Prospective, Multicenter, Head-to-Head Comparison Between Allergists Versus Nonallergists in Low-Risk Penicillin Allergy Delabeling: Effectiveness, Safety, and Quality of Life (HK-DADI2).

BACKGROUND: Penicillin "allergy" labels are prevalent but frequently misdiagnosed. Mislabelled allergies are associated with adverse outcomes and increased antimicrobial resistance. With an urgent need to delabel the overwhelming number of mislabeled allergies, nonallergist evaluations have been advocated for low-risk individuals. Despite growing interest in non-allergist-led initiatives, evidence on their effectiveness, safety, and impact by direct comparisons is lacking. OBJECTIVE: To assess the comparative outcomes of penicillin allergy evaluations conducted by allergists versus nonallergists. METHODS: A prospective, multicenter, pragmatic study was conducted at 4 tertiary hospitals (1 allergist- vs 3 non-allergist-led) for low-risk penicillin allergy patients in Hong Kong-the Hong Kong Drug Allergy Delabelling Initiative 2 (HK-DADI2). RESULTS: Among 228 low-risk patients who underwent testing (32.9% by allergists, 67.1% by nonallergists), only 14 (6.1%) had positive penicillin allergy testing results. Delabeling rates (94.1% vs 93.3%; P = .777), positive skin test results (2.6% vs 2.7%; P > .99), and drug provocation test results (3.3% vs 2.7%; P = 1.000) were similar between allergists and nonallergists. There were no systemic reactions in either cohort. All patients had significant improvements in health-related quality of life (Drug Hypersensitivity Quality of Life Questionnaire scores -5.00 vs -8.33; P = .072). Nonallergist evaluations had shorter waiting times (0.57 vs 15.7 months; P < .001), whereas allergists required fewer consultations with higher rate of completing evaluations within a single visit (odds ratio, 0.04; P < .001). CONCLUSIONS: With training and support, nonallergists can independently evaluate low-risk penicillin allergies. Compared with allergists, evaluation of low-risk penicillin allergy by nonallergists can be comparably effective, safe, and impactful on quality of life. More multidisciplinary partnerships to empower nonallergists to conduct allergy evaluations should be encouraged.

A machine learning-based risk score for prediction of infective endocarditis among patients with Staphylococcus aureus bacteraemia - The SABIER score.

BACKGROUND: Early risk assessment is needed to stratify Staphylococcus aureus infective endocarditis (SA-IE) risk among Staphylococcus aureus bacteraemia (SAB) patients to guide clinical management. The objective of this study is to develop a novel risk score independent of subjective clinical judgment and can be used early at the time of blood culture positivity. METHODS: We conducted a retrospective big data analysis from territory-wide electronic data and included hospitalized patients with SAB between 2009 and 2019. We applied a random forest risk scoring model to select variables from an array of parameters, according to the statistical importance of each feature in predicting SA-IE outcome. The data was divided into derivation and validation cohorts. The areas under the curve of the receiver operating characteristic (AUCROC) were determined. RESULTS: We identified 15,741 SAB patients, among them 4.18% had SA-IE. The AUCROC was 0.74 (95%CI 0.70-0.76), with a negative predictive value of 0.980 (95%CI 0.977-0.983). The four most discriminatory features were age, history of infective endocarditis, valvular heart disease, and being community-onset. CONCLUSION: We developed a novel risk score with good performance as compared to existing scores and can be used at the time of SAB and prior to subjective clinical judgment.

Bacterial infections in patients with COVID-19: the impact of procalcitonin testing on antibiotics prescription in the real world.

