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Background The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with wild-type strains from early 2020. Methods National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020. Results A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio [aOR], 4.90; 95% confidence interval [CI]: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI: .95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). Conclusions B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs.

Aims/hypothesisDiabetes progression and complication risk are different in Asian people compared with those of European ancestry. In this study, we sought to understand the epidemiology of diabetes-related lower extremity complications (DRLECs: symptomatic peripheral arterial disease, ulceration, infection, gangrene) and amputations in a multi-ethnic Asian population.MethodsThis was a retrospective observational study using data obtained from one of three integrated public healthcare clusters in Singapore. The population consisted of individuals with incident type 2 diabetes who were of Chinese, Malay, Indian or Other ethnicity. We examined incidence, time to event and risk factors of DRLECs and amputation.ResultsBetween 2007 and 2017, of the 156,593 individuals with incident type 2 diabetes, 20,744 developed a DRLEC, of whom 1208 underwent amputation. Age- and sex-standardised incidence of first DRLEC and first amputation was 28.29/1000 person-years of diabetes and 8.18/1000 person-years of DRLEC, respectively. Incidence of both was highest in individuals of Malay ethnicity (DRLEC, 36.09/1000 person-years of diabetes; amputation, 12.96/1000 person-years of DRLEC). Median time from diabetes diagnosis in the public healthcare system to first DRLEC was 30.5 months for those without subsequent amputation and 10.9 months for those with subsequent amputation. Median time from DRLEC to first amputation was 2.3 months. Older age (p p p p = 0.014), chronic comorbidities (nephropathy [p p p p p 1c(p p p = 0.002) eGFR, greater or missing BMI (p p p p p 1c(p p = 0.009) or missing (p p = 0.008) were associated with higher hazard of amputation in those with DRLEC. Indian ethnicity (p = 0.007) was associated with significantly lower hazard of amputation.Conclusions/interpretationThis study has revealed important ethnic differences in risk of diabetes-related lower limb complications, with Malays most likely to progress to DRLEC. Greater research efforts are needed to understand the aetiopathological and sociocultural processes that contribute to the higher risk of lower extremity complications among these ethnic groups.Graphical abstract

We estimated the generation interval distribution for coronavirus disease on the basis of serial intervals of observed infector-infectee pairs from established clusters in Singapore. The short mean generation interval and consequent high prevalence of presymptomatic transmission requires public health control measures to be responsive to these characteristics of the epidemic.

As of 27 October 2020, there have been 57,980 confirmed cases of COVID-19 in Singapore, with 28 fatalities. To summarise the Singapore experience in managing and containing COVID-19 based on available published data and from relevant sources, a review of literature using research databases such as PubMed and OVID Medline, along with non-peer-reviewed articles and other sources, was conducted with the search terms ‘COVID-19’ and ‘Singapore’. Research conducted in Singapore has provided insight into the clinical manifestations and period of infectivity of COVID-19, demonstrated evidence of pre-symptomatic transmission, linked infection clusters using serological tools, and highlighted aspects of hospital-based environmental contamination. It has also provided guidance for diagnostic testing and has described immune and virologic correlates with disease severity. Evidence of effectiveness of containment measures such as early border control, rigorous contact training, and calibrated social distancing measures have also been demonstrated. Singapore’s multipronged strategy has been largely successful at containing COVID-19 and minimising fatalities, but the risk of re-emergence is high. Keywords: Epidemiology, management, prevention, transmission

Presymptomatic transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), might pose challenges for disease control. The first case of COVID-19 in Singapore was detected on January 23, 2020, and by March 16, a total of 243 cases had been confirmed, including 157 locally acquired cases. Clinical and epidemiologic findings of all COVID-19 cases in Singapore through March 16 were reviewed to determine whether presymptomatic transmission might have occurred. Presymptomatic transmission was defined as the transmission of SARS-CoV-2 from an infected person (source patient) to a secondary patient before the source patient developed symptoms, as ascertained by exposure and symptom onset dates, with no evidence that the secondary patient had been exposed to anyone else with COVID-19. Seven COVID-19 epidemiologic clusters in which presymptomatic transmission likely occurred were identified, and 10 such cases within these clusters accounted for 6.4% of the 157 locally acquired cases. In the four clusters for which the date of exposure could be determined, presymptomatic transmission occurred 1-3 days before symptom onset in the presymptomatic source patient. To account for the possibility of presymptomatic transmission, officials developing contact tracing protocols should strongly consider including a period before symptom onset. Evidence of presymptomatic transmission of SARS-CoV-2 underscores the critical role social distancing, including avoidance of congregate settings, plays in controlling the COVID-19 pandemic.

Introduction: Data on drug utilisation among stroke patients of Asian ethnicities are lacking. The objectives of the study were to examine the temporal trends and patient characteristics associated with prescription of thrombolytic, antithrombotic and statin medications among patients with first-ever stroke. Materials and Methods: First-ever ischaemic and haemorrhagic stroke patients admitted to 2 Singapore tertiary hospitals between 2010‒2014 were included. Data were extracted from the National Healthcare Group Chronic Disease Management System. Association between drug utilisation and admission year, as well as characteristics associated with drug use, were explored using multivariable logistic regression. Results: There was an increasing trend in the combined use of all 3 guideline medications in ischaemic stroke patients (P

PURPOSE This retrospective cohort study aims to examine adherence to secondary stroke preventive medications and their association with risk of stroke recurrence and mortality in patients after first-ever ischemic stroke. METHODS Using data from the National Healthcare Group and Singapore Stroke Registry, patients with first-ever ischemic stroke between 2010 and 2014 were included, and categorized based on antithrombotic or statin adherence using the proportion of days covered: high (≥75%), intermediate (50%-74%), low (25%-49%), and very low (

Arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart muscle disease, is characterized by a progressive replacement of viable, in its classic form predominantly right ventricular myocardium by fibro-fatty tissue. These pathological alterations may provide the substrate for the occurrence of life-threatening ventricular tachyarrhythmias, heart failure, and sudden cardiac death. The clinical course in this young patient population is highly variable, diagnostic algorithms complex, and individualized treatment strategies yet to be refined. Molecular genetic analyses have revealed both heterozygous and compound mutations in genes encoding for desmosomal proteins that are an integral part of the intercellular architecture. However, its diagnostic and prognostic impact remains to be elucidated. Over time, other genetic (i.e., non-desmosomal) and non-genetic causes (phenocopies) have been identified, and biventricular and left dominant manifestations (ALVC) are known. Based on a qualitative scoring system, initially published in 1994, diagnostic criteria were revised and substantiated by quantitative criteria in 2010 followed by a critical appraisal 9 years later. In 1995, ARVC was included in the classification of cardiomyopathies of the World Health Organization but was recently proposed to be subsumed in a broader concept termed "arrhythmogenic cardiomyopathy" (AC). This review provides an update on the clinical diagnosis and differential diagnoses of ARVC as well as our current understanding of the underlying pathogenesis, and it sheds light on new efforts in risk stratification.

Summary Background Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. Methods We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. Findings As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days. Interpretation SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. Funding None.

Background: COVID-19 is a novel pandemic affecting almost all countries leading to lockdowns worldwide. In Singapore, locally-acquired cases emerged after the first wave of imported cases, and these two groups may have different health-seeking behaviour affecting disease transmission. Objective: We investigated differences in health-seeking behaviour between locally-acquired cases and imported cases, and within the locally-acquired cases, those who saw single versus multiple healthcare providers.Methods: We conducted a retrospective study of 258 patients who were diagnosed with COVID-19 from 23 January to 17 March 2020. Variables related to health-seeking behaviour included number of visits prior to hospitalisation, timing of the first visit, duration from symptom onset to admission, and places where the cases had at least one visit.Results: Locally-acquired cases had longer duration from symptoms onset to hospital admission (median 6 days, range 1-30) than imported cases (median 4 days, range 1-13) (pConclusion: Our study indicates the need to encourage individuals to seek medical attention early on in their patient journey, particularly from their family physician or the same doctor. This in turn, would facilitate early detection and isolation, hence limiting local transmission and enabling better control of the pandemic.

