An update and review of arthropod vector sensory systems: Potential targets for behavioural manipulation by parasites and other disease agents.

For over a century, vector ecology has been a mainstay of vector-borne disease control. Much of this research has focused on the sensory ecology of blood-feeding arthropods (black flies, mosquitoes, ticks, etc.) with terrestrial vertebrate hosts. Of particular interest are the cues and sensory systems that drive host seeking and host feeding behaviours as they are critical for a vector to locate and feed from a host. An important yet overlooked component of arthropod vector ecology are the phenotypic changes observed in infected vectors that increase disease transmission. While our fundamental understanding of sensory mechanisms in disease vectors has drastically increased due to recent advances in genome engineering, for example, the advent of CRISPR-Cas9, and high-throughput "big data" approaches (genomics, proteomics, transcriptomics, etc.), we still do not know if and how parasites manipulate vector behaviour. Here, we review the latest research on arthropod vector sensory systems and propose key mechanisms that disease agents may alter to increase transmission.

A retrospective cohort study of Paxlovid efficacy depending on treatment time in hospitalized COVID-19 patients.

Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.

Motivators and Demotivators for COVID-19 Vaccination Based on Co-Occurrence Networks of Verbal Reasons for Vaccination Acceptance and Resistance: Repetitive Cross-Sectional Surveys and Network Analysis.

BACKGROUND: Vaccine hesitancy is complex and multifaced. People may accept or reject a vaccine due to multiple and interconnected reasons, with some reasons being more salient in influencing vaccine acceptance or resistance and hence the most important intervention targets for addressing vaccine hesitancy. OBJECTIVE: This study was aimed at assessing the connections and relative importance of motivators and demotivators for COVID-19 vaccination in Hong Kong based on co-occurrence networks of verbal reasons for vaccination acceptance and resistance from repetitive cross-sectional surveys. METHODS: We conducted a series of random digit dialing telephone surveys to examine COVID-19 vaccine hesitancy among general Hong Kong adults between March 2021 and July 2022. A total of 5559 and 982 participants provided verbal reasons for accepting and resisting (rejecting or hesitating) a COVID-19 vaccine, respectively. The verbal reasons were initially coded to generate categories of motivators and demotivators for COVID-19 vaccination using a bottom-up approach. Then, all the generated codes were mapped onto the 5C model of vaccine hesitancy. On the basis of the identified reasons, we conducted a co-occurrence network analysis to understand how motivating or demotivating reasons were comentioned to shape people's vaccination decisions. Each reason's eigenvector centrality was calculated to quantify their relative importance in the network. Analyses were also stratified by age group. RESULTS: The co-occurrence network analysis found that the perception of personal risk to the disease (egicentrality=0.80) and the social responsibility to protect others (egicentrality=0.58) were the most important comentioned reasons that motivate COVID-19 vaccination, while lack of vaccine confidence (egicentrality=0.89) and complacency (perceived low disease risk and low importance of vaccination; egicentrality=0.45) were the most important comentioned reasons that demotivate COVID-19 vaccination. For older people aged ≥65 years, protecting others was a more important motivator (egicentrality=0.57), while the concern about poor health status was a more important demotivator (egicentrality=0.42); for young people aged 18 to 24 years, recovering life normalcy (egicentrality=0.20) and vaccine mandates (egicentrality=0.26) were the more important motivators, while complacency (egicentrality=0.77) was a more important demotivator for COVID-19 vaccination uptake. CONCLUSIONS: When disease risk is perceived to be high, promoting social responsibility to protect others is more important for boosting vaccination acceptance. However, when disease risk is perceived to be low and complacency exists, fostering confidence in vaccines to address vaccine hesitancy becomes more important. Interventions for promoting vaccination acceptance and reducing vaccine hesitancy should be tailored by age.

Intraoperative Acute Cardiac Tamponade as a Result of Intracardiac Perforation Requiring Emergency Continuous Pericardiocentesis and Open Sternotomy: A Case Report and Literature Review of a Rare but Fatal Complication.

