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BACKGROUND: Randomized controlled trials (RCTs) of lipid-lowering therapy (LLT) in which the control groups received placebo without background LLT offer unique insights into the placebo and nocebo effects of lipid-lowering RCTs. METHODS AND RESULTS: Embase and Medline were searched for hyperlipidaemia RCTs with placebo-controlled arms. Placebo arms with background LLT were excluded. A single arm meta-analysis of proportions was used to estimate major adverse cardiovascular events (MACE) and adverse events (AE). A meta-analysis of means was used to estimate the pooled mean differences of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL) and triglycerides (TG).A total of 40 RCTs and 37 668 placebo-treated participants were included. The pooled mean changes for TC, LDL, HDL, and TG were -0.019 mmol/L, -0.028 mmol/L, 0.013 mmol/L, and 0.062 mmol/L respectively among placebo-treated participants, indicating a modest placebo effect. The pooled average nocebo effect among placebo-treated participants was 42.62% for all AEs and 3.38% for musculoskeletal-related AEs, 11.36% for gastrointestinal-related AEs, and 6.62% for headaches. Placebo-treated participants in secondary prevention RCTs had a far higher incidence of these nocebo effects than primary prevention RCTs: any AEs (OR 6.76, 95% CI: 5.56-8.24, P < 0.001), and gastrointestinal-related AE (OR 1.23, 95% CI: 1.00-1.51, P = 0.049). No differences in nocebo effects were found between the placebo arms of statin and non-statin trials. CONCLUSION: Our meta-analysis of placebo-treated participants in RCTs with no background LLT indicate a modest placebo effect but prominent nocebo effect of musculoskeletal, headache, and gastrointestinal symptoms that was greatest among secondary prevention RCTs. These findings may inform the design of future LLT RCTs.

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BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes, hyperlipidemia, hypertension, and smoking, are used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. METHODS: Embase, Medline and Pubmed were searched for studies comparing SMuRF-less and SMuRF patients with first presentation of ACS. We conducted single-arm analyses to determine the proportion of SMuRF-less patients in the ACS cohort, and compared the clinical presentation and outcomes of these patients. RESULTS: Of 1,285,722 patients from 15 studies, 11.56% were SMuRF-less. A total of 7.44% of non-ST-segment-elevation ACS patients and 12.87% of ST-segment-elevation myocardial infarction (STEMI) patients were SMuRF-less. The proportion of SMuRF-less patients presenting with STEMI (60.71%) tended to be higher than those with SMuRFs (49.21%). Despite lower body mass index and fewer comorbidities such as chronic kidney disease, peripheral arterial disease, stroke and heart failure, SMuRF-less patients had increased in-hospital mortality (RR:1.57, 95%CI:1.38 to 1.80) and cardiogenic shock (RR:1.39, 95%CI:1.18 to 1.65), but lower risk of heart failure (RR:0.91, 95%CI:0.83 to 0.99). On discharge, SMuRF-less patients were prescribed less statins (RR:0.93, 95%CI:0.91 to 0.95), beta-blockers (RR:0.94, 95%CI:0.92 to 0.96), P2Y12 inhibitors (RR: 0.98, 95%CI: 0.96 to 0.99), and angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker (RR:0.92, 95%CI:0.75 to 0.91). CONCLUSION: In this study level meta-analysis, SMuRF-less ACS patients demonstrate higher mortality compared with patients with at least one traditional atherosclerotic risk factor. Underuse of guideline-directed medical therapy amongst SMuRF-less patients is concerning. Unraveling novel risk factors amongst SMuRF-less individuals is the next important step. SUMMARY: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes mellitus, hyperlipidemia, hypertension, and smoking, are often used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. Of 1,285,722 ACS patients, 11.56% were SMuRF-less. Despite lower body mass index and fewer comorbidities, SMuRF-less patients had increased in-hospital mortality and cardiogenic shock. However, despite worse outcomes, SMuRF-less patients were prescribed less guideline-directed medical therapies on discharge.

