Prevalence and Correlates of Heavy Alcohol use among People Living with HIV who use Unregulated Drugs in Vancouver, Canada.

Among people living with HIV (PLWH), heavy alcohol use is associated with many negative health consequences. However, the impacts of heavy alcohol use are not well described for PLWH who use drugs. Thus, we investigated the prevalence and correlates of heavy alcohol use among a cohort of people who use drugs (PWUD) living with HIV in Vancouver, Canada. We accessed data from an ongoing community-recruited prospective cohort of PLWH who use drugs with linked comprehensive HIV clinical monitoring data. We used generalized linear mixed-effects modeling to identify factors longitudinally associated with periods of heavy alcohol use between December 2005 and December 2019. Of the 896 participants included, 291 (32.5%) reported at least one period with heavy alcohol use. Periods of recent incarceration (Adjusted Odds Ratio [AOR] = 1.48, 95% Confidence Interval [CI]: 1.01-2.17), encounters with police (AOR = 1.87, 95% CI: 1.37-2.56), and older age (AOR = 1.05, 95% CI: 1.02-1.07) were positively associated with heavy alcohol use. Engagement in drug or alcohol treatment (AOR = 0.54, 95% CI: 0.42-0.70) and male gender (AOR = 0.46; 95% CI: 0.27-0.78) were negatively associated with heavy alcohol use. We observed that heavy alcohol use was clearly linked to involvement with the criminal justice system. These findings, together with the protective effects of substance use treatment, suggest the need to expand access for drug and alcohol treatment programs overall, and in particular through the criminal justice system to reduce alcohol-related harms among PLWH who use drugs.

Long-term prognostic impact of cardiovascular comorbidities in patients with prostate cancer receiving androgen deprivation therapy: A population-based competing risk analysis.

Our study investigated how adverse cardiovascular outcomes are impacted by cardiovascular comorbidities in patients with prostate cancer treated by androgen deprivation therapy (ADT). Using prospective, population-based data, all Hong Kong patients with prostate cancer who received ADT during 1 January 1993 to 3 March 2021 were identified and followed up for the endpoint of cardiovascular hospitalization/mortality until 31 September 2021, whichever earlier. Multivariable competing risk regression was used to compare the endpoint's cumulative incidence between different combinations of major cardiovascular comorbidities (heart failure [HF], myocardial infarction [MI], stroke and/or arrhythmia), with noncardiovascular death as competing event. Altogether, 13 537 patients were included (median age 75.9 [interquartile range 70.0-81.5] years old; median follow-up 3.3 [1.5-6.7] years). Compared to those with none of prior HF/MI/stroke/arrhythmia, the incidence of the endpoint was not different in those with only stroke (subhazard ratio [SHR] 1.06 [95% confidence interval (CI): 0.92-1.23], P = .391), but was higher in those with only HF (SHR 1.67 [1.37-2.02], P < .001), arrhythmia (SHR 1.63 [1.35-1.98], P < .001) or MI (SHR 1.43 [1.14-1.79], P = .002). Those with ≥2 of HF/MI/stroke/arrhythmia had the highest incidence of the endpoint (SHR 1.94 [1.62-2.33], P < .001), among whom different major cardiovascular comorbidities had similar prognostic impacts, with the number of comorbidities present being significantly prognostic instead. In conclusion, in patients with prostate cancer receiving ADT, the sole presence of HF, MI or arrhythmia, but not stroke, may be associated with elevated cardiovascular risks. In those with ≥2 of HF/MI/stroke/arrhythmia, the number of major cardiovascular comorbidities may be prognostically more important than the type of comorbidities.

Metformin use and mortality in Asian, diabetic patients with prostate cancer on androgen deprivation therapy: A population-based study.

BACKGROUND: This study aims to examine the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with prostate cancer (PCa). METHODS: This study identified diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 retrospectively, with follow-up until September 2021. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥180 days of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. The study used inverse probability treatment weighting to balance covariates. RESULTS: The analyzed cohort consisted of 1971 patients (1284 metformin users and 687 non-users; mean age 76.2 ± 7.8 years). Over a mean follow-up of 4.1 ± 3.2 years, metformin users had significantly lower risks of PCa-related mortality (weighted hazard ratio [wHR]: 0.49 [95% confidence interval, CI:  0.39-0.61], p < 0.001) and all-cause mortality (wHR 0.53 [0.46-0.61], p < 0.001), independent of diabetic control or status of chronic kidney disease. Such effects appeared stronger in patients with less advanced PCa, which is reflected by the absence of androgen receptor antagonist or chemotherapy use (p value for interaction: 0.017 for PCa-related mortality; 0.048 for all-cause mortality). CONCLUSIONS: Metformin use concurrent with ADT was associated with lower risks of mortality in Asian, diabetic patients with PCa.