Intraoperative acute cardiac tamponade associated with iatrogenic intracardiac perforation from percutaneous interventional cardiac procedures is a rare but potentially catastrophic complication. We report a case of intraoperative acute hemopericardium caused by a left atrial (LA) perforation resulting in cardiac tamponade in a patient undergoing a baffling procedure for the correction of two anomalous pulmonary veins draining into her superior vena cava (SVC) that required continuous pericardiocentesis with autologous blood transfusion via the femoral vein and an emergency intraoperative transfer from the interventional cardiology cath lab to the cardiac operating room for an open sternotomy and primary repair. An 86-year-old female with known right-ventricular (RV) failure with preserved ejection fraction (left ventricular ejection fraction (LVEF): 50-55% on transesophageal echocardiography (TEE) one week prior) and atrial fibrillation was admitted for her third heat failure exacerbation in two months despite being adherent to her aggressive diuresis medication regimen. Upon her readmission and due to her symptomatic and seemingly refractory heart failure, the patient underwent a cardiac computer tomography (CT) with 3D reconstruction that showed previously undiagnosed partial anomalous pulmonary venous return (PAPVR) of two of her four pulmonary veins aberrantly draining into the SVC. This anatomic pathology was deemed to be the likely etiology of her repeated episodes of recurring heart failure exacerbations, shortness of breath, peripheral edema, and fatigue. The patient was counseled and consented to a percutaneous baffle of the two anomalous veins to redirect more of the returning pulmonary venous blood away from the SVC and to the LA. While under general endotracheal anesthesia (GETA) with a TEE in place during the procedure, the patient suddenly developed acute hypotension, tachycardia, and a reduction in expired carbon dioxide (EtCO2) was noted quickly followed by evidence of a rapidly accumulating hemopericardium on TEE. Cardiothoracic surgery was urgently consulted to the interventional cardiology cath lab while the patient underwent an emergency pericardiocentesis that momentarily alleviated her hemodynamic instability, cardiac tamponade physiology, and deteriorating overall clinical picture. While performing continuous pericardiocentesis with autologous return of the aspirated blood via femoral venous access the patient was urgently transported to the cardiac operating room and prepped for emergency sternotomy for primary repair of the LA. Following primary repair via sternotomy, multiple drains were placed and the thoracic cavity was closed with wires. The patient was immediately transported to the surgical intensive care unit (SICU) intubated, mechanically ventilated, and sedated. During this time, the patient progressively required additional vasoactive and inotropic agents to support her mean arterial pressure (MAP), and following a multidisciplinary discussion with the patient's family regarding her goals of care, the decision was made to withdraw further resuscitation efforts and the patient expired four hours later.

Joint analysis of vaccination effectiveness and antiviral drug effectiveness for COVID-19: a causal inference approach.

OBJECTIVES: This study aims to estimate the causal effects of oral antivirals and vaccinations in the prevention of all-cause mortality and progression to severe COVID-19 in an integrative setting with both antivirals and vaccinations considered as interventions. METHODS: We identified hospitalized adult patients (i.e. aged 18 or above) in Hong Kong with confirmed SARS-CoV-2 infection between March 16, 2022, and December 31, 2022. An inverse probability-weighted (IPW) Andersen-Gill model with time-dependent predictors was used to address immortal time bias and produce causal estimates for the protection effects of oral antivirals and vaccinations against severe COVID-19. RESULTS: Given prescription is made within 5 days of confirmed infection, nirmatrelvir-ritonavir is more effective in providing protection against all-cause mortality and development into severe COVID-19 than molnupiravir. There was no significant difference between CoronaVac and Comirnaty in the effectiveness of reducing all-cause mortality and progression to severe COVID-19. CONCLUSIONS: The use of oral antivirals and vaccinations causes lower risks of all-cause mortality and progression to severe COVID-19 for hospitalized SARS-CoV-2 patients.

