Unveiling unique clinical phenotypes of hip fracture patients and the temporal association with cardiovascular events.

Cardiovascular events are the leading cause of death among hip fracture patients. This study aims to identify subphenotypes of hip fracture patients and investigate their association with incident cardiovascular events, all-cause mortality, and health service utilisation in Hong Kong and the United Kingdom populations. By the latent class analysis, we show three distinct clusters in the Hong Kong cohort (n = 78,417): Cluster 1 has cerebrovascular and hypertensive diseases, hyperlipidemia, and diabetes; Cluster 2 has congestive heart failure; Cluster 3 consists of relatively healthy patients. Compared to Cluster 3, higher risks of major adverse cardiovascular events are observed in Cluster 1 (hazard ratio 1.97, 95% CI 1.83 to 2.12) and Cluster 2 (hazard ratio 4.06, 95% CI 3.78 to 4.35). Clusters 1 and 2 are also associated with a higher risk of mortality, more unplanned accident and emergency visits and longer hospital stays. Self-controlled case series analysis shows a significantly elevated risk of major adverse cardiovascular events within 60 days post-hip fracture. Similar associations are observed in the United Kingdom cohort (n = 27,948). Pre-existing heart failure is identified as a unique subphenotype associated with poor prognosis after hip fractures.

Development and validation of sex-specific hip fracture prediction models using electronic health records: a retrospective, population-based cohort study.

Background: Hip fracture is associated with immobility, morbidity, mortality, and high medical cost. Due to limited availability of dual-energy X-ray absorptiometry (DXA), hip fracture prediction models without using bone mineral density (BMD) data are essential. We aimed to develop and validate 10-year sex-specific hip fracture prediction models using electronic health records (EHR) without BMD. Methods: In this retrospective, population-based cohort study, anonymized medical records were retrieved from the Clinical Data Analysis and Reporting System for public healthcare service users in Hong Kong aged ≥60 years as of 31 December 2005. A total of 161,051 individuals (91,926 female; 69,125 male) with complete follow-up from 1 January 2006 till the study end date on 31 December 2015 were included in the derivation cohort. The sex-stratified derivation cohort was randomly divided into 80% training and 20% internal testing datasets. An independent validation cohort comprised 3046 community-dwelling participants aged ≥60 years as of 31 December 2005 from the Hong Kong Osteoporosis Study, a prospective cohort which recruited participants between 1995 and 2010. With 395 potential predictors (age, diagnosis, and drug prescription records from EHR), 10-year sex-specific hip fracture prediction models were developed using stepwise selection by logistic regression (LR) and four machine learning (ML) algorithms (gradient boosting machine, random forest, eXtreme gradient boosting, and single-layer neural networks) in the training cohort. Model performance was evaluated in both internal and independent validation cohorts. Findings: In female, the LR model had the highest AUC (0.815; 95% Confidence Interval [CI]: 0.805-0.825) and adequate calibration in internal validation. Reclassification metrics showed the LR model had better discrimination and classification performance than the ML algorithms. Similar performance was attained by the LR model in independent validation, with high AUC (0.841; 95% CI: 0.807-0.87) comparable to other ML algorithms. In internal validation for male, LR model had high AUC (0.818; 95% CI: 0.801-0.834) and it outperformed all ML models as indicated by reclassification metrics, with adequate calibration. In independent validation, the LR model had high AUC (0.898; 95% CI: 0.857-0.939) comparable to ML algorithms. Reclassification metrics demonstrated that LR model had the best discrimination performance. Interpretation: Even without using BMD data, the 10-year hip fracture prediction models developed by conventional LR had better discrimination performance than the models developed by ML algorithms. Upon further validation in independent cohorts, the LR models could be integrated into the routine clinical workflow, aiding the identification of people at high risk for DXA scan. Funding: Health and Medical Research Fund, Health Bureau, Hong Kong SAR Government (reference: 17181381).

Low Bone Mineral Density With Risk of Dementia: A Prospective Cohort Study.