Temporal trends in cardiovascular burden among patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study.

BACKGROUND: Although androgen deprivation therapy (ADT) is associated with cardiovascular risks, the extent and temporal trends of cardiovascular burden amongst patients with prostate cancer receiving ADT are unclear. METHODS: This retrospective cohort study analyzed adults with PCa receiving ADT between 1993-2021 in Hong Kong, with follow-up until 31/9/2021 for the primary outcome of major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, and heart failure), and the secondary outcome of mortality. Patients were stratified into four groups by the year of ADT initiation for comparisons. RESULTS: Altogether, 13,537 patients were included (mean age 75.5 ± 8.5 years old; mean follow-up 4.7 ± 4.3 years). More recent recipients of ADT had more cardiovascular risk factors and used more cardiovascular or antidiabetic medications. More recent recipients of ADT had higher risk of MACE (most recent (2015-2021) vs least recent (1993-2000) group: hazard ratio 1.33 [1.11, 1.59], P = 0.002; Ptrend < 0.001), but lower risk of mortality (hazard ratio 0.76 [0.70, 0.83], P < 0.001; Ptrend < 0.001). The 5-year risk of MACE and mortality for the most recent group were 22.5% [20.9%, 24.2%] and 52.9% [51.3%, 54.6%], respectively. CONCLUSIONS: Cardiovascular risk factors were increasingly prevalent amongst patients with prostate cancer receiving ADT, with increasing risk of MACE despite decreasing mortality.

Association between duration of gonadotrophin-releasing hormone agonist use and cardiovascular risks: A population-based competing-risk analysis.

BACKGROUND: Although androgen deprivation therapy has known cardiovascular risks, it is unclear if its duration is related to cardiovascular risks. This study thus aimed to investigate the associations between gonadotrophin-releasing hormone (GnRH) agonist use duration and cardiovascular risks. METHODS: This retrospective cohort study included adult patients with prostate cancer receiving GnRH agonists in Hong Kong during 1999-2021. Patients who switched to GnRH antagonists, underwent bilateral orchidectomy, had <6 months of GnRH agonist, prior myocardial infarction (MI), or prior stroke was excluded. All patients were followed up until September 2021 for a composite endpoint of MI and stroke. Multivariable competing-risk regression using the Fine-Gray subdistribution model was used, with mortality from any cause as the competing event. RESULTS: In total, 4038 patients were analyzed (median age 74.9 years old, interquartile range (IQR) 68.7-80.8 years old). Over a median follow-up of 4.1 years (IQR 2.1-7.5 years), longer GnRH agonists use was associated with higher risk of the endpoint (sub-hazard ratio per year 1.04 [1.01-1.06], p = 0.001), with those using GnRH agonists for ≥2 years having an estimated 23% increase in the sub-hazard of the endpoint (sub-hazard ratio 1.23 [1.04-1.46], p = 0.017). CONCLUSION: Longer GnRH agonist use may be associated with greater cardiovascular risks.

The role of cardiac magnetic resonance in identifying appropriate candidates for cardiac resynchronization therapy - a systematic review of the literature.

Despite the strict indications for cardiac resynchronization therapy (CRT) implantation, a significant proportion of patients will fail to adequately respond to the treatment. This systematic review aims to present the existing evidence about the role of cardiac magnetic resonance (CMR) in identifying patients who are likely to respond better to the CRT. A systematic search in the MedLine database and Cochrane Library from their inception to August 2021 was performed, without any limitations, by two independent investigators. We considered eligible observational studies or randomized clinical trials (RCTs) that enrolled patients > 18 years old with heart failure (HF) of ischaemic or non-ischaemic aetiology and provided data about the association of baseline CMR variables with clinical or echocardiographic response to CRT for at least 3 months. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement). Following our search strategy, 47 studies were finally included in our review. CMR appears to have an additive role in identifying the subgroup of patients who will respond better to CRT. Specifically, the presence and the extent of myocardial scar were associated with increased non-response rates, while those with no scar respond better. Furthermore, existing data show that scar location can be associated with CRT response rates. CMR-derived markers of mechanical desynchrony can also be used as predictors of CRT response. CMR data can be used to optimize the position of the left ventricular lead during the CRT implantation procedure. Specifically, positioning the left ventricular lead in a branch of the coronary sinus that feeds an area with transmural scar was associated with poorer response to CRT. CMR can be used as a non-invasive optimization tool to identify patients who are more likely to achieve better clinical and echocardiographic response following CRT implantation.

Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis.

BACKGROUND: The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship. METHODS: Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations. RESULTS: In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001). CONCLUSION: A higher TyG index is an independent and causal risk factor for incident HF in the general population. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.

A Territory-Wide Study of Arrhythmogenic Right Ventricular Cardiomyopathy Patients from Hong Kong.

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterized by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD). The present study aims to investigate the risk of detrimental cardiovascular events in an Asian population of ARVC/D patients, including the incidence of malignant ventricular arrhythmias, new-onset heart failure with reduced ejection fraction (HFrEF), as well as long-term mortality. Methods and Results: This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019 in Hong Kong. This study consisted of 109 ARVC/D patients (median age: 61 [46-71] years; 58% male). Of these, 51 and 24 patients developed incident VT/VF and new-onset HFrEF, respectively. Five patients underwent cardiac transplantation, and 14 died during follow-up. Multivariate Cox regression identified prolonged QRS duration as a predictor of VT/VF (p < 0.05). Female gender, prolonged QTc duration, the presence of epsilon waves and T-wave inversion (TWI) in any lead except aVR/V1 predicted new-onset HFrEF (p < 0.05). The presence of epsilon waves, in addition to the parameters of prolonged QRS duration and worsening ejection fraction predicted all-cause mortality (p < 0.05). Clinical scores were developed to predict incident VT/VF, new-onset HFrEF and all-cause mortality, and all were significantly improved by machine learning techniques. Conclusions: Clinical and electrocardiographic parameters are important for assessing prognosis in ARVC/D patients and should in turn be used in tandem to aid risk stratification in the hospital setting.

Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study.

BACKGROUND: The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM). METHODS: This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation therapy were performed. RESULTS: The final study cohort consisted of 25,695 metformin users (mean [SD] age, 65.2 [11.8] years) and 25,695 matched sulfonylurea users (mean [SD] age, 65.3 [11.8] years) with a median follow-up duration of 119.6 months (interquartile range, 91.7-139.6 months) after 1:1 propensity score matching of 66,411 patients. Metformin users had lower risks of new-onset prostate cancer (hazard ratio, 0.80; 95% CI, 0.69-0.93; P=.0031) and all-cause mortality (hazard ratio, 0.89; 95% CI, 0.86-0.92; P<.0001) than sulfonylurea users. Metformin use was more protective against prostate cancer but less protective against all-cause mortality in patients aged <65 years (P for trend <.0001 for both) compared with patients aged ≥65 years. Metformin users had lower risk of all-cause mortality than sulfonylurea users, regardless of the use of androgen deprivation therapy (P for trend <.0001) among patients who developed prostate cancer. CONCLUSIONS: Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.

Arrhythmias and Conduction Disturbances in Patients with Systemic Sclerosis-A Systematic Literature Review.

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial fibrosis, which causes electrical inhomogeneity. The aim of this study was to determine the frequency of arrhythmias and conduction disturbances in SSc cohorts, and to identify the characteristics and risk factors associated with the occurrence of dysrhythmias in patients with SSc. A systematic literature review using PubMed, Embase, Web of Science and Scopus databases was performed. Full-text articles in English with arrhythmias as the main topic published until 21 April 2022 were included. Most prevalent arrhythmias were premature supraventricular and ventricular contractions, while the most frequent conduction disturbance was represented by right bundle branch block (RBBB). Elevated concentrations of N-terminal prohormones of brain natriuretic peptides (NT-pro BNP) were associated with numerous types of atrial and ventricular arrhythmias, and with the occurrence of RBBB. A lower value of the turbulence slope (TS) emerged as an independent predictor for ventricular arrhythmias. In conclusion, dysrhythmias are frequent in SSc cohorts. Paraclinical and laboratory parameters are useful instruments that could lead to early diagnosis in the course of the disease.

