Cost-utility analysis of hearing aid device for older adults in the community: a delayed start study.

BACKGROUND: Hearing aids (HA) is the primary medical intervention aimed to reduce hearing handicap. This study assessed the cost-effectiveness of HA for older adults who were volunteered to be screened for hearing loss in a community-based mobile hearing clinic (MHC). METHODS: Participants with (1) at least moderate hearing loss (≥40 dB HL) in at least one ear, (2) no prior usage of HA, (3) no ear related medical complications, and (4) had a Mini-Mental State Examination score ≥ 18 were eligible for this study. Using a delayed-start study design, participants were randomized into the immediate-start (Fitted) group where HA was fitted immediately or the delayed-start (Not Fitted) group where HA fitting was delayed for three months. Cost utility analysis was used to compare the cost-effectiveness of being fitted with HA combined with short-term, aural rehabilitation with the routine care group who were not fitted with HA. Incremental cost effectiveness ration (ICER) was computed. Health Utility Index (HUI-3) was used to measure utility gain, a component required to derive the quality adjusted life years (QALY). Total costs included direct healthcare costs, direct non-healthcare costs and indirect costs (productivity loss of participant and caregiver). Demographic data was collected during the index visit to MHC. Cost and utility data were collected three months after index visit and projected to five years. RESULTS: There were 264 participants in the Fitted group and 163 participants in the Not Fitted group. No between-group differences in age, gender, ethnicity, housing type and degree of hearing loss were observed at baseline. At 3 months, HA fitting led to a mean utility increase of 0.12 and an ICER gain of S$42,790/QALY (95% CI: S$32, 793/QALY to S$62,221/QALY). At five years, the ICER was estimated to be at S$11,964/QALY (95% CI: S$8996/QALY to S$17,080/QALY) assuming 70% of the participants continued using the HA. As fewer individuals continued using their fitted HA, the ICER increased. CONCLUSIONS: HA fitting can be cost-effective and could improve the quality of life of hearing-impaired older individuals within a brief period of device fitting. Long term cost-effectiveness of HA fitting is dependent on its continued usage.

Stathmin mediates neuroblastoma metastasis in a tubulin-independent manner via RhoA/ROCK signaling and enhanced transendothelial migration.

Neuroblastoma, the most common solid tumor of young children, frequently presents with aggressive metastatic disease and for these children the 5-year survival rates are dismal. Metastasis, the movement of cancer cells from one site to another, involves remodeling of the cytoskeleton including altered microtubule dynamics. The microtubule-destabilizing protein, stathmin, has recently been shown to mediate neuroblastoma metastasis although precise functions remain poorly defined. In this study we investigated stathmin's contribution to the metastatic process and potential mechanism(s) by which it exerts these effects. Stathmin suppression significantly reduced neuroblastoma cell invasion of 3D tumor spheroids into an extracellular matrix. Moreover, inhibiting stathmin expression significantly reduced transendothelial migration in two different neuroblastoma cell lines in vitro. Inhibition of ROCK, a key regulator of cell migration, in neuroblastoma cells highlighted that stathmin regulates transendothelial migration through ROCK signaling. Reduced stathmin expression in neuroblastoma cells significantly increased the activation of the RhoA small GTPase. Notably, re-expression of either wild type or a phospho-mimetic stathmin mutant (4E) made defective in tubulin binding returned cell migration and transendothelial migration back to control levels, indicating that stathmin may influence these processes in neuroblastoma cells independent of tubulin binding. Finally, stathmin suppression in neuroblastoma cells significantly reduced whole body, lung, kidney and liver metastases in an experimental metastases mouse model. In conclusion, stathmin suppression interferes with the metastatic process via RhoA/ROCK signaling in neuroblastoma cells. These findings highlight the importance of stathmin to the metastatic process and its potential as a therapeutic target for the treatment of neuroblastoma.

From matrix nano- and micro-phase tougheners to composite macro-properties.