Patients at high risk of bleeding requiring percutaneous coronary intervention (PCI) need careful evaluation of both their thrombotic and their bleeding risks. In these patients, a polymer-free metallic stent coated with biolimus-A9 (BA9-DCS) followed by 1‑month dual antiplatelet therapy (DAPT) could be a safe option; however, real-world data are still lacking. We analyzed the performance of the device in a real-world scenario.Patients assessed as being at high risk of bleeding with an indication for PCI were treated with BA9-DCS and DAPT consisting of aspirin (100 mg/day) and clopidogrel (75 mg/day) for at least 1 month, followed by either oral anticoagulation or single antiplatelet therapy. No exclusion criteria were used. The primary endpoint was the occurrence of an adverse event after PCI, i.e. severe bleeding requiring hospitalization, ischemic or hemorrhagic stroke, clinically driven stent thrombosis, myocardial infarction or cardiac death.Overall, 89 patients were enrolled in this study [median age 75 (66-81) years; 27 females (30%)] and 171 interventions were performed. During a median follow-up of 203 (145-273) days the primary endpoint occurred in 20 patients (23%): 12 (13%) had clinically significant bleeding, four (5%) ischemic stroke and four (5%) died from cardiac causes related neither to stent thrombosis nor to acute myocardial infarction. Female gender emerged as the only statistically significant predictor of an adverse event (adjusted hazard ratio (HR) 3.3; 95% confidence interval (CI): 1.2-8.7, p = 0.017).In real-world patients at high risk of bleeding, implantation of the polymer-free metallic stent coated with Biolimus-A9 (Biofreedom®; Biosensors Europe, Morges, Switzerland) followed by 1 -month DAPT showed encouraging results without any stent thrombosis.HINTERGRUND: Patienten mit hohem Blutungsrisiko, bei denen eine perkutane Koronarintervention (PCI) notwendig ist, müssen sorgfältig bezüglich ihres Thrombose- wie auch Blutungsrisikos beurteilt werden. Bei ihnen könnte der Einsatz eines mit Biolimus A9 beschichteten polymerfreien Metallstents (BA9-DCS) mit nachfolgender 1‑monatiger dualer Plättchenhemmung („dual antiplatelet therapy“ [DAPT]) eine sichere Option sein. Es fehlen allerdings immer noch Daten aus der Praxis. Daher haben wir den BA9-DCS unter Realbedingungen untersucht.Patienten mit hohem Blutungsrisiko und Indikation zur PCI wurden mit BA9-DCS und einer DAPT (Acetylsalicylsäure 100 mg/Tag und Clopidogrel 75 mg/Tag für mindestens 1 Monat) behandelt, worauf eine orale Antikoagulation oder einfache Plättchenhemmung folgte. Ausschlusskriterien gab es nicht. Als primärer Endpunkt wurde der Eintritt eines unerwünschten Ereignisses nach PCI definiert (schwere Blutung mit erforderlicher Krankenhausaufnahme, ischämischer oder hämorrhagischer Schlaganfall, klinisch begünstigte Stentthrombose, Myokardinfarkt oder kardial bedingter Tod).Insgesamt 89 Patienten wurden in die Studie eingeschlossen (medianes Alter 75 [66–81] Jahre; 27 weiblich [30 %]); es wurden 171 Interventionen durchgeführt. In einem medianen Follow-up von 203 (145–273) Tagen wurde der primäre Endpunkt bei 20 Patienten (23 %) erreicht: 12 (13 %) hatten eine klinisch relevante Blutung, 4 (5 %) einen ischämischen Schlaganfall und 4 (5 %) verstarben kardial bedingt, wobei die Ursache weder mit einer Stentthrombose noch mit einem akuten Myokardinfarkt zusammenhing. Weibliches Geschlecht erwies sich als einziger statistisch signifikanter Prädiktor für ein unerwünschtes Ereignis (adjustierte Hazard Ratio [HR] 3,3; 95 %-Konfidenzintervall [KI]: 1,2–8,7, p = 0,017).Bei Patienten unter Realbedingungen mit hohem Blutungsrisiko lieferte die Implantation des mit Biolimus A9 beschichteten polymerfreien Metallstents (Biofreedom®, Biosensors Europe, Morges, Schweiz) gefolgt von einer 1‑monatigen DAPT vielversprechende Ergebnisse, ohne dass es zu einer Stentthrombose kam.

Objective: Assessment and allocation of required staff time for postoperative pain management for two different patient-controlled technologies, sufentanil sublingual tablet system (SSTS) and intravenous analgesia (PCiA). Design: Activity-based evaluation. Setting: The study was conducted at four German hospitals based on the availability of the two technologies studied and their respective bed capacity broadly reflecting the German hospital landscape. Patients and participants: Staff activities were recorded for 162 SSTS and 154 PCiA procedures. Every hospital recorded around 40 procedures for each technology between December 2016 and July 2017. Interventions: Staff time was recorded if a patient received one of the two considered postoperative pain management technologies and was under treatment of a trained nurse. No further criteria were defined. Documentation of resource utilization covered all staff activities concerning the two technologies by detailed activity recording forms. Main outcome measure(s): Staff time for five identified process areas (preparation of therapy option, provisioning at patients’ bed, therapy, removal of therapy option, reprocessing, and storage) with significant impact on the entire process. Results: The average staff time required for SSTS to manage the entire process was 36 minutes whereas for PCiA it was 49 minutes (p < 0.0001). In all process areas, SSTS showed significantly less staff time requirements. Conclusions: In comparison to PCiA, SSTS requires significantly less staff time to manage postoperative pain in the studied setting.

As underlying heart diseases of right ventricular tachyarrhythmias, ARVC causes wall-motion abnormalities based on fibrofatty myocardial degeneration, while RVOT-VT and BrS are thought to lack phenotypic MR characteristics. To examine whether cardiac magnetic resonance (CMR) feature tracking (FT) in addition to ARVC objectively facilitates detection of myocardial functional impairments in RVOT-VT and BrS. Cine MR datasets of four retrospectively enrolled, age-matched study groups [n = 65; 16 ARVC, 26 RVOT-VT, 9 BrS, 14 healthy volunteers (HV)] were independently assessed by two distinctly experienced investigators regarding myocardial function using CMR-FT. Global strain (%) and strainrate (s−1) in radial and longitudinal orientation were assessed at RVOT as well as for left (LV) and right (RV) ventricle at a basal, medial and apical section with the addition of a biventricular circumferential orientation. RV longitudinal and radial basal strain (%) in ARVC (− 12.9 ± 4.2; 11.4 ± 5.1) were significantly impaired compared to RVOT-VT (− 18.0 ± 2.5, p ≤ 0.005; 16.4 ± 5.2, p ≤ 0.05). Synergistically, RVOT endocardial radial strain (%) in ARVC (33.8 ± 22.7) was significantly lower (p ≤ 0.05) than in RVOT-VT (54.3 ± 14.5). For differentiation against BrS, RV basal and medial radial strain values (%) (13.3 ± 6.1; 11.8 ± 2.9) were significantly reduced when compared to HV (21.0 ± 6.9, p ≤ 0.05; 20.1 ± 6.6, p ≤ 0.005), even in case of a normal RV ejection fraction (EF) (> 45%; n = 6) (12.0 ± 2.7 vs. 20.1 ± 6.6, p ≤ 0.05). CMR-FT facilitates relevant differentiation in patients with right ventricular tachyarrhythmias: between ARVC against RVOT-VT and HV as well as between BrS with even a preserved EF against HV.

