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Background Incidence estimates of Staphylococcus aureus infections rarely include the full spectrum of clinically relevant disease from both community and healthcare settings. Methods We conducted a prospective study capturing all S aureus infections in Fulton County, Georgia, during 2017. Medical records of patients with any incident infection (clinical cultures growing S aureus from any site, without prior positive culture in previous 14 days) were reviewed. Estimates of disease incidence were calculated using age-, race-, and sex-specific population denominators accounting for weighted sampling methods. Multivariable logistic regression models were used to identify risk factors for hospitalization among patients with skin and soft tissue infections (SSTIs). Results The overall incidence of clinically relevant S aureus infection was 405.7 cases per 100 000 people (standard error [SE], 5.62 [range, 400.1–411.3]). Overall incidence for those of Black race was 500.84 cases per 100 000 people (SE, 14.55), whereas White patients had overall incidence of 363.67 cases per 100 000 people (SE, 13.8). SSTIs were the most common infection (2351; 225.8 cases per 100 000 people [SE, 7.1]), and 30% required hospitalization. Among SSTIs, after adjusting for invasive disease, cellulitis, diabetes, and demographics, independent predictors of hospitalization included methicillin-resistant S aureus (adjusted odds ratio [aOR], 1.6 [95% confidence interval {CI}, 1.0–2.7]) and homelessness (aOR, 4.9 [95% CI, 1.1–22]). Conclusions The burden of clinically relevant S aureus infections is high, particularly among the Black population, and risks for hospitalization among SSTIs include isolate factors and factors related to patients' vulnerability. [ABSTRACT FROM AUTHOR]

Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is essential for diagnosis, treatment, and infection control. Polymerase chain reaction (PCR) fails to distinguish acute from resolved infections, as RNA is frequently detected after infectiousness. We hypothesized that nucleocapsid in blood marks acute infection with the potential to enhance isolation and treatment strategies. In a retrospective serosurvey of inpatient and outpatient encounters, we categorized samples along an infection timeline using timing of SARS-CoV-2 testing and symptomatology. Among 1860 specimens from 1607 patients, the highest levels and frequency of antigenemia were observed in samples from acute SARS-CoV-2 infection. Antigenemia was higher in seronegative individuals and in those with severe disease. In our analysis, antigenemia exhibited 85.8% sensitivity and 98.6% specificity as a biomarker for acute coronavirus disease 2019 (COVID-19). Thus, antigenemia sensitively and specifically marks acute SARS-CoV-2 infection. Further study is warranted to determine whether antigenemia may aid individualized assessment of active COVID-19. [ABSTRACT FROM AUTHOR]

Immunocompromised patients with prolonged coronavirus disease 2019 symptoms present diagnostic and therapeutic challenges. We measured viral nucleocapsid antigenemia in 3 patients treated with anti-CD20 immunotherapy who acquired severe acute respiratory syndrome coronavirus 2 infection and experienced protracted symptoms. Our results support nucleocapsid antigenemia as a marker of persistent infection and therapeutic response. [ABSTRACT FROM AUTHOR]

Background Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system. Methods During 2017–2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases. Results Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n = 66 [63.5%]), mucormycosis (n = 8 [7.7%]), and fusariosis (n = 4 [3.8%]); the most frequently affected body sites were pulmonary (n = 66 [63.5%]), otorhinolaryngologic (n = 17 [16.3%]), and cutaneous/deep tissue (n = 9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit–level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients. Conclusions IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases. [ABSTRACT FROM AUTHOR]

Background Pneumocystis jirovecii polymerase chain reaction (PCR) testing is a sensitive diagnostic tool but does not distinguish infection from colonization. Cycle threshold (CT) may correlate with fungal burden and could be considered in clinical decision making. Clinical use of PCR and significance of CT values have not previously been examined with the DiaSorin Molecular platform. Methods Retrospective review of P jirovecii PCR, CT values and clinical data from 18 months in a multihospital academic health system. The diagnostic performance of PCR with respect to pathology and correlation of CT with severity were examined. Results Ninety-nine of 1006 (9.8%) assays from 786 patients in 919 encounters were positive. Among 91 (9.9%) encounters in which P jirovecii pneumonia (PJP) was treated, 41 (45%) were influenced by positive PCR. Negative PCR influenced discontinuation of therapy in 35 cases. Sensitivity and specificity of PCR were 93% (95% CI, 68%–100%) and 94% (95% CI, 91%–96%) with respect to pathology. CT values from deep respiratory specimens were significantly different among treated patients (P  = .04) and those with positive pathology results (P <.0001) compared to patients not treated and those with negative pathology, respectively, and was highly predictive of positive pathology results (area under the curve = 0.92). No significant difference was observed in comparisons based on indicators of disease severity. Conclusions Pneumocystis jirovecii PCR was a highly impactful tool in the diagnosis and management of PJP, and use of CT values may have value in the treatment decision process in select cases. Further investigation in a prospective manner is needed. [ABSTRACT FROM AUTHOR]

