Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

BACKGROUND: Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). METHODS: Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. RESULTS: Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. CONCLUSIONS: PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

Effect of pneumococcal conjugate vaccines on viral respiratory infections: a systematic literature review.

BACKGROUND: In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTI) by affecting pneumococcal-viral interactions. METHODS: We performed a systematic review of interventional and observational studies published during 2000-2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTI. RESULTS: Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41-86% (n=4), except for the 2010-2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n=3). PCV13 VE ranged between 4-25% against viral lower RTI, 32-35% against COVID-19 outcomes, 24-51% against human seasonal coronavirus, and 13-36% against influenza A lower RTI, with some 95%CI spanning zero. No protection was found against adenovirus or rhinovirus in children or adults. CONCLUSIONS: PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs.

Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice.

Apolipoprotein E ε4 allele (APOE4) is the predominant genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 mouse models have provided advances in the understanding of disease pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects like food and bedding can be major sources of changes in rodent microflora. Alterations in intestinal microbial ecology can cause mucosal barrier impairment and increase pro-inflammatory signals. The present study examined the role of sterile and non-sterile food and housing on redox indicators and the immune status of humanized-APOE4 knock-in mice (hAPOe4). hAPOE4 mice were housed under sterile conditions until 22 months of age, followed by the transfer of a cohort of mice to non-sterile housing for 2 months. At 24 months of age, the redox/immunologic status was evaluated by flow cytometry/ELISA. hAPOE4 females housed under non-sterile conditions exhibited: (1) higher neuronal and microglial oxygen radical production and (2) lower CD68+ microglia (brain) and CD8+ T cells (periphery) compared to sterile-housed mice. In contrast, hAPOE4 males in non-sterile housing exhibited: (1) higher MHCII+ microglia and CD11b+CD4+ T cells (brain) and (2) higher CD11b+CD4+ T cells and levels of lipopolysaccharide-binding protein and inflammatory cytokines in the periphery relative to sterile-housed mice. This study demonstrated that sterile vs. non-sterile housing conditions are associated with the activation of redox and immune responses in the brain and periphery in a sex-dependent manner. Therefore, housing status may contribute to variable outcomes in both the brain and periphery.

Improved Radiosynthesis and Automation of [11C]2-(2,6-Difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2) for Positron Emission Tomography of the Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptor.

A new automated radiosynthesis of [11C]2-(2,6-difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2), a radiopharmaceutical for the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of [11C]K2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)-compliant synthesis of [11C]K2 using a commercial synthesis module. The new synthesis is fully automated and has been validated for clinical use. The total synthesis time is 33 min from end of bombardment, and the production method provides 2.66 ± 0.3 GBq (71.9 ± 8.6 mCi) of [11C]K2 in 97.7 ± 0.5% radiochemical purity and 754.1 ± 231.5 TBq/mmol (20,382.7 ± 6256.1 Ci/mmol) molar activity (n = 3). Batches passed all requisite quality control testing confirming suitability for clinical use.

Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study.

BACKGROUND: Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. METHODS: We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls. RESULTS: Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%-30.9%) against virus-associated pneumonia and 21.5% (10.9%-30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%-33.1%) and 18.6% (9.3%-27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses. CONCLUSIONS: Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Underascertainment of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing Limitations: A Systematic Literature Review and Meta-analysis.

BACKGROUND: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection. METHODS: EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types. RESULTS: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable. CONCLUSIONS: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.

Respiratory syncytial virus (RSV) is an important cause of illness and death among older adults. Most studies of how frequent RSV infection is among older adults use only nasal swab testing to identify RSV infection. These nasal swabs are checked for genetic material from the virus, known as polymerase chain reaction (PCR) testing. We examined published studies from January 2000 to December 2021 to estimate how many RSV infections would be missed by using only this approach to RSV testing. We found 154 studies had information to answer our question. Compared to PCR testing of nasal swab alone, adding sputum specimen PCR testing (ie, testing cough mucus or phlegm for RSV genetic material) increased RSV infections found by 52%. Adding blood testing increased RSV infections found by 44%. Adding mouth/throat swab PCR testing, increased RSV infections by 28%. In summary, adding additional specimen types to nasal swab PCR testing increased RSV detection. Impact of using 3 or more specimen types at the same time should be assessed, as this approach may further improve accuracy.

Host antibacterial defense of 6-10 Gy γ-irradiated mice subjected to lentiviral vector-based Gas5 gene therapy.

Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, all mice exposed to 8 Gy of whole body γ-irradiation (8 Gy GIARS-mice) died by sepsis stemming from bacterial translocation. M1Mϕ located in the bacterial translocation site (i.e., the mesenteric lymph nodes, MLNs) have been characterized as major antibacterial effector cells. However, M2bMϕ, inhibitor cells for M1Mϕ polarization, predominated in the MLNs of these mice. The reduced expression of long noncoding RNA Gas5 was associated with M2bMϕ polarization. In this study, we tried to reduce the mortality rate of 8 Gy GIARS-mice through Gas5 gene transduction using lentivirus (Gas5 lentivirus). After Gas5 lentivirus injection, Gas5 RNA was overexpressed in MLN-F4/80+ cells of 8 Gy GIARS-mice, and these cells were identified as non-M2bMϕ. All of the 8 Gy GIARS-mice injected with Gas5 lentivirus survived 30 days or more after irradiation, and bacterial translocation and subsequent sepsis were shown to be minimal in these mice. These results indicate that the antibacterial resistance of 8 Gy GIASR-mice can be restored through the modulation of M2bMϕ located in the bacterial translocation site by Gas5 transduction.

Distribution of Serotypes Causing Invasive Pneumococcal Disease in Children From High-Income Countries and the Impact of Pediatric Pneumococcal Vaccination.

BACKGROUND: The introduction and adoption of pneumococcal conjugate vaccines (PCVs) into pediatric national immunization programs (NIPs) has led to large decreases in invasive pneumococcal disease (IPD) incidence caused by vaccine serotypes. Despite these reductions, the global IPD burden in children remains significant. METHODS: We collected serotype-specific IPD data from surveillance systems or hospital networks of all 30 high-income countries that met inclusion criteria. Data sources included online databases, surveillance system reports, and peer-reviewed literature. Percentage of serotyped cases covered were calculated for all countries combined and by PCV type in the pediatric NIP. RESULTS: We identified 8012 serotyped IPD cases in children <5 or ≤5 years old. PCV13 serotype IPD caused 37.4% of total IPD cases, including 57.1% and 25.2% for countries with PCV10 or PCV13 in the pediatric NIP, respectively, most commonly due to serotypes 3 and 19A (11.4% and 13.3%, respectively, across all countries). In PCV10 countries, PCV15 and PCV20 would cover an additional 45.1% and 55.6% of IPD beyond serotypes contained in PCV10, largely due to coverage of serotype 19A. In PCV13 countries, PCV15 and PCV20 would cover an additional 10.6% and 38.2% of IPD beyond serotypes contained in PCV13. The most common IPD serotypes covered by higher valency PCVs were 10A (5.2%), 12F (5.1%), and 22F and 33F (3.5% each). CONCLUSIONS: Much of the remaining IPD burden is due to serotypes included in PCV15 and PCV20. The inclusion of these next generation PCVs into existing pediatric NIPs may further reduce the incidence of childhood IPD.

Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States.

BACKGROUND: Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. METHODS: We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. RESULTS: Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. CONCLUSIONS: Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.

Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Human Infection Challenge with Serotype 3 Pneumococcus.

Rationale: Streptococcus pneumoniae serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programs, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. Objectives: To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. Methods: In a human challenge study involving three well-characterized and antibiotic-sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade], and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, and 160,000 cfu/100 µl) were escalated until maximal colonization rates were achieved, with concurrent acceptable safety. Measurement and Main Results: Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples, assessed using microbiological culture and molecular methods, on Days 2, 7, and 14 postinoculation. A total of 96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n = 6-10 per dose group, 10 groups). Colonization rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% [24/29] developed a sore throat); one developed otitis media requiring antibiotics. No serious adverse events occurred. Conclusions: An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established Serotype 6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.

Automated production of 11 C-labeled carboxylic acids and esters via "in-loop" 11 C-carbonylation using GE FX synthesis modules.

An in-loop 11 C-carbonylation process for the radiosynthesis of 11 C-carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room temperature under mild conditions and enables 11 C-carbonylation of both electron deficient and electron rich (hetero)aromatic halides to provide 11 C-carboxylic acids and esters in good to excellent radiochemical yields, high radiochemical purity, and excellent molar activity. The process has been fully automated using commercial radiochemistry synthesis modules, and application to clinical production is demonstrated via validated cGMP radiosyntheses of [11 C]bexarotene and [11 C]acetoacetic acid.