BACKGROUND: Bacterial infections are not prevalent among patients hospitalized with COVID-19, while unnecessary prescription of antibiotics was commonly observed. This study aimed to determine the impact of procalcitonin testing on antibiotics prescription in the real-world setting. METHODS: We performed a territory-wide retrospective cohort study involving all laboratory-confirmed patients hospitalized in public hospitals in Hong Kong in 2020 with COVID-19. We determined the prevalence of bacterial co-infections (documented infections within 72 h of admission) and secondary bacterial infections (infections after 72 h of admission) and antibiotics consumption, and the correlation between procalcitonin testing and antibiotics prescription. RESULTS: The cohort included 8666 patients, with mean age 45.3 ± 19.9 years, 48.5% male, and comorbidities in 26.9%. Among 2688 patients with bacterial cultures performed, 147 (5.5%) had bacterial co-infections, and 222 (8.3%) had secondary bacterial infections. Antibiotics were prescribed for 2773 (32.0%) patients during the hospital admission. Procalcitonin tests were performed for 2543 (29.3%) patients. More patients with procalcitonin testing received antibiotics (65.9% vs. 17.9%, p < 0.001). Procalcitonin testing was associated with 5-fold increased risk of antibiotics prescription after adjusting for confounding variables. At hospital level, procalcitonin testing correlated with antibiotics prescription. Patients with procalcitonin level < 0.5 ng/mL had a lower probability of antibiotics initiation and shorter duration of antibiotics therapy. CONCLUSIONS: Procalcitonin testing was not associated with lower prescription of antibiotics. Patients with low procalcitonin level had lower antibiotics exposure, supporting the use of procalcitonin to exclude bacterial infections aiding early stopping of antibiotics among patients hospitalized with COVID-19.

Reducing thrombotic risks in video gamers: investigating the benefits of walking and compression sleeves on blood hemodynamics.

With the growing popularity of video gaming, deep vein thromboses are increasingly being reported in gamers. This study aimed to compare the effects of lower leg graduated compression sleeves and a 6-min walking break during prolonged gaming on blood flow and hemodynamics in competitive sport players to help mitigate this risk. Ten healthy gamers (19.6 ± 1.2 yr old; 9 men) consented to participate in this mixed-model crossover design study that consisted of three visits. In visit 1, participants engaged in continuous 2-h video game play wearing no compression (continuous). Visits 2 and 3 involved 2-h play wearing compression sleeves (compression) and 2-h game play interrupted at 1 h by a 6-min walk (walk). Doppler ultrasound measurements of the left popliteal artery were taken at 30, 60, 90, and 120 min, to record vessel diameter, blood flow velocity, and blood flow volume. Participants completed a survey to assess their perception of each approach. There was a significant interaction between conditions for blood flow and blood velocity (P = 0.01, P < 0.001). Post hoc analysis demonstrated a greater decrease in blood flow and blood velocity in the continuous group compared with the walk group at the 90-min mark (P = 0.04, P = 0.01). No differences were found between the compression and walk groups or between the continuous and compression groups (P = 0.42, P = 0.69). No interactions were observed in diameter, mean arterial pressure, or heart rate. This study suggests that incorporating a 6-min walk every 60 min during prolonged gaming is advisable to counteract the negative effects on blood flow hemodynamics.NEW & NOTEWORTHY A 6-min light-intensity walking break during gaming can effectively combat the adverse effects of prolonged sitting, surpassing compression garments. Prolonged sitting reduces blood flow velocity, potentially leading to deep vein thrombosis (DVT). Compression sleeves help, with superior results after a 6-min walk at 60 min. Although compression stockings offer moderate improvements, a 6-min active break proves more effective. These findings offer promising interventions for gamers' health, initiating guidelines to mitigate DVT risk during gaming.

Delabeling, safety, and impact of ß-lactam allergy testing: A systematic review.

Background: To improve ß-lactam delabeling outcomes, we need to understand current practice and the evidence base regarding its outcomes, safety, and impact. Objectives: We sought to assess the existing published evidence reporting on the effectiveness of penicillin allergy testing and delabeling. Methods: We conducted a systematic review of studies reporting ß-lactam delabeling practices and outcomes after testing, including ß-lactam use and patient understanding of the delabeling result. Searches of the PubMed, Scopus, and Embase databases; clinical trial registries; and websites of professional organizations were conducted. Data were extracted from the included studies in duplicate, with a third extraction if discrepancies remained. Results: We included 284 publications (covering 98,316 participants); 173 were prospective studies, with no randomized controlled trials. The overall study quality was low. In all, 95.6% of individuals who underwent provocation testing were delabeled. Factors associated with successful delabeling could not be determined because of significant heterogeneity between studies. Anaphylaxis due to testing occurred in 0.3% of participants (95 of 31,667). Subjects who did not undergo skin testing (6,980 patients in 31 studies) before challenge had higher rates of provocation test positivity (8.8% vs 4.1% [P < .0001]) and anaphylaxis (15.9% vs 2.7% [P < .0001]) than those subjects who underwent skin testing (51,607 patients in 177 studies). Six studies (2.1%) followed patients after testing to assess their adherence to prescribing recommendations. In all, 136 participants (20.6%) were actively avoiding ß-lactams despite delabeling. Conclusions: The available data suggest that penicillin allergy testing is safe and effective in delabeling most individuals, but the evidence base is incomplete and more work is required to assess the role of skin testing and the impact that delabeling is having on prescribing habits.

