HbA1c variability, in addition to mean HbA1c, predicts incident hip fractures in Chinese people with type 2 diabetes.

Type 2 diabetes is associated with an increased risk of hip fractures. We hypothesize that long-term glycemic variability predicts incident hip fractures. We demonstrated that HbA1c variability predicted incident hip fractures independent of mean HbA1c, suggesting the potential benefits of minimizing glycemic variability in addition to optimizing mean glycemia for bone health. INTRODUCTION: Type 2 diabetes is associated with an increased risk of hip fractures, and a linear relationship between HbA1c levels and hip fracture incidence has been observed. We hypothesize that HbA1c variability also predicts incident hip fractures in type 2 diabetes. METHODS: Chinese individuals with type 2 diabetes aged ≥ 60 years were identified from electronic health records in Hong Kong between 2008 and 2012 and observed for incident hip fractures. Hip fracture was defined by the International Classification of Diseases (Ninth Revision) code 820. HbA1c variability was determined using standard deviation, adjusted standard deviation, and coefficient of variation of HbA1c measurements in the 5 years preceding the entry date. Multivariable Cox regression analysis was used to evaluate associations between HbA1c variability and incident hip fractures. RESULTS: A total of 83,282 participants were included. Their mean age was 71.3 ± 7.5 years, duration of diabetes 11.7 ± 7.7 years, baseline HbA1c 56.6 ± 13.5 mmol/mol (7.33 ± 1.23%), and median follow-up 6.8 years. All indices of HbA1c variability were significant independent predictors of incident hip fractures, with an adjusted hazard ratio of up to 1.29 (all p < 0.001), and remained to be independent predictors across groups of different intensity of glycemic control. Mean HbA1c ≥ 64 mmol/mol (8.0%) was associated with a 25% increase in incident hip fractures compared with mean HbA1c < 53 mmol/mol (7.0%). CONCLUSION: HbA1c variability is an independent positive predictor of hip fracture in type 2 diabetes, across the spectrum of varying degree of glycemic control, while a high HbA1c is also not advisable from the perspective of bone health.

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Epilepsy is defined as drug-resistant after failure of two adequate trials of appropriately chosen and administered antiepileptic drugs. Approximately 30% of patients with epilepsy have drug-resistant epilepsy. Reasons for treatment failure include failure to recognise epilepsy syndrome, poor drug compliance, and lifestyle factors. Patients with drug-resistant epilepsy should be encouraged to have early referral to a tertiary epilepsy centre for presurgical evaluation. Comprehensive neurophysiology, structural neuroimaging, neuropsychological, and psychiatric assessments are regarded as essential for determining suitability for epilepsy surgery. Epilepsy surgery, whether resection, disconnection, or neuromodulation, should be recommended only after multidisciplinary consensus agreement based on these assessments.

Guidance on the management of familial hypercholesterolaemia in Hong Kong: an expert panel consensus viewpoin.

In 2016, meetings of groups of physicians and paediatricians with a special interest in lipid disorders and familial hypercholesterolaemia were held to discuss several domains of management of familial hypercholesterolaemia in adults and children in Hong Kong. After reviewing the evidence and guidelines for the diagnosis, screening, and management of familial hypercholesterolaemia, consensus was reached on the following aspects: clinical features, diagnostic criteria, screening in adults, screening in children, management in relation to target plasma low-density lipoprotein cholesterol levels, detection of atherosclerosis, lifestyle and behaviour modification, and pharmacotherapy.

An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong.

OBJECTIVE: New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong. PARTICIPANTS: Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society. EVIDENCE: A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution. CONSENSUS PROCESS: Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature. CONCLUSIONS: Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.

Covert stroke after non-cardiac surgery: a prospective cohort study.

