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.

Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

In vitro antibacterial activity and physicochemical properties of a crude methanol extract of the larvae of the blow fly Lucilia cuprina.

The emergence of multidrug-resistant bacterial strains has prompted the reintroduction of maggot therapy in the treatment of chronic, infected wounds. Many previous studies have demonstrated the potent antibacterial activity of larval excretions/secretions of the blowfly Lucilia sericata (Meigen) (Diptera:Calliphoridae) against bacteria. However, the antibacterial activity of its sibling species, Lucilia cuprina (Wiedemann) (Diptera:Calliphoridae) against a wide range of pathogenic bacteria has never been determined. The aim of this study was to develop a new procedure to produce whole body extract of larvae of L. cuprina via methanol extraction as well as to demonstrate the in vitro antibacterial activity of this extract against seven selected wound pathogens (Staphylococcus aureus, methicillin-resistant S. aureus, S. epidermidis, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli). The turbidimetric assay demonstrated that L. cuprina larval extract was significantly potent against all bacteria tested (P < 0.001). Additionally, colony-forming unit (CFU), agar well diffusion and minimum inhibitory concentration assays have confirmed the apparent potency of larval extract against P. aeruginosa. The reconstituted larval extract was highly robust and thermally stable. These observations substantiated the feasibility of the methanol extraction method in the production of larval extract.

Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria.

BACKGROUND: Long-term overall survival after liver resection in patients with hepatocellular carcinoma (HCC) within the Milan criteria has been reported to improve in recent years. This study systematically reviewed the outcomes of surgical resection for HCC in patients with good liver function and meeting the Milan criteria for early HCC, published in the past 10 years. METHODS: A literature search was conducted in PubMed for papers on outcomes of surgical resection for HCC published between January 2000 and December 2010. Cochrane systematic review methodology was used for this review. The primary outcome was overall survival. Secondary outcomes included operative mortality and disease-free survival. Studies that focused on geriatric populations, paediatric populations, a subset of the Milan criteria (such solitary tumours) or included patients with incidental tumours were excluded, as were case reports, conference abstracts, and studies with a large proportion of Child-Pugh grade C liver cirrhosis or unknown Child-Pugh status. RESULTS: Of 152 studies reviewed, two randomized clinical trials and 27 retrospective case series were eligible for inclusion. The 5-year overall survival rate after resection of HCC ranged from 27 to 81 (median 67) per cent, and the median disease-free survival rate from 21 to 57 (median 37) per cent. There was a trend towards improved overall survival in recent years. The operative mortality rate ranged from 0 to 5 (median 0·7) per cent. CONCLUSION: Surgical resection offers good overall survival for patients with HCC within the Milan criteria and with good liver function, although recurrence rates remain high. Outcomes have tended to improve in more recent years.

Meteorological factors and El Niño Southern Oscillation are independently associated with dengue infections.

Our objective was to determine the association between temperature, humidity, rainfall and dengue activity in Singapore, after taking into account lag periods as well as long-term climate variability such as the El Niño Southern Oscillation Index (SOI). We used a Poisson model which allowed for autocorrelation and overdispersion in the data. We found weekly mean temperature and mean relative humidity as well as SOI to be significantly and independently associated with dengue notifications. There was an interaction effect by periods of dengue outbreaks, but periods where El Niño was present did not moderate the relationship between humidity and temperature with dengue notifications. Our results help to understand the temporal trends of dengue in Singapore, and further reinforce the findings that meteorological factors are important in the epidemiology of dengue.

Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC. METHODS: From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day(-1)). End points were overall survival (OS) and quality of life. RESULTS: An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92-1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting. CONCLUSION: Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

Lack of association of dengue activity with haze.

Dengue activity depends on fluctuations in Aedes populations which in turn are known to be influenced by climate factors including temperature, humidity and rainfall. It has been hypothesized that haze may reduce dengue transmission. Due to its geographical location Singapore suffers almost every year from hazes caused by wildfires from Indonesia. Such hazes have a significant impact on pollution indexes in Singapore. We set out to study the relationship of dengue activity and haze (measured as pollution standard index) in Singapore, using ARIMA models. We ran different univariate models, each encompassing a different lag period for the effects of haze and temperature (from lag 0 to lag 12 weeks). We analysed the data on a natural logarithmic scale to stabilize the variance and improve the estimation. No association between dengue activity and haze was found. Our findings do not lend support to the hypothesis that haze is associated with reduced dengue activity in Singapore.

Diagnostic utility of F waves in cervical radiculopathy: electrophysiological and magnetic resonance imaging correlation.

