Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study.

BACKGROUND: Molnupiravir and nirmatrelvir-ritonavir are orally administered pharmacotherapies for mild to moderate COVID-19. However, the effectiveness of these drugs among very old (≥80 years), hospitalised patients remains unclear, limiting the risk-benefit assessment of these antivirals in this specific group. This study investigates the effectiveness of these antivirals in reducing mortality among this group of hospitalised patients with COVID-19. METHODS: Using a territory-wide public healthcare database in Hong Kong, a target trial emulation study was conducted with data from 13 642 eligible participants for the molnupiravir trial and 9553 for the nirmatrelvir-ritonavir trial. The primary outcome was all-cause mortality. Immortal time and confounding bias was minimised using cloning-censoring-weighting approach. Mortality odds ratios were estimated by pooled logistic regression after adjusting confounding biases by stabilised inverse probability weights. RESULTS: Both molnupiravir (HR: 0.895, 95% CI: 0.826-0.970) and nirmatrelvir-ritonavir (HR: 0.804, 95% CI: 0.678-0.955) demonstrated moderate mortality risk reduction among oldest-old hospitalised patients. No significant interaction was observed between oral antiviral treatment and vaccination status. The 28-day risk of mortality was lower in initiators than non-initiators for both molnupiravir (risk difference: -1.09%, 95% CI: -2.29, 0.11) and nirmatrelvir-ritonavir (risk difference: -1.71%, 95% CI: -3.30, -0.16) trials. The effectiveness of these medications was observed regardless of the patients' prior vaccination status. CONCLUSIONS: Molnupiravir and nirmatrelvir-ritonavir are moderately effective in reducing mortality risk among hospitalised oldest-old patients with COVID-19, regardless of their vaccination status.

Does gambling expenditure have any effect on crime?

BACKGROUND AND AIMS: Australians spend more per capita on gambling than any other country in the world. Electronic gaming machines (EGM) expenditure accounts for almost 90% of this expenditure. No study to date has conducted a rigorous longitudinal analysis of the relationship between gambling expenditure and crime. This study aimed to estimate the short- and long-run relationship between gambling expenditure and crime. DESIGN: Longitudinal analysis using panel autoregressive distributed lag (ARDL) modelling. SETTING AND CASES: Recorded property and violent crimes committed in New South Wales (NSW), Australia, between 28 December 2015 and 5 January 2020. MEASUREMENTS: Monthly gross EGM expenditure profit, broken down by Local Government Area (LGA). Monthly recorded rates of assault, break enter and steal (dwelling), break enter and steal (non-dwelling), break enter and steal (total), motor vehicle theft, stealing from a motor vehicle, stealing from a retail store, stealing from the person, stealing (total) and fraud. FINDINGS: Each 10% increase in gambling expenditure in NSW is associated with annual: 7.4% increase in assaults, 10.5% increase in break and enter (dwelling) offences; 10.3% increase in break and enter (non-dwelling) offences; 11% increase in motor vehicle theft offences; 8.2% increase in stealing from motor vehicle offences; and 7.4% increase in fraud offences. CONCLUSION: Electronic gaming expenditure appears to be positively associated with property and violent crime in New South Wales, Australia.

Non-contrasted computed tomography (NCCT) based chronic thromboembolic pulmonary hypertension (CTEPH) automatic diagnosis using cascaded network with multiple instance learning.

ObjectiveThe diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is challenging due to nonspecific early symptoms, complex diagnostic processes, and small lesion sizes. This study aims to develop an automatic diagnosis method for CTEPH using non-contrasted computed tomography (NCCT) scans, enabling automated diagnosis without precise lesion annotation. ApproachA novel Cascade Network with Multiple Instance Learning (CNMIL) framework was developed to improve the diagnosis of CTEPH. This method uses a cascade network architecture combining two Resnet-18 CNN networks to progressively distinguish between normal and CTEPH cases. Multiple Instance Learning (MIL) is employed to treat each 3D CT case as a "bag" of image slices, using attention scoring to identify the most important slices. An attention module helps the model focus on diagnostically relevant regions within each slice. The dataset comprised NCCT scans from 300 subjects, including 117 males and 183 females, with an average age of 52.5 ± 20.9 years, consisting of 132 normal cases and 168 cases of lung diseases, including 88 instances of CTEPH. The CNMIL framework was evaluated using sensitivity, specificity, and the area under the curve (AUC) metrics, and compared with common 3D supervised classification networks and existing CTEPH automatic diagnosis networks. Main ResultsThe CNMIL framework demonstrated high diagnostic performance, achieving an AUC of 0.807, accuracy of 0.833, sensitivity of 0.795, and specificity of 0.849 in distinguishing CTEPH cases. Ablation studies revealed that integrating MIL and the cascade network significantly enhanced performance, with the model achieving an AUC of 0.993 and perfect sensitivity (1.000) in normal classification. Comparisons with other 3D network architectures confirmed that the integrated model outperformed others, achieving the highest AUC of 0.8419. SignificanceThe CNMIL network requires no additional scans or annotations, relying solely on NCCT. This approach can improve timely and accurate CTEPH detection, resulting in better patient outcomes.