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

An efficient approach to estimate the risk of coronary artery disease for people living with HIV using machine-learning-based retinal image analysis.

BACKGROUND: People living with HIV (PLWH) have increased risks of non-communicable diseases, especially cardiovascular diseases. Current HIV clinical management guidelines recommend regular cardiovascular risk screening, but the risk equation models are not specific for PLWH. Better tools are needed to assess cardiovascular risk among PLWH accurately. METHODS: We performed a prospective study to determine the performance of automatic retinal image analysis in assessing coronary artery disease (CAD) in PLWH. We enrolled PLWH with ≥1 cardiovascular risk factor. All participants had computerized tomography (CT) coronary angiogram and digital fundus photographs. The primary outcome was coronary atherosclerosis; secondary outcomes included obstructive CAD. In addition, we compared the performances of three models (traditional cardiovascular risk factors alone; retinal characteristics alone; and both traditional and retinal characteristics) by comparing the area under the curve (AUC) of receiver operating characteristic curves. RESULTS: Among the 115 participants included in the analyses, with a mean age of 54 years, 89% were male, 95% had undetectable HIV RNA, 45% had hypertension, 40% had diabetes, 45% had dyslipidemia, and 55% had obesity, 71 (61.7%) had coronary atherosclerosis, and 23 (20.0%) had obstructive CAD. The machine-learning models, including retinal characteristics with and without traditional cardiovascular risk factors, had AUC of 0.987 and 0.979, respectively and had significantly better performance than the model including traditional cardiovascular risk factors alone (AUC 0.746) in assessing coronary artery disease atherosclerosis. The sensitivity and specificity for risk of coronary atherosclerosis in the combined model were 93.0% and 93.2%, respectively. For the assessment of obstructive CAD, models using retinal characteristics alone (AUC 0.986) or in combination with traditional risk factors (AUC 0.991) performed significantly better than traditional risk factors alone (AUC 0.777). The sensitivity and specificity for risk of obstructive CAD in the combined model were 95.7% and 97.8%, respectively. CONCLUSION: In this cohort of Asian PLWH at risk of cardiovascular diseases, retinal characteristics, either alone or combined with traditional risk factors, had superior performance in assessing coronary atherosclerosis and obstructive CAD. SUMMARY: People living with HIV in an Asian cohort with risk factors for cardiovascular disease had a high prevalence of coronary artery disease (CAD). A machine-learning-based retinal image analysis could increase the accuracy in assessing the risk of coronary atherosclerosis and obstructive CAD.

Sarcopenia in people living with HIV in Hong Kong: which definition correlates with health outcomes?

