Heightened long-term cardiovascular risks after exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To examine the risk of adverse cardiovascular (CV) events following an exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: This retrospective cohort study identified patients with COPD using administrative data from Alberta, Canada from 2014 to 2019. Exposure periods were 12 months following moderate or severe exacerbations; the reference period was time preceding a first exacerbation. The primary outcome was the composite of all-cause death or a first hospitalisation for acute coronary syndrome, heart failure (HF), arrhythmia or cerebral ischaemia. Time-dependent Cox regression models estimated covariate-adjusted risks associated with six exposure subperiods following exacerbation. RESULTS: Among 1 42 787 patients (mean age 68.1 years and 51.7% men) 61 981 (43.4%) experienced at least one exacerbation and 34 068 (23.9%) died during median follow-up of 64 months. The primary outcome occurred in 43 564 (30.5%) patients with an incidence rate prior to exacerbation of 5.43 (95% CI 5.36 to 5.50) per 100 person-years. This increased to 95.61 per 100 person-years in the 1-7 days postexacerbation (adjusted HR 15.86, 95% CI 15.17 to 16.58) and remained increased for up to 1 year. The risk of both the composite and individual CV events was increased following either a moderate or a severe exacerbation, though greater and more prolonged following severe exacerbation. The highest magnitude of increased risk was observed for HF decompensation (1-7 days, HR 72.34, 95% CI 64.43 to 81.22). CONCLUSION: Moderate and severe COPD exacerbations are independent risk factors for adverse CV events, especially HF decompensation. The impact of optimising COPD management on CV outcomes should be evaluated.

Pediatric Profound Dengue Shock Syndrome and Use of Point-of-Care Ultrasound During Mechanical Ventilation to Guide Treatment: Single-Center Retrospective Study, 2013-2021.

OBJECTIVES: Profound dengue shock syndrome (DSS) complicated by severe respiratory failure necessitating mechanical ventilation (MV) accounts for high case fatality rates among PICU-admitted patients. A major challenge to management is the assessment of intravascular volume, which can be hampered by severe plasma leakage and the use of MV. DESIGN: Retrospective cohort, from 2013 to 2021. PATIENTS: Sixty-seven children with profound DSS supported by MV, some of whom underwent bedside point-of-care ultrasound (POCUS) for assessment and monitoring of hemodynamics and fluid administration. SETTING: PICU of the tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data clinical and laboratory data during PICU stay. In particular, during use of MV (i.e., at times 0-, 6-, and 24-hr after commencement) and fluid resuscitation. The primary study outcome was 28-day in-hospital mortality, and the secondary outcomes were associations with changes in hemodynamics, blood lactate, and vasoactive-inotrope score (VIS). Patients had a median age of 7 years (interquartile range, 4-9). Use of POCUS during fluid management (39/67), as opposed to not using (28/67), was associated with lower mortality (6/39 [15%] vs. 18/28 [64%]; difference 49 % [95% CI, 28-70%], p < 0.001). Use of POCUS was associated with lower odds of death (adjusted odds ratio 0.17 [95% CI, 0.04-0.76], p = 0.02). The utilization of POCUS, versus not, was associated with greater use of resuscitation fluid, and reductions in VIS and pediatric logistic organ dysfunction (PELOD-2) score at 24 hours after MV and PICU discharge. CONCLUSIONS: In our experience of pediatric patients with profound DSS and undergoing MV (2013-2021), POCUS use was associated with lower odds of death, a higher volume of resuscitation fluid, and improvements in the blood lactate levels, VIS, and PELOD-2 score.

Injecting drug use increases the risk of death in HIV patients on antiretroviral therapy in Vietnam.