Comparative effectiveness of combination therapy with nirmatrelvir-ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir-ritonavir in patients hospitalised with COVID-19: a target trial emulation study.

BACKGROUND: Remdesivir (Veklury, Gilead Sciences, Foster City, CA, USA) and nirmatrelvir-ritonavir (Paxlovid, Pfizer, New York, NY, USA) were reported to improve the outcome of patients with mild-to-moderate COVID-19 symptoms. Preclinical data suggest that nirmatrelvir-ritonavir might be more effective than remdesivir alone or in combination with nirmatrelvir-ritonavir for people at high risk of severe COVID-19. We aimed to assess the safety and effectiveness of combining remdesivir and nirmatrelvir-ritonavir compared with using each drug alone for adults hospitalised with COVID-19. METHODS: In this target trial emulation study, we used electronic health records of patients aged 18 years or older who received either combination treatment of nirmatrelvir-ritonavir and remdesivir or monotherapy of either drug between March 16 and Dec 31, 2022, within 5 days of hospitalisation for COVID-19 in Hong Kong. Inverse probability of treatment weighting was applied to balance baseline patient characteristics across the treatment groups. The primary outcome was all-cause mortality. Cox proportional hazards regression adjusting weighting was used to compare the risk of all-cause mortality, intensive care unit (ICU) admission, or ventilatory support for 90 days of follow-up between groups. FINDINGS: Between March 16 and Dec 31, 2022, 18 196 participants were identified from electronic health records and assigned to receive remdesivir (n=4232), nirmatrelvir-ritonavir (n=13 656), or nirmatrelvir-ritonavir and remdesivir (n=308). By applying an inverse probability of treatment weighting, a weighted sample composed of 18 410 recipients of nirmatrelvir-ritonavir and remdesivir combination treatment, 18 178 recipients of remdesivir monotherapy, and 18 287 recipients of nirmatrelvir-ritonavir monotherapy was obtained. After a median follow-up of 84 days (IQR 45-90), risk of mortality was lower in patients who received nirmatrelvir-ritonavir monotherapy (hazard ratio [HR] 0·18 [95% CI 0·15 to 0·20]; absolute risk reduction [ARR] -16·33% [95% CI -16·98 to -15·68]) or remdesivir and nirmatrelvir-ritonavir combination therapy (HR 0·66 [95% CI 0·49 to 0·89]; ARR -6·52% [95% CI -7·29 to -5·74]) than in patients who received remdesivir monotherapy. Similar results were observed for ICU admission or ventilatory support (nirmatrelvir-ritonavir monotherapy: HR 0·09 [95% CI 0·07 to 0·11]; ARR -10·04% [95% CI -10·53 to -9·56]; combination therapy: HR 0·68 [95% CI 0·42 to 1·12]; ARR -3·24% [95% CI -3·84 to -2·64]). Compared with combination therapy, nirmatrelvir-ritonavir monotherapy was associated with lower risk of mortality (HR 0·27 [95% CI 0·20 to 0·37]; ARR -9·81% [95% CI -10·39 to -9·24]) and ICU admission or ventilatory support (HR 0·13 [95% CI 0·08 to 0·22]; ARR -6·80% [95% CI -7·22 to -6·39]). INTERPRETATION: Our study highlighted the potential for reduced risk of mortality, ICU admission, or the need for ventilatory support in patients hospitalised with COVID-19 treated with nirmatrelvir-ritonavir as a monotherapy compared with treatment regimens based on nirmatrelvir-ritonavir and remdesivir combination therapy or remdesivir monotherapy. Further randomised controlled trials are needed to support the validity of the current results. FUNDING: The Health and Medical Research Fund Commissioned Research on COVID-19. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Systemic Inflammation Disrupts Circadian Rhythms and Diurnal Neuroimmune Dynamics.