INTRODUCTION: Sarcopenia is an important clinical syndrome in older people living with HIV (PLWH). With a change to the Asia sarcopenia definition in 2019, we aimed to determine whether health outcomes were associated with different definitions of sarcopenia among Asian PLWH. METHODS: We performed a prospective cross-sectional study enrolling PLWH aged ≥35 years from January 2018 to November 2021. We defined sarcopenia by the Asia Working Group of Sarcopenia (AWGS) criteria in 2014 and 2019. AWGS-2014 included low muscle mass plus weak handgrip strength and/or slow gait speed. AWGS-2019 included low muscle mass plus low muscle strength or physical performance, while the presence of all defines severe sarcopenia. We measured appendicular skeletal muscle mass using dual-energy X-ray absorptiometry, handgrip strength, usual gait speed, five-time chair stand test and Short Physical Performance Battery. Correlations between each sarcopenia definition and health-related quality of life (using EQ-5D-5L and SF-36) and functional disability were determined. RESULTS: One hundred and fifty Asian PLWH were enrolled, 132 (88%) were male, mean age was 60±10 years, duration of HIV diagnosis was 13 (IQR 8-18) years and current CD4 count was 574 (IQR 362-762) cells/mm3 , 67 (45%) had multimorbidity, 64 (43%) had polypharmacy. Prevalence of sarcopenia by AWGS-2014, AWGS-2019 and severe sarcopenia was 17.3%, 27.3% and 18.0%, respectively. Age, education and polypharmacy were associated with sarcopenia. Sarcopenia (AWGS-2014) and severe sarcopenia were associated with mobility, physical functioning and physical component score (SF-36). All three criteria were associated with impaired instrumental activities of daily living (IADL). After age and sex adjustment, sarcopenia (AWGS-2014) (adjusted odds ratio/aOR 5.4, 95% confidence interval/CI 2.0-15.1) and severe sarcopenia (aOR 5.1, 95% CI 1.9-14.0) were associated with mobility and physical component score (SF-36) (ß coefficients -5.3342, p = 0.022 and -5.412, p = 0.019). Sarcopenia (AWGS 2014) (aOR 5.2, 95% CI 1.7-16.2), sarcopenia (AWGS-2019) (aOR 4.5, 95% CI 1.5-13.1) and severe sarcopenia (aOR 3.5, 95% CI 1.1-10.9) were associated with impaired IADL in fully adjusted models. CONCLUSIONS: In a sample of Asian PLWH, 17.3%, 27.3% and 18.0% had sarcopenia as defined by AWGS-2014, AWGS-2019 and severe sarcopenia, respectively. Sarcopenia by AWGS-2014 and severe sarcopenia correlated with parameters of poor health outcomes, while sarcopenia by AWGS-2019 correlated with functional disability.

Positional Behavior of Introduced Monk Parakeets (Myiopsitta monachus) in an Urban Landscape.

Positional behaviors have been broadly quantified across the Order Primates, and in several other mammalian lineages, to contextualize adaptations to, and evolution within, an arboreal environment. Outside of Mammalia, however, such data are yet to be reported. In this study, we present the first quantitative report of positional behavior within Aves, presenting 11,246 observations of scan sampling data from a colony of Monk Parakeets (Myiopsitta monachus) from Brooklyn, New York City. Each scan recorded locomotor and postural behavior and information about weather condition, temperature, and substrate properties (e.g., type, size, orientation). A distinction was also recorded between natural and artificial substrates. Parrots exhibited a strong preference for small and terminal branches, a selection which may reflect targeted foraging of new fruit growth and leaf-buds. We further observed that the gait transition from walking to sidling appears primarily driven by substrate size, with the former preferred on the ground and on large, broad substrates and the latter used to navigate smaller branches. Finally, we observed an increase in locomotor diversity on artificial versus naturally occurring substrates. This demonstrates the importance of a flexible behavioral repertoire in facilitating a successful transition towards an urban landscape in introduced species.

Hong Kong Drug Allergy Delabelling Initiative (HK-DADI) consensus statements for penicillin allergy testing by nonallergists.

Introduction: Penicillin allergy testing has been traditionally performed by allergists, but there remains a huge deficit of specialists. A multidisciplinary effort with nonallergists would be invaluable to overcome the magnitude of penicillin allergy labels via the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). These consensus statements (CSs) offer recommendations and guidance to enable nonallergists to screen for low-risk (LR) patients and perform penicillin allergy testing. Methods: CSs were formulated by the HK-DADI Group using the Delphi method. An agreement was defined as greater than or equal to 80% consensus. Results: A total of 26 CSs reached consensus after multiple rounds of Delphi. CSs were categorized into risk assessment, skin testing, drug provocation testing (DPT), and post-testing management. For risk assessment, the essentials of allergy history and exclusion criteria were detailed. Patients with only LR features can proceed with testing by nonallergists. Skin tests should be performed prior to DPT. Details regarding the timing, preparation, and interpretation of skin tests were elaborated. DPT remains the gold standard to diagnose genuine allergy or tolerance and should be performed when there is a low pretest probability following negative skin testing. Details of DPT preparations, dosing protocols, and interpretation were elaborated. For post-testing management, inaccurate allergy labels should be delabeled following negative DPT with proper patient counseling. Conclusion: CSs support penicillin allergy testing by nonallergists in Hong Kong. LR cases can be managed by nonallergists at Spoke Clinics, with training and support of an allergist-led Hub.