FUS contributes to mTOR-dependent inhibition of translation.

The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-linked RNA-binding protein called FUS (fused in sarcoma) has been implicated in several aspects of RNA regulation, including mRNA translation. The mechanism by which FUS affects the translation of polyribosomes has not been established. Here we show that FUS can associate with stalled polyribosomes and that this association is sensitive to mTOR (mammalian target of rapamycin) kinase activity. Specifically, we show that FUS association with polyribosomes is increased by Torin1 treatment or when cells are cultured in nutrient-deficient media, but not when cells are treated with rapamycin, the allosteric inhibitor of mTORC1. Moreover, we report that FUS is necessary for efficient stalling of translation because deficient cells are refractory to the inhibition of mTOR-dependent signaling by Torin1. We also show that ALS-linked FUS mutants R521G and P525L associate abundantly with polyribosomes and decrease global protein synthesis. Importantly, the inhibitory effect on translation by FUS is impaired by mutations that reduce its RNA-binding affinity. These findings demonstrate that FUS is an important RNA-binding protein that mediates translational repression through mTOR-dependent signaling and that ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the translation of mRNA at polyribosomes.

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study.

BACKGROUND: This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). METHODS: Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. RESULTS: A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). CONCLUSION(S): The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients.

The modified Rajan's heart failure risk score predicts all-cause mortality in patients hospitalized for heart failure with reduced ejection fraction: a retrospective cohort study.

Background: The dimensionless Rajan's heart failure (R-hf) risk score was proposed to predict all-cause mortality in patients hospitalized with chronic heart failure (HF) and reduced ejection fraction (EF) (HFrEF). Purpose: To examine the association between the modified R-hf risk score and all-cause mortality in patients with HFrEF. Methods: Retrospective cohort study included adults hospitalized with HFrEF, as defined by clinical symptoms of HF with biplane EF less than 40% on transthoracic echocardiography, at a tertiary centre in Dalian, China, between 1 November 2015, and 31 October 2019. All patients were followed up until 31 October 2020. A modified R-hf risk score was calculated by substituting brain natriuretic peptide (BNP) for N-terminal prohormone of BNP (NT-proBNP) using EF× estimated glomerular filtration rate (eGFR)× haemoglobin (Hb))/BNP. The patients were stratified into tertiles according to the R-hf risk score. The measured outcome was all-cause mortality. The score performance was assessed using C-statistics. Results: A total of 840 patients were analyzed (70.2% males; mean age, 64±14 years; median (interquartile range) follow-up 37.0 (27.8) months). A lower modified R-hf risk score predicted a higher risk of all-cause mortality, independent of sex and age [1st tertile vs. 3rd tertile: adjusted hazard ratio (aHR), 3.46; 95% CI: 2.11-5.67; P<0.001]. Multivariate Cox regression analysis indicated that a lower modified R-hf risk score was associated with increased cumulative all-cause mortality [univariate: (1st tertile vs. 3rd tertile: aHR, 3.45; 95% CI: 2.11-5.65; P<0.001) and multivariate: (1st tertile vs. 3rd tertile: aHR 2.21, 95% CI: 1.29-3.79; P=0.004)]. The performance of the model, as reported by C-statistic was 0.67 (95% CI: 0.62-0.72). Conclusion: The modified R-hf risk score predicted all-cause mortality in patients hospitalized with HFrEF. Further validation of the modified R-hf risk score in other cohorts of patients with HFrEF is needed before clinical application.

Comparing sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors on new-onset depression: a propensity score-matched study in Hong Kong.

INTRODUCTION: The risk of new onset depression associated with sodium-glucose co-transporter 2 inhibitor (SGLT2I) use in patients with type 2 diabetes mellitus (T2DM) remains unclear. This study investigated the risk of new onset depression between SGLT2I and dipeptidyl peptidase 4 inhibitor (DPP4I) users. METHODS: This was a population-based cohort study of T2DM patients in Hong Kong between January 1st, 2015, and December 31st, 2019. T2DM patients over 18 with either SGLT2I or DPP4I use were included. 1:1 propensity-score matching using the nearest-neighbour method was conducted based on demographics, past comorbidities and non-DPP4I/SGLT2I medication use. Cox regression analysis models were used to identify significant predictors for new onset depression. RESULTS: The study cohort included a total of 18,309 SGLT2I users and 37,269 DPP4I users (55.57% male, mean age: 63.5 ± 12.9 years) with a median follow-up duration of 5.56 (IQR: 5.23-5.8) years. After propensity score matching, SGLT2I use was associated with a lower risk of new onset depression compared to DPP4I use (HR: 0.52, 95% CI: [0.35, 0.77], P = 0.0011). These findings were confirmed by Cox multivariable analysis and sensitive analyses. CONCLUSION: SGLT2I use is associated with significantly lower risk of depression compared to DPP4 use in T2DM patients using propensity score matching and Cox regression analyses.