Circadian rhythms regulate physiological processes in approximately 24 h cycles, and their disruption is associated with various diseases. Inflammation may perturb circadian rhythms, though these interactions remain unclear. This study examined whether systemic inflammation induced by an intraperitoneal injection of lipopolysaccharide (LPS) could alter central and peripheral circadian rhythms and diurnal neuroimmune dynamics. Mice were randomly assigned to two groups: the saline control group and the LPS group. The diurnal expression of circadian clock genes and inflammatory cytokines were measured in the hypothalamus, hippocampus, and liver. Diurnal dynamic behaviors of microglia were also assessed. Our results revealed that the LPS perturbed circadian gene oscillations in the hypothalamus, hippocampus, and liver. Furthermore, systemic inflammation induced by the LPS could trigger neuroinflammation and perturb the diurnal dynamic behavior of microglia in the hippocampus. These findings shed light on the intricate link between inflammation and circadian disruption, underscoring their significance in relation to neurodegenerative diseases.

Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity: a territory-wide target trial emulation.

OBJECTIVES: Older individuals with multimorbidity are at an elevated risk of infection and complications from COVID-19. Effectiveness of post-COVID-19 interventions or care models in reducing subsequent adverse outcomes in these individuals have rarely been examined. This study aims to examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged 85 years or above with multimorbidity. DESIGN: Retrospective cohort study emulating a randomised target trial using electronic health records. SETTING: We used data from the Hospital Authority and the Department of Health in Hong Kong, which provided comprehensive electronic health records, COVID-19 confirmed case data, population-based vaccination records and other individual characteristics for the study. PARTICIPANTS: Adults aged 85 years or above with multimorbidity who were discharged after hospitalisation for COVID-19 between January 2020 and August 2022. INTERVENTIONS: Attending a general outpatient within 30 days of last COVID-19 discharge defined the exposure, compared to no outpatient visit. MAIN OUTCOME MEASURES: Primary outcome was all-cause mortality within one year. Secondary outcomes included mortality from respiratory, cardiovascular and cancer causes. RESULTS: A total of 6183 eligible COVID-19 survivors were included in the analysis. The all-cause mortality rate following COVID-19 hospitalisation was lower in the general outpatient visit group (17.1 deaths per 100 person-year) compared with non-visit group (42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI 8.1% to 14.4%). We also observed significantly better survival from respiratory diseases in the general outpatient visit group (difference in 1-year survival: 6.3%, 95% CI 3.5% to 8.9%). In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a general outpatient visit after COVID-19 discharge, the better the survival. CONCLUSIONS: Timely primary care consultations after COVID-19 hospitalisation may improve survival following COVID-19 hospitalisation among older adults aged 85 or above with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population's recovery and well-being.

Comparative effectiveness and safety of BNT162b2 and CoronaVac in Hong Kong: A target trial emulation.

OBJECTIVES: To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety. METHODS: This target trial emulation study included individuals aged ≥12 during 2022. Propensity score matching was applied to ensure group balance. The Cox proportional hazard model was used to compare the effectiveness outcomes including COVID-19 infection, severity, 28-day hospitalization, and 28-day mortality after infection. Poisson regression was used for safety outcomes including 32 adverse events of special interests between groups. RESULTS: A total of 639,818 and 1804,388 individuals were identified for the 2-dose and 3-dose comparison, respectively. In 2-dose and 3-dose comparison, the hazard ratios (95% confidence intervals [CI]) were 0.844 [0.833-0.856] and 0.749 [0.743-0.755] for COVID-19 infection, 0.692 [0.656-0.731] and 0.582 [0.559-0.605] for hospitalization, 0.566 [0.417-0.769] and 0.590 [0.458-0.76] for severe COVID-19, and 0.563 [0.456-0.697] and 0.457 [0.372-0.561] for mortality for BNT162b2 recipients versus CoronaVac recipients, respectively. Regarding safety, 2-dose BNT162b2 recipients had a significantly higher incidence of myocarditis (incidence rate ratio [IRR] [95% CI]: 8.999 [1.14-71.017]) versus CoronaVac recipients, but the difference was insignificant in 3-dose comparison (IRR [95% CI]: 2.000 [0.500-7.996]). CONCLUSION: BNT162b2 has higher effectiveness among individuals aged ≥12 against COVID-19-related outcomes for SARS-CoV-2 omicron compared to CoronaVac, with almost 50% lower mortality risk.

Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics.

INTRODUCTION: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines. RESEARCH DESIGN AND METHODS: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications. RESULTS: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m2, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes. CONCLUSIONS: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events. TRIAL REGISTRATION NUMBER: NCT04049149.

Janus and Amphiphilic MoS2 2D Sheets for Surface-Directed Orientational Assemblies toward Ex Vivo Dual Substrate Release.

The two-dimensional (2-D) Janus and amphiphilic molybdenum disulfide (MoS2) nanosheet with opposite optical activities on each side (amphichiral) is synthesized by modifying sandwich-like bulk MoS2 with tannic acid and cholesterol through biphasic emulsion method. This new type of amphichiral Janus MoS2 nanosheet consists of a hydrophilic and positive optical activity tannic acid side as well as a hydrophobic and negative optical activity cholesterol side thereby characterized by circular dichroism. Surface-directed orientational differentiation assemblies are performed for the as-synthesized 2D material and are characterized by contact angle, infrared spectroscopy, X-ray photoelectron, and circular dichroism spectroscopies. The amphiphilic nature of the materials is demonstrated by the pre-organization of the nanosheets on either hydrophobic or hydrophilic surfaces, providing unprecedented properties of circular dichroism signal enhancement and wettability. Selective detachment of the surface organic groups (cholesterol and tannic acid fragments) is realized by matrix-assisted laser desorption/ionisation - time-of-flight (MALDI-TOF) mass spectrometry, and the dual substrate release in tissue is detected by ex vivo mass spectrometry imaging.

Engagement With a Mobile Chat-Based Intervention for Smoking Cessation: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Determining how individuals engage with digital health interventions over time is crucial to understand and optimize intervention outcomes. Objective: To identify the engagement trajectories with a mobile chat-based smoking cessation intervention and examine its association with biochemically validated abstinence. Design, Setting, and Participants: A secondary analysis of a pragmatic, cluster randomized clinical trial conducted in Hong Kong with 6-month follow-up. From June 18 to September 30, 2017, 624 adult daily smokers were recruited from 34 community sites randomized to the intervention group. Data were analyzed from March 6 to October 30, 2023. Intervention: Chat-based cessation support delivered by a live counselor via a mobile instant messaging app for 3 months from baseline. Main Outcomes and Measures: Group-based trajectory modeling was used to identify engagement trajectories using the participants' weekly responses to the messages from the counselor over the 3-month intervention period. The outcome measures were biochemically validated tobacco abstinence at 3-month (end of treatment) and 6-month follow-ups. Covariates included sex, age, educational level, nicotine dependence, past quit attempt, and intention to quit at baseline. Results: Of 624 participants included in the analysis, 479 were male (76.8%), and the mean (SD) age was 42.1 (16.2) years. Four distinct engagement trajectories were identified: low engagement group (447 [71.6%]), where participants maintained very low engagement throughout; rapid-declining group (86 [13.8%]), where participants began with moderate engagement and rapidly decreased to a low level; gradual-declining group (58 [9.3%]), where participants had high initial engagement and gradually decreased to a moderate level; and high engagement group (58 [5.3%]), where participants maintained high engagement throughout. Compared with the low engagement group, the 6-month validated abstinence rates were significantly higher in the rapid-declining group (adjusted relative risk [ARR], 3.30; 95% CI, 1.39-7.81), gradual-declining group (ARR, 5.17; 95% CI, 2.21-12.11), and high engagement group (ARR, 4.98; 95% CI, 1.82-13.60). The corresponding ARRs (95% CI) of 3-month validated abstinence were 4.03 (95% CI, 1.53-10.59), 5.25 (95% CI, 1.98-13.88), and 9.23 (95% CI, 3.29-25.86). Conclusions and Relevance: The findings of this study suggest that higher levels of engagement with the chat-based smoking cessation intervention were associated with greater biochemically validated tobacco abstinence. Improving engagement with digital interventions may increase intervention benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03182790.

Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity: a territory-wide target trial emulation.

BACKGROUND: Older adults with multimorbidity are at high risk of mortality following COVID-19 hospitalisation. However, the potential benefit of timely primary care follow-up on severe outcomes post-COVID-19 has not been well established. AIM: To examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged ≥85 years, with multimorbidity. METHOD: We emulated a target trial using a comprehensive public healthcare database in Hong Kong. The cloning-censoring-weighting technique was used to minimise immortal time bias and confounding bias by adjusting for demographics, hospitalisation duration and ICU admission, baseline chronic conditions, and medication history. The outcome included all-cause and cause-specific mortality. RESULTS: Of 6183 eligible COVID-19 survivors, the all-cause mortality rate following COVID-19 hospitalisation was lower in general out-patient clinics (GOPC) group compared to non-GOPC group (17.1 versus 42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI = 8.1% to 14.4%). We also observed better survival from respiratory diseases in the GOPC group. In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a GOPC visit after COVID-19 discharge, the better the survival. CONCLUSION: Timely primary care consultations after discharge may improve survival following COVID-19 hospitalisation among older adults aged ≥85 years, with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population's recovery and well-being.

Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study.

BACKGROUND: Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited. OBJECTIVE: The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals. METHODS: Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not. RESULTS: A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history. CONCLUSIONS: Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.

Development and validation of risk prediction model for recurrent cardiovascular events among Chinese: the Personalized CARdiovascular DIsease risk Assessment for Chinese model.

Aims: Cardiovascular disease (CVD) is a leading cause of mortality, especially in developing countries. This study aimed to develop and validate a CVD risk prediction model, Personalized CARdiovascular DIsease risk Assessment for Chinese (P-CARDIAC), for recurrent cardiovascular events using machine learning technique. Methods and results: Three cohorts of Chinese patients with established CVD were included if they had used any of the public healthcare services provided by the Hong Kong Hospital Authority (HA) since 2004 and categorized by their geographical locations. The 10-year CVD outcome was a composite of diagnostic or procedure codes with specific International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariate imputation with chained equations and XGBoost were applied for the model development. The comparison with Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2°P) and Secondary Manifestations of ARTerial disease (SMART2) used the validation cohorts with 1000 bootstrap replicates. A total of 48 799, 119 672 and 140 533 patients were included in the derivation and validation cohorts, respectively. A list of 125 risk variables were used to make predictions on CVD risk, of which 8 classes of CVD-related drugs were considered interactive covariates. Model performance in the derivation cohort showed satisfying discrimination and calibration with a C statistic of 0.69. Internal validation showed good discrimination and calibration performance with C statistic over 0.6. The P-CARDIAC also showed better performance than TRS-2°P and SMART2. Conclusion: Compared with other risk scores, the P-CARDIAC enables to identify unique patterns of Chinese patients with established CVD. We anticipate that the P-CARDIAC can be applied in various settings to prevent recurrent CVD events, thus reducing the related healthcare burden.

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in CKD Patients With COVID-19.

Introduction: Even with effective vaccines, patients with CKD have a higher risk of hospitalization and death subsequent to COVID-19 infection than those without CKD. Molnupiravir and nirmatrelvir-ritonavir have been approved for emergency use, but their effectiveness for the CKD population is still unknown. This study was conducted to determine the effectiveness of these drugs in reducing mortality and severe COVID-19 in the CKD population. Methods: This was a target trial emulation study using electronic health databases in Hong Kong. Patients with CKD aged 18 years or older who were hospitalized with COVID-19 were included. The per-protocol average treatment effect among COVID-19 oral antiviral initiators, including all-cause mortality, intensive care unit (ICU) admission, and ventilatory support within 28 days, were compared to noninitiators. Results: Antivirals have been found to lower the risk of all-cause mortality, with Molnupiravir at a hazard ratio (HR) of 0.85 (95% confidence interval [CI], 0.77 to 0.95] and nirmatrelvir-ritonavir at an HR of 0.78 [95% CI, 0.60 to 1.00]. However, they do not significantly reduce the risk of ICU admission (molnupiravir: HR, 0.88 [95% CI, 0.59 to 1.30]; nirmatrelvir-ritonavir: HR, 0.86 [95% CI, 0.56 to 1.32]) or ventilatory support (molnupiravir: HR, 1.00 [95% CI, 0.76 to 1.33]; nirmatrelvir-ritonavir: HR, 1.01 [95% CI, 0.74 to 1.37]). There was a greater risk reduction in males and those with higher Charlson Comorbidity Index (CCI). The nirmatrelvir-ritonavir trial also showed reduced risk for those who had antiviral treatment and received 3 or more vaccine doses. Conclusion: Both molnupiravir and nirmatrelvir-ritonavir reduced mortality rates for hospitalized COVID-19 patients with CKD.