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BACKGROUND AND PURPOSE: There are limited treatment options for patients with neurodegenerative ataxia and spasticity. Non-invasive electrostimulation (NES) is receiving increasing interest because of its ease of implementation, cost-effectiveness and safety. A meta-analysis was conducted to evaluate the efficacy of NES. METHODS: MEDLINE and Embase were screened for studies using NES in ataxias and spasticity. Key outcome measurements of effectiveness included changes in (1) Modified Ashworth Scale (MAS) scores, (2) cerebellar brain inhibition (CBI), (3) the nine-hole peg test (9HPT), (4) the 8-m walking time (8MWT), (5) International Cooperative Ataxia Rating Scale (ICARS) score and (6) the Scale for Assessment and Rating of Ataxia (SARA) scores. RESULTS: Seven randomized controlled trials involving 203 patients were included. There were significant improvements in MAS (mean difference [MD] -0.42, 95% confidence interval [CI] -0.76 to -0.08, p = 0.015), CBI (MD -0.35%, 95% CI -0.42 to -0.28, p < 0.001), 8MWT (MD -1.88 s, 95% CI -3.26 to -0.49, p = 0.008), ICARS (MD -7.84, 95% CI -11.90 to -3.78, p < 0.001) and SARA (MD -3.01, 95% CI -4.74 to -1.28, p < 0.001). There was almost no heterogeneity across all outcomes except for CBI (I2  = 79%). No significant changes in the 9HPT were observed comparing NES to a sham procedure (MD -3.52 s, 95% CI -9.15 to 2.10, p = 0.220). Most included studies were at low risk of bias, and no severe adverse effects were reported. CONCLUSION: It was demonstrated that NES is an effective treatment for improving coordination and balance and increased exercise capacity in patients with ataxia and spasticity. There was also a significant modulation of CBI in ataxic patients.

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Background: An increasing proportion of patients with acute myocardial infarction (AMI) are presenting without standard modifiable risk factors (SMuRFs) of hypertension, hypercholesterolemia, diabetes, and smoking, but with an unexpectedly increased mortality. This study examined the SMuRF-less patients presenting with AMI in a multiethnic Asian population. Methods: We recruited patients presenting with AMI from 2011 to 2021 and compared the prevalence, clinical characteristics, and outcomes of SMuRF-less and SMuRF patients. Multivariable analysis was used to compare the outcomes of 30-day cardiovascular mortality, all-cause mortality, readmission, cardiogenic shock, stroke, and heart failure. Kaplan-Meier curves were constructed for 30-day cardiovascular mortality, with stratification by ethnicity, gender and AMI type, and 10-year all-cause mortality. Results: Standard modifiable risk factor-less patients, who made up 8.6% of 8,680 patients, were significantly younger with fewer comorbidities that include stroke and chronic kidney disease, but higher rates of ventricular arrhythmias and inotropic or invasive ventilation requirement. Multivariable analysis showed higher rates of cardiovascular mortality (HR 1.48, 95% CI: 1.09-1.86, p = 0.048), cardiogenic shock (RR: 1.31, 95% CI: 1.09-1.52, p = 0.015), and stroke (RR: 2.51, 95% CI: 1.67-3.34, p = 0.030) among SMuRF-less patients. A 30-day cardiovascular mortality was raised in the SMuRF-less group, with similar trends in men, patients with ST-segment elevation myocardial infarction (STEMI), and the three Asian ethnicities. All-cause mortality remains increased in the SMuRF-less group for up to 5 years. Conclusion: There is a significant proportion of patients with AMI without standard risk factors in Asia, who have worse short-term mortality. This calls for greater focus on the management of this unexpectedly high-risk subgroup of patients.

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Background and Aims: Data are emerging on 10-year mortality comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with stenting for multivessel disease (MVD) without left main (LM) involvement. We conducted an updated two-stage meta-analysis using reconstructed individual patient data to compare long-term mortality between CABG and PCI for patients with MVD without significant LM coronary disease. Methods: Medline and Embase databases were searched for articles comparing CABG with PCI for MVD. A two-stage meta-analysis was conducted using reconstructed patient level survival data for all-cause mortality with subgroups by SYNTAX score. The shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results: We screened 1,496 studies and included six randomized controlled trials with 7,181 patients. PCI was associated with greater 10-year all-cause mortality risk (HR: 1.282, CI: 1.118-1.469, p < 0.001) compared with CABG. In patients with low SYNTAX score, 10-year all-cause mortality after PCI was comparable to CABG (HR: 1.102, 0.822-1.479, p = 0.516). However, in patients with moderate to high SYNTAX score, 10-year all-cause mortality was significantly higher after PCI compared with CABG (HR: 1.444, 1.122-1.858, p < 0.001; HR: 1.856, 1.380-2.497, p < 0.001, respectively). Conclusion: This updated reconstructed individual patient-data meta-analysis revealed a sustained lower cumulative all-cause mortality of CABG over PCI for multivessel disease without LM involvement.