BACKGROUND: Overt stroke after non-cardiac surgery has a substantial impact on the duration and quality of life. Covert stroke in the non-surgical setting is much more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac, non-carotid artery surgery. METHODS: We undertook a prospective, international cohort study to determine the incidence of covert stroke after non-cardiac, non-carotid artery surgery. Eligible patients were ≥65 yr of age and were admitted to hospital for at least three nights after non-cardiac, non-carotid artery surgery. Patients underwent a brain magnetic resonance study between postoperative days 3 and 10. The main outcome was the incidence of perioperative covert stroke. RESULTS: We enrolled a total of 100 patients from six centres in four countries. The incidence of perioperative covert stroke was 10.0% (10/100 patients, 95% confidence interval 5.5-17.4%). Five of the six centres that enrolled patients reported an incident covert stroke, and covert stroke was found in patients undergoing major general (3/27), major orthopaedic (3/41), major urological or gynaecological (3/22), and low-risk surgery (1/12). CONCLUSIONS: This international multicentre study suggests that 1 in 10 patients ≥65 yr of age experiences a perioperative covert stroke. A larger study is required to determine the impact of perioperative covert stroke on patient-important outcomes. CLINICAL TRIAL REGISTRATION: NCT01369537.

Update to the Hong Kong Epilepsy Guideline: evidence-based recommendations for clinical management of women with epilepsy throughout the reproductive cycle.

Since the publication of the Hong Kong Epilepsy Guideline in 2009, there has been significant progress in antiepileptic drug development. New AEDs have emerged, and data about their uses have been published. Women require special attention in epilepsy care. Drug teratogenicity, pregnancy, breastfeeding, contraception, reproduction technology, menopause, and catamenial epilepsy are major topics. Antiepileptic drugs should be chosen individually for patients who are pregnant or may become pregnant with consideration of their teratogenicity and seizure control properties. Folate is commonly prescribed for women of childbearing age who are taking antiepileptic drugs. Spontaneous vaginal delivery and breastfeeding are not contra-indicated in most cases but need to be considered individually based on the patient's medical condition and wishes. Serum drug level monitoring of certain antiepileptic drugs during pregnancy and puerperium can guide dosage adjustment. For catamenial epilepsy, intermittent benzodiazepines such as clobazam during the susceptible phase of the menstrual cycle could be a treatment option.

MoCA-assessed cognitive function and excellent outcome after aneurysmal subarachnoid hemorrhage at 1 year.

BACKGROUND AND PURPOSE: After aneurysmal subarachnoid hemorrhage (aSAH), cognitive impairment, even mild and relatively isolated, can be devastating, especially in working-age persons. The Montreal Cognitive Assessment (MoCA) is accepted as a valid screening tool for mild cognitive impairment due to cerebral ischaemia. Whether MoCA is independently associated with excellent outcome [a score of 0 on the modified Rankin Scale (mRS) or 18/18 on the Lawton Instrumental Activities of Daily Living (IADL) scale] 1 year after aSAH was assessed. METHODS: Hong Kong Chinese aSAH patients were assessed prospectively by means of the MoCA, Mini-Mental State Examination (MMSE), mRS and IADL scale at 1 year. This multicenter prospective observational study is registered at ClinicalTrials.gov of the US National Institutes of Health (NCT01038193). RESULTS: In all, 194 patients completed the assessments at 1 year. After adjustment for age, both excellent IADL and mRS outcomes were associated with MoCA (OR 1.2, 95% CI 1.1-1.3, P < 0.001, and OR 1.1, 95% CI 1.0-1.2, P = 0.001, respectively). CONCLUSIONS: MoCA-assessed cognitive function is an important determinant for excellent outcomes after aSAH.

Geriatric hip fracture clinical pathway: the Hong Kong experience.

Geriatric hip fracture is one of the commonest fractures in orthopaedic trauma. There is a trend of further increase in its incidence in the coming decades. Besides the development of techniques and implants to overcome the difficulties in fixation of osteoporosis bone, the general management of the hip fracture is also very challenging in terms of the preparation of the generally poorer pre-morbid state and complicate social problems associated with this group of patients. In order to cope with the increasing demand, our hospital started a geriatric hip fracture clinical pathway in 2007. The aim of this pathway is to provide better care for this group of patients through multidisciplinary approach. From year 2007 to 2009, we had managed 964 hip fracture patients. After the implementation of the pathway, the pre-operative and the total length of stay in acute hospital were shortened by over 5 days. Other clinical outcomes including surgical site infection, 30 days mortality and also incidence of pressure sore improved when compared to the data before the pathway. The rate of surgical site infection was 0.98%, and the 30 days mortality was 1.67% in 2009. The active participation of physiotherapists, occupational therapists as well as medical social workers also helped to formulate the discharge plan as early as the patient is admitted. In conclusion, a well-planned and executed clinical pathway for hip fracture can improve the clinical outcomes of the geriatric hip fractures.