Effects of an online mindfulness-based program for parents of children with attention deficit/hyperactivity disorder: a pilot, mixed methods study.

Objectives: Online mindfulness-based program (MBP) for parents and families especially in clinical population is limited. Engagement and significant dropout are major issues in MBP implementation. This pilot study examined the effects of an online mindfulness-based program (MBP) on parents of children with Attention Deficit/Hyperactivity Disorder (ADHD). Methods: A mixed methods study was applied to evaluate the effects of the MBP. A total of 43 parents were recruited and were randomly assigned into intervention group and waitlist control group. The online MBP lasted for 28 days, including 20 psychoeducation videos, homework audio guidance, and four instructor-led online group meetings. Purposive sampling was used to recruit parents who completed the program to share their experiences and suggestions for improving the program in semi-structured online interviews. Results: Quantitative data showed that participants from the online MBP reported a medium to large effect on the reduction of child ADHD symptoms. In semi-structured interviews, participants reported positive experiences in their help seeking intention, and personal changes, such as emotion regulation and quality attention to their children. Participants further made suggestions for improvement. Conclusions: The effect of online MBP is promising, and the program should be conducted. A large scale randomized controlled trial should be conducted to investigate the effects of MBP in clinical populations. Clinical trial registration: ClinicalTrials.gov NCT05480423.

Characterization of the Tissue and Strain-Specific Microbiota of Anopheles funestus Giles (Diptera: Culicidae).

The mosquito microbiota is a critical determinant of mosquito life history. It is therefore a target for novel vector control strategies like paratransgenesis. However, the microbiota in Anopheles funestus, a major African malaria vector, is poorly characterized. Thus, the study aimed to investigate the overall bacterial landscape in the salivary glands, ovaries and midguts of three laboratory strains of An. funestus differing in insecticide-resistant phenotype by sequencing the V3-V4 hypervariable region of bacterial 16S rRNA genes. When examining alpha diversity, the salivary glands harbored significantly more bacteria in terms of species richness and evenness compared to ovaries and midguts. On the strain level, the insecticide-susceptible FANG strain had significantly lower bacterial diversity than the insecticide-resistant FUMOZ and FUMOZ-R strains. When looking at beta diversity, the compositions of microbiota between the three tissues as well as between the strains were statistically different. While there were common bacteria across all three tissues and strains of interest, each tissue and strain did exhibit differentially abundant bacterial genera. However, overall, the top five most abundant genera across all tissues and strains were Elizabethkingia, Acinetobacter, Aeromonas, Cedecea and Yersinia. The presence of shared microbiota suggests a core microbiota that could be exploited for paratransgenesis efforts.

Genomic diversity and antimicrobial susceptibility of invasive Neisseria meningitidis in South Africa, 2016-2021.