Risk of SARS-CoV-2 breakthrough infection following NVX-CoV2373 and BNT162b2 vaccinations in Korean Adults: A population-based observational study.

South Korea experienced a low prevalence of SARS-CoV-2 until the emergence of the omicron in early 2022, triggering a major community epidemic. To evaluate effectiveness of NVX-CoV2373 and BNT162b2 vaccines in Korean population, we conducted an observational study utilizing individual-level case data on laboratory-confirmed SARS-CoV-2 infection, along with vaccination record. A total of 47,078 recipients of NVX-CoV2373 vaccine and 7,561 recipients of BNT162b2 vaccine were eligible for the study. Thirty days post-second doses, COVID-19 rates were 7.9% (595 out of 7561) of NVX-CoV2373 recipients and 8.6 % (647 out of 7561) of BNT162b2 recipients experienced COVID-19. NVX-CoV2373 rates increased to 9.8 % and 11.2 % at 60 and 90 days, while BNT162b2 rates were 10.5 % and 11.3 % at the same intervals. The 22-weeks risk ratios for recipients of the NVX-CoV2373 vaccine as compared with recipients of the BNT162b2 vaccine were 1.11 (95 % CI, 0.99 to 1.25) for laboratory-confirmed SARS-CoV-2 infection. Continued monitoring is essential to evaluate the duration of protection across different vaccine platforms and schedules.

Intrinsic and extrinsic cues time somite progenitor contribution to the vertebrate primary body axis.

During embryonic development, the timing of events at the cellular level must be coordinated across multiple length scales to ensure the formation of a well-proportioned body plan. This is clear during somitogenesis, where progenitors must be allocated to the axis over time whilst maintaining a progenitor population for continued elaboration of the body plan. However, the relative importance of intrinsic and extrinsic signals in timing progenitor addition at the single-cell level is not yet understood. Heterochronic grafts from older to younger embryos have suggested a level of intrinsic timing whereby later staged cells contribute to more posterior portions of the axis. To determine the precise step at which cells are delayed, we performed single-cell transcriptomic analysis on heterochronic grafts of somite progenitors in the chicken embryo. This revealed a previously undescribed cell state within which heterochronic grafted cells are stalled. The delayed exit of older cells from this state correlates with expression of posterior Hox genes. Using grafting and explant culture, we find that both Hox gene expression and the migratory capabilities of progenitor populations are intrinsically regulated at the population level. However, by grafting varied sizes of tissue, we find that small heterochronic grafts disperse more readily and contribute to more anterior portions of the body axis while still maintaining Hox gene expression. This enhanced dispersion is not replicated in explant culture, suggesting that it is a consequence of interaction between host and donor tissue and thus extrinsic to the donor tissue. Therefore, we demonstrate that the timing of cell dispersion and resulting axis contribution is impacted by a combination of both intrinsic and extrinsic cues.

Comparing the glycaemic outcomes between real-time continuous glucose monitoring (rt-CGM) and intermittently scanned continuous glucose monitoring (isCGM) among adults and children with type 1 diabetes: A systematic review and meta-analysis of randomized controlled trials.