Trajectory patterns of SARS-CoV-2 neutralising antibody response in convalescent COVID-19 patients.

Background: The adaptive immune responses of COVID-19 patients contributes to virus clearance, restoration of health and protection from re-infection. The patterns of and the associated characteristics with longitudinal neutralising antibody (NAb) response following SARS-CoV-2 infection are important in their potential association with the population risks of re-infection. Methods: This is a longitudinal study with blood samples and clinical data collected in adults aged 18 or above following diagnosis of SARS-CoV-2 infection. NAb levels were measured by the SARS-CoV-2 surrogate virus neutralisation test (sVNT). Anonymous clinical and laboratory data were matched with surveillance data for each subject for enabling analyses and applying latent class mixed models for trajectory delineation. Logistic regression models were performed to compare the characteristics between the identified classes. Results: In 2020-2021, 368 convalescent patients in Hong Kong are tested for NAb. Their seroconversion occur within 3 months in 97% symptomatic patients, the level of which are maintained at 97% after 9 months. The NAb trajectories of 200 symptomatic patients are classified by the initial response and subsequent trend into high-persistent and waning classes in latent class mixed models. High-persistent (15.5%) class patients are older and most have chronic illnesses. Waning class patients (84.5%) are largely young adults who are mildly symptomatic including 2 who serorevert after 10 months. Conclusions: Characteristic sub-class variabilities in clinical pattern are noted especially among patients with waning NAb. The heterogeneity of the NAb trajectory patterns and their clinical association can be important for informing vaccination strategy to prevent re-infection.

Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study.

BACKGROUND AND AIM: Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients. METHODS: This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5. RESULTS: Twenty-five consecutive COVID-19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS-CoV-2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF-α), and IL-1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS-CoV-2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by week 4 and week 5. CONCLUSIONS: This proof-of-concept study suggested that the use of a novel gut microbiota-derived synbiotic formula, SIM01, hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID-19 patients.

The clinical presentation and treatment outcomes of ocular tuberculosis: a 5-year experience in an endemic area.

PURPOSE: To report the clinical presentations of ocular tuberculosis infection (OTB) and the treatment regimen and outcome in an endemic area. METHODS: This is a retrospective case series of patients with presumed OTB treated in a tertiary teaching hospital in Hong Kong in 2014-2019. RESULTS: Among the nineteen patients recruited, the most common clinical presentation of OTB was retinal vasculitis (42.1%), followed by scleritis, intermediate uveitis, and choroidal tuberculoma (15.8% respectively). 94.7% and 94.4% of the subjects were treated with ATT and steroid, respectively, and 31.6% were put on systemic immunosuppressant prior to the initiation of ATT. Apart from those suffering from intermediate uveitis, most demonstrated good clinical response within 8 weeks of ATT initiation. CONCLUSION: Ocular involvement of TB has been increasingly recognized, especially in endemic regions like Hong Kong. High index of suspicion is recommended for OTB in typical clinical phenotypes or recurrent/resistant ocular inflammation unresponsive to conventional therapy. TB retinal vasculitis was the most common presentation of OTB in this study and OTB generally requires treatment with either regional or systemic steroid together with ATT.

Risks of AKI and Major Adverse Clinical Outcomes in Patients with Severe Acute Respiratory Syndrome or Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear. METHODS: This retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. RESULTS: We identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event. CONCLUSIONS: AKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.

Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19.

OBJECTIVE: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus. METHODS: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma. RESULTS: Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. CONCLUSION: Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

Significantly Lower Case-fatality Ratio of Coronavirus Disease 2019 (COVID-19) than Severe Acute Respiratory Syndrome (SARS) in Hong Kong-A Territory-Wide Cohort Study.