In this paper, firstly, the morphology and toughness of a range of bulk epoxy polymers, which incorporate a second phase of well-dispersed silica nanoparticles and/or rubber microparticles, have been determined. Secondly, the macro-properties of natural-fibre reinforced-plastic (NFRP) composites based upon these epoxy polymers have been ascertained, using (i) unidirectional flax fibres or (ii) regenerated-cellulose fibres in the architecture of a plain-woven fabric. Thirdly, the toughening mechanisms which are induced in these materials by the presence of the silica nanoparticles, the rubber microparticles and the natural fibres have been identified. Finally, the values of the toughness of the bulk epoxy polymers and corresponding NFRPs have been quantitatively modelled. The increased toughness recorded for the bulk epoxy polymer due to the presence of the silica nanoparticles and/or rubber microparticles was indeed typically transferred to the NFRP composites when using such epoxies as the matrices for the fibres. Thus, the important role that may be played by modifications to the epoxy matrices in order to increase the toughness of the composites was very clearly demonstrated by these results. However, notwithstanding, the toughening mechanisms induced by the fibres were essentially responsible for the very high toughnesses of the NFRP composites, compared with the bulk epoxy polymers. The modelling studies successfully predicted the values of toughness of the bulk epoxy polymers and of the NFRP composites. These studies also quantified the extent to which each toughening mechanism, induced by the second-phase nano- and microparticles and the natural fibres, contributed to the overall values of toughness of the materials. This article is part of the themed issue 'Multiscale modelling of the structural integrity of composite materials'.

Economic impact analysis of an end-of-life programme for nursing home residents.

BACKGROUND: Due to limited end-of-life discussions and the absence of palliative care, hospitalisations are frequent at the end of life among nursing home residents in Singapore, resulting in high health-care costs. AIM: Our objective was to evaluate the economic impact of Project Care at the End-of-Life for Residents in homes for the Elderly (CARE) programme on nursing home residents compared to usual end-of-life care. DESIGN AND SETTINGS/PARTICIPANTS: Project CARE was introduced in seven nursing homes to provide advance care planning and palliative care for residents identified to be at risk of dying within 1 year. The cases consisted of nursing home residents enrolled in the Project CARE programme for at least 3 months. A historical group of nursing home residents not in any end-of-life care programme was chosen as the matched controls. Cost differences between the two groups were analysed over the last 3 months and final month of life. RESULTS: The final sample comprised 48 Project CARE cases and 197 controls. Compared to the controls, the cases were older with more comorbidities and higher nursing needs. After risk adjustment, Project CARE cases demonstrated per-resident cost savings of SGD$7129 (confidence interval: SGD$4544-SGD$9714) over the last 3 months of life and SGD$3703 (confidence interval: SGD$1848-SGD$5557) over the last month of life (US$1 = SGD$1.3). CONCLUSION: This study demonstrated substantial savings associated with an end-of-life programme. With a significant proportion of the population in Singapore requiring nursing home care in the near future, these results could assist policymakers and health-care providers in decision-making on allocation of health-care resources.

c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer.

The HER2 (ERBB2) and MYC genes are commonly amplified in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self-renewal and tumour-propagating capability of cells transformed with Her2 and c-Myc. Coexpression of both oncoproteins in cultured cells led to the activation of a c-Myc transcriptional signature and acquisition of a self-renewing phenotype independent of an epithelial-mesenchymal transition programme or regulation of conventional cancer stem cell markers. Instead, Her2 and c-Myc cooperated to induce the expression of lipoprotein lipase, which was required for proliferation and self-renewal in vitro. HER2 and MYC were frequently coamplified in breast cancer, associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in HER2(+) breast cancer patients receiving adjuvant chemotherapy (but not targeted anti-Her2 therapy), MYC amplification is associated with a poor outcome. These findings demonstrate the importance of molecular and cellular context in oncogenic transformation and acquisition of a malignant stem-like phenotype and have diagnostic and therapeutic consequences for the clinical management of HER2(+) breast cancer.