AIM: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the effectiveness of real-time continuous glucose monitoring (rtCGM) versus intermittently scanned continuous glucose monitoring (isCGM) on key glycaemic metrics (co-primary outcomes HbA1c and time-in-range [TIR] 70-180 mg/dL, 3.9-10.0 mmol/L) among people with type 1 diabetes (T1D). METHODS: Medline, PubMed, Scopus, Web of Science and Cochrane Central Register of clinical trials were searched. Inclusion criteria were RCTs; T1D populations of any age and insulin regimen; comparing any type of rtCGM with isCGM (only the first generation had been compared to date); and reporting the glycaemic outcomes. Glycaemic outcomes were extracted post-intervention and expressed as mean differences and 95% CIs between the two comparators. Results were pooled using a random-effect meta-analysis. The risk of bias was assessed using the Cochrane RoB2 tool. The quality of evidence was assessed by the GRADE approach. RESULTS: Five RCTs met the inclusion criteria (4 parallel and 1 crossover design; 4 with CGM use <8 weeks), involving 446 participants (354 adults; 92 children and adolescents). Overall, meta-analysis showed rtCGM compared to isCGM improved absolute TIR by +7.0% (95% CI: 5.8%-8.3%, I2 = 0%, p < 0.01) accompanied by a favorable effect on time-below-range <70 mg/dL (3.9 mmol/L) - 1.7% (95%CI: -3.0% to -0.4%; p = 0.03). No differences were seen regarding HbA1c. CONCLUSIONS: This meta-analysis highlights that for people with T1D, rtCGM confers benefits over isCGM primarily related to increased TIR, with improvements in hypo- and hyperglycaemia.

DNA barcoding continues to identify endangered species of shark sold as food in a globally significant shark fin trade hub.

Shark fins are a delicacy consumed throughout Southeast Asia. The life history characteristics of sharks and the challenges associated with regulating fisheries and the fin trade make sharks particularly susceptible to overfishing. Here, we used DNA barcoding techniques to investigate the composition of the shark fin trade in Singapore, a globally significant trade hub. We collected 505 shark fin samples from 25 different local seafood and Traditional Chinese Medicine shops. From this, we identified 27 species of shark, three species are listed as Critically Endangered, four as Endangered and ten as Vulnerable by the International Union for Conservation of Nature (IUCN). Six species are listed on CITES Appendix II, meaning that trade must be controlled in order to avoid utilization incompatible with their survival. All dried fins collected in this study were sold under the generic term "shark fin"; this vague labelling prevents accurate monitoring of the species involved in the trade, the effective implementation of policy and conservation strategy, and could unwittingly expose consumers to unsafe concentrations of toxic metals. The top five most frequently encountered species in this study are Rhizoprionodon acutus, Carcharhinus falciformis, Galeorhinus galeus, Sphyrna lewini and Sphyrna zygaena. Accurate labelling that indicates the species of shark that a fin came from, along with details of where it was caught, allows consumers to make an informed choice on the products they are consuming. Doing this could facilitate the avoidance of species that are endangered, and similarly the consumer can choose not to purchase species that are documented to contain elevated concentrations of toxic metals.

Antibiotic use in hospitalized patients with COVID-19: a population-based study in Hong Kong.

Background: Hong Kong experienced four epidemic waves caused by the ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020-2021 and a large Omicron wave in 2022. Few studies have assessed antibacterial prescribing for coronavirus disease 2019 (COVID-19) inpatients throughout the pandemic. Objectives: To describe inpatient antibacterial prescribing and explore factors associated with their prescription. Methods: Electronic health records of patients with COVID-19 admitted to public hospitals in Hong Kong from 21 January 2020 to 30 September 2022 were used to assess the prevalence and rates of inpatient antibacterial drug use (days of therapy/1,000 patient days [DOT/1,000 PD]). We used multivariable logistic regression to investigate potential associations between patients' baseline characteristics and disease severity and prescription of an antibacterial drug during hospital admission. Results: Among 65,810 inpatients with COVID-19, 54.0% were prescribed antibacterial drugs (550.5 DOT/1,000 PD). Compared to waves 1-2 (46.7%; 246.9 DOT/1,000 PD), the prescriptions were lowest during wave 4 (28.0%; 246.9; odds ratio (OR): 0.39, 95% CI: 0.31-0.49) and peaked in early wave 5 (64.6%; 661.2; 0.82, 0.65-1.03). Older age (≥80 years: OR 2.66, 95% CI, 2.49-2.85; 60-79 years: 1.59, 1.51-1.69, compared with 20-59 years), more severe disease (fatal: 3.64, 3.2-4.16; critical: 2.56, 2.14-3.06, compared with severe), and COVID-19 vaccine doses (two doses: 0.74, 0.69-0.78; three doses: 0.69, 0.64-0.74; four doses: 0.52, 0.44-0.62, compared with unvaccinated) were associated with inpatient antibacterial drug use. Conclusions: Antibacterial prescribing changed over time for hospitalized patients with confirmed COVID-19 and was potentially related to patients' demographics, medical conditions, and COVID-19 vaccination status as well as healthcare capacity during epidemic waves.