Aim To compare the risk of death, the prevalence of comorbid chronic physical illness and mortality among an Asian population of patients with mental disorders. Methods This was a retrospective data analysing of medical records of patients with schizophrenia, depression, anxiety, bipolar disorder, alcohol use disorder (AUD) or substance use disorder and the comorbid chronic physical illnesses. The hazard risk of death was calculated with Cox regression and compared between patients with and without comorbid chronic physical illness(es). Odds ratios of specific comorbid chronic physical illness were calculated with logistic regression and mean crude death rate was calculated for patients with different mental disorders. Results A total of 56,447 patients with mental disorders were included in the analysis. Compared to patients without comorbid physical illness, patients with mental-physical comorbidity were associated with a higher risk of death [2.36 (2.22–2.52); hazard ratio (95% CI)] and less estimated survival days [2157 (2142–2172) vs 2508 (2504–2513)]. Compared to other mental disorders, those with AUD had the highest prevalence of two or more comorbid chronic physical illnesses and associated with the highest odds of comorbid hypertension, diabetes mellitus, stroke, nephritis, chronic kidney disease, and cancer. The highest one-year crude death rate was similarly observed in patients with AUD. Conclusions Mental-physical comorbidity was associated with a higher risk of death compared to patients with mental disorders only. The highest prevalence of mental-physical comorbidity and mortality were observed in patients with AUD. More attention and resources may be needed to tackle the burden of AUD.

Background: The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective cohort study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020. Methods: National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all SARS-CoV-2 patients with VOC infection admitted to our centre between 20-December-2020 and 12-May-2021 were analysed. Outcomes were compared with a cohort of 846 patients admitted January-April 2020. Findings: There were 838 VOC infections in Singapore in the study period. After adjusting for age and gender, B.1.617.2 infection was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4·90, [95% CI 1·43-30·78]. 157 patients with VOCs were admitted to our centre. After adjusting for age, gender, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1·88 [95% CI 0·95-3·76]) compared with wild-type. B.1.617.2 was associated with significantly lower PCR Ct values and significantly longer duration of Ct value ≤30 (estimated median duration 18 days for B.1.617.2, 13 days for wild-type). Vaccine breakthrough cases were less severe. Interpretation: There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide a strong impetus for the rapid implementation of vaccination programmes. Funding Information: National Medical Research Council grants COVID19RF-001 and COVID19RF-008. Declaration of Interests: BEY reports personal fees from Roche and Sanofi, outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: Informed consent for retrospective data collection was waived as approved by the institutional review board (NHG-DSRB reference number 2020/01122).

AIMS: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. METHODS AND RESULTS: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P

BackgroundEarly diagnosis is crucial in securing optimal outcomes in the HIV care cascade. Recent HIV infection (RHI) serves as an indicator of early detection in the course of HIV infection. Surveillance of RHI is important in uncovering at-risk groups in which HIV transmission is ongoing. The study objectives are to estimate the proportion of RHI among persons newly-diagnosed in 2013–2017, and to elucidate epidemiological factors associated with RHI in Singapore.MethodsAs part of the National HIV Molecular Surveillance Programme, residual plasma samples of treatment-naïve HIV-1 positive individuals were tested using the biotinylated peptide-capture enzyme immunoassay with a cutoff of normalized optical density ≤ 0.8 for evidence of RHI. A recent infection testing algorithm was applied for the classification of RHI. We identified risk factors associated with RHI using logistic regression analyses.ResultsA total of 701 newly-diagnosed HIV-infected persons were included in the study. The median age at HIV diagnosis was 38 years (interquartile range, 28–51). The majority were men (94.2%), and sexual route was the predominant mode of HIV transmission (98.3%). Overall, 133/701 (19.0, 95% confidence interval [CI] 16.2–22.0%) were classified as RHI. The proportions of RHI in 2015 (31.1%) and 2017 (31.0%) were significantly higher than in 2014 (11.2%). A significantly higher proportion of men having sex with men (23.4, 95% CI 19.6–27.6%) had RHI compared with heterosexual men (11.1, 95% CI 7.6–15.9%). Independent factors associated with RHI were: age 15–24 years (adjusted odds ratio [aOR] 4.18, 95% CI 1.69–10.31) compared with ≥55 years; HIV diagnosis in 2015 (aOR 2.36, 95% CI 1.25–4.46) and 2017 (aOR 2.52, 95% CI 1.32–4.80) compared with 2013–2014; detection via voluntary testing (aOR 1.91, 95% CI 1.07–3.43) compared with medical care; and self-reported history of HIV test(s) prior to diagnosis (aOR 1.72, 95% CI 1.06–2.81).ConclusionAlthough there appears to be an increasing trend towards early diagnosis, persons with RHI remain a minority in Singapore. The strong associations observed between modifiable behaviors (voluntary testing and HIV testing history) and RHI highlight the importance of increasing the accessibility to HIV testing for at-risk groups.

Summary Background Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. Methods In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. Findings Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. Interpretation Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. Funding National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).

The transition period from the hospital to the outpatient setting is a critical phase when managing heart failure. A well-structured transition is paramount and helps to ensure a tight follow-up schedule for the heart failure patient, thereby improving treatment outcomes. This article aims to provide guidance for the first three follow-up visits after hospital discharge, with a focus on monitoring heart failure patients and up-titrating their medication in primary care.

ObjectiveTo assess the temporal trend and identify risk factors associated with the absence of previous HIV testing prior to their diagnosis among HIV-positive persons in Singapore.Study designCross-sectional.Setting and participantsWe analysed data of HIV-positive persons infected via sexual transmission, who were notified to the National HIV Registry in 2012–2017.OutcomesEpidemiological factors associated with the absence of HIV testing prior to diagnosis were determined separately for two groups of HIV-positive persons: early and late stages of HIV infection at diagnosis.Results2188 HIV-positive persons with information on HIV testing history and CD4 cell count were included in the study. The median age at HIV diagnosis was 40 years (IQR 30–51). Nearly half (45.1%) had never been tested for HIV prior to their diagnosis. The most common reason cited for no previous HIV testing was ‘not necessary to test’ (73.7%). The proportion diagnosed at late-stage HIV infection was significantly higher among HIV-positive persons who had never been tested for HIV (63.9%) compared with those who had undergone previous HIV tests (29.0%). Common risk factors associated with no previous HIV testing in multivariable logistic regression analysis stratified by stage of HIV infection were: older age at HIV diagnosis, lower educational level, detection via medical care and HIV infection via heterosexual transmission. In the stratified analysis for persons diagnosed at early-stage of HIV infection, in addition to the four risk factors, women and those of Malay ethnicity were also less likely to have previous HIV testing prior to their diagnosis.ConclusionTargeted prevention efforts and strategies are needed to raise the level of awareness of HIV/AIDS and to encourage early and regular screening among the at-risk groups by making HIV testing more accessible.

