Win ratio analyses of piperacillin-tazobactam versus meropenem for ceftriaxone non-susceptible Escherichia coli or Klebsiella pneumoniae bloodstream infections: Post-hoc insights from the MERINO trial.

BACKGROUND: Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritise outcome measures by relative clinical importance. METHODS: The win ratio methodology was applied post-hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse and secondary infection. A win ratio of one would correspond to no difference between the two antibiotics, while a ratio less than one favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. RESULTS: With the hierarchy of all-cause mortality, microbiological relapse and secondary infection, the win ratio estimate was 0.40 (95% CI: 0.22, 0.71; p=0.002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI: 0.68, 0.92). The addition of length of stay to the primary composite, greatly minimised the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI: 0.60-0.99; p=0.04). CONCLUSIONS: The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials.

Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO).

BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Individualised, short-course antibiotic treatment versus usual long-course treatment for ventilator-associated pneumonia (REGARD-VAP): a multicentre, individually randomised, open-label, non-inferiority trial.

BACKGROUND: Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged hospitalisation, excessive antibiotic use and, consequently, increased antimicrobial resistance. In this phase 4, randomised trial, we aimed to establish whether a pragmatic, individualised, short-course antibiotic treatment strategy for VAP was non-inferior to usual care. METHODS: We did an individually randomised, open-label, hierarchical non-inferiority-superiority trial in 39 intensive care units in six hospitals in Nepal, Singapore, and Thailand. We enrolled adults (age ≥18 years) who met the US Centers for Disease Control and Prevention National Healthcare Safety Network criteria for VAP, had been mechanically ventilated for 48 h or longer, and were administered culture-directed antibiotics. In culture-negative cases, empirical antibiotic choices were made depending on local hospital antibiograms reported by the respective microbiology laboratories or prevailing local guidelines. Participants were assessed until fever resolution for 48 h and haemodynamic stability, then randomly assigned (1:1) to individualised short-course treatment (≤7 days and as short as 3-5 days) or usual care (≥8 days, with precise durations determined by the primary clinicians) via permuted blocks of variable sizes (8, 10, and 12), stratified by study site. Independent assessors for recurrent pneumonia and participants were masked to treatment allocation, but clinicians were not. The primary outcome was a 60-day composite endpoint of death or pneumonia recurrence. The non-inferiority margin was prespecified at 12% and had to be met by analyses based on both intention-to-treat (all study participants who were randomised) and per-protocol populations (all randomised study participants who fulfilled the eligibility criteria, met fitness criteria for antibiotic discontinuation, and who received antibiotics for the duration specified by their allocation group). This study is registered with ClinicalTrials.gov, number NCT03382548. FINDINGS: Between May 25, 2018, and Dec 16, 2022, 461 patients were enrolled and randomly assigned to the short-course treatment group (n=232) or the usual care group (n=229). Median age was 64 years (IQR 51-74) and 181 (39%) participants were female. 460 were included in the intention-to-treat analysis after excluding one withdrawal (231 in the short-course group and 229 in the usual care group); 435 participants received the allocated treatment and fulfilled eligibility criteria, and were included in the per-protocol population. Median antibiotic treatment duration for the index episodes of VAP was 6 days (IQR 5-7) in the short-course group and 14 days (10-21) in the usual care group. 95 (41%) of 231 participants in the short-course group met the primary outcome, compared with 100 (44%) of 229 in the usual care group (risk difference -3% [one-sided 95% CI -∞ to 5%]). Results were similar in the per-protocol population. Non-inferiority of short-course antibiotic treatment was met in the analyses, although superiority compared with usual care was not established. In the per-protocol population, antibiotic side-effects occurred in 86 (38%) of 224 in the usual care group and 17 (8%) of 211 in the short-course group (risk difference -31% [95% CI -37 to -25%; p<0·0001]). INTERPRETATION: In this study of adults with VAP, individualised shortened antibiotic duration guided by clinical response was non-inferior to longer treatment durations in terms of 60-day mortality and pneumonia recurrence, and associated with substantially reduced antibiotic use and side-effects. Individualised, short-course antibiotic treatment for VAP could help to reduce the burden of side-effects and the risk of antibiotic resistance in high-resource and resource-limited settings. FUNDING: UK Medical Research Council; Singapore National Medical Research Council. TRANSLATIONS: For the Thai and Nepali translations of the abstract see Supplementary Materials section.