The Human Immunodeficiency Virus (HIV) epidemic remains a major public health issue worldwide. In Vietnam, the HIV epidemic is essentially driven by people who inject drugs (PWID). This study aims to compare mortality and loss to follow-up (LTFU) between PWID and other patients. From June 2017 to April 2018, HIV-infected adults were enrolled in a prospective cohort from time of ART initiation in six provinces of North Vietnam. The end date was July 2020. Mortality and LTFU were described using competing-risk survival models. Factors associated with mortality and with LTFU were identified using Cox models with a competing-risk approach. Of the 578 participants, 261 (45.2%) were PWID and almost exclusively male. 49 patients died, corresponding to a mortality rate (95% confidence interval (CI)) of 3.7 (2.8-4.9) per 100 person-months, and 79 were lost to follow-up, corresponding to a rate (95% CI) of 6.0 (4.8-7.4) per 100 person-months. PWID were at higher risk of death but not of LTFU. Overall, LTFU was high in both groups. Latecomers to clinical visits were more at risk of both death and LTFU. Therefore, this should be a warning to clinical teams and preventive actions taken in these patients.Trial registration: ClinicalTrials.gov identifier: NCT03249493..

Migraine Treatment and Healthcare Resource Utilization in Alberta, Canada.

BACKGROUND: Migraine poses a significant burden worldwide; however, there is limited evidence as to the burden in Canada. This study examined the treatment patterns, healthcare resource use (HRU), and costs among newly diagnosed or recurrent patients with migraine in Alberta, Canada, from the time of diagnosis or recurrence. METHODS: This retrospective observational study utilized administrative health data from Alberta, Canada. Patients were included in the Total Migraine Cohort if they had: (1) ≥1 International Classification of Diseases diagnostic code for migraine; or (2) ≥1 prescription dispense(s) for triptans from April 1, 2012, to March 31, 2018, with no previous diagnosis or dispensation code from April 1, 2010, to April 1, 2012. RESULTS: The mean age of the cohort (n = 199,931) was 40.0 years and 72.3% were women. The most common comorbidity was depression (19.7%). In each medication class examined, less than one-third of the cohort was prescribed triptans and fewer than one-fifth was prescribed a preventive. Among patients with ≥1 dispense, the mean rate of opioid prescriptions was 4.61 per patient-year, compared to 2.28 triptan prescriptions per patient-year. Migraine-related HRU accounted for 3%-10% of all use. CONCLUSION: Comorbidities and high all-cause HRU were observed among newly diagnosed or recurrent patients with migraine. There is an underutilization of acute and preventive medications in the management of migraine. The high rate of opioid use reinforces the suboptimal management of migraine in Alberta. Migraine management may improve by educating healthcare professionals to optimize treatment strategies.

Burden of Episodic Migraine, Chronic Migraine, and Medication Overuse Headache in Alberta.

OBJECTIVE: To describe demographic and clinical characteristics, healthcare resource use, costs, and treatment patterns in three migraine cohorts. METHODS: This retrospective observational study using administrative data examined patients with episodic migraine (EM), chronic migraine (CM) (without medication overuse headache [MOH]), and medication overuse headache in Alberta, Canada. Migraine patients were identified between 2012 and 2018 based on ≥ 1 diagnostic codes or triptan prescription. Patients with CM were defined using parameter estimates of a logistic regression model, and MOH was defined as patients with an average of ≥ 15 supply days covered of acute medications. EM was defined as patients without CM or MOH. Study outcomes were summarized using descriptive statistics. RESULTS: Patients with EM (n = 144,574), CM (n = 27,283), and MOH (n = 11,485) were included. Higher rates of healthcare use and costs were observed for CM (mean [SD] all-cause cost: ($12,693 [40,664]) and MOH ($16,611.5 [$38,748]) versus episodic migraine ($4,251 [$40,637]). Across all cohorts, opioids were the most dispensed acute medication (range across cohorts: 31.7%-89.8%), while antidepressants and anticonvulsants were the most dispensed preventive medication. Preventative medication classes were used by a minority of patients in each cohort, except anticonvulsants, where 50% of medication overuse patients had a dispensation. CONCLUSIONS: Patients with CM and MOH have a greater burden of illness compared to patients with EM. The overutilization of acute medication, particularly opioids, and the underutilization of preventive medications highlight an unmet need to more effectively manage migraine.

Assessment of HIV viral load monitoring in remote settings in Vietnam - comparing people who inject drugs to the other patients.

INTRODUCTION: Increasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID. METHODS: Prospective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure (VL ≥1,000 copies/mL) at 6, 12 and 24 months of ART. RESULTS: Overall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p = 0.001). PWID status was not associated with DBS coverage (p = 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 (p = 0.023 and p = 0.001, respectively). The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (p<0.001). In multivariate analysis, PWID were more at risk of failure (p = 0.001), as were patients who were late to clinical visits (p<0.001) and not fully adherent (p<0.001). CONCLUSIONS: Despite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care. TRIAL REGISTRATION: Clinical Trial Number: NCT03249493.