Pneumocystis carinii (jirovecii) pneumonia (PCP): the most common opportunistic infection observed in HIV/AIDS cases at the University Malaya Medical Centre, Kuala Lumpur, Malaysia.

This retrospective study was conducted among 59 HIV/AIDS patients with opportunistic infections admitted to the University Malaya Medical Centre between 2000 and 2009. Fifty-five point nine percent of cases were Chinese, 25.4% were Malays, 11.9% were Indians and 6.8% were of unknown ethnic origin. The male:female ratio was 2.9:1 (44 males and 15 females). The highest prevalence (38.9%) occurred in the 30-39 year old age group. Men comprised 47.7% and women 53.3%; the majority of both were married. The majority of cases were Malaysians (89.8%) and the rest (10.2%) were immigrants. Most of the patients (18.6%) were non-laborers, followed by laborers (11.9%), the unemployed (5.1%) and housewives (3.4%). The most common risk factor was unprotected sexual activity (20.3%). The two most common HIV/AIDS related opportunistic infections were Pneumocystis carinii (jirovecii) pneumonia (PCP) (62.7%) and toxoplasmosis (28.8%). Seventy-two point nine percent of patients had a CD4 count <200 cells/microl and 5.1% had a CD4 count >500 cells/microl. Eleven point nine percent of cases died during study period. A low CD4 count had a greater association with opportunistic infections. Most of the patients presented with fever (44.1%), cough (42.4%) and shortness of breath (28.8%). Detection of the etiologic pathogens aids clinicians in choosing appropriate management strategies.

Economic burden of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: The aim of this study was to estimate the direct medical costs of COPD in two public health clusters in Singapore from 2005 to 2009. METHODS: Patients aged 40 years and over, who had been diagnosed with COPD, were identified in a Chronic Disease Management Data-mart. Annual utilization of health services in inpatient, specialist outpatient, emergency department and primary care settings was extracted from the Chronic Disease Management Data-mart. Trends in attributable costs, proportions of costs and health-care utilization were analyzed across each level of care. A weighted attribution approach was used to allocate costs to each health-care utilization episode, depending on the relevance of co-morbidities. RESULTS: The mean total cost was approximately $9.9 million per year. Inpatient admissions were the major cost driver, contributing an average of $7.2 million per year. The proportion of hospitalization costs declined from 75% in 2005 to 68% in 2009. Based on the 5-year average, attendances at primary care clinics, emergency department and specialist clinics contributed 3%, 5% and 17%, respectively, of overall COPD costs. On average, 42% of the total cost burden was incurred for the medical management of COPD. The share of cost incurred for the treatment of conditions related and unrelated to COPD were 29% and 26%, respectively, of the total average costs. CONCLUSIONS: COPD is likely to represent a significant burden to the public health system in most countries. The findings are particularly relevant to understanding the allocation of health-care resources and informing appropriate cost containment strategies.

Novel electrogram device with web-based service centre for ambulatory ECG monitoring.

INTRODUCTION: Arrhythmias are often intermittent, and a normal electrocardiogram (ECG) may not be diagnostic. The purpose of this study was to evaluate the usefulness of HeartWave500 (HW), a novel web-based ambulatory ECG monitoring device. METHODS: A total of 120 patients from the National Heart Centre, Singapore were prospectively randomised in a three to one ratio to either HW or a standard transtelephonic (TT) event recorder. HW records five leads and transmits to an internet server, while TT transmits audio data to a central station. Monitoring was conducted for two weeks. The diagnostic yield was calculated in two ways: the percentage of patients successfully diagnosed as a function of time, and the absolute number of new diagnoses per patient per week. RESULTS: 33 patients (14 male, 19 female; mean age 49.6 + or - 11.1 years) were randomised to TT. 87 patients (32 male, 55 female; mean age 43.7 + or - 12.2 years) were randomised to HW. At the end of two weeks, the percentage of patients diagnosed with any arrhythmia was similar for both groups (66.7 percent for TT versus 67.8 percent for HW). There was a trend toward significance for the number of diagnoses per patient per week for Week 2 between TT and HW (0.58 + or - 0.75 versus 0.34 + or - 0.55, p is 0.06). Transmitted ECGs were read earlier for HW (18 minutes versus 1107 minutes, Mann-Whitney non-parametric test, p is less than 0.05). Transmitted recordings that were unreadable were also significantly lower for HW (8.0 percent versus 17.6 percent, chi-square test, p is less than 0.05). CONCLUSION: HW and TT have similar diagnostic yields. There is a trend toward a shorter monitoring time for HW. The ability of HW to record and transmit via the web, the earlier review of data and low unreadable data make HW an attractive alternative to TT.