An expedited stroke triage pathway: the key to shortening the door-to-needle time in delivery of thrombolysis.

OBJECTIVES: To assess time management of stroke thrombolysis triage and functional outcomes in patients receiving recombinant tissue plasminogen activator for hyperacute stroke, and identify bottlenecks in delivery of the treatment. DESIGN: Prospective study. SETTING: A university teaching hospital in Hong Kong. PATIENTS: Patients with suspected hyperacute stroke referred to the stroke thrombolysis team during October 2008 to September 2009. MAIN OUTCOME MEASURES: Time performance records including door-to-stroke team, door-to-needle, and onset-to-thrombolysis times. Functional outcomes by modified Rankin Scale score at 3 months, and thrombolysis-related complications including haemorrhagic transformations and mortality. RESULTS: During the 12-month period, 95 thrombolysis calls were received; recombinant tissue plasminogen activator was given intravenously to 17 (18%) of the patients and intra-arterially to 11 (12%). The mean (standard deviation) door-to-stroke team and the door-to-needle times for intravenous recombinant tissue plasminogen activator patients were 33 (25) and 80 (25) minutes, respectively; both were about 20 minutes longer than that recommended by the National Institute of Neurological Disorders and Stroke. The mean National Institute of Health Stroke Scale score for patients received intravenous recombinant tissue plasminogen activator was 16 (standard deviation, 7). The mean (standard deviation) onset-to-treatment time was 144 (42) minutes. Nine (53%) patients who received intravenous recombinant tissue plasminogen activator achieved favourable outcomes at 3 months, with a modified Rankin Scale score of 0 to 1. Symptomatic haemorrhage and mortality occurred in one (6%) patient. CONCLUSION: A dedicated stroke triage pathway is essential to ensure efficient and safe delivery of thrombolysis therapy. Improvements in door-to-stroke team time through integration with emergency medicine staff and neuroradiologists may improve thrombolysis eligibility.

Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients.

BACKGROUND: Common risk factors exist in colorectal neoplasia (cancer or adenoma) and coronary artery disease. AIM: To investigate in a retrospective study if there is coexistence of the two events in patients > OR =50 years. METHODS: Computer data on colonoscopies performed on symptomatic patients, the corresponding medical record and colonic histology in 1997-2000 were retrieved. History of coronary artery disease was recorded. To adjust for the factors of age and sex, bivariate logistic regression analysis was used to test for coexistence. RESULTS: 1382 patients were recruited. Colorectal neoplasia and history of coronary artery disease were present in 27% (373) and 12% (167) of patients, respectively. The mean age of patients was older in colorectal neoplasia+ (75 +/- 11 vs. 69 +/- 13 years, P < 0.0001) and in coronary artery disease+ (79 +/- 9 vs. 69 +/- 12 years, P < 0.0001) patients. Male was the predominant sex in colorectal neoplasia+: 33% vs. 22% (P < 0.0001), but not in coronary artery disease+ (P = 0.29). Colorectal neoplasia+ patients were more likely to have coronary artery disease+ [21.2% (79/373) vs. 8.8% (89/1098) (P < 0.0001)]. Bivariate logistic regression analysis showed strong association between the two events (OR: 2.12, 95% CI: 1.5, 3.0). CONCLUSION: There is strong coexistence of colorectal neoplasia and coronary artery disease, probably due to exposure to common risk factors.

Generation and Characterization of Patient-Specific iPSC Model for Cardiovascular Disease.