OBJECTIVES: Osteoporosis and dementia often coexist, but the association between the 2 diseases remains unclear. This study aimed to investigate the relationship between bone mineral density (BMD) and the risk of incident dementia. DESIGN: Prospective cohort study, the Hong Kong Osteoporosis Study (HKOS). SETTING AND PARTICIPANTS: Data were from the HKOS and the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. A total of 5803 participants aged ≥40 years and free of dementia were included in the HKOS. METHODS: The baseline BMD at the lumbar spine, femoral neck, trochanter, and total hip were measured using dual-energy x-ray absorptiometry (DXA). The incidence of dementia was identified using their International Classification of Diseases, Ninth Revision, codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: The median follow-up time of the HKOS was 16.8 years. Higher BMD T scores at the lumbar spine, trochanter, and total hip were significantly associated with the reduced risk of dementia with the respective HR of 0.85 (95% CI 0.76-0.95; P = .004), 0.78 (95% CI 0.68-0.90; P < .001), and 0.82 (95% CI 0.72-0.93; P = .003). The subgroup analyses showed that associations were significant in women but not in men, whereas the associations were unaltered after adjusting for serum estradiol. CONCLUSIONS AND IMPLICATIONS: Low BMD was associated with an increased risk of dementia, particularly in women. Future studies evaluating the clinical usefulness of BMD on dementia prediction and management are warranted.

Hip Fracture as a Predictive Marker for the Risk of Dementia: A Population-Based Cohort Study.

OBJECTIVES: This study aimed to investigate the association between hip fracture and the risk of dementia. DESIGN: A retrospective real-world propensity score-matched cohort study was conducted using the real-world hip fracture cohort (RHFC). SETTING AND PARTICIPANTS: Electronic health record data from the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong were used. A total of 52,848 patients aged ≥65 years and with at least an event of fall from 2006 to 2015 were included in the RHFC. METHODS: The incidence of fall, hip fracture, and dementia was determined using their International Classification of Diseases, Ninth Revision (ICD-9) codes. Competing risk regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Hip fracture was associated with an increased risk of dementia (HR 1.09, 95% CI 1.04-1.15, P < .001). The subgroup analysis showed that association was significant in women but not in men. CONCLUSIONS AND IMPLICATIONS: Hip fracture was associated with the increased risk of dementia among older adults. Further studies investigating the potential roles of hip fracture in the development of dementia could benefit the management of both conditions in older adults.

Immediate Risk for Cardiovascular Events in Hip Fracture Patients: A Population-Based Cohort Study.

BACKGROUND: Emerging evidence showed that bone metabolism and cardiovascular disease (CVD) are closely related. We previously observed a potential immediate risk of cardiovascular mortality after hip fracture. However, whether there is an immediate risk of cardiovascular events after hip fracture is unclear. The aim of this study was to evaluate the risk for major adverse cardiovascular events (MACEs) between patients having experienced falls with and without hip fracture. METHODS: This retrospective population-based cohort study used data from a centralized electronic health record database managed by Hong Kong Hospital Authority. Patients having experienced falls with and without hip fracture were matched by propensity score (PS) at a 1:1 ratio. Adjusted associations between hip fracture and risk of MACEs were evaluated using competing risk regression after accounting for competing risk of death. RESULTS: Competing risk regression showed that hip fracture was associated with increased 1-year risk of MACEs (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.21-1.33; p < .001), with a 1-year cumulative incidence difference of 2.40% (1.94%-2.87%). The HR was the highest in the first 90-days after hip fracture (HR of 1.32), and such an estimate was continuously reduced in 180 days, 270 days, and 1 year after hip fracture. CONCLUSIONS: Hip fracture was associated with increased immediate risk of MACEs. This study suggested that a prompt evaluation of MACE among older adults aged 65 years and older who are diagnosed with hip fracture irrespectively of cardiovascular risk factors may be important, as early management may reduce subsequent risk of MACE.

Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

INTRODUCTION: Perampanel is a first-in-class antiepileptic drug approved for adjunctive treatment of partial-onset seizure in patients aged 12 years or older. Published randomised controlled trials (RCTs) had small sample sizes, and meta-analyses have included too few studies to draw conclusive results for the assessment of tolerability, efficacy and safety of perampanel. There is a need to conduct a meta-analysis with a larger dataset and an appropriate study design. OBJECTIVE: The aim of this study was to systematically review the efficacy and safety of perampanel in the treatment of partial-onset epilepsy. METHODS: Electronic and clinical trials databases were searched for RCTs of perampanel published up to March 2013. Outcomes of interest were 50 % responder rates, seizure freedom, treatment-emergent adverse events (TEAEs) and incidence of withdrawal. Meta-analysis was performed to investigate the outcomes of interest. RESULTS: Five RCTs with a total of 1,678 subjects were included. The 50 % responder rates were significantly greater in patients receiving 4, 8 and 12 mg perampanel versus placebo, with risk ratios of 1.54 (95 % CI 1.11-2.13), 1.80 (95 % CI 1.38-2.35) and 1.72 (95 % CI 1.17-2.52), respectively. There was no statistical evidence of a difference in seizure freedom between 8 or 12 mg perampanel and placebo. Of the five commonly reported TEAEs included, both dizziness and somnolence were statistically associated with 8 mg perampanel, whilst dizziness was statistically associated with 12 mg perampanel. Incidences of withdrawal due to adverse events were significantly higher in the 8 mg and 12 mg perampanel groups versus placebo. CONCLUSION: The use of perampanel resulted in a statistically significant reduction of seizure frequency with respect to the 50 % responder rate in patients with partial-onset epilepsy. Perampanel is well tolerated at 4 mg and reasonably tolerated at 8 and 12 mg. Further clinical and pharmacovigilance studies are required to investigate the long-term efficacy and safety of perampanel in the management of other types of epilepsy.

Urinary findings and renal function in adult Navajo Indians and associations with type 2 diabetes.

We screened a sample of adult Navajo Indians for signs of renal disease that might underlie their increasing rates of renal failure. Nondiabetics had modest rates of hypertension, which was more common in males and increased with age. Microscopic hematuria was very common, and only a fraction was associated with progressive nephropathy. Microalbuminuria, mostly undetected by routine dipstick, was present in 14.6% of subjects; overt albuminuria was present in 2%. Increasing albuminuria was related to renal insufficiency, which was more common in males. Hypertension was associated with greater then threefold increases in both albuminuria and renal insufficiency. Cardiovascular disease was uncommon and had no discernible relationship to albuminuria. Most diabetic patients (58.4%) had hypertension, with equal rates for males and females. Fully half of all diabetic patients had unsatisfactory blood pressure levels at screening. Rates and patterns of hematuria were like those of nondiabetics. Microalbuminuria was present in 36.1% and overt albuminuria in 17.9%, four and eight times the rates in matched nondiabetics, respectively; these differences persisted after controlling for blood pressure. Renal insufficiency was associated with progressive albuminuria and was present in 10.6%, with equal rates in males and females. Hypertension, albuminuria, and renal insufficiency, but not hematuria, increased with increasing diabetes duration. Hypertension was associated with a twofold increase in albuminuria, a threefold increase in overt albuminuria, and an eightfold increase in renal insufficiency. Cardiovascular disease had no detectable association with microalbuminuria, but had a strong relationship to overt albuminuria. The high rates of hematuria are not well explained. It probably has nonrenal as well as renal origins, the latter including mesangial proliferative glomerulonephritis. The impressive rates of albuminuria among diabetic patients mark a large reservoir of renal disease and fore-shadow even larger burdens of end-stage renal disease and cardiovascular disease in the near future. Improved detection and treatment of hypertension is needed to slow the progression of renal disease in nondiabetics and diabetics, together with screening and treatment protocols for albuminuric diabetic patients. Prevention of albuminuria probably involves population-based modification of blood pressure and metabolic profiles.