Slow infusion of calcium channel blockers compared with intravenous adenosine in the emergency treatment of supraventricular tachycardia.

INTRODUCTION: The emergency treatment of supraventricular tachycardia (SVT) has, over the last two decades, changed from verapamil to adenosine primarily owing to documented hypotensive episodes occurring with rapid bolus infusions of the calcium channel blocker. Slow infusions of calcium channel blockers have not previously demonstrated hypotension to any significant degree. The aim of this study was to compare the efficacy and safety of bolus intravenous adenosine and slow infusion of the calcium channel blockers verapamil and diltiazem in the emergency treatment of spontaneous SVT. METHODS: A prospective randomized controlled trial with one group receiving bolus intravenous adenosine 6 mg followed, if conversion was not achieved, by adenosine 12 mg; and the other group receiving a slow infusion of either verapamil at a rate of 1mg per minute up to a maximum dose of 20mg, or diltiazem at a rate of 2.5mg per minute up to a maximum dose of 50mg. These infusions would be stopped at time of conversion of the SVT or when the whole dose was administered. Heart rate and blood pressure was continuously monitored during drug infusion and for up to 2h post-conversion. RESULTS: A total of 206 patients with spontaneous SVT were analysed. Of these, 102 were administered calcium channel blockers (verapamil=48, diltiazem=54) and 104 were given adenosine. The conversion rates for the calcium channel blockers (98%) were statistically higher than the adenosine group (86.5%), p=0.002, RR 1.13, 95% CI 1.04-1.23. The initial mean change in blood pressure post-conversion in the calcium channel blocker group was -13.0/-8.1 mmHg (verapamil) and -7.0/-9.4 mmHg (diltiazem) and 2.6/-1.7 mmHg for adenosine. Only one patient in the calcium channel group (0.98%) (95% CI 0.025-5.3) developed hypotension, and none in the adenosine group. CONCLUSION: Slow infusion of calcium channel blockers is an alternative to adenosine in the emergency treatment of stable patients with SVT. Calcium channel blockers are safe and affordable for healthcare systems where the availability of adenosine is limited.

Electrocardiographical case. Young woman with frequent syncope attacks.

A 29-year-old woman with frequent syncope attacks was referred for electrophysiological study and consideration for radio-frequency ablation of her ventricular arrhythmias. Her ECG showed features of right ventricular outflow tract premature contraction. Differential diagnoses for the causes of syncope in this patient include: right ventricular outflow tract tachycardia, arrythmogenic right ventricular dysplasia, and neurocardiogenic syncope. She underwent a tilt table test, which showed a malignant cardioinhibitory response. She developed abrupt syncope with 32 seconds of asystole during the test. She was given intravenous atropine and was resuscitated. A dual chamber rate-responsive pacemaker was implanted for her the next day. She was discharged well subsequently. Although the prognosis in patients with prolonged aystole in malignant vasovagal syncope is unknown, most doctors will still choose to implant a permanent pacemaker for patients with malignant neurocardiogenic syncope when the sinus arrest is prolonged.