Super-Resolution Reconstruction of CT Images Based on Multi-scale Information Fused Generative Adversarial Networks.

The popularization and widespread use of computed tomography (CT) in the field of medicine evocated public attention to the potential radiation exposure endured by patients. Reducing the radiation dose may lead to scattering noise and low resolution, which can adversely affect the radiologists' judgment. Hence, this paper introduces a new network called PANet-UP-ESRGAN (PAUP-ESRGAN), specifically designed to obtain low-dose CT (LDCT) images with high peak signal-to-noise ratio (PSNR) and high resolution (HR). The model was trained on synthetic medical image data based on a Generative Adversarial Network (GAN). A degradation modeling process was introduced to accurately represent realistic degradation complexities. To reconstruct image edge textures, a pyramidal attention model call PANet was added before the middle of the multiple residual dense blocks (MRDB) in the generator to focus on high-frequency image information. The U-Net discriminator with spectral normalization was also designed to improve its efficiency and stabilize the training dynamics. The proposed PAUP-ESRGAN model was evaluated on the abdomen and lung image datasets, which demonstrated a significant improvement in terms of robustness of model and LDCT image detail reconstruction, compared to the latest real-esrgan network. Results showed that the mean PSNR increated by 19.1%, 25.05%, and 21.25%, the mean SSIM increated by 0.4%, 0.4%, and 0.4%, and the mean NRMSE decreated by 0.25%, 0.25%, and 0.35% at 2[Formula: see text], 4[Formula: see text], and 8[Formula: see text] super-resolution scales, respectively. Experimental results demonstrate that our method outperforms the state-of-the-art super-resolution methods on restoring CT images with respect to peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and normalized root-mean-square error (NRMSE) indices.

The burden and dynamics of hospital-acquired SARS-CoV-2 in England.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance.

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.

COVID-19 vaccination is associated with enhanced efficacy of anti-PD-(L)1 immunotherapy in advanced NSCLC patients: a real-world study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine has played a major role in ending the pandemic. However, little is known about the influence of COVID-19 vaccine on the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). OBJECTIVES: The goal of this study is to explore whether COVID-19 vaccine impacts the efficacy of immune checkpoint inhibitors (ICIs) in NSCLC patients. METHODS: We retrospectively analyzed the survival data of ICI-treated 104 patients with stage III-IV NSCLC, who either received COVID-19 vaccination (n = 25) or no vaccination (n = 79). The potential risk factors, in particular roles of COVID-19 vaccination in the efficacy of ICIs in these patients, were evaluated. RESULTS: Our results showed significantly improved ORR (28.0% vs. 11.39%, p = 0.05) and DCR (88.0% vs. 54.43%, p = 0.005) in the COVID-19 vaccinated group compared with the non-vaccinated group. Regarding the long-term survival benefits, COVID-19 vaccine showed profound influence both on the PFS (HR = 0.16, p = 0.021) and OS (HR = 0.168, p = 0.019) in patients with NSCLC under ICIs treatment. The PFS (p < 0.001) or OS (p < 0.001) was significantly improved in the COVID-19 vaccinated group, compared with the non-vaccinated group. Moreover, CD4 T cell (p = 0.047) level was higher in the COVID-19 vaccinated group than in the non-vaccinated group. CONCLUSIONS: COVID-19 vaccination enhances anti-PD-1 immunotherapy efficacy in patients with stage III-IV NSCLC, suggesting that COVID-19 vaccination may provide additional benefit to NSCLC patients.

IL-33 Orchestrated the Interaction and Immunoregulatory Functions of Alternatively Activated Macrophages and Regulatory T Cells In Vitro.

