Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

Secondary prevention of fragility fractures in Asia Pacific: an educational initiative.

The Asia -Pacific Bone Academy (APBA) Fracture Liaison Service (FLS) Focus Group educational initiative has stimulated activity across the Asia -Pacific region with the intention of supporting widespread implementation of new FLS. In 2017, the APBA FLS Focus Group developed a suite of tools to support implementation of FLS across the Asia-Pacific region as a component of a multi-faceted educational initiative. This article puts this initiative into context with a narrative review describing the burden of fragility fractures in the region, the current secondary fracture prevention care gap and a summary of emerging best practice. The results of a survey to evaluate the impact of the APBA educational initiative is presented, in addition to commentary on recent activities intended to improve the care of individuals who sustain fragility fractures across the Asia -Pacific. A FLS Toolbox for Asia-Pacific was developed which included the following sections:1. The burden of fragility fractures in the Asia-Pacific region.2. A summary of evidence for FLS in the Asia-Pacific.3. A generic, fully referenced FLS business plan template.4. Potential cost savings accrued by each country, based on a country-specific FLS Benefits Calculator.5. How to start and expand FLS programmes in the Asia-Pacific context.6. A step-by-step guide to setting up FLS in countries in the Asia-Pacific region.7. Other practical tools to support FLS establishment.8. FLS online resources and publications.The FLS Toolbox was provided as a resource to support FLS workshops immediately following the 5th Scientific Meeting of the Asian Federation of Osteoporosis Societies (AFOS) held in Kuala Lumpur in October 2017. The FLS workshops addressed three key themes:• The FLS business case.• Planning the FLS patient pathway.• The role of the FLS coordinator in fragility fracture care management.A follow-up survey of 142 FLS workshop participants was conducted in August-September 2018. The survey included questions regarding how FLS were developed, funded, the scope of service provision and the support provided by the educational initiative. Almost one-third (30.3%) of FLS workshop participants completed the survey. Survey responses were reported for those who had established a FLS at the time the survey was conducted and, separately, for those who had not established a FLS. Findings for those who had established a FLS included:• 78.3% of respondents established a multidisciplinary team to develop the business case for their FLS.• 87.0% of respondents stated that a multidisciplinary team was established to design the patient pathway for their FLS.• 26.1% of respondents stated that their FLS has sustainable funding.• The primary source of funding for FLS was from public hospitals (83.3%) as compared with private hospitals (16.7%).Most hospitals that had not established a FLS at the time the survey was conducted were either in the process of setting-up a FLS (47%) or had plans in place to establish a FLS for which approval is being sought (29%). The primary barrier to establishing a new FLS was lack of sustainable funding. The APBA FLS Focus Group educational initiative has stimulated activity across the Asia-Pacific region with the intention of supporting widespread implementation of new FLS. A second edition of the FLS Toolbox is in development which is intended to complement ongoing efforts throughout the region to expedite widespread implementation of FLS.

Hip fractures in Singapore: ethnic differences and temporal trends in the new millennium.

Despite an increase in absolute numbers, the age-standardized incidence of hip fractures in Singapore declined in the period 2000 to 2017. Among the three major ethnic groups, Chinese women had the highest fracture rates but were the only group to show a temporal decline. INTRODUCTION: A study published in 2001 predicted a 30-50% increase in Singapore hip fracture incidence rates over the ensuing 30 years. To test that prediction, we examined the incidence of hip fracture in Singapore from 2000 to 2017. METHODS: We carried out a population-based study of hip fractures among Singapore residents aged ≥ 50 years. National medical insurance claims data were used to identify admissions with a primary discharge diagnosis of hip fracture. Age-adjusted rates, based on the age distribution of the Singapore population of 2000, were analyzed separately by sex and ethnicity (Chinese, Malay, or Indian). RESULTS: Over the 18-year study period, 36,082 first hip fractures were recorded. Total hip fracture admissions increased from 1487 to 2729 fractures/year in the years 2000 to 2017. Despite this absolute increase, age-adjusted fracture rates declined, with an average annual change of - 4.3 (95% CI - 5.0, - 3.5) and - 1.1 (95% CI - 1.7, - 0.5) fractures/100,000/year for women and men respectively. Chinese women had 1.4- and 1.9-fold higher age-adjusted rates than Malay and Indian women: 264 (95% CI 260, 267) versus 185 (95% CI 176, 193) and 141 (95% CI 132, 150) fractures/100,000/year, respectively. Despite their higher fracture rates, Chinese women were the only ethnic group exhibiting a decline, most evident in those ≥ 85 years, in age-adjusted fracture rate of - 5.3 (95% CI - 6.0, - 4.5) fractures/100,000/year. CONCLUSION: Although the absolute number of fractures increased, steep drops in elderly Chinese women drove a reduction in overall age-adjusted hip fracture rates. Increases in the older population will lead to a rise in total number of hip fractures, requiring budgetary planning and new preventive strategies.

