GOS recruited a random, population-based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX-L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.

Dietary omega-3 fatty acids and depression in a community sample.

To evaluate the association between omega-3 polyunsaturated essential fatty acids and depression, data regarding prevalence rates of self-reported depression and median daily dietary intakes of these fatty acids were obtained from an age-stratified, population-based sample of women (n = 755; 23-97 year) in the Barwon Statistical Division of south-eastern Australia. A self-report questionnaire based on Diagnostic and Statistical Manual-IV criteria was utilised to determine 12-month prevalence rates of depression in this sample, and data from biennial food frequency questionnaires examining seafood and fish oil consumption over a 6-year period were examined. Differences in median dietary intakes of omega-3 fatty acids between the depressed and nondepressed cohorts were analysed and results were adjusted for age, weight and smoking status. No significant differences in median intakes were identified between the two groups of women (median, interquartile range; depressed = 0.09g/day, 0.04-0.18 versus nondepressed = 0.11 g/day, 0.05-0.22, p = 0.3), although overall average intakes of omega-3 fatty acids were lower than recommended and rates of depression within this sample higher than expected, based on previous data. Further research that takes into account ratios of omega-6 to omega-3 polyunsaturated essential fatty acids, as well as other dietary sources of omega-3 fatty acids, is warranted.

Fracture thresholds revisited. Geelong Osteoporosis Study.

Osteoporosis, in the absence of fracture, is defined as a deficit in bone mineral density (BMD) of 2.5 SD or more below the young adult reference mean in postmenopausal Caucasian populations. BMD is a measure of fracture risk but not the sole predictor. We have assessed a combination of easily accessible measures of age, height, weight, and BMD to improve fracture risk assessment. Women with low trauma fractures and a control group were recruited from south-eastern Australia. Discriminant analysis derived multivariate equations that assessed fracture risk. Age was not in the best models at the spine and forearm sites. Weight and height contributed to the relationship for the forearm sites only. At the proximal femur, the BMD level that separates fracture cases from nonfracture cases, increases with age. These separation levels of BMD were higher than the WHO's level of osteoporosis (T-score < -2.5 SD) at ages older than 62 years. This increasing BMD threshold with age suggests that other age-related risk factors assume increasing importance among the elderly.