Our group has previously demonstrated elevated serum-soluble ST2 in patients with active systemic lupus erythematosus, suggesting a role of IL-33 in the underlying pathogenesis. However, inconsistent results have been reported on the effect of exogenous IL-33 on murine lupus activity, which may be mediated by concerted actions of various immune cells in vivo. This study aimed to examine the function of IL-33 on macrophage polarization and regulatory T cells (Treg) and their interactive effects in the lupus setting by in vitro coculture experiments of macrophages and T cells that were performed in the presence or absence of IL-33-containing medium. Compared to IL-4-polarized bone marrow-derived macrophages (BMDM) from MRL/MpJ mice, adding IL-33 enhanced mRNA expression of markers of alternatively activated macrophages, including CD206 and Arg1. IL-33 and IL-4 copolarized BMDM produced higher TGF-ß but not IL-6 upon inflammatory challenge. These BMDM induced an increase in the Foxp3+CD25+ Treg population in cocultured allogeneic T cells from MRL/MpJ and predisease MRL/lpr mice. These copolarized BMDM also showed an enhanced suppressive effect on T cell proliferation with reduced IFN-γ and IL-17 release but increased TGF-ß production. In the presence of TGF-ß and IL-2, IL-33 also directly promoted inducible Treg that expressed a high level of CD25 and more sustained Foxp3. Unpolarized BMDM cocultured with these Treg displayed higher phagocytosis. In conclusion, TGF-ß was identified as a key cytokine produced by IL-4 and IL-33 copolarized alternatively activated macrophages and the induced Treg, which may contribute to a positive feedback loop potentiating the immunoregulatory functions of IL-33.

Implications of reducing antibiotic treatment duration for antimicrobial resistance in hospital settings: A modelling study and meta-analysis.

BACKGROUND: Reducing antibiotic treatment duration is a key component of hospital antibiotic stewardship interventions. However, its effectiveness in reducing antimicrobial resistance is uncertain and a clear theoretical rationale for the approach is lacking. In this study, we sought to gain a mechanistic understanding of the relation between antibiotic treatment duration and the prevalence of colonisation with antibiotic-resistant bacteria in hospitalised patients. METHODS AND FINDINGS: We constructed 3 stochastic mechanistic models that considered both between- and within-host dynamics of susceptible and resistant gram-negative bacteria, to identify circumstances under which shortening antibiotic duration would lead to reduced resistance carriage. In addition, we performed a meta-analysis of antibiotic treatment duration trials, which monitored resistant gram-negative bacteria carriage as an outcome. We searched MEDLINE and EMBASE for randomised controlled trials published from 1 January 2000 to 4 October 2022, which allocated participants to varying durations of systemic antibiotic treatments. Quality assessment was performed using the Cochrane risk-of-bias tool for randomised trials. The meta-analysis was performed using logistic regression. Duration of antibiotic treatment and time from administration of antibiotics to surveillance culture were included as independent variables. Both the mathematical modelling and meta-analysis suggested modest reductions in resistance carriage could be achieved by reducing antibiotic treatment duration. The models showed that shortening duration is most effective at reducing resistance carriage in high compared to low transmission settings. For treated individuals, shortening duration is most effective when resistant bacteria grow rapidly under antibiotic selection pressure and decline rapidly when stopping treatment. Importantly, under circumstances whereby administered antibiotics can suppress colonising bacteria, shortening antibiotic treatment may increase the carriage of a particular resistance phenotype. We identified 206 randomised trials, which investigated antibiotic duration. Of these, 5 reported resistant gram-negative bacteria carriage as an outcome and were included in the meta-analysis. The meta-analysis determined that a single additional antibiotic treatment day is associated with a 7% absolute increase in risk of resistance carriage (80% credible interval 3% to 11%). Interpretation of these estimates is limited by the low number of antibiotic duration trials that monitored carriage of resistant gram-negative bacteria, as an outcome, contributing to a large credible interval. CONCLUSIONS: In this study, we found both theoretical and empirical evidence that reducing antibiotic treatment duration can reduce resistance carriage, though the mechanistic models also highlighted circumstances under which reducing treatment duration can, perversely, increase resistance. Future antibiotic duration trials should monitor antibiotic-resistant bacteria colonisation as an outcome to better inform antibiotic stewardship policies.