Aims This study describes the incidence and predictive factors for development of Type II Diabetes Mellitus (T2DM), Acute Myocardial Infarction (AMI) and stroke, among subjects with IFG over a five-year period. Methods This is a retrospective cohort study of subjects with newly diagnosed IFG from the Singapore National Healthcare Group hospitals and primary care clinics from 1 January 2008 to 31 December 2010. Clinical data were collected over a five-year period from the date of diagnosis. Outcomes of interest were T2DM, AMI and stroke based on first occurrence of the ICD-9 diagnoses from the chronic disease registry. Demographic characteristics, laboratory tests, anthropometric measurements and medical history were adjusted for in the multivariate logistic regression. Results Out of 2295 eligible subjects, 552(24.1%) developed at least one of the outcomes. 492(21.4%) developed T2DM, 20(0.9%) developed AMI and 62(2.7%) developed stroke. Predictive factors for development of any of the three outcomes included age 40–49 [Adjusted OR = 2.25; 95% CI 1.44–3.51], blood pressure of 140/90 mmHg and above [Adjusted OR = 1.62, 95% CI 1.26–2.10] and BMI of 27.5 kg/m2 or more [Adjusted OR = 2.35; 95% CI 1.61–3.41]. Females were more likely to develop T2DM [Adjusted OR = 1.43; 95% CI 1.10–1.85] but less likely to develop AMI and/or stroke compared to males [Adjusted OR = 0.43; 95% CI 0.24–0.76]. Conclusions Development of T2DM/AMI/stroke within the first five years of IFG is significantly high for subjects age 40–49 and those with high BMI. Frequency of cardiovascular risk screening, which is currently once every three years, could be increased.

We investigated the temporal trends of short-term mortality (death within 1 year of diagnosis) and cause-specific deaths in human immunodeficiency virus (HIV)-infected persons by stage of HIV infection at diagnosis. We also assessed the impact of late diagnosis (LD) on short-term mortality.Epidemiological records of HIV-infected Singapore residents from the National HIV Registry were linked to death records from the Registry of Births and Deaths for observational analyses. Newly-diagnosed HIV cases with available cluster of differentiation 4 count at time of diagnosis in a 5-year period from 2012 to 2016 were included in the study. Hazard ratios (HRs) and 95% confidence interval (CI) of LD for all deaths excluding suicides and self-inflicted or accidental injuries, and HIV/ acquired immunodeficiency syndrome (AIDS)-related deaths occurring within 1 year post-diagnosis were calculated using Cox proportional hazards regression models with adjustment for age at HIV/AIDS diagnosis. Population attributable risk proportions (PARPs) were then calculated using the adjusted HRs.Of the 1990 newly-diagnosed HIV cases included in the study, 7.2% had died by end of 2017, giving an overall mortality rate of 2.16 per 100 person-years (PY) (95% CI 1.82-2.54). The mortality rate was 3.81 per 100 PY (95% CI 3.15-4.56) in HIV cases with LD, compared with 0.71 (95% CI 0.46-1.05) in non-LD (nLD) cases. Short-term mortality was significantly higher in LD (9.1%) than nLD cases (1.1%). Of the 143 deaths reported between 2012 and 2017, 58.0% were HIV/AIDS-related (nLD 28.0% vs LD 64.4%). HIV/AIDS-related causes represented 70.4% of all deaths which occurred during the first year of diagnosis (nLD 36.4% vs LD 74.7%). The PARP of short-term mortality due to LD was 77.8% for all deaths by natural causes, and 87.8% for HIV/AIDS-related deaths.The mortality rate of HIV-infected persons with LD was higher than nLD, especially within 1 year of diagnosis, and HIV/AIDS-related causes constituted majority of these deaths. To reduce short-term mortality, persons at high risk of late-stage HIV infection should be targeted in outreach efforts to promote health screening and remove barriers to HIV testing and treatment.

Summary Background Acne vulgaris is a common skin condition which can have a negative impact on a patient's quality of life. Patients and Methods A survey was distributed among students at tertiary institutions. Data was collected on participants’ own rating of acne grade and how acne affected their social life. A clinician on-site graded the participants’ acne. Results Of the 429 students who participated in the survey, 59.8 % felt embarrassed or self-conscious because of their acne. There was a low but statistically significant correlation (Spearman's Correlation Coefficient = 0.471, p < 0.001) between participants’ and clinicians’ grading of acne. Conclusions Acne vulgaris causes a considerable amount of psychosocial stress. There are unfounded beliefs surrounding acne and unawareness of treatment options available.

Aims Diabetic kidney disease (DKD) incidence is rising in Singapore. While measures to prevent onset and early detection of diabetes as well as optimal diabetes and blood pressure control are important, early detection and treatment of DKD at primary care are crucial to ameliorate its course. This study aimed to evaluate the prevalence of DKD in a primary care cluster in Singapore and identify its risk factors in a multi-ethnic Asian population. Methods A total of 57 594 patients with type 2 diabetes mellitus (T2DM) followed-up at the National Healthcare Group Polyclinics with estimated glomerular filtration rate and at least two urine albumin/creatinine ratio (UACR) were stratified into DKD stages: normoalbuminuria (UACR

ObjectiveWe investigated the impact of cardiac presynaptic norepinephrine recycling in patients with long-QT syndrome (LQTS) using positron emission tomography (PET) with 11C-meta-hydroxyephedrine ([11C]mHED-PET).Methods[11C]mHED-PET was performed in 25 patients with LQTS (LQT1: n=14; LQT2: n=11) and 20 healthy controls and correlated with clinical parameters. [11C]mHED-PET images were analysed for global and regional retention indices (RI) and washout rates (WO) reflecting dynamic parameters of the tracer activity.ResultsGlobal and regional RI values were similar between patients with LQTS and controls. Although the global WO rates were similar between these groups, regional WO rates were on average higher in the lateral left ventricle (LV) wall in patients with LQTS (dose, mean ±SD; 0.08±0.14 vs 0.00%±0.09% min–1; p=0.033). In addition, patients with LQTS with a longer QTc interval showed a higher global WO rate. Clinical symptoms correlated with higher global WO rates. In the presence of normal global WO rates, asymptomatic LQTS patients showed higher global RI values.ConclusionThe increased regional WO rate of [11C]mHED in the lateral LV suggests an imbalance of presynaptic catecholamine reuptake and release, resulting in a higher synaptic catecholamine concentration, in particular in LQT1 patients. This might enhance β-adrenoceptor signalling and thereby aggravate inherited ion channel dysfunction and may facilitate occurrence of ventricular tachyarrhythmias. Detection of regional differences in LV sympathetic nervous function may modify disease expression and potentially serve as a non-invasive risk marker in congenital LQTS.Trial registration number2006-002767-41;Results.

Cardiovascular magnetic resonance (CMR) perfusion imaging and fractional flow reserve (FFR) assess myocardial ischemia. FFR measures the pressure loss across a stenosis determining hemodynamic significance but does not assess the area subtended by the stenotic vessel. CMR perfusion imaging measures the extent of myocardial blood flow reduction (=ischemic burden). Both techniques allow for continuous rather than categorical evaluation, but their relationship is poorly understood. This study investigates the relationship between the FFR value and the extent of myocardial ischemia. Forty-nine patients with angina underwent CMR perfusion imaging. FFR was measured in vessels with a visual diameter stenosis40%. The extent of ischemia for each coronary artery was measured by delineating the perfusion defect on the CMR images and expressing as a percentage of the left ventricular myocardium. The correlation between the extent of ischemia measured by CMR and FFR was good (r = -0.85, p 0.0005). The mean FFR value was 0.67 ± 0.17, and the mean perfusion defect was 8.9 ± 9.3%. An FFR value of ≥0.75 was not associated with ischemia on CMR. The maximum amount of ischemia (23.0 ± 1.5%) was found at FFR values 0.4 to 0.5. In patients with 1 vessel disease (49%), the mean ischemic burden was 15.3 ± 8.3%. In patients with 2 vessel diseases (18%), the mean ischemic burden was 26.0 ± 12%. Reproducibility for the measurement of ischemic burden was very good with a Kappa coefficient (k = 0.826, p = 0.048). In conclusion, there is good correlation between the FFR value and the amount of myocardial ischemia in the subtended myocardium.