Generation of functional human T cell development in NOD/SCID/IL2rγnull humanized mice without using fetal tissue: Application as a model of HIV infection and persistence.

Humanization of mice with functional T cells currently relies on co-implantation of hematopoietic stem cells from fetal liver and autologous fetal thymic tissue (so-called BLT mouse model). Here, we show that NOD/SCID/IL2rγnull mice humanized with cord blood- derived CD34+ cells and implanted with allogeneic pediatric thymic tissues excised during cardiac surgeries (CCST) represent an alternative to BLT mice. CCST mice displayed a strong immune reconstitution, with functional T cells originating from CD34+ progenitor cells. They were equally susceptible to mucosal or intraperitoneal HIV infection and had significantly higher HIV-specific T cell responses. Antiretroviral therapy (ART) robustly suppressed viremia and reduced the frequencies of cells carrying integrated HIV DNA. As in BLT mice, we observed a complete viral rebound following ART interruption, suggesting the presence of HIV reservoirs. In conclusion, CCST mice represent a practical alternative to BLT mice, broadening the use of humanized mice for research.

MiRNA-103 downmodulates CCR5 expression reducing human immunodeficiency virus type-1 entry and impacting latency establishment in CD4+ T cells.

Activated-to-memory transitioning CD4+ T cells display elevated expression of the HIV-1 co-receptor CCR5 and are more prone to HIV-1 latent infection. Here, we show that p53-regulated miRNA-103 downmodulates CCR5 levels in CD4+ T lymphocytes. We reveal that miRNA-103 mimics, as well as Nutlin-3, an inhibitor of Mdm2-mediated p53 degradation, decrease CCR5-dependent HIV-1 infection. Using a dual-reporter virus, we subsequently validate that in transitioning CD4+ T cells, Nutlin-3 treatment decreases the frequency of both productively and latently infected cells via upregulation of miRNA-103. Importantly, we provide evidence that CD4+ T cells from HIV-1 elite controllers express less CCR5 than those from antiretroviral therapy-naïve progressors, an effect linked to a significant increase in miRNA-103 levels. By contributing to the control of CCR5 expression in CD4+ T cells, miRNA-103 is likely to play a key role in countering the establishment of latent HIV-1 reservoirs in vivo.

Distinctive Roles of Furin and TMPRSS2 in SARS-CoV-2 Infectivity.

The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directs infection of the lungs and other tissues following its binding to the angiotensin-converting enzyme 2 (ACE2) receptor. For effective infection, the S protein is cleaved at two sites: S1/S2 and S2'. The "priming" of the surface S protein at S1/S2 (PRRAR685↓) [the underlined basic amino acids refer to critical residues needed for the furin recognition] by furin has been shown to be important for SARS-CoV-2 infectivity in cells and small-animal models. In this study, for the first time we unambiguously identified by proteomics the fusion activation site S2' as KPSKR815↓ (the underlined basic amino acids refer to critical residues needed for the furin recognition) and demonstrated that this cleavage was strongly enhanced by ACE2 engagement with the S protein. Novel pharmacological furin inhibitors (BOS inhibitors) effectively blocked endogenous S protein processing at both sites in HeLa cells, and SARS-CoV-2 infection of lung-derived Calu-3 cells was completely prevented by combined inhibitors of furin (BOS) and type II transmembrane serine protease 2 (TMPRSS2) (camostat). Quantitative analyses of cell-to-cell fusion and S protein processing revealed that ACE2 shedding by TMPRSS2 was required for TMPRSS2-mediated enhancement of fusion in the absence of S1/S2 priming. We further demonstrated that the collectrin dimerization domain of ACE2 was essential for the effect of TMPRSS2 on cell-to-cell fusion. Overall, our results indicate that furin and TMPRSS2 act synergistically in viral entry and infectivity, supporting the combination of furin and TMPRSS2 inhibitors as potent antivirals against SARS-CoV-2. IMPORTANCE SARS-CoV-2, the etiological agent of COVID-19, has so far resulted in >6.1 million deaths worldwide. The spike protein (S) of the virus directs infection of the lungs and other tissues by binding the angiotensin-converting enzyme 2 (ACE2) receptor. For effective infection, the S protein is cleaved at two sites: S1/S2 and S2'. Cleavage at S1/S2 induces a conformational change favoring the S protein recognition by ACE2. The S2' cleavage is critical for triggering membrane fusion and virus entry into host cells. Our study highlights the complex dynamics of interaction between the S protein, ACE2, and the host proteases furin and TMPRSS2 during SARS-CoV-2 entry and suggests that the combination of a nontoxic furin inhibitor with a TMPRSS2 inhibitor significantly reduces viral entry in lung cells, as evidenced by an average synergistic ∼95% reduction of viral infection. This represents a powerful novel antiviral approach to reduce viral spread in individuals infected by SARS-CoV-2 or future related coronaviruses.