Estimate of COVID-19 Deaths, China, December 2022-February 2023.

China announced a slight easing of its zero-COVID rules on November 11, 2022, and then a major relaxation on December 7, 2022. We estimate that the ensuing wave of SARS-CoV-2 infections caused 1.41 million deaths in China during December 2022-February 2023, substantially higher than that reported through official channels.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in the granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and end point (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety and the change in biochemistry, biomarkers, and concomitant drug use. RESULTS: The mean age, eGFR, and UACR were 65 years, 56.7 ml/min per 1.73 m 2 , and 753 mg/g, respectively. Ninety-five percent ( n =141) of end point primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95% confidence interval [CI], -0.1 to -3.9) and -4.7 (95% CI, -2.9 to -6.5) ml/min per 1.73 m 2 in participants treated with add-on Chinese medicine or standard care alone, resulting in a 2.7 ml/min per 1.73 m 2 per year (95% CI, 0.1 to 5.3; P = 0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (95% CI, 0.75 to 1.02) and 0.99 (95% CI, 0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone, respectively. The intergroup proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95% CI, 0.72 to 1.10; P = 0.28) did not reach statistical significance. Eighty-five adverse events were recorded from 50 participants (add-on Chinese medicine versus control: 22 [31%] versus 28 [36%]). CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2-3 CKD, and severely increased albuminuria. CLINICAL TRIAL REGISTRY: Semi-individualized Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252 .

Alveolar repair following LPS-induced injury requires cell-ECM interactions.

During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if ß1-containing integrins are required during repair following acute injury, we administered E. coli lipopolysaccharide (LPS) by intratracheal injection to mice with a postdevelopmental deletion of ß1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, ß1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells coexpressing AT2 epithelial, AT1 epithelial, and mixed intermediate cell state markers, with few mature type 1 cells. AT2 cells deficient in ß1 showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that ß1-deficient AT2 cells failed to differentiate into mature AT1 epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires ß1-containing integrins.

Short-course, high-dose primaquine regimens for the treatment of liver-stage vivax malaria in children.

OBJECTIVES: To assess the pharmacokinetics, safety, and tolerability of two high-dose, short-course primaquine (PQ) regimens compared with standard care in children with Plasmodium vivax infections. METHODS: We performed an open-label pediatric dose-escalation study in Madang, Papua New Guinea (Clinicaltrials.gov NCT02364583). Children aged 5-10 years with confirmed blood-stage vivax malaria and normal glucose-6-phosphate dehydrogenase activity were allocated to one of three PQ treatment regimens in a stepwise design (group A: 0.5 mg/kg once daily for 14 days, group B: 1 mg/kg once daily for 7 days, and group C: 1 mg/kg twice daily for 3.5-days). The study assessments were completed at each treatment time point and fortnightly for 2 months after PQ administration. RESULTS: Between August 2013 and May 2018, 707 children were screened and 73 met the eligibility criteria (15, 40, and 16 allocated to groups A, B, and C, respectively). All children completed the study procedures. The three regimens were safe and generally well tolerated. The pharmacokinetic analysis indicated that an additional weight adjustment of the conventionally recommended milligram per kilogram PQ doses is not necessary to ensure the therapeutic plasma concentrations in pediatric patients. CONCLUSIONS: A novel, ultra-short 3.5-day PQ regimen has potential benefits for improving the treatment outcomes in children with vivax malaria that warrants further investigation in a large-scale clinical trial.