Background Diabetes mellitus (DM) is recognised as a major health problem. Objectives The aims of this study are two-fold: (1) to describe the methods used in the identified cost-of-illness (COI) studies of DM and (2) to summarise their study findings regarding the economic impact of DM. Methods This is a systematic review of MEDLINE and Scopus journal articles reporting the cost of type 1 and/or 2 DM that were published in English from 2007 to 2011. Costs reported in the included studies were converted to US dollars. Results The systematic search yielded 30 articles. The studies varied considerably in their study design, perspective and included cost categories. Estimates for the total annual costs of DM ranged from US$141.6 million to US$174 billion; direct costs ranged from US$150 to US$14,060 per patient per year (pppy) whereas indirect costs ranged from US$39.6 to US$7,164 pppy. Inpatient cost was the major contributor to direct cost in half of the studies that included inpatient costs, physician services and medications. Conclusion There is a considerable economic burden associated with DM. Future research should focus on improving methods of estimating costs, enhancing the interpretation of study findings and facilitating comparisons between studies.

□ Die arrhythmogene rechtsventrikulare Kardiomyopathie (ARVC) ist charakterisiert durch regional betonte Degeneration und Atrophie des rechtsventrikularen Myokards mit nachfolgendem Ersatz durch Fett- und Bindewebe. Die Erkrankung manifestiert sich im Jugend- oder jungen Erwachsenenalter, Manner sind haufiger betroffen. Leitsymptome der ARVC sind ventrikulare Tachyarrhythmien mit linksschenkelblockartiger Konfiguration. Auch plotzliche Herztodesfalle konnen die primare Manifestation der ARVC darstellen.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death especially in times of increased sympathetic tone, for example, during sports, which have been confirmed by nuclear imaging studies. However, the underlying biochemical pathways remain to be delineated. Therefore, we investigated the expression levels of proteins of the signaling cascade in patients with ARVC. Methods During diagnostic work-up, right ventricular endomyocardial biopsies (EMBs) were sampled from 15 consecutive male ARVC patients (52 ± 14 years). Tissue levels of key proteins of the signaling cascade were analyzed. Results were compared to those obtained from EMBs of 10 patients with idiopathic right ventricular outflow-tract tachycardia (RVOT; 41 ± 14 years) and of five control subjects without identifiable structural heart disease (42 ± 13 years; P = ns). Results Among the proteins analyzed, only tissue levels of norepinephrine (NE; P < 0.04) and cyclic adenosine-3´,5´-monophospate (cAMP; P < 0.01) were significantly lower in ARVC when compared to RVOT patients. When compared to controls, mean cAMP levels were lower in patients with ARVC but did not reach statistical significance. No differences in cAMP were observed between RVOT and controls. Conclusions The current findings confirm and expand the concept of adrenergic dysfunction in ARVC: the reduction of NE in ARVC could lead to an impaired stimulation of β-adrenoceptor subsequent signaling pathways with potential implication for cardiac fibrosis and arrhythmogenesis.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritable myocardial disease accounting for ventricular tachycardia and sudden death in the young and arising from areas of fibrofatty replacement of predominantly right ventricular myocardium. That some patients manifest life-threatening ventricular tachycardia in the absence of substantial myocardial replacement suggests that gap junction remodeling might be acting synergistically to ventricular remodeling to promote arrhythmogenesis. Hence, we sought to verify gap junction composition and distribution by analyzing the expression and occurrence of specific gap junction proteins (connexins [Cxs]) in patients with ARVC. Right ventricular endomyocardial biopsy specimens were taken from 16 patients with definite ARVC (age 48 ± 16 years) and analyzed for Cx40, Cx43, and Cx45 messenger ribonucleic acid expression (relative to glyceraldehyde-3-phosphate-dehydrogenase messenger ribonucleic acid expression). The results were compared to those obtained from nondiseased donor hearts (n = 6; age 32 ± 11 years). The patients with ARVC showed a significant reduction in the messenger ribonucleic acid expression of Cx40 (p0.0001) and Cx45 (p0.0001) compared to that of the controls. The expression of Cx43 was similar in patients with ARVC and controls (p = 0.098). Mutations in plakophilin-2 were identified in 7 of 16 patients (25%). The Cx expression levels were comparable between the mutation carriers and noncarriers (p = NS). In conclusion, ARVC features alterations in the expression of Cxs and their distribution at cardiac intercalated discs. Apart from the deposition of extracellular matrix, the potential loss of gap junctions and shift in the composition of gap junctional Cxs in the ventricular conduction system might further contribute to the development of ventricular arrhythmias in patients with ARVC.

This study assesses the relationship between classical anatomical jeopardy scores, functional jeopardy scores (combined anatomical and haemodynamic data), and the extent of ischaemia identified on cardiovascular magnetic resonance (CMR) perfusion imaging. In 42 patients with stable angina and suspected coronary artery disease (CAD), CMR perfusion imaging was performed. Fractional Flow Reserve (FFR) was measured in vessels with ≥50 % stenosis. The APPROACH and BCIS jeopardy scores were calculated based on QCA results with both a 70 % (APP70 and BCIS70) and a 50 % stenosis (APP50, and BCIS50) used as the threshold for significance, as well as after integration of FFR and compared with the extent of ischaemia identified on CMR. The correlation between the extent of ischaemia measured by CMR and the anatomical jeopardy scores was moderate (APPROACH: r = 0.58; BCIS: r = 0.48, p = 0.001). Integrating physiological information improved this significantly to r = 0.82, p = 0.0001 for APPROACH and r = 0.82, p = 0.0001 for BCIS scores (z-statistic = −2.04, p = 0.04; z-statistic = −2.63, p = 0.009). In relation to CMR, the APPROACH and BCIS scores overestimated the volume of ischaemic myocardium by 29.2 and 25.2 %, respectively, which was reduced to 12.8 and 12 % after integrating functional data. Anatomical and functional jeopardy scores overestimate ischaemic burden when compared to CMR. Integrating physiological information from FFR to generate a functional score improves ischaemic burden estimation.

We appreciated the interest of Barison and colleagues in our International Consensus Statement on the treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).1 Our document provided a comprehensive overview and recommendations for risk stratification and therapy of patients fulfilling the diagnostic criteria for ARVC/D. These criteria had been addressed by a previous International Task Force consensus document dedicated to diagnosis of ARVC/D.2 According to the revised criteria proposed by the International Task Force in 2010, the diagnosis of ARVC/D is based on the presence of major and minor criteria encompassing electrocardiographic, arrhythmic, morphological, histopathologic, and genetic factors. Diagnosis of definite ARVC/D is fulfilled in the presence of 2 major criteria or 1 major plus 2 minor or 4 minor criteria from different groups; the ARVC/D diagnosis is possible or borderline in the presence of insufficient criteria. In their Letter to the Editor, Barison and colleagues emphasized the valuable role of cardiac magnetic resonance (CMR) for diagnosis of ARVC/D, which relies on its ability to combine evaluation of ventricular size, function, and regional wall motion with characterization by late-gadolinium enhancement (LGE) of fibro-fatty myocardial scar, which is the hallmark lesion of ARVC/D. We totally agree that CMR is becoming the gold standard tool for detection of structural and functional ventricular abnormalities in ARVC/D. In the 2010 International Task Force consensus document, CMR was appropriately included among the diagnostic imaging techniques, and specific CMR reference values for normal (and abnormal) ventricular size, systolic function, and regional dyssynergy were provided. Tissue characterization by LGE was not included among these diagnostic criteria because of the potential risk of misdiagnosis of ARVC/D related to the difficulty of assessing LGE at the level of the thin right ventricular wall and possible confusion with normal epicardial fat tissue. More recently, the frequent involvement by the disease of the left ventricular wall in the form of epicardial-mediomural LGE has been recognized. As pointed out by the authors, LV LGE may enhance sensitivity for early/minor or predominant left variants of the ARVC/D; however, its diagnostic accuracy remains to be established. The prognostic role of CMR and, in particular, of postcontrast sequences for tissue characterization in patients with a diagnosis of definitive ARVC/D remains elusive. In our consensus statement on the treatment of ARVC/D, we performed a systematic review of outcome studies on ARVC/D available in the literature to identify predictor variables that were associated with an increased risk of major arrhythmic events (ie, sudden cardiac death, appropriate defibrillator interventions, or defibrillator therapy on fast ventricular tachycardia/ventricular fibrillation), nonsudden cardiac death, or heart transplantation in at least 1 published multivariable analysis. Although the predicting value of CMR for worse arrhythmic outcome was shown in the general population of patients showing premature ventricular beats with a left bundle branch morphology4 and in patients with suspected diagnosis of ARVC/D,5 no specific features of CMR, either alone or in combination, have been reported yet as independent predictors of life-threatening arrhythmic events in patients with a definite diagnosis of ARVC/D. This lack of evidence underscores the importance of undertaking future studies on this field.