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Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) for patients with left main coronary artery disease (LMCAD) have reported conflicting results. We performed a systematic review up to May 23, 2021, and 1-stage reconstructed individual patient data meta-analysis (IPDMA) to compare outcomes between both groups. The primary outcome was 10-year all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, and unplanned revascularization at 5 years. We performed individual patient data meta-analysis using published Kaplan-Meier curves to provide individual data points in coordinates and numbers at risk were used to increase the calibration accuracy of the reconstructed data. Shared frailty model or, when proportionality assumptions were not met, a restricted mean survival time model were fitted to compare outcomes between treatment groups. Of 583 articles retrieved, 5 RCTs were included. A total of 4,595 patients from these 5 RCTs were randomly assigned to PCI (n = 2,297) or CABG (n = 2,298). The cumulative 10-year all-cause mortality after PCI and CABG was 12.0% versus 10.6%, respectively (hazard ratio [HR] 1.093, 95% confidence interval [CI] 0.925 to 1.292; p = 0.296). PCI conferred similar time-to-MI (restricted mean survival time ratio 1.006, 95% CI 0.992 to 1.021, p=0.391) and stroke (restricted mean survival time ratio 1.005, 95% CI 0.998 to 1.013, p = 0.133) at 5 years. Unplanned revascularization was more frequent after PCI than CABG (HR 1.807, 95% CI 1.524 to 2.144, p <0.001) at 5 years. This meta-analysis using reconstructed participant-level time-to-event data showed no statistically significant difference in cumulative 10-year all-cause mortality between PCI versus CABG in the treatment of LMCAD.

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BACKGROUND: Aortic stenosis (AS) and acute coronary syndrome (ACS) share similar cardiovascular risk factors. The incidence of concomitant AS and ACS is increasing with aging population, yet studies investigating the prognosis of these patients remain scarce. METHODS: This retrospective single-centre cohort study examined consecutive patients who presented with ACS and AS from January 1, 2011, to March 31, 2021. The cohort was divided into mild, moderate, and severe AS based on the index echocardiogram. The primary outcome was all-cause mortality. RESULTS: Of 563 patients, 264 (46.9%) had mild, 193 (34.3%) moderate, and 106 (18.8%) severe AS. The mean follow-up duration was 2.5 years. All-cause mortality was higher among patients with moderate and severe AS compared with mild AS within 30 days (17.0% vs 13.0% vs 6.4%, respectively; P = 0.005) and in the long term (49.7% vs 51.4% vs 35.6%; P = 0.002). Concomitant moderate (hazard ratio [HR] 1.453, 95% confidence interval [CI] 1.020-2.068; P = 0.038) or severe AS (HR 1.873, 95% CI 1.176-2.982; P = 0.008) was an independent predictor of all-cause mortality. Kaplan-Meier curves demonstrated higher mortality in patients with moderate and severe AS compared with mild AS (P < 0.001). Similar survival trends were observed regardless of ACS type and in those with preserved left ventricular ejection fraction. Patients with reduced left ventricular ejection fraction had poor prognosis regardless of AS severity. CONCLUSIONS: ACS patients with concomitant moderate or severe AS have similar high long-term mortality, regardless of ACS type. The high early mortality in moderate and severe AS emphasises the imperative to attempt to mitigate this risk urgently.