OBJECTIVE: F wave study is a simple, non-invasive method commonly utilized for evaluation of cervical root lesions. Its diagnostic sensitivity is low. There are no large series comparing F wave studies with MRI as a reference standard. PATIENTS AND METHODS: We performed F wave studies in 30 controls (15 men; mean age: 50 years; standard deviation: 17.9 years; range: 21-80 years) and, prospectively, 31 patients (19 men; mean age: 48 years; standard deviation: 16.2 years; range: 26-79 years) referred for evaluation of cervical spondylotic radiculopathy (CSR). All patients' MRIs were compared with F wave parameters. RESULTS: Combined utilization of minimal F latency, F chronodispersion, F persistence and side to side differences resulted in 55% sensitivity and 100% side concordance for detecting CSR, with MRI as a comparison standard. F wave parameters also provided complementary information to needle electromyography in the diagnostic evaluation of CSR. Although F waves were not indicative of radiculopathy levels, 4/31 (13%) of cases had at least one abnormal F wave parameter, despite normal electromyography findings. CONCLUSIONS: Combined utilization of multiple F wave parameters is a useful, diagnostic adjunct in the electrophysiological evaluation of CSR.

The value of bilateral ipsilateral and contralateral motor evoked potential monitoring in scoliosis surgery.

Intraoperative monitoring (IOM) of the motor pathways is a routine procedure for ensuring integrity of corticospinal tracts during scoliosis surgery. We have previously demonstrated presence of ipsilateral motor evoked potentials (MEPs) during IOM for scoliosis surgery, but its significance was uncertain. In this case series, we show concurrent ipsilateral and contralateral MEP amplitude changes obtained with cortical stimulation are of value in reducing false positive observations during IOM. The use of this easily recordable MEP is thus advocated as a diagnostic adjunct to contralateral MEPs for scoliosis and spinal surgery.

Cutaneous silent periods in the evaluation of cord compression in cervical spondylosis.

OBJECTIVE: The clinical diagnosis of cervical spondylotic myelopathy (CSM) may be challenging in patients with cervical spondylosis (CS). Routine nerve conduction studies (NCS) may not evaluate cord compression adequately. METHODS: We obtained cutaneous silent periods (CSP) in 26 consecutive patients presenting with clinical features of CS, in comparison with 30 normal controls. The results were also compared with transcranial magnetic stimulation (TMS) findings, and magnetic resonance imaging of the cervical cord as the gold standard. RESULTS: CSP findings showed similarly high sensitivity of up to 96% with TMS in evaluating cervical cord dysfunction. CONCLUSION: In specific clinical settings, CSP is of value for the diagnosis of CSM in CS. CSP measurement is advocated as a simple and rapid diagnostic adjunct to NCS in evaluating CS patients with possible cord compromise.

Biometrical aspects of drug development.

Once the activity of a compound has been established in the laboratory (usually by use of experimental animals) the next stage of development is to bring this forward to humans in early-phase clinical trials. A pharmacokinetic study aims to establish an effective dosing regimen for the compound in order to reach concentrations within the therapeutic window as quickly as possible. The aim of the phase I trials is typically to determine a maximal safe dose with which more rigorous investigation of activity in a phase II trial can be conducted. This chapter deals with statistical issues related to the design of phase I studies.

Traction and spica casting for closed femoral shaft fractures in children.

PURPOSE: To evaluate the treatment outcome of skin traction followed by spica casting for closed femoral shaft fractures in children. METHODS: Between September 1997 and December 2001 inclusive, outcomes of 63 children aged one month to 15 (mean, 5.3) years with closed femoral shaft fractures managed with skin traction and spica casting were reviewed. Depending on age, patients were kept in traction from 2 to 15 (median, 9) days, then in spica casts for 2 to 8 (median, 5) weeks. RESULTS: Bony union took 3 to 12 (median, 6) weeks. There were no malunion, nonunion, or rotational deformities. Nor were there any significant limb length discrepancies, pressure sores, or nerve palsies. On no occasion was a spica cast removed and reapplied for loss of fracture reduction. At final follow-up, limb length discrepancy was noted in 14 (22%) of the patients, but none had a discrepancy of greater than 1.5 cm or a short-legged gait. CONCLUSION: Skin traction followed by spica casting for closed femoral shaft fractures in children is safe, cost-effective and associated with a low complication rate. It is effective in children below 5 years of age and no less effective in older children, except in instances of open fracture, multiple fractures, or older children with large statures, which conditions render them intolerant to spica casts.

Transcranial magnetic stimulation screening for cord compression in cervical spondylosis.