Prevention of Coronavirus Disease 2019 Among Older Adults Receiving Pneumococcal Conjugate Vaccine Suggests Interactions Between Streptococcus pneumoniae and Severe Acute Respiratory Syndrome Coronavirus 2 in the Respiratory Tract.

BACKGROUND: While secondary pneumococcal pneumonia occurs less commonly after coronavirus disease 2019 (COVID-19) than after other viral infections, it remains unclear whether other interactions occur between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae. METHODS: We probed potential interactions between these pathogens among adults aged ≥65 years by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]). We estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models with doubly robust inverse-propensity weighting. We assessed effect modification by antibiotic exposure to further test the biologic plausibility of a causal role for pneumococci. RESULTS: Among 531 033 adults, there were 3677 COVID-19 diagnoses, leading to 1075 hospitalizations and 334 fatalities, between 1 March and 22 July 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval [CI], .59-.72), 0.68 (95% CI, .57-.83), and 0.68 (95% CI, .49-.95), respectively. Prior PPSV23 receipt was not associated with protection against the 3 outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (95% CI, .50-.84) and 0.62 (95% CI, .56-.70) during the risk periods 91-365 days and >365 days, respectively, following antibiotic receipt. CONCLUSIONS: Reduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests that pneumococci may interact with SARS-CoV-2.

Vaccine-Preventable Disease Incidence Based on Clinically, Radiologically, and Etiologically Confirmed Outcomes: Systematic Literature Review and Re-analysis of Pneumococcal Conjugate Vaccine Efficacy Trials.

BACKGROUND: Vaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes with radiologically/etiologically confirmed outcomes. METHODS: We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator). RESULTS: Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 (95% CI not calculable), 2.1 (1.5-3.0), and 3.7 (1.0-10.2); the VPDI ratios comparing clinically defined with radiologically confirmed pneumonia ranged from not calculable to 2.7 (1.2-10.4); the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) with laboratory-confirmed IPD was 3.8 (95% CI not calculable). Among adults, the ratio comparing clinically defined with radiologically confirmed pneumonia was 1.9 (-6.0 to 9.1) and with vaccine serotype-confirmed pneumonia was 2.9 (.5-7.8). CONCLUSIONS: While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine's public health value.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Medically Attended Lower Respiratory Tract Infection and Pneumonia Among Older Adults.

BACKGROUND: Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. METHODS: We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. RESULTS: Among 42 700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, -.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. CONCLUSIONS: PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.

Systematic Review and Meta-analysis of Lyme Disease Data and Seropositivity for Borrelia burgdorferi, China, 2005‒2020.

Since its initial identification in 1986, Lyme disease has been clinically diagnosed in 29 provinces in China; however, national incidence data are lacking. To summarize Lyme disease seropositivity data among persons across China, we conducted a systematic literature review of Chinese- and English-language journal articles published during 2005‒2020. According to 72 estimates that measured IgG by using a diagnostic enzyme-linked assay (EIA) alone, the seropositivity point prevalence with a fixed-effects model was 9.1%. A more conservative 2-tier testing approach of EIA plus a confirmatory Western immunoblot (16 estimates) yielded seropositivity 1.8%. Seropositivity by EIA for high-risk exposure populations was 10.0% and for low-risk exposure populations was 4.5%; seropositivity was highest in the northeastern and western provinces. Our analysis confirms Lyme disease prevalence, measured by seropositivity, in many Chinese provinces and populations at risk. This information can be used to focus prevention measures in provinces where seropositivity is high.

SWIFT: A deep learning approach to prediction of hypoxemic events in critically-Ill patients using SpO2 waveform prediction.

Hypoxemia is a significant driver of mortality and poor clinical outcomes in conditions such as brain injury and cardiac arrest in critically ill patients, including COVID-19 patients. Given the host of negative clinical outcomes attributed to hypoxemia, identifying patients likely to experience hypoxemia would offer valuable opportunities for early and thus more effective intervention. We present SWIFT (SpO2 Waveform ICU Forecasting Technique), a deep learning model that predicts blood oxygen saturation (SpO2) waveforms 5 and 30 minutes in the future using only prior SpO2 values as inputs. When tested on novel data, SWIFT predicts more than 80% and 60% of hypoxemic events in critically ill and COVID-19 patients, respectively. SWIFT also predicts SpO2 waveforms with average MSE below .0007. SWIFT predicts both occurrence and magnitude of potential hypoxemic events 30 minutes in the future, allowing it to be used to inform clinical interventions, patient triaging, and optimal resource allocation. SWIFT may be used in clinical decision support systems to inform the management of critically ill patients during the COVID-19 pandemic and beyond.