BACKGROUND: Invasive meningococcal isolates in South Africa have in previous years (<2008) been characterized by serogroup B, C, W and Y lineages over time, with penicillin intermediate resistance (peni) at 6%. We describe the population structure and genomic markers of peni among invasive meningococcal isolates in South Africa, 2016-2021. METHODS: Meningococcal isolates were collected through national, laboratory-based invasive meningococcal disease (IMD) surveillance. Phenotypic antimicrobial susceptibility testing and whole-genome sequencing were performed, and the mechanism of reduced penicillin susceptibility was assessed in silico. RESULTS: Of 585 IMD cases reported during the study period, culture and PCR-based capsular group was determined for 477/585 (82%); and 241/477 (51%) were sequenced. Predominant serogroups included NmB (210/477; 44%), NmW (116/477; 24%), NmY (96/477; 20%) and NmC (48/477; 10%). Predominant clonal complexes (CC) were CC41/44 in NmB (27/113; 24%), CC11 in NmW (46/56; 82%), CC167 in NmY (23/44; 53%), and CC865 in NmC (9/24; 38%). Peni was detected in 16% (42/262) of isolates, and was due to the presence of a penA mosaic, with the majority harboring penA7, penA9 or penA14. CONCLUSION: IMD lineages circulating in South Africa were consistent with those circulating prior to 2008, however peni was higher than previously reported, and occurred in a variety of lineages.

Association between tobacco industry denormalisation beliefs and support for tobacco endgame policies: a population-based study in Hong Kong.

OBJECTIVES: To examine the associations between tobacco industry denormalisation (TID) beliefs and support for tobacco endgame policies. METHODS: A total of 2810 randomly selected adult respondents of population-based tobacco policy-related surveys (2018-2019) were included. TID beliefs (agree vs disagree/unsure) were measured by seven items: tobacco manufacturers ignore health, induce addiction, hide harm, spread false information, lure smoking, interfere with tobacco control policies and should be responsible for health problems. Score of each item was summed up and dichotomised (median=5, >5 strong beliefs; ≤5 weak beliefs). Support for tobacco endgame policies on total bans of tobacco sales (yes/no) and use (yes/no) was reported. Associations between TID beliefs and tobacco endgame policies support across various smoking status were analysed, adjusting for sociodemographics. RESULTS: Fewer smokers (23.3%) had strong beliefs of TID than ex-smokers (48.4%) and never smokers (48.5%) (p<0.001). Support for total bans on tobacco sales (74.6%) and use (76.9%) was lower in smokers (33.3% and 35.3%) than ex-smokers (74.3% and 77.9%) and never smokers (76.0% and 78.3%) (all p values<0.001). An increase in the number of TID beliefs supported was positively associated with support for a total ban on sales (adjusted risk ratio 1.06, 95% CI 1.05 to 1.08, p<0.001) and use (1.06, 95% CI 1.05 to 1.07, p<0.001). The corresponding associations were stronger in smokers than non-smokers (sales: 1.87 vs 1.25, p value for interaction=0.03; use: 1.78 vs 1.21, p value for interaction=0.03). CONCLUSION: Stronger TID belief was associated with greater support for total bans on tobacco sales and use. TID intervention may increase support for tobacco endgame, especially in current smokers.

Rapid point-of-care test for diagnosis of peritonitis in peritoneal dialysis patients.

BACKGROUND: Periplex® is a rapid point-of-care test based on the detection of interleukin-6 (IL-6) or matrix metalloproteinase-8 (MMP-8) to diagnose peritonitis in peritoneal dialysis (PD) patients. METHODS: This single-centre study was conducted in Singapore General Hospital from 2019 to 2022. The study recruited PD patients suspected of having peritonitis. Periplex was performed at the presentation and recovery of peritonitis. Primary outcomes were sensitivity and specificity of Periplex at presentation. The positive and negative predictive values of tests were also performed. RESULTS: A total of 120 patients were included in the study. The mean age was 60.9 ± 14.9 years, 53% were male, 79% were Chinese and 47.5% had diabetes mellitus. Periplex was positive in all patients with peritonitis (n = 114); sensitivity of 100%; 95% confidence interval (CI): 100-100%. Periplex was falsely positive in three patients with non-infective eosinophilic peritonitis, resulting in a low specificity of 50%; 95% CI: 41.1-59.0%. Periplex had a positive predictive value of 97.4% and a negative predictive value of 100%. During recovery from peritonitis, Periplex had high specificity (93.6%) and negative predictive value (98.7%) to indicate the resolution of infection. MMP-8 was more sensitive than IL-6 in detecting peritonitis. Periplex was positive in all patients with peritonitis regardless of the types of PD solutions used. CONCLUSIONS: Periplex had high sensitivity, and positive and negative predictive values in the diagnosis of peritonitis can be considered as a screening tool for peritonitis. Given its high specificity and negative predictive value, it may also be used to document the resolution of peritonitis.