OBJECTIVE: Cervical spondylosis (CS) often results in various degrees of cord compression, which can be evaluated functionally with transcranial magnetic stimulation (TMS). We investigate the use of TMS as a screening tool for myelopathy in CS. METHODS: We prospectively studied 231 patients classified into Groups 1 to 4 based on MRI grading of severity of cord compromise. TMS elicited central motor conduction times and motor evoked potential (MEP) amplitudes in all 4 limbs. The results were compared with those from 45 healthy controls. RESULTS: TMS showed 98% sensitivity and 98% specificity for cord abnormality using MRI as reference standard. CONCLUSIONS: MEP abnormalities are useful for electrophysiological evaluation of cord compression in CS. While TMS is not a substitute for MRI, it is of value as a rapid, inexpensive and non-invasive technique for screening patients before MRI studies.

Intraoperative monitoring study of ipsilateral motor evoked potentials in scoliosis surgery.

Ipsilateral motor evoked potentials (MEPs) in spinal cord surgery intraoperative monitoring is not well studied. We show that ipsilateral MEPs have significantly larger amplitudes and were elicited with lower stimulation intensities than contralateral MEPs. The possible underlying mechanisms are discussed based on current knowledge of corticospinal pathways. Ipsilateral MEPs may provide additional information on the integrity of descending motor tracts during spinal surgery monitoring.

Effects of vitamin B fortified sucrose solution on the longevity and reproductive potentials of laboratory-bred Culex quinquefasciatus Say adult.

Laboratory colonised mosquitoes are usually maintained on vitamin B complex fortified sucrose solution, however only few studies were conducted to evaluate the effects of such practice. This study aimed to determine the effects of different concentrations of sucrose solution fortified with and without 1% vitamin B complex on the longevity and reproductive potential of adult female of a local strain of Culex quinquefasciatus Say. Two arms of studies were carried out separately and each arm was triplicated. In one arm, concentrations of sucrose solution at 0%, 1%, 3%, 5% and 10% fortified with 1% Vitamin B complex were fed to the mosquitoes, while in the other arm, similar sucrose concentrations were used but without 1% vitamin B complex. Adult Cx. quinquefasciatus maintained on 5% sucrose solution fortified with 1% vitamin B complex exhibited significant extended vitality and longevity in stimulating ovarian development, compared with other vitamin fortified sucrose concentrations (p<0.05). The vitality and longevity of F0 and F1 males were 76.67±2.19 days and 57.67±8.19 days respectively. The F0 females survived the longest duration of 107.67±5.61 days and the F1 females survived 90.67±12.47 days with higher number of eggs laid, i.e. 1427.67±62.89 eggs at a higher hatchability rate of 57.05±8.39% or 814.49 eggs hatched. Thus, 5% sucrose solution fortified with 1% Vitamin B complex should be used to produce colonies of homogenous mosquitoes as this exerts positive biological effects on laboratory-bred Cx. quinquefasciatus.

Pectoralis major motor evoked potentials in cervical spondylosis.

Myelopathy is a severe complication of cervical spondylosis (CS). We studied 27 consecutive patients with CS referred for evaluation for possible myelopathy using transcranial magnetic stimulation. The findings were compared with those from 20 normal controls. Magnetic resonance imaging was utilized to assess the degree of cord compromise. Central motor conduction time (CMCT) abnormalities showed equivalent diagnostic yield with pectoralis major (PM) recordings, as compared with combined first dorsal interossei and abductor hallucis recordings. Our findings show that CMCT measurement with PM recordings is of value as a diagnostic adjunct in the electrophysiological evaluation of myelopathy in CS.

Candida spondylodiscitis and epidural abscess: management with shorter courses of anti-fungal therapy in combination with surgical debridement.

Epidural abscess associated with candidal spondylodiscitis is rarely seen, particularly when it involves the cervical and thoracic spine. We report two such cases that were successfully managed with early surgical debridement, as well as medical therapy with intravenous amphotericin followed by oral fluconazole. The literature related to candidal spinal infection is reviewed, and a rational approach to the management of this uncommon condition is proposed. A good outcome may generally be expected with early diagnosis as well as appropriate surgical and pharmacological treatment. Oral fluconazole appears to be useful in the management of candida spondylodiscitis complicated by epidural abscess formation. Treatment until a normal ESR is attained is ideal, and this may be as short as 3 months when surgical drainage has been adequately performed.

p53 and bcl-2 expression in invasive and pre-invasive uterine papillary serous carcinoma and atrophic endometrium.