Electrocardiographical case. Asymptomatic patient with deep T-wave inversions.

A 45-year-old man was found to have an abnormal myocardial perfusion scan. He was asymptomatic, with no chest pain, breathlessness or palpitations. Clinical examination was unremarkable. The 12-lead electrocardiography (ECG) showed increased QRS voltage in leads V3-V6, and deep T-wave inversions noted in leads V3-V6, with an absence of septal Q waves. These ECG features were characteristic of apical variant hypertrophic cardiomyopathy (HCM). He underwent a coronary angiogram that revealed normal coronary arteries, and a left ventriculogram which showed apical HCM. Transthoracic echocardiography further confirmed the diagnosis. No drug therapy was instituted as he was asymptomatic. Apical HCM is discussed.

Electrocardiographical case. Acute severe chest tightness.

The early diagnosis of acute myocardial infarction is crucial for the institution of appropriate reperfusion therapy. We describe a 56-year-old man who developed sudden onset of severe chest tightness. Inferior, posterior and right ventricular ST elevation myocardial infarction was diagnosed on electrocardiography (ECG). The ECG interpretation, differential diagnosis and management are discussed.

Electrocardiographical case. An elderly lady with chest pain. Diagnosis: isolated posterior myocardial infarct (MI).

A 72-year-old woman with diabetes mellitus, hypertension and dyslipidaemia presented with severe chest pain of four hours duration. Her electrocardiogram (ECG) showed tall R waves in leads V1-2, and ST segment depression in leads V1- 4, consistent with an isolated posterior myocardial infarction (MI). Emergency coronary angiogram showed an occluded left circumflex coronary artery, and primary angioplasty and stenting was performed. The ECG criteria for isolated posterior MI and pitfalls in using the conventional 12-lead ECG are discussed.

Electrocardiographical case. Elderly woman with sudden onset of post-operative dyspnoea.

A 70-year-old Chinese woman developed breathlessness, tachycardia and hypotension on the fourth day after total hip replacement. 12-lead electrocardiogram (ECG) showed sinus tachycardia with ST depression in I, II, V5 and V6. The ECG changes of sinus tachycardia along with a typical history is suggestive of pulmonary embolism. Diagnosis, treatment and the use of IVC filter for pulmonary embolism are discussed.

Electrocardiographical case. Asymptomatic patient with ST-segment elevation.

A 46-year-old man complained of recurrent episodes of giddiness which was not associated with chest pain or breathlessness. There was no family history of sudden death. Clinical examination was unremarkable.12-lead electrocardiogram (ECG) showed ST segment elevation in the right precordial leads, with coved ST segment elevation at its J point followed by a negative T wave with no isoelectric separation, specifically in V2. These ECG features are characteristic of the Brugada syndrome. He underwent a flecanide challenge which produced further elevation of ST segment at its J point and spontaneous ventricular ectopy. Electrophysiological studies induced ventricular fibrillation with 3 extra stimuli. An implantable cardioverter-defibrillator was implanted for prevention of sudden cardiac death. The Brugada syndrome is discussed.

Treatment of heart failure--role of biventricular pacing for heart failure not responding well to drug therapy.

OBJECTIVE: Patients with heart failure may have conduction abnormalities in up to 30%, further aggravating cardiac output. Drugs worsen these abnormalities and resynchronisation therapy with biventricular pacing improves cardiac function by effecting a more coordinated and efficient ventricular contraction. We report here the technique of biventricular pacing and its results. METHODOLOGY: Patients with NYHA Class III to IV heart failure, widened QRS (> or = 130 ms) complex on the ECG and impaired LVEF < or = 40% were enrolled. RESULTS: Biventricular pacing was performed in 29 patients (26 males, three females) from August 1999 to December 2001. The mean age of the patients was 59.6 +/- 12.8 years and 62% had underlying ischemic heart disease. All were in NYHA class III or more. Twenty-three had LBBB, four RBBB and two had widened paced QRS complex. The QRS duration was 161 +/- 21 ms and LVEF was 22 +/- 8%. All the left ventricular leads were implanted successfully. The procedure time was 167.0 +/- 79.6 mins and the fluoroscopy time was 43.8 +/- 41.4 mins. There were no significant complications. The NYHA class improved from a mean of 3.1 to 2.0 and exercise time from 252 +/- 95 seconds to 392 +/- 152 seconds at six months post implant (p=0.049). On follow-up (one month to 28 months), 25 (86%) patients had improvement in heart failure symptoms and 26 (90%) of the patients remained alive. CONCLUSION: Biventricular pacing can be safely performed and results in improvement in symptoms and exercise tolerance in heart failure patients with ventricular dyssynchrony not responding to drug therapy.