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BACKGROUND: Current guidelines recommend psychological support for patients with pulmonary hypertension suffering from psychological adversity. However, little is known about the prevalence and risk factors of depression and anxiety in patients with pulmonary hypertension (PH). METHODS: Medline and Embase were searched from inception to 6 May 2021. Meta-analysis of proportions using the generalized linear mixed model was conducted to analyze the pooled prevalence rates of depression and anxiety in PH patients. Risk factors for depression and anxiety in PH patients were evaluated using meta regression. RESULTS: A total of 24 studies involving 2,161 PH patients were included. The pooled prevalence of depression in PH was 28.0% (95% CI: 20.5-36.8) and pooled prevalence of anxiety was 37.1% (95% CI: 28.7-46.4). There was a significantly higher prevalence of anxiety (p = 0.0013) amongst PH patients in Asia (61.1%) compared to Europe (40.3%) and North America (22.9%). In terms of risk factors, congenital heart disease-related pulmonary arterial hypertension (PAH-CHD) were significantly associated with both depression (OR: 1.68, 95% CI: 1.27-2.23, p = 0.024) and anxiety (OR: 1.63, 95% CI: 1.45-1.83, p = 0.002). On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH, OR: 1.18, 95% CI: 1.10-1.26, p = 0.004) was significantly associated with depression, whereas worse pulmonary vascular resistance (ß: 0.30, 95% CI: 0.09-0.52, p = 0.005) and cardiac index (ß: -0.96, 95% CI: -1.58 to -0.35, p = 0.002) were significantly correlated with anxiety. CONCLUSION: The prevalence of anxiety and depression in PH patients is alarmingly high, with an increased prevalence of anxiety in Asia compared to Europe or North America. Psychological support is warranted for patients with PH, particularly those with underlying congenital heart disease, CTEPH, and severe disease. SYSTEMATIC REVIEW REGISTRATION: CRD42021251733.

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Current guidelines on the management of patients with aortic valvular disease have widened the use of transcatheter aortic valve implantation (TAVI) with an emphasis on avoidance of prosthesis-patient mismatch (PPM). This study sought to examine the incidence, risk factors, and all-cause mortality of PPM after TAVI. Medline and Embase databases were searched from inception to August 10, 2021. Patients were compared along 2 arms: (1) any degree of PPM and those without PPM, (2) severe PPM, and nonsevere PPM. A total of 22 articles involving 115,442 patients after TAVI were included. Pooled incidence for any degree of PPM was 30.1% and 10.7% in severe PPM. Incidence was significantly higher (p <0.001) for any degree of PPM in Europe (33.1%) and North America (34.4%) compared with Asia (10.4%). Incidence of severe PPM was higher (p = 0.015) in older generation (13.6%) compared with current-generation valves (6.3%). Severe PPM increased the risk of all-cause mortality relative to nonsevere PPM (hazard ratio: 1.86, 95% confidence interval: 1.05 to 3.29, p = 0.034). Patients of younger age, increased body surface area, lower left ventricular ejection fraction, and classified New York Heart Association Class III/IV were at greater risk of both any degree and severe PPM. Smaller prosthesis size increased the risk of any degree of PPM, whereas postdilation and larger prostheses were protective factors. In conclusion, all-cause mortality was significantly affected in severe PPM compared with nonsevere cases, whereas this excess mortality was not observed between those with any degree of PPM and those without. Closer attention to patient and bioprosthetic valve factors is required to minimize the occurrence of severe PPM.

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Literature of patients with severe high-gradient aortic stenosis (HG AS) (mean pressure gradient [MPG] ≥ 40 mmHg and aortic valve area [AVA] ≥ 1.0 cm2) remains limited. This study seeks to compare the prognostic outcomes of patients with high-gradient concordant (HGCON-AS) and discordant AS (HGDIS-AS) in an Asian cohort. From 2010 to 2015, patients with moderate-to-severe AS with preserved left ventricular ejection fraction (LVEF ≥ 50%) were recruited and stratified into 3 groups based on index echocardiogram-(1) HGDIS-AS, (2) HGCON-AS and (3) moderate AS (MOD-AS). The primary study endpoints was all-cause mortality, with secondary endpoints of congestive heart failure (CHF) admissions and aortic valve replacement (AVR). Multivariable Cox regression was used and Kaplan-Meier curves were constructed to evaluate associations between HGDIS-AS, HGCON-AS and MOD-AS, and the study outcomes. A total of 467 patients were studied, comprising of 6.2% HGDIS-AS, 13.9% HGCON-AS and 79.9% MOD-AS patients. There was significantly higher AVR rates in the HGCON-AS group (58.5%), followed by HGDIS-AS (31.0%) and MOD-AS (4.6%), p < 0.001) groups. After adjusting for confounders, HGCON-AS was significantly associated with all-cause mortality (HR 3.082, 95% CI 1.479-6.420, p = 0.003) and CHF admissions (HR 12.728, 95% CI 2.922-55.440 p = 0.001) but not HGDIS-AS, with MOD-AS as the reference group. Both HGDIS-AS (HR 7.715, 95% CI 2.927-20.338; p < 0.001) and HGCON-AS (HR 21.960, 95% CI 10.833-44.515, p < 0.001) were independent predictors of AVR. After exclusion of reversible high-flow states, HGDIS-AS patients appear to have a more favourable prognostic profile compared to HGCON-AS patients. Large prospective interventional studies examining the prognostic differences between the two groups will be the next important step.