Purpose An isolated perfused pig heart model has recently been proposed for the development of novel methods in standard clinical magnetic resonance (MR) scanners. The original set-up required the electrical system to be within the safe part of the MR-room, which introduced significant background noise. The purpose of the current work was to refine the system to overcome this limitation so that all electrical parts are completely outside the scanner room. Methods Four pig hearts were explanted under terminal anaesthesia from large white cross landrace pigs. All hearts underwent cardiovascular magnetic resonance (CMR) scanning in the MR part of a novel combined 3T MR and x-ray fluoroscopy (XMR) suite. CMR scanning included real-time k-t SENSE functional imaging, k-t SENSE accelerated perfusion imaging and late gadolinium enhancement imaging. Interference with image quality was assessed by spurious echo imaging and compared to noise levels acquired while operating the electrical parts within the scanner room. Results Imaging was performed successfully in all hearts. The system proved suitable for isolated heart perfusion in a novel 3T XMR suite. No significant additional noise was introduced into the scanner room by our set-up. Conclusions We have substantially improved a previous version of an isolated perfused pig heart model and made it applicable for MR imaging in a state of the art clinical 3T XMR imaging suite. The use of this system should aid novel CMR sequence development and translation into clinical practice.

Aims Clinical and electrocardiographic (ECG) presentation of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow-tract tachycardia (RVOT) may be similar. The aim of the study was to assess the validity and utility of T-wave integral measurement as an ECG discriminator of patients with ARVC and RVOT using a body surface mapping (BSM). Methods and results A 120-channel BSM with quantitative signal analysis of the T-wave integral was performed in 10 patients with ARVC. Results were compared with those obtained from 13 patients with RVOT and a control group of 12 healthy subjects (controls). Age, body mass index, and QRS-axis on surface ECG were not significantly different between the groups. Arrhythmogenic right ventricular cardiomyopathy patients showed a significantly negative T-wave integral in the right lower anterior region of the torso when compared with RVOT ( P < 0.001). There was no statistically significant difference between RVOT patients and controls. At a cut-off level of −0.3 mV ms, sensitivity and specificity were 83% [area under curve (AUC) 0.85 ± 0.04 for the comparison of ARVC and RVOT]. These differences were pronounced in ARVC patients with a plakophlin-2 mutation ( P < 0.001). Conclusion Quantitative analysis of the BSM T-wave integral in distinct anatomical regions discriminates ARVC patients from RVOT patients and controls and may serve as an additional diagnostic tool.

Diabet. Med. 29, e241–e248 (2012) Abstract Aims To investigate the health-related quality of life of patients with diabetes mellitus in Singapore and its associations with diabetes-related characteristics and glycaemic control. Methods An interviewer-administered, cross-sectional survey was conducted in a sample of 301 adult diabetes patients under primary care. The survey questionnaire included both a generic health-related quality of life measure, the Euroqol 5-D and a diabetes-specific instrument, the Audit of Diabetes-dependent Quality of Life. Patients’ most recent HbA1c values were extracted from their medical records. Results After excluding patients who lacked the 90-day HbA1c test result, the final number of responses analysed was 282. Pain/discomfort was the most common complaint among the five Euroqol 5-D domains (by 28.0% of the respondents). Lack of freedom to eat was the Audit of Diabetes-dependent Quality of Life domain with the greatest negative average weighted impact (= −3.8, on a scale of −9 to 3). A significant association was observed between Audit of Diabetes-dependent Quality of Life average weighted impact and both duration of diabetes and use of insulin. A negative correlation was found between health-related quality of life and HbA1c values in both health-related quality of life measures (both r = −0.2, P = 0.001). Conclusions Patients with diabetes in primary-care settings frequently reported problems with pain/discomfort and restrictions in diet. Poorer health-related quality of life was found to be associated with higher HbA1c values. The chronicity of diabetes and insulin therapy may have a negative impact on patients’ diabetes-related health-related quality of life. This study indicates the importance of achieving better disease management to improve the health-related quality of life of patients with diabetes.

Background: The aims of the present study were to estimate the rate of progression from newly diagnosed impaired fasting glycemia (IFG) to type 2 diabetes mellitus (T2DM) in Singapore and to identify factors associated with the progression to T2DM in individuals with newly diagnosed IFG. Methods: The present study was a retrospective cohort study of newly diagnosed IFG from the National Healthcare Group Diabetes Registry between 1 January 2006 and 31 December 2007 to estimated the rate of progression to T2DM. Univariate survival analysis, followed by multivariate survival analysis, was performed and interactions were tested in the final model. Results: Over a mean follow-up period of 1.65 ± 0.13 years, 85 of 490 participants with newly diagnosed IFG developed T2DM, giving an annual progression rate of 6.8%. The factors associated with the development of T2DM were higher fasting plasma glucose level in the year of IFG diagnosis (hazard ratio [HR] = 14.6; 95% confidence interval [CI] 5.66–37.5), Chinese race (HR = 2.70; 95% CI 1.44–5.06), and body mass index (HR = 1.11; 95% CI, 1.06–1.15). Conclusions: The progression rate to T2DM is high in subjects with newly diagnosed IFG. Intensive lifestyle modification can be incorporated into their current yearly follow-up to prevent progression to T2DM, which is a growing problem in Singapore.

Objective We aim to determine whether healthcare costs for patients diagnosed with Type 2 Diabetes Mellitus (T2DM) are associated with the severity of diabetes complications as measured by the Diabetes Complication Severity Index (DCSI). Methods Retrospective cohort analysis was performed on a 2007 primary care cohort of T2DM patients. The DCSI is a 13-point scale, which comprises 7 categories of complications and their severity levels. Healthcare cost data from 2008 and 2009 were used as primary outcome. Inpatient and outpatient costs incurred for services consumed by patients within the provider network were included. Generalized linear model with log-link and gamma distribution was used to predict healthcare costs. Results Of the 59,767 T2DM patients, 2977 (5.0%) deaths occurred and 1336 (2.2%) were lost to follow up. Healthcare cost was strongly associated with increase in DCSI score. Compared to patients without complications, those with more complications (higher DCSI score) had an increased risk of higher healthcare costs. Risk ratio (RR) increased from 1.25 (95%CI: 1.19–1.32) for DCSI = 1 to 1.61 (1.51–1.72) for DCSI = 2; 2.10 (1.91–2.31) for DCSI = 3; 2.52 (2.21–2.87) for DCSI = 4 and 3.62 (3.09–4.25) for DCSI ≥ 5. As a continuous score, a one-point increase in the DCSI was associated with a cost increase of 27% (95%CI: 1.25–1.29). Conclusion The DCSI score is a useful tool for predicting direct healthcare costs. The DCSI can be used to triage high-risk patients for more focused secondary prevention interventions at primary care level, in a bid to lower overall healthcare costs.