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

Heavy metal contamination along the China coastline: A comprehensive study using Artificial Mussels and native mussels.

A comprehensive study was carried out to assess metal contamination in five cities spanning from temperate to tropical environment along the coastal line of China with different hydrographical conditions. At each of the five cities, Artificial Mussels (AM) were deployed together with a native species of mussel at a control site and a polluted site. High levels of Cr, Cu and Hg were found in Qingdao, high level of Cd, Hg and Pb was found in Shanghai, and high level of Zn was found in Dalian. Furthermore, level of Cu contamination in all the five cities was consistently much higher than those reported in similar studies in other countries (e.g., Australia, Portugal, Scotland, Iceland, Korea, South Africa and Bangladesh). Levels of individual metal species in the AM showed a highly significant correlation with that in the native mussels (except for Zn in Mytilus edulis and Cd in Perna viridis), while no significant difference can be found between the regression relationships of metal in the AM and each of the two native mussel species. The results demonstrated that AM can provide a reliable time-integrated estimate of metal concentration in contrasting environments over large biogeographic areas and different hydrographic conditions, and overcome the shortcomings of monitoring metals in water, sediment and the use of biomonitors.

Secondary prevention of osteoporotic fractures--an "OPTIMAL" model of care from Singapore.

UNLABELLED: A significant care gap exists in the management of osteoporotic fractures. Osteoporosis Patient Targeted and Integrated Management for Active Living (OPTIMAL) is a secondary fracture prevention program instituted in the public hospitals of Singapore. We aim to describe the operational characteristics of OPTIMAL and initial audit data of patients who were recruited into the program at Singapore General Hospital. INTRODUCTION: Fractures often represent the first opportunity for care of osteoporosis. However, a significant care gap still exists in the management of these sentinel events and underdiagnosis and undertreatment of osteoporotic fractures are prevalent worldwide. Fracture liaison services run by care coordinators have been shown to reduce the fracture care gap. OPTIMAL is a clinician champion-driven, case manager-run secondary fracture prevention program set up in the public hospitals of Singapore in 2008. METHODS: We present the operational characteristics and initial audit data of OPTIMAL from the largest tertiary teaching hospital in Singapore. RESULTS: One thousand and fourteen patients have been recruited into OPTIMAL at our hospital since 2008, and 476 patients are currently in active follow-up. Two hundred and eighty-seven patients had completed a 2-year follow-up at the hospital as of August 2012 and were evaluated; 97.5% of these patients had DXA evaluation upon enrollment into the program, and 62% of the patients reported compliance with an exercise program over the 2-year follow-up. Compliance to osteoporosis medications as estimated by the medication possession ratio (MPR) was 72.8 ± 34.5% at 2 years with patients maintaining good compliance (MPR ≥ 80%) for an average of 20.2 months (95% CI 19.3-21.1). CONCLUSION: Our report provides the first compelling evidence of the potential success of a secondary fracture prevention program from an Asian country. The ultimate success of the program will be determined by fracture outcomes and cost effectiveness, but in the interim, clear evidence of enhanced assessment and treatment rates has been demonstrated.

Achieving treat to target in gout: a clinical practice improvement project.

OBJECTIVE: Gout care is suboptimal because of lack of translation of knowledge into real-world practice, despite evidence-based guidelines. We have developed processes to ensure systematic care for gout patients and determined the predictors for achievement of a target serum uric acid (SUA) concentration of < 360 µmol/L in a prospective cohort of Asian gout patients requiring allopurinol therapy. METHODS: A 1-year clinical practice improvement project was undertaken using evidence-based guidelines and quality planning tools. Interventions included comprehensive patient education, enhanced telephone access, reappointments and refills, upward titration of allopurinol with no limitation specified by renal function, and increased frequency of visits until the target SUA concentration was achieved. The primary outcome was the time to achieve an SUA level of <360 µmol/L. RESULTS: We recruited 126 gout patients. The median time to achieving the target SUA concentration was 36.9 weeks [95% confidence interval (CI) 29.3-44.4]. Based on survival analysis, the proportion of patients achieving the target was 8.1% (95% CI 3.2-13.0), 40.6% (95% CI 31.4-50.8), and 72.0% (95% CI 61.2-82.8) at 3, 6, and 12 months, respectively. On average, our patients who achieved the target were seen once every 2 months and achieved the target after a mean of 2.5 (SD = 1.1) visits. Frequency of follow-up visits and older patients not taking aspirin were independent predictors associated with achieving the target outcome, regardless of renal function. CONCLUSIONS: Optimization of control of SUA is achievable, even in the setting of renal impairment, by redesigning and implementing processes involving changes in physician prescribing habits, enhanced nursing interventions, and patient empowerment and education.