Perspectives of Pediatric Rheumatologists on Initiating and Tapering Biologics in Patients with Juvenile Idiopathic Arthritis: A Formative Qualitative Study.

BACKGROUND: Few studies have examined pediatric rheumatologists' approaches to treatment decision making for biologic therapy for patients with juvenile idiopathic arthritis (JIA). This study presents the qualitative research undertaken to support the development of a Best-Worst Scaling (BWS) survey for tapering in JIA. The study objectives were to (1) describe the treatment decision-making process of pediatric rheumatologists to initiate and taper biologics; and (2) select attributes for a BWS survey. METHODS: Pediatric rheumatologists across Canada were recruited to participate in interviews using purposeful sampling. Interviews were conducted until saturation was achieved. Interview recordings were transcribed verbatim and transcripts were analyzed using deductive thematic analysis. Initial codes were organized into themes and subthemes using an iterative process. Attributes for the BWS survey were developed from these themes and a literature review was conducted in parallel to inform survey development. Further refinement of the attributes was done through consultation with the research team. RESULTS: Five pediatric rheumatologists participated in the interviews. Shared decision making was part of the approach to initiating and tapering biologics in their practice. Tapering approaches differed; some pediatric rheumatologists preferred to stop biologics immediately, while others tapered by reducing dose and/or increasing the dose interval over time. A total of 14 attributes were developed for the BWS. Thirteen attributes were selected from the themes that emerged from the qualitative interviews and one attribute was included after review with the research team. Attributes related to patient characteristics included JIA subtype, time in remission, history or presence of joint damage or erosive disease, how challenging it was to achieve remission, and history of flares. Contextual attributes included accessibility of biologics and willingness to taper biologics. CONCLUSION: This study contributes to the limited literature on pediatric rheumatologists' approaches to treatment decision making for biologics in JIA and identifies attributes that affect the decision to both initiate and taper. Further research is planned to implement the BWS survey to understand the importance of the attributes identified. Additional investigation is required to determine if these characteristics align with patient and parent preferences.

Patient and rheumatologist perspectives on tapering DMARDs in rheumatoid arthritis: a qualitative study.

OBJECTIVES: To understand the perspectives of patients and rheumatologists for tapering DMARDs in RA. METHODS: Using semi-structured interview guides, we conducted individual interviews and focus groups with RA patients and rheumatologists, which were audiotaped and transcribed. We conducted a pragmatic thematic analysis to identify major themes, comparing and contrasting different views on DMARD tapering between patients and rheumatologists. RESULTS: We recruited 28 adult patients with RA (64% women; disease duration 1-54 y) and 23 rheumatologists (52% women). Attitudes across both groups towards tapering DMARDs were ambivalent, ranging from wary to enthusiastic. Both groups expressed concerns, particularly the inability to 'recapture' the same level of disease control, while also acknowledging potential positive outcomes such as reduced drug harms. Patient tapering perspectives (whether to and when) changed over time and commonly included non-biologic DMARDs. Patient preferences were influenced by lived experiences, side effects, previous tapering experiences, disease trajectory, remission duration and current life roles. Rheumatologists' perspectives varied on timing and patient profile to initiate tapering, and were informed by both data and clinical experience. Patients expressed interest in shared decision-making (SDM) and close monitoring during tapering, with ready access to their health-care team if problems arose. Rheumatologists were generally open to tapering (not stopping), though sometimes only when requested by their patients. CONCLUSION: The perspectives of patients and rheumatologists on tapering DMARDs in RA vary and evolve over time. Rheumatologists should periodically discuss DMARD tapering with patients as part of SDM, and ensure monitoring and flare management plans are in place.