BACKGROUND: The case-fatality ratios (CFR) of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) appeared to differ substantially. We aimed to compare the CFR and its predictors of COVID-19 and SARS patients using a territory-wide cohort in Hong Kong. METHODS: This was a territory-wide retrospective cohort study using data captured from all public hospitals in Hong Kong. Laboratory-confirmed COVID-19 and SARS patients were identified. The primary endpoint was a composite endpoint of intensive care unit admission, use of mechanical ventilation, and/or death. RESULTS: We identified 1013 COVID-19 patients (mean age, 38.4 years; 53.9% male) diagnosed from 23 January to 14 April 2020 and 1670 SARS patients (mean age, 44.4 years; 44.0% male) from March to June 2003. Fifty-five (5.4%) COVID-19 patients and 432 (25.9%) SARS patients had reached the primary endpoint in 30 days. By 30 June 2003, 286 SARS patients had died (CFR, 17.1%). By 7 June 2020, 4 COVID-19 patients had died (CFR, 0.4%). After adjusting for demographic and clinical parameters, COVID-19 was associated with a 71% lower risk of primary endpoint compared with SARS (adjusted hazard ratio, 0.29; 95% confidence interval, .21-.40; P < .0001). Age, diabetes mellitus, and laboratory parameters (high lactate dehydrogenase, high C-reactive protein, and low platelet count) were independent predictors of the primary endpoint in COVID-19 patients, whereas use of antiviral treatments was not associated with primary endpoint. CONCLUSIONS: The CFR of COVID-19 was 0.4%. Age and diabetes were associated with worse outcomes, whereas antiviral treatments were not.

Liver injury is independently associated with adverse clinical outcomes in patients with COVID-19.

OBJECTIVE: Data on serial liver biochemistries of patients infected by different human coronaviruses (HCoVs) are lacking. The impact of liver injury on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains unclear. DESIGN: This was a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19, severe acute respiratory syndrome (SARS) and other HCoV patients were identified by diagnosis codes and/or virological results. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2 × upper limit of normal (ie, 80 U/L). The primary end point was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation and/or death. RESULTS: We identified 1040 COVID-19 patients (mean age 38 years, 54% men), 1670 SARS patients (mean age 44 years, 44% men) and 675 other HCoV patients (mean age 20 years, 57% men). ALT/AST elevation occurred in 50.3% SARS patients, 22.5% COVID-19 patients and 36.0% other HCoV patients. For COVID-19 patients, 53 (5.1%) were admitted to ICU, 22 (2.1%) received invasive mechanical ventilation and 4 (0.4%) died. ALT/AST elevation was independently associated with primary end point (adjusted OR (aOR) 7.92, 95% CI 4.14 to 15.14, p<0.001) after adjusted for albumin, diabetes and hypertension. Use of lopinavir-ritonavir ±ribavirin + interferon beta (aOR 1.94, 95% CI 1.20 to 3.13, p=0.006) and corticosteroids (aOR 3.92, 95% CI 2.14 to 7.16, p<0.001) was independently associated with ALT/AST elevation. CONCLUSION: ALT/AST elevation was common and independently associated with adverse clinical outcomes in COVID-19 patients. Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids was independently associated with ALT/AST elevation.

Using a behavioural framework to optimize antibiotic prescribing by family medicine residents.

This article was migrated. The article was marked as recommended. Background and objectives:Overprescribing of antibiotics in primary care is a prominent concern in the context of increasing antimicrobial resistance worldwide. Medical trainees are a key group to deliver thoughtful antimicrobial stewardship training. This study examined the factors influencing antibiotic prescribing for upper respiratory tract infections (URTI) by family medicine residents in order to identify educational interventions. Methods: Using purposive sampling of family medicine residents, semi-structured interviews were conducted until thematic saturation was reached. Interviews were coded into the domains of the Theoretical Domains Framework (TDF). Belief statements were created to characterize each domain and categorized as enablers or barriers to appropriate prescribing. Domains were plotted on the Behaviour Change Wheel (BCW) and intervention functions identified. Results:Twelve participants were interviewed. Nine domains of the TDF were relevant to antibiotic prescribing. Social influence was a prominent theme with the preceptor and patient being key influences on resident prescribing. Learning goals were also a key theme including the desire to strengthen independent clinical decision-making skills and improve antibiotic knowledge. Residents' beliefs about capabilities were challenged when faced with diagnostic uncertainty. Additional domains included: professional role; environmental context and resources; intentions; beliefs about consequences and capabilities, and knowledge. Using the BCW, nine intervention functions were identified to change antibiotic prescribing behaviour. Conclusion: This study found nine domains of the TDF were relevant to family medicine resident antibiotic prescribing for URTI. Nine intervention functions could be used to guide intervention design.