INTRODUCTION: Uterine papillary serous carcinoma (UPSC), a high-grade tumour, is known to be associated in some cases with an identifiable intraepithelial neoplasia (IEN) component. Biomarker studies incorporating this latter component are not well documented. One aim of the present study was to compare levels of immunohistochemical (IHC) expression of p53 tumour suppressor gene and bcl-2 oncoprotein between UPSC and IEN, as well as normal endometrium to determine its biologic significance. The other major aim was to determine if these IHC results have any bearing on survival data in this tumour. MATERIALS AND METHODS: An immunoreactivity score was assigned for examination of p53 and bcl-2 expression in a total of 21 cases of UPSC, 9 with an evaluable IEN component and 11 with associated non-neoplastic endometrium. Statistical analysis of IHC results was performed, in addition to correlation with survival data and disease stage. RESULTS: p53 was identified in 16/21 cases of UPSC (76%) and 8/9 cases of IEN (89%), and no cases of normal endometrium. By contrast, bcl-2 was positive in all normal endometria with less expression in UPSC leaving 15/21 (71%) cases positive, and in IEN, leaving 5/9 (55%) of cases positive. Differences in immunoreactive scores for both p53 and bcl-2 between UPSC and benign glands, as well as between IEN and benign glands reached statistical significance with P values of 0.006 and 0.014 for p53, and 0.003 and 0.027 for bcl-2 respectively. There was no statistical significance between values for UPSC and IEN. Cox regression analysis found no statistically significant relationship between patient survival time in early and late stages of disease, and p53 and bcl-2 immunoscores. CONCLUSIONS: The lack of a significant difference between the bcl-2 and p53 values for both UPSC and IEN suggests that these molecular alterations occur at an early stage of tumour pathogenesis. A potential advantage of the use of immunohistochemical markers is their application to routinely processed surgical specimens. In this case, bcl-2 and p53 were applied in UPSC to determine any potential significance, but neither marker proved to be a useful predictor of survival time or disease stage.

Risk perception is affected by modes of risk presentation among Singaporeans.

INTRODUCTION: Not much is known about how Singaporeans perceive and react to risk presentation. There is no consensus on whether the European Union guidelines for describing the risk of side effects are valid. This study investigated the effect of different modes of risk presentation on how Singaporeans perceive and react to medical risk. Furthermore, we investigated the practical usage of qualitative phrases, the European Union's adjectives in particular, in describing levels of risk. MATERIALS AND METHODS: A hypothetical situation about the risk of side effects of an influenza vaccine was presented in either a probability format (i.e., 5%; n = 42) or a frequency format (i.e., 1 out of 20; n = 43). The 2 versions of questionnaire were handed out in an alternate order to a convenience sample of 47 healthcare professionals and 38 university students. RESULTS: Respondents presented with a "5% risk" were more likely to describe the risk as "uncommon" or "rare", as compared to respondents presented with a risk of "one out of twenty" (P <0.01). Furthermore, the former showed more willingness to accept the influenza vaccine described in the hypothetical situation than in the latter, but this was not statistically different (67% versus 54%; P >0.1). CONCLUSIONS: Modes of risk presentation affect how people perceive risk, even among people who are highly educated.

Motor and somatosensory abnormalities are significant etiological factors for adolescent idiopathic scoliosis.

OBJECTIVE: In adolescent idiopathic scoliosis (AIS), we explore the role of lateralized motor and somatosensory abnormalities as a possible etiological factor. METHODS: Intraoperative transcranial electrical stimulation was performed in 15 AIS and 14 adult degenerative scoliosis (ADS) patients. Inter-side motor output balance (MOB) by comparing the ratios of right to left motor evoked potentials (MEP) amplitudes, and inter-side motor output excitability (MOE) computed with MEP amplitude, was determined separately for both patients groups. For somatosensory evoked potentials (SSEP), peak to peak P37 amplitudes from right and left lower limb SSEP and inter-side P37 amplitude ratios were obtained. RESULTS: Inter-side MOB was significantly asymmetric in AIS patients, contributed mainly by inter-side MOB changes in the upper than the lower limbs. Inter-side MOE comparisons of ipsilateral and contralateral MEP amplitudes were significantly different between AIS and ADS patients. Mean upper limb MEP amplitudes were significantly reduced in AIS patients. Amplitude of the right upper limb MEPs were positively correlated with inter-side MEP ratio. AIS patients show larger mean MEP amplitudes on the same side as the scoliotic curve. Overall, no correlation of Cobb's angle or total levels of scoliosis involvement with inter-side MOB and MOE parameters was found. Inter-side SSEP ratios were significantly higher in AIS patients. CONCLUSIONS: Primary dysfunctional and distributed motor output contributing to abnormalities of inter-side MOB and MOE changes involving the upper limbs is evident in AIS. Simultaneous but independent somatosensory and motor observations seen these patients suggest a central mechanism as an etiological factor.