Association between serum uric acid and prostate cancer mortality in androgen deprivation therapy: A population-based cohort study.

OBJECTIVE: This population-based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)-related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). METHODS: Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa-related mortality. RESULTS: Altogether, 4126 patients (median follow-up 3.1[interquartile range 1.4-6.0] years) were included. A J-shaped association was observed between baseline UA level and PCa-related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above-mean baseline UA levels (hazard ratio (HR) per standard deviation-increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with below-mean baseline UA levels (HR 0.78[0.67,0.92], p = 0.003). The former remained significant on competing risk regression, but not the latter. CONCLUSIONS: A J-shaped relationship between baseline UA level and PCa-related mortality risk was identified. This study was mainly limited by potential unmeasured and residual confounders. Further validation studies are warranted.

HbA1c Variability and Cardiovascular Events in Patients with Prostate Cancer Receiving Androgen Deprivation Therapy.

Background: Androgen deprivation therapy (ADT) worsens glycaemic control and cardiovascular outcomes. The prognostic value of visit-to-visit HbA1c variability (VVHV) has been unexplored in prostate cancer (PCa) patients receiving ADT. Objective: To explore the effect of ADT on VVHV and the cardiovascular prognostic value of VVHV. Design setting and participants: PCa patients receiving ADT in Hong Kong between January 1, 1993 and March 31, 2021 were included in this retrospective cohort study. Those with fewer than three HbA1c results available within 3 yr after ADT initiation, <6 mo of ADT, missing baseline HbA1c, prior diagnosis of any component of major adverse cardiovascular events (MACEs), and MACEs occurring within 3 yr were excluded. Patients were followed up until September 31, 2021. Outcome measurements and statistical analysis: The outcome was MACEs (composite of heart failure, myocardial infarction, stroke, and cardiovascular mortality). VVHV was calculated from HbA1c levels within 3 yr after and, separately where available, before ADT initiation using coefficient of variation (CV; standard deviation [SD] divided by mean) and average real variability (ARV; average difference between consecutive measurements). Results and limitations: Altogether, 1065 patients were analysed (median age 74.4 yr old [interquartile range 68.3-79.5 yr]). In 709 patients with VVHV available before and after ADT initiation, VVHV increased after ADT initiation (p < 0.001), with 473 (66.2%) and 474 (66.9%) having increased CV and ARV, respectively. Over a median follow-up of 4.3 yr (2.8-6.7 yr), higher VVHV was associated with a higher risk of MACEs (adjusted hazard ratio [per SD] for CV 1.21 [95% confidence interval: 1.02, 1.43], p = 0.029; ARV 1.25 [1.06, 1.48], p = 0.008). Limitations included residual confounding and selection bias. Conclusions: In PCa patients receiving ADT, VVHV increased after ADT initiation. Higher VVHV was associated with an increased risk of MACEs. Patient summary: In prostate cancer patients receiving androgen deprivation therapy (ADT), glycaemic control is less stable after initiating ADT, which was associated with an increased cardiovascular risk.

Metformin use and hospital attendance-related resources utilization among diabetic patients with prostate cancer on androgen deprivation therapy: A population-based cohort study.