HIV-1 Vpu Promotes Phagocytosis of Infected CD4+ T Cells by Macrophages through Downregulation of CD47.

Human immunodeficiency virus (HIV) remodels the cell surface of infected cells to facilitate viral dissemination and promote immune evasion. The membrane-associated viral protein U (Vpu) accessory protein encoded by HIV-1 plays a key role in this process by altering cell surface levels of multiple host proteins. Using an unbiased quantitative plasma membrane profiling approach, we previously identified CD47 as a putative host target downregulated by Vpu. CD47 is a ubiquitously expressed cell surface protein that interacts with the myeloid cell inhibitory receptor signal regulatory protein-alpha (SIRPα) to deliver a "don't-eat-me" signal, thus protecting cells from phagocytosis. In this study, we investigate whether CD47 modulation by HIV-1 Vpu might promote the susceptibility of macrophages to viral infection via phagocytosis of infected CD4+ T cells. Indeed, we find that Vpu downregulates CD47 expression on infected CD4+ T cells, leading to enhanced capture and phagocytosis by macrophages. We further provide evidence that this Vpu-dependent process allows a C-C chemokine receptor type 5 (CCR5)-tropic transmitted/founder (T/F) virus, which otherwise poorly infects macrophages in its cell-free form, to efficiently infect macrophages. Importantly, we show that HIV-1-infected cells expressing a Vpu-resistant CD47 mutant are less prone to infecting macrophages through phagocytosis. Mechanistically, Vpu forms a physical complex with CD47 through its transmembrane domain and targets the latter for lysosomal degradation. These results reveal a novel role of Vpu in modulating macrophage infection, which has important implications for HIV-1 transmission in early stages of infection and the establishment of viral reservoir. IMPORTANCE Macrophages play critical roles in human immunodeficiency virus (HIV) transmission, viral spread early in infection, and as a reservoir of virus. Selective capture and engulfment of HIV-1-infected T cells was shown to drive efficient macrophage infection, suggesting that this mechanism represents an important mode of infection notably for weakly macrophage-tropic T/F viruses. In this study, we provide insight into the signals that regulate this process. We show that the HIV-1 accessory protein viral protein U (Vpu) downregulates cell surface levels of CD47, a host protein that interacts with the inhibitory receptor signal regulatory protein-alpha (SIRPα), to deliver a "don't-eat-me" signal to macrophages. This allows for enhanced capture and phagocytosis of infected T cells by macrophages, ultimately leading to their productive infection even with transmitted/founder (T/F) virus. These findings provide new insights into the mechanisms governing the intercellular transmission of HIV-1 to macrophages with implications for the establishment of the macrophage reservoir and early HIV-1 dissemination in vivo.

L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.

HIV Infection and Persistence in Pulmonary Mucosal Double Negative T Cells In Vivo.