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Newer generation durable polymer drug-eluting stents (DP-DES) and biodegradable polymer DES (BP-DES) have similar efficacy with dual-antiplatelet therapy (DAPT) duration of > 6 months. However, this difference in outcomes have not been well studied in shorter DAPT regime. This study compares the safety and efficacy profiles of DP-DES and BP-DES based on short-term (1-3 months), intermediate-term (4-6 months) and standard DAPT (6-12 months) durations. A search was conducted on Embase and Medline for Randomized Controlled Trials (RCTs) comparing stent types, and DAPT durations. Primary endpoints include cardiac death, myocardial infarction (MI), definite stent thrombosis, stroke, target vessel revascularization (TVR) and major bleeding. Network analysis was conducted to summarize the evidence. A total of 15 RCTs involving 43,875 patients were included. DP-DES was associated with significantly lower major bleeding rates compared to BP-DES (RR 0.44, Crl 0.22-0.83) in short-term DAPT. Among DP-DES patients, short-term DAPT was associated with lower major bleeding risk compared to standard DAPT (RR 0.47, CrI 0.32-0.69). This favorable bleeding profile with short DAPT was not found in BP-DES patients. Cardiac death, MI, definite stent thrombosis, stroke and TVR rates were similar across the various DAPT durations and stent types. Our preliminary findings demonstrated comparable efficacy and safety outcomes between BP-DES and newer generation BP-DES across various DAPT durations. In patients requiring short DAPT, DP-DES had more favourable major bleeding profile compared to BP-DES, without compromising anti-thrombotic efficacy.

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AIMS: The cardioprotective effects of glucose-lowering medications in diabetic patients with heart failure (HF) are well known. Several large randomized controlled trials (RCTs) have recently suggested that the cardioprotective effects of glucose-lowering medications extend to HF patients regardless of diabetic status. The aim of this study was to conduct a Bayesian network meta-analysis to evaluate the impact of various glucose-lowering medications on the outcomes of non-diabetic HF patients. METHODS AND RESULTS: Medline and Embase were searched for RCTs investigating the use of glucose-lowering medications in non-diabetic HF patients in August 2021. Studies were included in accordance with the inclusion and exclusion criteria, and data were extracted with a pre-defined datasheet. Primary outcomes include serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction (LVEF), and maximal oxygen consumption (PVO2 ). A Bayesian network meta-analysis was performed to compare the effectiveness of different classes of glucose-lowering medications in improving HF outcomes. Risk-of-bias was assessed using Cochrane Risk-of-Bias tool 2.0 for randomized trials (ROB2). Seven RCTs involving 2897 patients were included. Sodium-glucose transporter 2 inhibitor (SGLT2i) was the most favourable in lowering NT-proBNP, with the significant reduction in NT-proBNP when compared with glucagon-like peptide-1 receptor agonists (GLP1-RA) [mean differences (MD): -229.59 pg/mL, 95%-credible intervals (95%-CrI): -238.31 to -220.91], metformin (MD: -237.15 pg/mL, 95%-CrI: -256.19 to -218.14), and placebo (MD: -228.00 pg/mL, 95%-CrI: -233.99 to -221.99). SGLT2i was more effective in improving LVEF for HF with reduced ejection fraction patients relative to GLP1-RA (MD: 8.09%, 95%-CrI: 6.30 to 9.88) and placebo (MD: 6.10%, 95%-CrI: 4.37 to 7.84). SGLT2i and GLP1-RA were more favourable to placebo in improving PVO2 , with significant increase of PVO2 at a MD of 1.60 mL/kg/min (95%-CrI: 0.63 to 2.57) and 0.86 mL/kg/min (95%-CrI: 0.66 to 1.06), respectively. All three drugs had comparable safety profiles when compared with placebo. CONCLUSIONS: This Bayesian network meta-analysis demonstrated that SGLT2i, when compared with GLP1-RA and metformin, was superior in improving LVEF in HF with reduced ejection fraction patients, as well as improving PVO2 and NT-proBNP in non-diabetic HF patients. Further large-scale prospective studies are needed to confirm these preliminary findings.