Discordant assessment of lupus activity between patients and their physicians: the Singapore experience.

Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.

Enhanced expression of interferon-inducible protein-10 correlates with disease activity and clinical manifestations in systemic lupus erythematosus.

Our objective was to investigate the serum levels of interferon-inducible protein-10 (IP-10) in systemic lupus erythematosus (SLE) and their correlation with disease activity and organ manifestations. Serum IP-10 levels were assessed in 464 SLE patients and 50 healthy donors. Disease activity was assessed by the revised SLE Activity Measure, and the concomitant active organ manifestations, anti-ds DNA antibody titres, complement levels and erythrocyte sedimentation rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP-10 in SLE patients and controls was determined by in vitro cultures stimulated with mitogen or lipopolysaccharide. Elevated serum IP-10 levels were observed in SLE patients, which were significantly higher in the presence of active haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced spontaneous IP-10 production in vitro. Serial IP-10 levels correlated with longitudinal change in SLE activity, even at low levels where anti-dsDNA antibody and complement levels remain unchanged. These data demonstrate that IP-10 levels are increased in SLE and serum IP-10 may represent a more sensitive marker for monitoring disease activity than standard serological tests.

Field validation, in Scotland and Iceland, of the artificial mussel for monitoring trace metals in temperate seas.

The artificial mussel (AM), a novel chemical sampling device, has been developed for monitoring dissolved trace metals in marine environments. The AM consists of Chelex-100 suspended in artificial seawater within Perspex tubing and enclosed with semi-permeable polyacrylamide gel at both ends. To validate the field performance of the AM in temperate waters, we deployed AMs alongside transplanted blue mussels Mytilus edulis in coastal environments in Scotland (Holy Loch, Loch Fyne, Loch Striven and Millport) and Iceland (Reykjavikurhöfn, Gufunes, South of thornerney, Hofsvik, Hvalfjörethur and Sandgerethi) for monitoring trace metals. While uptake patterns of Cd between the AM and M. edulis were highly comparable, discrepancies were found in the accumulation profiles of the other metals (Cu, Cr, Pb and Zn), in particular Zn. Nonetheless, the AMs gave a better resolution to accurately reveal the spatial difference in dissolved metal contamination when compared with M. edulis. AMs complement the use of mussels since AMs indicate dissolved metals in seawater, whereas uptake by mussels indicates a mixture of dissolved and particulate metals. Our results also indicated that historical metal exposure of the transplanted M. edulis could significantly confound their metal concentrations especially when the deployment period was short (i.e. <34d). This study suggested that the AM can overcome problems associated with variable biological attributes and pre-exposure history in the mussel, and provides a standardized and representative time-integrated estimate of dissolved metal concentrations in different marine environments.

An 'artificial mussel' for monitoring heavy metals in marine environments.

A new chemical sampling device, artificial mussel (AM), has been developed for monitoring metals in marine environments. This device consists of a polymer ligand suspended in artificial seawater within a Perspex tubing, and enclosed with semi-permeable gel at both ends. Laboratory and field experiments were carried out to examine the uptake of five metals (Cd, Cr, Cu, Pb and Zn) by the AM. Uptake of metals by AM was proportional to the exposure metal concentrations, and the AM was able to accumulate the ASV labile fractions of metals. Uptake and release of the metals of AM are similar to those of the mussel Perna viridis, but less affected by salinity and temperature. Field studies demonstrated that the AM can not only provide a time-integrated estimate of metals concentrations, but also allows comparisons of metal levels in different environments and geographical areas beyond the natural distribution limits of biomonitors.

Removal of phosphate from water by a highly selective La(III)-chelex resin.

A new polymer ligand exchanger (PLE) has been developed for the removal of phosphate in wastewater. This PLE, consisting of lanthanum(III) bound to chelex-100 resin, was prepared by passing LaCl3 solution through a column of chelex-100. Uptake of phosphate from water by this La-chelex resin was investigated in the column mode. The La-chelex resin was able to remove phosphate efficiently from water, and the uptake of phosphate was not affected by the presence of large amounts of anions (0.1M) such as chloride and sulfate. The La-chelex resin was also able to efficiently remove phosphate from seawater to <0.1mg-Pl(-1), and regenerated for reuse by removing the sorbed phosphate by eluting with 6M HCl.