BACKGROUND: Androgen deprivation therapy (ADT), used increasingly in the treatment of prostate cancer (PCa), negatively influences glycemic control in diabetes and is associated with an increased risk of diabetes complications where hospitalization commonly ensues. Metformin could decrease the metabolic consequences of ADT and enhance its effect. This study examined the association of metformin use with healthcare resources utilization among diabetic, PCa patients receiving ADT. METHODS: Diabetic adults with PCa on ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with <6 months of concurrent metformin and ADT use were excluded. All included patients were followed up until September 2021. The outcomes were hospital attendances and related costs. RESULTS: In total, 1,284 metformin users and 687 non-users were studied. Over 8,045 person-years, 9,049 accident and emergency (A&E), and 21,262 inpatient attendances, with 11,2781 days of hospitalization were observed. Metformin users had significantly fewer A&E attendances (incidence rate ratio (IRR): 0.61 [95% confidence interval 0.54-0.69], p < 0.001), inpatient attendances (IRR: 0.57 [0.48-0.67], p < 0.001), and days of hospitalization (IRR: 0.55 [0.42-0.72], p < 0.001). Annual attendance costs were lower for metformin users than non-users (cost ratio: 0.28 [0.10-0.80], p = 0.017). CONCLUSIONS: Metformin use was associated with decreased hospital attendances, days of hospitalization, and associated costs, which could help reduce healthcare resource utilization following ADT in the treatment of PCa.

Arrhythmias Beyond Atrial Fibrillation Detection Using Smartwatches: A Systematic Review.

BACKGROUND: Over the past few years, smartwatches have become increasingly popular in the monitoring of arrhythmias. Although the detection of atrial fibrillation with smartwatches has been the subject of various articles, there is no comprehensive research on the detection of arrhythmias other than atrial fibrillation. In this study, we included individual cases from the literature to identify the characteristics of patients with smartwatch-detected arrhythmias other than atrial fibrillation. METHODS: PubMed, Embase, and SCOPUS were searched for case reports, case series, or cohort studies that reported individual participant-level data, until January 6, 2022. The following search string was used for each databases: ('Smart Watch' OR 'Apple Watch' OR 'Samsung Gear') AND ('Supraventricular Tachycardia' OR 'Cardiac Arrhythmia' OR 'Ventricular Tachycardia' OR 'Atrioventricular Nodal Reentry Tachycardia' OR 'Atrioventricular Reentrant Tachycardia' OR 'Heart Block' OR 'Atrial Flutter' OR 'Ectopic Atrial Tachycardia' OR 'Bradyarrhythmia'). RESULTS: A total of 52 studies from PubMed, 20 studies from Embase, and 200 studies from SCOPUS were identified. After screening, 18 articles were included. A total of 22 patients were obtained from 14 case reports or case series. Four cohort studies evaluating various arrhythmias were included. Arrhythmias, including ventricular tachycardia, atrial fibrillation, atrial flutter, atrioventricular nodal reentry tachycardia, atrioventricular reentrant tachycardia, second- or third-degree atrioventricular block, and sinus bradycardia, were detected with smartwatches. CONCLUSIONS: Cardiac arrhythmias other than atrial fibrillation are also commonly detected with smartwatches. Smartwatches have an important potential besides traditional methods in the detection of arrhythmias and clinical practice.

Spiked Helmet Electrocardiographic Sign-A Systematic Review of Case Reports.

First reported in 2011, the spiked helmet sign (SHS) is an electrocardiographic pattern of ST-segment elevation anecdotally associated with poor prognosis. This study aims to systematically evaluate the electrocardiographic characteristics, clinical presentations, and outcomes of all cases of SHS reported in the literature. PubMed, Scopus, Web of Science, and EMBASE were searched electronically from their inception until November 2022. The Joanna Briggs Institute Critical Appraisal Checklist for Case Reports was used to critically appraise included studies. Studies written in English describing at least one patient with SHS were included. Altogether, 26 case reports or series describing 39 patients with SHS were included. All included studies were rated of acceptable quality. Associated conditions were heterogeneous, with intracranial hemorrhagic complications being the most common (9 patients), followed by pneumothorax (6 patients) or severe pneumonia (4 patients), bowel ischemia or obstruction (6 patients), and autonomic dysfunction (3 patients with Takotsubo cardiomyopathy and 3 patients with spinal injury, cocaine overuse, and stellate gangliectomy). Two patients had multiple complications and 12 other patients suffered from sepsis, myocardial infarction, etc. Clinical outcomes were reported for 32 patients, of whom 19 (59%) died during hospitalization (6 patients with pneumothorax or pneumonia, 4 patients with intracranial hemorrhagic complications, 2 patients with bowel ischemia or obstruction, and 7 patients due to other reasons). SHS may be associated with poor prognosis, necessitating its prompt recognition by clinicians and swift evaluation for underlying causes. Larger studies are needed to elucidate its prevalence, clinical implications, and precipitating mechanisms.