The lungs are relatively unexplored anatomical human immunodeficiency virus (HIV) reservoirs in the antiretroviral therapy (ART) era. Double negative (DN) T cells are a subset of T cells that lack expression of CD4 and CD8 (CD4- CD8-) and may have both regulatory and effector functions during HIV infection. Notably, circulating DN T cells were previously described as cellular HIV reservoirs. Here, we undertook a thorough analysis of pulmonary versus blood DN T cells of people living with HIV (PLWH) under ART. Bronchoalveolar lavage (BAL) fluid and matched peripheral blood were collected from 35 PLWH on ART and 16 uninfected volunteers without respiratory symptoms. Both PLWH and HIV-negative (HIV-) adults displayed higher frequencies of DN T cells in BAL versus blood, and these cells mostly exhibited an effector memory phenotype. In PLWH, pulmonary mucosal DN T cells expressed higher levels of HLA-DR and several cellular markers associated with HIV persistence (CCR6, CXCR3, and PD-1) than blood. We also observed that DN T cells were less senescent (CD28- CD57+) and expressed less immunosuppressive ectonucleotidase (CD73/CD39), granzyme B, and perforin in the BAL fluid than in the blood of PLWH. Importantly, fluorescence-activated cell sorter (FACS)-sorted DN T cells from the BAL fluid of PLWH under suppressive ART harbored HIV DNA. Using the humanized bone marrow-liver-thymus (hu-BLT) mouse model of HIV infection, we observed higher infection frequencies of lung DN T cells than those of the blood and spleen in both early and late HIV infection. Overall, our findings show that HIV is seeded in pulmonary mucosal DN T cells early following infection and persists in these potential cellular HIV reservoirs even during long-term ART.IMPORTANCE Reservoirs of HIV during ART are the primary reasons why HIV/AIDS remains an incurable disease. Indeed, HIV remains latent and unreachable by antiretrovirals in cellular and anatomical sanctuaries, preventing its eradication. The lungs have received very little attention compared to other anatomical reservoirs despite being immunological effector sites exhibiting characteristics ideal for HIV persistence. Furthermore, PLWH suffer from a high burden of pulmonary non-opportunistic infections, suggesting impaired pulmonary immunity despite ART. Meanwhile, various immune cell populations have been proposed to be cellular reservoirs in blood, including CD4- CD8- DN T cells, a subset that may originate from CD4 downregulation by HIV proteins. The present study aims to describe DN T cells in human and humanized mice lungs in relation to intrapulmonary HIV burden. The characterization of DN T cells as cellular HIV reservoirs and the lungs as an anatomical HIV reservoir will contribute to the development of targeted HIV eradication strategies.

Determination of Rheumatoid Arthritis Incidence and Prevalence in Alberta Using Administrative Health Data.

OBJECTIVE: The objective of the study was to estimate the incidence and prevalence of rheumatoid arthritis (RA) in Alberta using administrative health data. METHODS: We identified RA cases in patients 16 years and older by applying a national case definition to linked administrative health data (ie, hospital discharge abstract records, physician claims, and health insurance registry records) using a unique personal identifier. Incidence and prevalence are reported for the 2015-2016 fiscal year and a trend analysis from 2011-2012 to 2015-2016. Incidence and prevalence estimates were standardized using the 2011 Canadian census population. RESULTS: In 2015-2016, the overall crude incidence was 0.74 [95% confidence interval (CI): 0.71-0.77] per 1000 and crude prevalence was 1.08% (95% CI: 1.07-1.09). The women-to-men crude incidence and prevalence sex ratios were 2.04 and 2.19, respectively. People aged 65 to 79 years had the highest incidence of RA, and the highest prevalence was observed among those 80 years and older. From 2011-2012 to 2015-2016, the overall age-standardized incidence decreased [0.97 (95% CI: 0.94-1.01) to 0.79 (95% CI: 0.76-0.82) per 1000], whereas age-standardized prevalence remained constant [1.17 (95% CI: 1.15-1.18) to 1.18 (95% CI: 1.17-1.19)]. CONCLUSION: In Alberta, there was a decreasing trend in RA incidence over the study period, whereas prevalence was stable. These estimates, combined with clinical data, will be used to measure system performance for quality improvement and to inform simulation modeling for planning the expected demand for health services for patients living with RA.

Feasibility of dried blood spots for HIV viral load monitoring in decentralized area in North Vietnam in a test-and-treat era, the MOVIDA project.