A novel approach to estimate the local population denominator to calculate disease incidence for hospital-based health events in England.

While incidence studies based on hospitalisation counts are commonly used for public health decision-making, no standard methodology to define hospitals' catchment population exists. We conducted a review of all published community-acquired pneumonia studies in England indexed in PubMed and assessed methods for determining denominators when calculating incidence in hospital-based surveillance studies. Denominators primarily were derived from census-based population estimates of local geographic boundaries and none attempted to determine denominators based on actual hospital access patterns in the community. We describe a new approach to accurately define population denominators based on historical patient healthcare utilisation data. This offers benefits over the more established methodologies which are dependent on assumptions regarding healthcare-seeking behaviour. Our new approach may be applicable to a wide range of health conditions and provides a framework to more accurately determine hospital catchment. This should increase the accuracy of disease incidence estimates based on hospitalised events, improving information available for public health decision making and service delivery planning.

Glycyrrhizin Protects γ-Irradiated Mice from Gut Bacteria-Associated Infectious Complications by Improving miR-222-Associated Gas5 RNA Reduction in Macrophages of the Bacterial Translocation Site.

Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, gut bacteria-associated sepsis caused high mortality rates in mice exposed to 6-9 Gy of γ-rays. IL-12+CD38+ iNOS+ Mϕ (M1Mϕ) located in the bacterial translocation site (mesenteric lymph nodes [MLNs]) of unirradiated mice were characterized as host defense antibacterial effector cells. However, cells isolated from the MLNs of GIARS mice were mostly CCL1+IL-10+LIGHT+miR-27a+ Mϕ (M2bMϕ, inhibitor cells for the M1Mϕ polarization). Reduced long noncoding RNA Gas5 and increased miR-222 expression in MLN-Mϕ influenced by the irradiation were shown to be associated with M2bMϕ polarization. In this study, the mortality of mice exposed to 7 Gy of γ-rays (7 Gy GIARS mice) was completely controlled after the administration of glycyrrhizin (GL), a major active ingredient in licorice root (Glycyrrhiza glabra). Bacterial translocation and subsequent sepsis were minimal in 7 Gy GIARS mice treated with GL. Increased Gas5 RNA level and decreased miR-222 expression were shown in MLN-Mϕ isolated from 7 Gy GIARS mice treated with GL, and these macrophages did not display any properties of M2bMϕ. These results indicate that gut bacteria-associated sepsis in 7 Gy GIARS mice was controlled by the GL through the inhibition of M2bMϕ polarization at the bacteria translocation site. Expression of Ccl1, a gene required for M2bMϕ survival, is silenced in the MLNs of 7 Gy GIARS mice because of Gas5 RNA, which is increased in these cells after the suppression of miR-222 (a Gas5 RNA expression inhibitor) by the GL.

Reducing the stigma surrounding opioid use disorder: evaluating an opioid overdose prevention training program applied to a diverse population.

BACKGROUND: The opioid epidemic is a rapidly growing public health concern in the USA, as the number of overdose deaths continues to increase each year. One strategy for combating the rising number of overdoses is through opioid overdose prevention programs (OOPPs). OBJECTIVE: To evaluate the effectiveness of an innovative OOPP, with changes in knowledge and attitudes serving as the primary outcome measures. METHODS: The OOPP was developed by a group of medical students under guidance from faculty advisors. Training sessions focused on understanding stigmatizing factors of opioid use disorder (OUD), as well as protocols for opioid overdose reversal through naloxone administration. Pre- and post-surveys were partially adapted from the opioid overdose attitudes and knowledge scales and administered to all participants. Paired t-tests were conducted to assess differences between pre- and post-surveys. RESULTS: A total of 440 individuals participated in the training; 381 completed all or the majority of the survey. Participants came from a diverse set of backgrounds, ages, and experiences. All three knowledge questions showed significant improvements. For attitude questions, significant improvements were found in all three questions evaluating confidence, two of three questions assessing attitudes towards overdose reversal, and four of five questions evaluating stigma and attitudes towards individuals with OUD. CONCLUSIONS: Our innovative OOPP was effective not only in increasing knowledge but also in improving attitudes towards overdose reversal and reducing stigma towards individuals with OUD. Given the strong improvements in attitudes towards those with OUD, efforts should be made to incorporate the unique focus on biopsychosocial and sociohistorical components into future OOPPs.