Highlights ► Study the willingness to be vaccinated for H1N1 among Singapore healthcare workers. ► Only 39.4% of respondents were willing to be vaccinated against H1N1. ► Barriers to vaccination were “fear of side effects” and “unsure of effectiveness”. ► People with chronic conditions were not more likely to accept H1N1 vaccination. ► People wanted to know more about the vaccine's side effects and effectiveness., Introduction A novel H1N1 vaccine was manufactured in response to the pandemic in 2009. This study describes the willingness to be vaccinated for H1N1 among healthcare workers (HCWs) in primary healthcare clinics with and without chronic medical conditions, their reasons for refusing vaccination and whether they sought additional information to make an informed decision for the vaccination. Materials and methods An anonymous survey was conducted in November 2009 among all medical, nursing, allied health and operations HCWs in nine primary care clinics in Singapore. Participants were asked if they had any chronic medical conditions associated with influenza-related complications (example: asthma, stroke, heart disease, cancer, diabetes mellitus, renal disease), their perception towards vaccination for H1N1 and against seasonal influenza within the preceding 2 years. Results The initial response rate was 80%, of which 711 (54.7%) of the completed surveys were analysed. Among the 711 respondents, 16.6% reported having at least 1 chronic disease. Asthma (10.8%), hypertension (10.4%) and dyslipidaemia (9.8%) were the main chronic conditions. Only 39.4% of respondents were willing to be vaccinated against H1N1. Males were 2.07 (95% CI 1.19–3.62) times more likely than females to receive the H1N1 vaccination; the 45–54 and 55+ years old were 2.12 (95% CI 1.06–4.24) and 2.44 (95% CI 1.13–5.27) times more willing than those below 25 years old; and those who considered accepting the seasonal influenza vaccine were 7.0 times more likely than those who did not (95%CI 4.48–10.92). The 2 principal barriers were “fear of side effects” and “unsure of vaccine's effectiveness”. Although 78% attended some H1N1-related talks, only 7% of all HCWs felt that they had sufficient information. Most wanted more information about the vaccine's safety profile and contraindications. Conclusion Fewer than 40% of HCWs expressed willingness to receive the H1N1 vaccination, lower than past rates of influenza vaccine. HCWs in primary care clinics who had a chronic condition did not perceive themselves to be at higher risk of developing H1N1-related complications and were not more willing than the rest of the HCWs to accept H1N1 vaccination. Vaccine's side effects and effectiveness were the main concerns. Uptake of H1N1 vaccine may improve with targeted health information covering the vaccine's safety profile.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a nonischaemic cardiomyopathy and leading cause of sudden death in the young. It has been shown that microvascular dysfunction reflected by an impaired myocardial blood flow (MBF) response to stress is present in patients with other forms of nonischaemic cardiomyopathy, e.g. dilated cardiomyopathy, and that the reduced MBF may be related to a poor prognosis. Therefore, we quantified MBF, coronary flow reserve and coronary vascular resistance in patients with nonfailing ARVC using H 2 15 O and PET. In ten male patients with ARVC (mean age 49 ± 14 years), MBF was quantified at rest and during adenosine-induced hyperaemia using H 2 15 O PET. Results were compared with those obtained in 20 age-matched healthy male control subjects (mean age 46 ± 14 years). Resting MBF was not significantly different between patients with ARVC and controls (MBFrest 1.19 ± 0.29 vs. 1.12 ± 0.20 ml/min/ml). However, hyperaemic MBF was significantly lower in patients with ARVC than in controls (2.60 ± 0.96 vs. 3.68 ± 0.84 ml/min/ml; p = 0.005). Consequently, patients with ARVC had a significantly lower coronary flow reserve than control subjects (2.41 ± 1.34 vs. 3.39 ± 0.93; p = 0.030). In addition, hyperaemic coronary vascular resistance was increased in patients with ARVC (36.79 ± 12.91 vs. 26.31 ± 6.49 mmHg × ml-1 × min × ml; p = 0.007), but was found to be unchanged at rest. In this small well-characterized cohort of patients with nonfailing ARVC, we found a significantly reduced hyperaemic MBF and increased coronary vascular resistance. Further studies are necessary to corroborate this potential new functional aspect of the pathophysiological mechanisms underlying ARVC.

Objectives The aim of the present study was to assess the feasibility and safety of target-directed sampling of right ventricular (RV) endomyocardial biopsies (EMB) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Background EMB is an integral part of the diagnostic evaluation of ARVC. Due to safety concerns, EMB are often obtained from the RV septum, which is usually spared from characteristic alterations. At our institution, EMB in ARVC patients were sampled target-directed from predilection areas and areas with abnormal contraction. Methods Under fluoroscopic guidance, 3,777 EMB samples from 6 different RV sites were obtained in 482 patients who were evaluated for unclear cardiomyopathy (n = 280; 58%), assumed myocarditis (n = 59; 12%), or unexplained ventricular tachyarrhythmias (n = 143; 30%). Complication rates were compared with those from exclusively septal EMB procedures (n = 2,321) in 271 patients after heart transplantation (HTx). Results Overall, no procedure-related deaths or sustained ventricular tachyarrhythmias occurred. A pericardial effusion was reported in 6 of 161 patients with the final diagnosis of ARVC (3.7%) needing no further intervention in all but 1 patient (0.6%) who required pericardiocentesis. Among the non-ARVC patients (n = 321), the incidence of a minor pericardial effusion (3.9%) and cardiac tamponade (2.2%) was comparable to that in ARVC (p = NS) but was higher when compared with HTx (p Conclusions Multisite target-directed EMB sampling in ARVC is a safe procedure when performed by experienced interventionalists. The procedure-related complication rates were low and comparable to those in other cardiomyopathies.

Background: In patients with Brugada syndrome (BrS), life-threatening ventricular tachyarrhythmias predominantly occur during vagal stimulation at rest or during sleep. Previous imaging studies displayed an impaired autonomic function in BrS patients. However, it remains unclear whether these alterations primarily stem from a reduction of synaptic release of norepinephrine (NE) or an enhanced presynaptic reuptake. Both conditions could lead to reduced NE concentrations in the synaptic cleft. Therefore, we analyzed key components of the sympathoadrenergic signaling pathways in patients with BrS. Methods and Results: Endomyocardial biopsies were obtained from eight BrS patients (seven male; age 49 ± 15 years) and five controls (three male; age 43 ± 13 years; P = ns). The concentrations of NE, epinephrine (Epi), NE transport (NET) carrier protein, cyclic adenosine 5′monophosphate (cyclic adenosine monophosphate [cAMP]), inhibitory G-proteins (Gi1,2α), troponin-I (TNI), and phosphorylated TNI were analyzed. Levels of NET, Gi1,2α, TNI, Epi, and phosphorylated TNI were comparable between the groups. Compared to controls, patients with BrS showed reduced cAMP and NE concentrations. Conclusions: The current findings expand the concept of adrenergic dysfunction in BrS: the reduction of NE in BrS could lead to an impaired stimulation of β-adrenoceptors resulting in a reduction of cAMP and alterations of the subsequent signaling pathway with potential implication for arrhythmogenesis. (PACE 2011; 34:1147–1153)

Aims To evaluate whether the three-dimensional (3D) left atrial volume index (LAVI) and/or the presence of carotid plaques (CP) can predict the result of dobutamine stress echocardiography (DSE), thereby aiding interpretation. Methods and results We studied 130 patients (52 male, mean age 63 ± 11 years) with normal resting wall motion (WM) undergoing DSE. All patients had the end-systolic 2D and 3D LAVI measured, as well as bilateral carotid scanning. DSE was reported as abnormal in 50 (38.5%) patients. 3D end-systolic LAVI measurements were significantly higher (31.5 ± 8.2 vs 27.4 ± 7.4 mL/m2, P = 0.004) in those with an abnormal DSE. The two groups did not differ significantly on the 2D derived maximum LAVI measurements (36.2 ± 9.5 vs 34.2 ± 11.2, P = 0.299) and the presence of plaques in the carotid arteries (89.1 vs. 76.2%, P = 0.100). Receiver operating characteristic curves were created to define cut-offs that could predict the DSE result for the 3D LAVI. A 3D LAVI of >24.5 mL/m2 had a sensitivity of 80% for predicting an abnormal DSE, whereas a value of >36.0 mL/m2 had a specificity of 93% for the same cause. Intra-observer ( r = 0.997, P < 0.0001) and inter-observer ( r = 0.961, P < 0.0001) variability for 3D LAVI measurements was found to be excellent. Conclusion Three-dimensional (but not 2D) assessment of LAVI may offer additional information in predicting the result of DSE. Carotid scanning did not offer additional information for the same cause.