N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis.

Accumulating evidence indicates that RNA methylation at N6-methyladenosine (m6A) plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers. However, little is known whether and how m6A-modification impacts long non-coding RNA (lncRNA) and lncRNA-mediated tumorigenesis, particularly in pancreatic ductal adenocarcinoma (PDAC). In the present study, we report that a previously uncharacterized lncRNA, LINC00901, promotes pancreatic cancer cell growth and invasion and moreover, LINC00901 is subject to m6A modification which regulates its expression. In this regard, YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level. Notably, two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1. Finally, RNA sequencing (RNA-seq) and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2, a known RNA binding protein that can enhance MYC mRNA stability. Together, our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.

Circulating eosinophils associated with responsiveness to COVID-19 vaccine and the disease severity in patients with SARS-CoV-2 omicron variant infection.

OBJECTIVE: This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China. METHODS: We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.2 variant in Shanghai, China. These patients were diagnosed or admitted between Feb 20, 2022, and May 10, 2022, and were classified as asymptomatic (n = 705), mild (n = 286) and severe (n = 166) groups. We compiled and analyzed data of patients' clinical demographic characteristics, laboratory findings, and clinical outcomes. RESULTS: COVID-19 vaccine reduced the incidence of severe cases. Severe patients were shown to have declined peripheral blood EOS. Both the 2 doses and 3 doses of inactivated COVID-19 vaccines promoted the circulating EOS levels. In particular, the 3rd booster shot of inactivated COVID-19 vaccine was shown to have a sustained promoting effect on circulating EOS. Univariate analysis showed that there was a significant difference in age, underlying comorbidities, EOS, lymphocytes, CRP, CD4, and CD8 T cell counts between the mild and the severe patients. Multivariate logistic regression analysis and ROC curve analysis indicate that circulating EOS (AUC = 0.828, p = 0.025), the combination of EOS and CD4 T cell (AUC = 0.920, p = 0.017) can predict the risk of disease severity in patients with SARS-CoV-2 Omicron BA.2 variant infection. CONCLUSIONS: COVID-19 vaccine promotes circulating EOS and reduces the risk of severe illness, and particularly the 3rd booster dose of COVID-19 vaccine sustainedly promotes EOS. Circulating EOS, along with T cell immunity, may have a predictive value for the disease severity in SARS-CoV-2 Omicron infected patients.

Interleukin-33 Ameliorates Murine Systemic Lupus Erythematosus and Is Associated with Induction of M2 Macrophage Polarisation and Regulatory T Cells.

The innate cytokine IL-33 is increasingly recognised to possess biological effects on various immune cells. We have previously demonstrated elevated serum level of soluble ST2 in patients with active systemic lupus erythematosus suggesting involvement of IL-33 and its receptor in the lupus pathogenesis. This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone mice and the underlying cellular mechanisms. Recombinant IL-33 was administered to MRL/lpr mice for 6 weeks, whereas control group received phosphate-buffered saline. IL-33-treated mice displayed less proteinuria, renal histological inflammatory changes, and had lower serum levels of pro-inflammatory cytokines including IL-6 and TNF-α. Renal tissue and splenic CD11b+ extracts showed features of M2 polarisation with elevated mRNA expression of Arg1, FIZZI, and reduced iNOS. These mice also had increased IL-13, ST2, Gata3, and Foxp3 mRNA expression in renal and splenic tissues. Kidneys of these mice displayed less CD11b+ infiltration, had downregulated MCP-1, and increased infiltration of Foxp3-expressing cells. Splenic CD4+ T cells showed increased ST2-expressing CD4+Foxp3+ population and reduced IFN-γ+ population. There were no differences in serum anti-dsDNA antibodies and renal C3 and IgG2a deposit in these mice. Exogenous IL-33 was found to ameliorate disease activity in lupus-prone mice with induction of M2 polarisation, Th2 response, and expansion of regulatory T cells. IL-33 likely orchestrated autoregulation of these cells through upregulation of ST2 expression.

Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice.

Although gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leading to an anticancer effect on lung cancer. We evaluated the effects of gut endogenous or gavaged exogenous Akk on the tumorigenesis using the Lewis lung cancer mouse model. Feces, blood, and tumor tissue samples were collected for 16S rDNA sequencing. We then conducted spatially resolved metabolomics profiling to discover cancer metabolites in situ directly and to characterize the overall Akk-regulated metabolic features, followed by the correlation analysis of intratumoral bacteria with metabolic network. Our results showed that both endogenous and exogenous gavaged Akk significantly inhibited tumorigenesis. Moreover, we detected increased Akk abundance in blood circulation or tumor tissue by 16S rDNA sequencing in the Akk gavaged mice, compared with the control mice. Of great interest, gavaged Akk may migrate into tumor tissue and influence the composition of intratumoral microbiome. Spatially resolved metabolomics analysis revealed that the gut-derived Akk was able to regulate tumor metabolic pathways, from metabolites to enzymes. Finally, our study identified a significant correlation between the gut Akk-regulated intratumoral bacteria and metabolic network. Together, gut-derived Akk may migrate into blood circulation, and subsequently colonize into lung cancer tissue, which contributes to the suppression of tumorigenesis by influencing tumoral symbiotic microbiome and reprogramming tumoral metabolism, although more studies are needed.

Exosomal miR-1304-3p promotes breast cancer progression in African Americans by activating cancer-associated adipocytes.

Breast cancer displays disparities in mortality between African Americans and Caucasian Americans. However, the exact molecular mechanisms remain elusive. Here, we identify miR-1304-3p as the most upregulated microRNA in African American patients. Importantly, its expression significantly correlates with poor progression-free survival in African American patients. Ectopic expression of miR-1304 promotes tumor progression in vivo. Exosomal miR-1304-3p activates cancer-associated adipocytes that release lipids and enhance cancer cell growth. Moreover, we identify the anti-adipogenic gene GATA2 as the target of miR-1304-3p. Notably, a single nucleotide polymorphism (SNP) located in the miR-1304 stem-loop region shows a significant difference in frequencies of the G allele between African and Caucasian American groups, which promotes the maturation of miR-1304-3p. Therefore, our results reveal a mechanism of the disparity in breast cancer progression and suggest a potential utility of miR-1304-3p and the associated SNP as biomarkers for predicting the outcome of African American patients.

Severe Periodontitis Is a Major Contributory Factor to Unmet Dental Healthcare Needs among Rheumatoid Arthritis Patients in Hong Kong.

Objective: This study aimed to examine the frequency and predictive factors of adverse oral and dental outcomes in patients with rheumatoid arthritis (RA) with the goal to address their unmet dental healthcare needs in the metropolitan city of Hong Kong. Methods: 238 RA patients followed up at local public hospitals were recruited in this cross-sectional study. A full dental examination was performed. Data were compared with the retrospective data collected from age-matched control groups in the community conducted in a territory-wide oral health survey in 2011. Predictive factors for severe periodontitis including various demographic and disease-specific factors were examined by multiple logistic regression analysis. Results: Loose teeth and gum bleeding were frequent dental complaints. Only 85.0% of RA patients had >20 natural teeth. Total edentulism was observed in 3.8% of patients, which was higher among adult (22-64 years) and elderly (>65 years old) RA patients than their respective age-matched community control groups. RA patients had a higher decayed, missing, and filled tooth score. Adult RA patients had a 5.3-fold increase in risk of severe periodontitis than their community counterparts. The plaque index was the main predisposing factor for severe periodontitis (odds ratio 17.5, p=0.001), which was worse among the 22-34 age group of patients. More RA patients required tooth extraction compared to dental filling for their community controls. Conclusion: Severe periodontitis is a major cause of unmet dental healthcare needs among RA patients in Hong Kong. It is recommended that dental care plans for RA patients be commenced early among newly diagnosed patients.