A case series of sotalol-induced torsade de pointes in patients with atrial fibrillation--a tale with a twist.

INTRODUCTION: Sotalol is a potent antiarrhythmic often used in patients with atrial fibrillation. However, it has been associated with a risk of provoking other potentially dangerous arrhythmias, especially if used in high doses and in patients with uncorrected electrolyte imbalance or impaired renal and cardiac function. CLINICAL PICTURE: We present 4 patients with atrial fibrillation treated with sotalol who developed torsade de pointes due to marked prolongation of the QT interval. While 1 patient had renal failure, all had normal left ventricular function. One patient had been treated with sotalol for more than 10 months before developing torsade de pointes precipitated by hypokalaemia, while another had tolerated sotalol for a 3-month period before the drug was discontinued, and only developed torsade de pointes when the drug was restarted 2 years later. Significantly, the doses used in all patients were relatively low, in contrast to most other reported cases where higher doses were used. CONCLUSION: As with all antiarrhythmic therapy, these cases illustrate the need for close follow-up of patients treated with sotalol, even if relatively low doses are used. In addition, patients who had previously tolerated the drug well are still susceptible to its proarrhythmic effects.

Immediate and mid-term safety and efficacy of single lead VDD pacemakers for patients with atrioventricular block and normal sinus node function--a single centre experience.

INTRODUCTION: Single lead atrial synchronous ventricular pacing (VDD) is increasingly being used in place of conventional dual chamber pacing (DDD) for patients with atrioventricular block and preserved sinus node function. Compared to the latter, VDD pacemakers provide similar haemodynamic benefits derived from atrial synchronous pacing, with the added benefit of an easier implant procedure. OBJECTIVE: To review the use, safety and efficacy of VDD pacing in a single tertiary referral centre. MATERIALS AND METHODS: A review of all patients with atrioventricular block and normal sinus node function implanted with a VDD pacemaker over a 2-year period at a local tertiary cardiac referral centre. Data on complications, atrial sensing performance and maintenance of atrioventricular synchrony during implant and at subsequent follow-up visits were obtained from a prospectively maintained registry and analysed. RESULTS: Forty-one patients (17 males, 24 females) with a mean age of 72 +/- 9 years received VDD pacing for various forms of high-grade atrioventricular block. The average implantation time was 46.8 +/- 17.1 minutes, and a pneumothorax in 1 patient was the only complication. Electrical measurements at implantation and subsequent follow-up visits revealed an initial rapid decrease in atrial signal amplitude (mean atrial P wave at implant 3.1 +/- 1.1 mV, predischarge 1.9 +/- 1.3 mV) which began to stabilise after 3 months, reaching a mean atrial P wave value of 1.3 +/- 0.3 mV at 24 months. The atrial sensing performance (percentage of atrial synchronous ventricular complexes) was 97% over a mean follow-up period of 9.9 months. Four patients (10%) developed paroxysmal atrial tachyarrhythmias. Sinus node dysfunction was not observed in any of our patients during the follow-up period. CONCLUSION: In patients with atrioventricular block and preserved sinus node function, single lead VDD pacing is safe and effective in maintaining a physiological atrial synchronous pacing mode.