Aim The aim of this study was to investigate whether interventricular asynchrony (IVA) can be measured by electrocardiography. Methods Sixty-two patients (New York Heart Association heart failure functional class III: age, mean ± SD: 64 ± 9 years; ejection fraction, mean ± SD: 24% ± 8%; dilative cardiomyopathy/ischemic cardiomyopathy, n = 39/23) with left bundle branch block (QRS duration, mean ± SD: 165 ± 21 milliseconds) underwent a 120-channel body surface mapping. QRS integral was analyzed and compared with IVA (echo). Results Interventricular asynchrony was associated with significantly decreased QRS integrals 15 cm cranial and 6 cm lateral from V1 in patients with normal axis (n = 36): At a cutoff value of −26 milliseconds ⁎ mV, receiver operating characteristic analysis to predict IVA revealed a sensitivity of 89% and a specificity of 83% (area under curve, mean ± SEM: 0.9 ± 0.07; P < .001). In patients with left axis deviation (n = 26), IVA showed significantly decreased QRS integrals 10 cm caudal from V1: at a cutoff value of −89 milliseconds ⁎ mV, receiver operating characteristic analysis to predict IVA revealed a sensitivity of 83% and a specificity of 100% (area under curve, mean ± SEM: 0.9 ± 0.07; P < .002). Conclusions Interventricular asynchrony strongly correlates with QRS integral. Key lead positions, however, are axis dependent and outside standard leads.

Cardiomyopathies (diseases of the heart muscle) are a relevant but heterogeneous group of cardiac diseases. The underlying structural myocardial alterations, detectable with contemporary cardiac imaging modalities and also on twelve-lead surface ECG, embody both linkage and differentiation of the respective clinical forms. Most of these are defined to the heart, however, cardiac involvement is also known in the presence of specific metabolic or muscular systemic diseases. In many of the known cardiomyopathies, a genetic background has been elucidated thus indicating a potential familial disease. This, in turn, also harbors the risk that more family members may be affected besides the index patient.

Background— Brugada syndrome (BrS) is characterized by the presence of coved ST-segment elevations in the right precordial leads (so-called type I ECG) and additional clinical features. Caused by cardiac ion channel gene mutations, BrS may be associated with ventricular and atrial conduction disturbances as well as ventricular fibrillation. Recent studies have discussed whether BrS is merely a primary electric disorder or whether inflammatory or other histopathologic abnormalities in the right ventricle (RV) underlie the ECG phenotype. Methods and Results— We retrospectively analyzed BrS biopsy samples from 21 unrelated patients for histopathologic abnormalities (hypertrophy, fibrosis, inflammation, fatty tissue) together with the patients’ clinical, genetic, and imaging data. Eleven patients (52%) had normal RV imaging (by angiography, echocardiography, or cardiac MRI). Results of myocardial biopsies were normal in 3 patients (14%) and revealed mostly moderate abnormalities in the others. Four patients (19%) had predominant fatty tissue in the RV myocardium. Using immunohistochemistry and conventional tissue staining, we could not detect inflammatory tissue changes, an observation compatible with the clinical absence of signs for myocarditis. Conclusions— Imaging and histopathologic evaluation may detect moderate but uncharacteristic cardiac abnormalities in patients with BrS. None of the patients had arrhythmogenic RV cardiomyopathy or overt myocarditis. Only in a small subset did predominant histopathologic abnormalities in the biopsy samples of the RV outflow tract occur that could provide a link to the ECG phenotype. A variety of mechanisms, including genetic and structural RV alterations, may underlie the Brugada ECG phenotype.

Background We investigated whether multichannel ECG-recordings are useful to risk-stratify patients with congenital long-QT syndrome (LQTS) for risk of sudden cardiac death under optimized medical treatment. Methods In 34 LQTS-patients (11 male; age 31±13 years, QTc 478±51ms; LQT1 n = 8, LQT2 n = 15) we performed a standard 12-channel ECG and a 120-channel body surface potential mapping. The occurrence of clinical events (CE; syncope, torsade de pointes (TdP), sudden cardiac arrest (SCA)) was documented and correlated with different ECG-parameters in all lead positions. Results Seven patients developed TdP, four survived SCA and 12 experienced syncope. 12/34 had at least one CE. CE was associated with a longer QTc-interval (519±43ms vs. 458±42ms; p = 0.001), a lower T-wave integral (TWI) on the left upper chest (-1.2±74.4mV*ms vs. 63.0±29.7mV*ms; p = 0.001), a lower range of T-wave amplitude (TWA) in the region of chest lead V8 (0.10±0.08mV vs. 0.18±0.07mV; p = 0.008) and a longer T-peak-T-end time (TpTe) in lead V1 (98±23ms vs. 78±26ms; p = 0.04). Receiver-operating-characteristic (ROC) analyses revealed a sensitivity of 96% and a specificity of 75% (area under curve (AUC) 0.89±0.06, p = 0.001) at a cut-off value of 26.8mV*ms for prediction of CE by TWI, a sensitivity of 86% and a specificity of 83% at a cut-off value of 0.11mV (AUC 0.83±0.09, p = 0.002) for prediction of CE by TWA and a sensitivity of 83% and a specificity of 73% at a cut-off value of 87ms (AUC 0.80±0.07, p = 0.005) for prediction of CE by TpTe. Conclusions Occurrence of CE in LQTS-patients seems to be associated with a prolonged, low-amplitude T-wave.

Background Perfusion cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) are emerging as the most accurate tools for the assessment of myocardial ischemia noninvasively or in the catheter laboratory. However, there is limited data comparing CMR and FFR in patients with multi-vessel disease. This study aims to evaluate the correlation between myocardial ischemia detected by CMR with FFR in patients with multivessel coronary disease at angiography. Methods and results Forty-one patients (123 vascular territories) with angiographic 2- or 3-vessel coronary artery disease (visual stenosis >50 %) underwent high-resolution adenosine stress perfusion CMR at 1.5 T and FFR measurement. An FFR value of On a per patient basis, CMR and FFR detected identical ischemic territories in 19 patients (46 %) (mean number of territories 0.7+/−0.7 in both (p = 1.0)). On a per vessel basis, 89 out of 123 territories demonstrated concordance between the CMR and FFR results (72 %). In 34 % of the study population, CMR resulted in fewer ischemic territories than FFR; in 12 % CMR resulted in more ischemic territories than FFR. There was good concordance between the two methods to detect myocardial ischemia on a per-patient (k =0.658 95 % CI 0.383-0.933) level and moderate concordance on a per-vessel (k = 0.453 95 % CI 0.294–0.612) basis. Conclusions There is good concordance between perfusion CMR and FFR for the identification of myocardial ischemia in patients with multi-vessel disease. However, some discrepancy remains and at this stage it is unclear whether CMR underestimates or FFR overestimates the number of ischemic segments in multi-vessel disease.