Advances in differentiation of cardiomyocytes from human induced pluripotent stem cell (hiPSC) were emerged as a tool for modeling of cardiovascular disease that recapitulates the phenotype for the purpose of drug screening, biomarker discovery, and testing of single-nucleotide polymorphism (SNP) as a modifier for disease stratification. Here, we describe the (1) retroviral reprogramming strategies in the generation of human iPSC, (2) methodology in characterization of iPSC in order to identify the stem cell clones with the best quality, and (3) protocol of cardiac differentiation by modulation of Wnt signaling and ß-catenin pathway.

Pathologic hip fractures secondary to amyloidoma. Case report and review of the literature.

Amyloidoma primarily involving bone and lymph node is described in a 60-year-old male patient. The patient had pathologic fractures of both hips through a deposit of amyloid in the neck of the femur. The prolonged insidious course of the disease was uncomplicated by hypercalcemia, hematologic abnormalities, or renal failure so characteristic of untreated myeloma. The bone marrow contained less than 10 percent plasma cells in different stages of maturity. Radionuclide bone scanning demonstrated other osseous amyloid lesions that were not detected by routine radiologic examination. This is the first reported case of pathologic fractures of both hips secondary to amyloidoma.

A standardized technique for lower limb radiography. Practice, applications, and error analysis.

The normal standing radiograph, which provides a view of the knee only, is prone to errors of parallax and poor control of patient positioning. A standardized radiographic procedure was developed to control these sources of error. Anteroposterior and lateral views of the lower limb (hip and knee) are obtained without moving the patient from a standardized position; this includes control of ankle position and limb rotation. To correct for parallax error, radiopaque markers are positioned between the patient and the x-ray source. The locations of bone landmarks and reference markers on the radiographs are digitized, and a software package provides a display of key parameters. Error analysis of the method confirmed that most angles were sensitive to contrived positional variations, especially limb rotation and knee flexion. Load distribution between limbs was not critical. The greatest error was random. Most angles were reproducible within +/- 1.3 degrees or less at 95% confidence.

Tibial anatomy and functional axes.

Articular geometry of the tibia has been studied in relation to the functional axis and extra-articular bone landmarks, using a Cartesian coordinate system. Thirty-one cadaver limbs were used, 26 of them paired. The donor age range was 61 to 89 years (17 females, 14 males), none of whom showed evidence of significant arthritic deterioration. Most linear parameters were greater in males than females (p less than 0.005), and correlations between these parameters were noted, e.g., tibial length versus plateau width (r = 0.7, p less than 0.01) with both genders combined. Gender differences occurred in only two of the angular parameters--tibial torsion (p less than 0.025) and foot rotation (p less than 0.005). For the latter, mean rotation was internal (-5 degrees) for males, and external (11 degrees) for females. No correlations between angular parameters were found. In the paired limbs, there was asymmetrical distribution of just two parameters--varus tilt of the tibial plateau margins (p less than 0.005) and lateral deviation of the tuberosity (p less than 0.025). The data complement a previous report on the femur. These studies are relevant to the kinematics of the lower limb, design and sizing of resurfacing components, and possibly to the pathogenesis of osteoarthritis.

Geometry of the first metatarsophalangeal joint.

This study aimed to define the articular geometry of the metatarsophalangeal (MTP) joint of the great toe. Embedded in resin blocks, five pairs of cadaveric first MTP joints (all from men) were sequentially cut in the sagittal plane with a milling machine, removing 0.5 mm of bone in each cut. The photographed cartilaginous outline of each cut was digitized against reference markers, which enabled a computer system to superimpose each outline in three dimensions. The intersesamoidal ridge was found to be parallel to the lateral shaft. The peak of the ridge was just lateral to the midline of the MT head. The articular outline, through the ridge of each sample, was circular; however, other surface contours were noncircular. The undulating plantar aspect of the MTP head formed by the intersesamoidal ridge and related grooves was found to have symmetric relationships to the sesamoid bones and a consistent orientation to the shaft. The rounded distal dorsal aspect of the MTP head showed consistent differences to the concavity formed by the phalangeal base. The sample size is too small for the sizing of prostheses but it is adequate to study the geometry of the MTP joint. More data are needed for the accurate replication of a resurfacing prosthesis and understanding of joint kinematics.