Trace/heavy metal pollution monitoring in estuary and coastal area of Bay of Bengal, Bangladesh and implicated impacts.

Using artificial mussels (AMs), this study reports and compares time-integrated level of eleven trace metals (Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, U, Zn) in Karnafuli River estuary and coastal area of the Bay of Bengal, Bangladesh. Through this study, "hot spots" of metal pollution were identified. The results may demonstrate that the Karnafuli Estuary, and adjacent coastal area of Chittagong, Bangladesh are highly polluted by high risk metals (cadmium, chromium, copper, mercury, nickel, lead, uranium). Agricultural, domestic and industrial wastes directly discharged into the waterways have been identified as the main causes of metal pollution in Chittagong, Bangladesh. The high level of metal pollution identified may impact on local water quality, and seafood catch, livelihoods of people and public health resulting from seafood consumption. There is a need for regular monitoring to ascertain that local water quality with respect to metal levels are within acceptable levels to safeguards both environmental health and public health.

Monitoring of metal pollution in waterways across Bangladesh and ecological and public health implications of pollution.

Using innovative artificial mussels technology for the first time, this study detected eight heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, U, Zn) on a regular basis in waterways across Bangladesh (Chittagong, Dhaka and Khulna). Three heavy metals, viz. Co, Cr and Hg were always below the instrumental detection levels in all the sites during the study period. Through this study, seven metal pollution "hot spots" have been identified, of which, five "hot spots" (Cu, Fe, Mn, Ni, Pb) were located in the Buriganga River, close to the capital Dhaka. Based on this study, the Buriganga River can be classified as the most polluted waterway in Bangladesh compared to waterways monitored in Khulna and Chittagong. Direct effluents discharged from tanneries, textiles are, most likely, reasons for elevated concentrations of heavy metals in the Buriganga River. In other areas (Khulna), agriculture and fish farming effluents may have caused higher Cu, U and Zn in the Bhairab and Rupsa Rivers, whereas untreated industrial discharge and ship breaking activities can be linked to elevated Cd in the coastal sites (Chittagong). Metal pollution may cause significant impacts on water quality (irrigation, drinking), aquatic biodiversity (lethal and sub-lethal effects), food contamination/food security (bioaccumulation of metals in crops and seafood), human health (diseases) and livelihoods of people associated with wetlands.

A novel approach for estimating the removal efficiencies of endocrine disrupting chemicals and heavy metals in wastewater treatment processes.

The wide occurrence of endocrine disrupting chemicals (EDCs) and heavy metals in coastal waters has drawn global concern, and thus their removal efficiencies in sewage treatment processes should be estimated. However, low concentrations coupled with high temporal fluctuations of these pollutants present a monitoring challenge. Using semi-permeable membrane devices (SPMDs) and Artificial Mussels (AMs), this study investigates a novel approach to evaluating the removal efficiency of five EDCs and six heavy metals in primary treatment, secondary treatment and chemically enhanced primary treatment (CEPT) processes. In general, the small difference between maximum and minimum values of individual EDCs and heavy metals measured from influents/effluents of the same sewage treatment plant suggests that passive sampling devices can smooth and integrate temporal fluctuations, and therefore have the potential to serve as cost-effective monitoring devices for the estimation of the removal efficiencies of EDCs and heavy metals in sewage treatment works.

A multivariate regression model predicted falls in residents living in intermediate hostel care.

BACKGROUND AND OBJECTIVE: To evaluate whether individual falls risk could be predicted in a frail elderly population. STUDY DESIGN AND SETTING: We developed and tested an assessment tool and falls risk score for predicting falls based on a multivariate regression model in a prospective cohort study of intermediate care residents. RESULTS: During the follow-up period, 1,736 falls by 1,107 subjects were recorded with an average of 170 falls per 100 person-years. Fifty percent of the study population had at least one fall within a year. Significant independent risk factors were poor balance, cognitive impairment, incontinence, higher illness severity rating, and older age. Twenty-two percent of participants with a falls risk score > or =7 accounted for 42% of the total falls, with a falls rate of 317 per 100 person-years. This rate was a sixfold increase from the falls rate of 52 per 100 person-years observed in participants with a score < 3. A high score (> or =7) indicated almost a 2 in 3 chance of falling, while a low score (<3) indicated approximately a 1 in 7 chance of falling within 6 months. CONCLUSION: The assessment tool and falls risk score could identify individuals in this frail elderly population at high risk of falls.