Environment- and epigenome-wide association study of obesity in 'Children of 1997' birth cohort.

Background: Increasing childhood obesity is a global issue requiring potentially local solutions to ensure it does not continue into adulthood. We systematically identified potentially modifiable targets of obesity at the onset and end of puberty in Hong Kong, the most economically developed major Chinese city. Methods: We conducted an environment-wide association study (EWAS) and an epigenome-wide association study of obesity to systematically assess associations with body mass index (BMI) and waist-hip ratio (WHR) in Hong Kong's population-representative 'Children of 1997' birth cohort. Univariable linear regression was used to select exposures related to obesity at ~11.5 years (BMI and obesity risk n ≤ 7119, WHR n = 5691) and ~17.6 years (n = 3618) at Bonferroni-corrected significance, and multivariable regression to adjust for potential confounders followed by replicated multivariable regression (n = 308) and CpG by CpG analysis (n = 286) at ~23 years. Findings were compared with evidence from published randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. Results: At ~11.5 and~17.6 years the EWAS identified 14 and 37 exposures associated with BMI, as well as 7 and 12 associated with WHR, respectively. Most exposures had directionally consistent associations at ~23 years. Maternal second-hand smoking, maternal weight, and birth weight were consistently associated with obesity. Diet (including dairy intake and artificially sweetened beverages), physical activity, snoring, binge eating, and earlier puberty were positively associated with BMI at ~17.6 years, while eating before sleep was inversely associated with BMI at ~17.6 years. Findings for birth weight, dairy intake, and binge eating are consistent with available evidence from RCTs or MR studies. We found 17 CpGs related to BMI and 17 to WHR. Conclusions: These novel insights into potentially modifiable factors associated with obesity at the outset and the end of puberty could, if causal, inform future interventions to improve population health in Hong Kong and similar Chinese settings. Funding: This study including the follow-up survey and epigenetics testing was supported by the Health and Medical Research Fund Research Fellowship, Food and Health Bureau, Hong Kong SAR Government (#04180097). The DNA extraction of the samples used for epigenetic testing was supported by CFS-HKU1.

Epidemiology and risk factors for carbapenemase-producing Enterobacteriaceae carriage in the hospital: A population-based nested case-control study.

OBJECTIVES: This study aims to study the epidemiology of carbapenemase-producing Enterobacteriaceae (CPE) in Hong Kong. METHODS: This is a longitudinal population-based study reporting monthly CPE incidence rate and a nested case-control study for identifying risk factors for CPE carriage. The cases were patients with at least one CPE-positive genotypic test, while the controls were randomly selected from the cohort with negative tests. Up to four controls per case were matched by sex, age group, and admission year-month. The independent risk factors were identified from a conditional logistic regression with potential covariates. RESULTS: From 1 January 2008 to 31 December 2019, 8588 patients received CPE genotyping tests, and 2353 had at least one positive result. Class B carbapenemase was the predominant enzyme in the samples (78.6%). The incidence rate increased from 0.04 in 2015 to 1.62 in 2019 per 10,000 person-year. In the nested case-control study, 1709 cases and 6664 controls were matched. Previous use of any beta-lactam antibiotics (odds ratio:1.37 [1.22-1.53], P < 0.001) was found as an independent risk factor for carriage of CPE. CONCLUSION: The carriage of CPE was found with an increasing trend in Hong Kong. Previous use of any beta-lactam antibiotics is a risk factor for CPE.

The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households.

Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases including SARS-CoV-2. However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2- to 4.2-fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study.

BACKGROUND: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain. OBJECTIVE: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak. DESIGN: Target trial emulation study. SETTING: Electronic health databases in Hong Kong. PARTICIPANTS: The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (n = 7119). INTERVENTION: Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir. MEASUREMENTS: Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days. RESULTS: The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people. LIMITATION: The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist. CONCLUSION: Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed. PRIMARY FUNDING SOURCE: Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.