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OBJECTIVES: This study draws on qualitative insights on the barriers and facilitators to HIV testing, as well as perceptions of HIV self-testing (HIVST), to propose a framework to understand not only the benefits but also potential knock-on implications of introducing HIVST in the context of other STI testing. METHODS: We conducted semistructured, in-depth interviews with 30 gay, bisexual and other men who have sex with men aged 18 and 39 years old in Singapore. Interview topics included barriers and facilitators to HIV and other STI testing, as well as perceptions of HIVST. Interviews were audio-recorded, transcribed, coded and analysed using thematic analysis. RESULTS: For HIV testing, participants cited the perceived risk of acquiring, susceptibility to and symptoms of HIV as internal motivators, while social influence and accessibility of HIV testing services were external motivators. For STI testing, perceived symptoms and partner notification of STI were reported as internal and external motivators, respectively. Availability of bundle tests, starting a new relationship and instances of mandatory testing motivated both simultaneous HIV and other STI testing. The fear of a positive diagnosis and lack of confidentiality were cited as internal and external barriers to HIV testing, respectively, while low perceived severity of other STI and the cost of STI tests were cited as internal and external barriers to other STI testing, respectively. We identified pathways to HIV and other STI testing and discussed how the introduction of HIVST may reduce opportunities for other STI testing. CONCLUSIONS: The findings of this study suggest that introducing HIVST might weaken linkages to other STI testing if alternative strategies of promoting other STI testing are not simultaneously implemented. We recommend that future interventions address both the risks of HIV and other STI simultaneously, and that structural interventions promoting HIV and other STI preventions be balanced accordingly.

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PrEP is effective in preventing HIV transmission among at-risk HIV-negative MSM. A qualitative descriptive study with five focus group discussions (N = 33) involving a purposively recruited sample of Singaporean MSM was conducted from August 2016 to April 2017 to understand local perspectives on potential barriers and motivators to the adoption of PrEP, prior to the implementation of PrEP services in Singapore. Knowledge of PrEP was high, and many viewed PrEP as an attractive alternative to condoms for HIV prevention. Concerns about PrEP included the cost of PrEP and related services, the frequency of PrEP-related clinic visits, fear of side effects, and the stigma associated with using PrEP. Participants felt PrEP was best provided by MSM-friendly providers, and more needed to be done to increase awareness of the effectiveness of PrEP. Access to PrEP for MSM in Singapore has to be affordable, patient-centered, and convenient to maximize the potential benefits of PrEP.

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BACKGROUND: Sexualised substance use, or 'chemsex' has been shown to be a major factor driving the syndemic of HIV/AIDS in communities of gay, bisexual, and other men who have sex with men (GBMSM) around the world. However, there is a paucity of research on chemsex among GBMSM in Singapore due to punitive drug laws and the criminalisation of sexual behaviour between men. This qualitative descriptive study is the first to explore perceptions towards, motivators to engaging in, and the barriers to addressing the harms associated with chemsex among GBMSM in Singapore. METHODS: We conducted 30 semi-structured in-depth interviews with self-identifying GBMSM between the ages of 18-39 in Singapore following a purposive sampling strategy. Interview topics included participants' perceptions of drug use among GBMSM in Singapore, perceptions towards chemsex, reasons for drug use and chemsex, and recommendations to address the harms associated with chemsex in Singapore. Interviews were audio-recorded, transcribed, coded, and analysed using thematic analysis. RESULTS: Participants reported that it was common to encounter chemsex among GBMSM in Singapore as it could be easily accessed or initiated using social networking phone apps. Enhancement and prolongation of sexual experiences, fear of rejection from sexual partners and peers, and its use as a means of coping with societal rejection were three main reasons cited for engaging in chemsex. The impact of punitive drug laws on disclosure and stigmatisation of GBMSM who use drugs were reported to be key barriers towards addressing chemsex. Participants suggested using gay-specific commercial venues as avenues for awareness and educational campaigns, and social media to reach out to younger GBMSM. CONCLUSIONS: This study highlights the complexities behind chemsex use among GBMSM in Singapore, and the range of individual to institutional factors to be addressed. We recommend that community-based organisations and policy-makers find ways to destigmatise discussion of chemsex and provide safe spaces to seek help for drug use.

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