BACKGROUND: Access to HIV viral load is crucial to efficiently monitor patients on antiretroviral treatment (ART) and prevent HIV drug resistance acquisition. However, in some remote settings, access to viral load monitoring is still complex due to logistical and financial constraints. Use of dried blood spots (DBS) for blood collection could overcome these difficulties. This study aims to describe feasibility and operability of DBS use for routine viral load monitoring. METHODS: From June 2017 to April 2018, HIV-infected adults who initiated ART were enrolled in a prospective cohort in 43 clinical sites across 6 provinces in North Vietnam. Following national guidelines, the first viral load monitoring was planned 6 months after ART initiation. DBS were collected at the clinical site and sent by post to a central laboratory in Hanoi for viral load measurement. RESULTS: Of the 578 patients enrolled, 537 were still followed 6 months after ART initiation, of which DBS was collected for 397 (73.9%). The median (inter quartile range) delay between DBS collection at site level and reception at the central laboratory was 8 (6-19) days and for 70.0% viral load was measured ≤30 days after blood collection. The proportion of patients with viral load ≥1000 copies/mL at the 6 month evaluation was 15.9% (n = 59). Of these, a DBS was collected again to confirm virological failure in 15 (24.4%) of which virological failure was confirmed in 11 (73.3%). CONCLUSION: Delay of DBS transfer to the central laboratory was acceptable and most viral loads were measured in ≤30 days, in-line with routine follow-up. However, the level of DBS coverage and the proportion of patients in failure for whom a confirmatory viral load was available were suboptimal, indicating that integration of viral load monitoring in the field requires, among other things, careful training and strong involvement of the local teams. The proportion of patients experiencing virological failure was in line with other reports; interestingly those who reported being non-adherent and those with a low BMI were more at risk of failure.

The emergence of plasmid-borne cfr-mediated linezolid resistant-staphylococci in Vietnam.

OBJECTIVES: Linezolid is one of the last resort antibiotics effectively used in the treatment of infections caused by multidrug-resistant Gram-positive bacteria. Recent outbreaks of Linezolid resistance have been the great concern worldwide, while many countries have not experienced it. In this work, we aimed to evaluate the existence of linezolid resistance and further clarify potential resistance mechanism(s) in staphylococcal isolates obtained from the hospital in Vietnam, a country in which linezolid resistance had not been previously detected. METHODS: Seventy staphylococcal clinical isolates including MRSA (n=63) and methicillin-resistant coagulase-negative staphylococci (MRCNS, n=7) were collected and analyzed for linezolid resistance. Linezolid-resistant isolates were submitted for whole genome sequencing to search for the resistance determinants. RESULTS: We identified two coagulase-negative staphylococcal isolates that were resistant to linezolid. Whole genome sequencing revealed several alterations in the 23S rRNA and L3, L17, L22, L24, L30 ribosomal proteins. Importantly, both isolates harbour the chloramphenicol/florfenicol resistance (cfr) gene on a plasmid. The plasmid was closely identical to the pLRSA417 plasmid that was originally reported in China. CONCLUSIONS: To the best of our knowledge, this is the first report of cfr-mediated linezolid resistance in clinically isolated staphylococci in Vietnam. We suggest that adequate surveillance is necessary to monitor the dissemination of linezolid resistance among staphylococcal species and other important pathogens.

Structure and Catalytic Characterization of a Second Framework Al(IV) Site in Zeolite Catalysts Revealed by NMR at 35.2 T.

Ultrahigh field 27Al{1H} 2D correlation NMR experiments demonstrate that at least two framework Al(IV) sites with hydroxyl groups can exist in acidic zeolite catalysts in their dehydrated and catalytically active states. In addition to the known Al(IV) at the framework bridging acid site (BAS), a new site created by a second tetrahedral Al atom and its hydroxyl group protons in zeolite HZSM-5 is clearly resolved at 35.2 T field strengths, enabled by recently developed series-connected hybrid (SCH) magnet technology. Coupled with computational modeling, extensive 27Al MQMAS experiments at multiple field strengths, and 1H MAS NMR experiments, these data indicate that this second tetrahedrally coordinated Al site (denoted Al(IV)-2) experiences an increased chemical shift and unique quadrupolar parameters relative to the BAS in both dehydrated and hydrated states. These new experimental data, supported by computational and catalytic reaction work, indicate that the second site arises from partially bonded framework (SiO)4-n-Al(OH)n species that significantly increase catalyst reactivity in benzene hydride-transfer and n-hexane cracking reactions. Al(IV)-2 sites result either from framework crystallization defects or from incomplete postsynthetic hydrolysis of a framework Al, prior to the formation of extraframework Al. Populations of this second acidic proton site created by the Al(IV)-2 species are shown to be controlled via postsynthetic catalyst treatments, should be general to different catalyst structures, and significantly enhance catalyst reactivity in the cited probe reactions when they are present. The results herein communicate the highest magnetic field strength data on active zeolite catalyst structures to date and enable for the first time the detection of Al and H association on a dry HZSM-5 catalyst, i.e., under conditions representative of typical end-use processes.