Background Variation in the complement factor H gene (CFH) is associated with risk of late age-related macular degeneration (AMD). Previous studies have been case–control studies in populations of European ancestry with little differentiation in AMD subtype, and insufficient power to confirm or refute effect modification by smoking.Methods To precisely quantify the association of the single nucleotide polymorphism (SNP rs1061170, ‘Y402H’) with risk of AMD among studies with differing study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n = 2759) combined with data from 24 published studies (26 studies, 26 494 individuals, including 14 174 cases of AMD) of European ancestry, 10 of which provided individual-level data used to test gene–smoking interaction; and 16 published studies from non-European ancestry.Results In individuals of European ancestry, there was a significant association between Y402H and late-AMD with a per-allele odds ratio (OR) of 2.27 [95% confidence interval (CI) 2.10–2.45; P = 1.1 x 10−161]. There was no evidence of effect modification by smoking (P = 0.75). The frequency of Y402H varied by ancestral origin and the association with AMD in non-Europeans was less clear, limited by paucity of studies.Conclusion The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic association. [ABSTRACT FROM PUBLISHER]

Background. Previous studies have focused on the treatment received by rural cancer patients and have not examined their diagnostic pathways as reasons for poorer outcomes in rural Australia. Objectives. To compare and explore diagnostic pathways and diagnostic intervals in patients with breast, lung, prostate or colorectal cancer from rural Western Australia (WA) to inform future interventions aimed at reducing time to cancer diagnosis. Methods. Mixed methods study of people recently diagnosed with breast, lung, prostate or colorectal cancer from the Goldfields and Great Southern Regions of WA. Qualitative interviews explored participants’ diagnostic pathways and factors underlying differences observed between individuals and cancers. Data were extracted from general practice and hospital records to calculate intervals from first presentation in general practice to final diagnosis. Results. Sixty-six participants were recruited (43 Goldfields and 23 Great Southern region; 24 breast, 20 colorectal, 14 prostate and 8 lung cancers). There were significant overall differences between cancers in time from presentation in general practice to referral (P = 0.045), from referral to seeing a specialist (P = 0.010) and from specialist appointment to cancer diagnosis (P ≤ 0.001). These differences were due to the nature of presenting symptoms, access to diagnostic tests and multiple visits to specialists. Breast cancer was diagnosed more quickly because its symptoms are more specific and due to better access to diagnostic tests and specialist one-stop clinics. Conclusions. Interventions to improve cancer diagnosis in rural Australia should focus on better case selection in general practice and better access to diagnostic tests, especially for prostate and colorectal cancers. [ABSTRACT FROM AUTHOR]

Background. Previous studies have focused on the treatment received by rural cancer patients and have not examined their diagnostic pathways as reasons for poorer outcomes in rural Australia. Objectives. To compare and explore symptom appraisal and help-seeking behaviour in patients with breast, lung, prostate or colorectal cancer from rural Western Australia (WA). Methods. A mixed-methods study of people recently diagnosed with breast, lung, prostate or colorectal cancer from rural WA. The time from first symptom to diagnosis (i.e. total diagnostic interval, TDI) was calculated from interviews and medical records. Results. Sixty-six participants were recruited (24 breast, 20 colorectal, 14 prostate and 8 lung cancer patients). There was a highly significant difference in time from symptom onset to seeking help between cancers (P = 0.006). Geometric mean symptom appraisal for colorectal cancer was significantly longer than that for breast and lung cancers [geometric mean differences: 2.58 (95% confidence interval, CI: 0.64–4.53), P = 0.01; 3.97 (1.63–6.30), P = 0.001, respectively]. There was a significant overall difference in arithmetic mean TDI (P = 0.046); breast cancer TDI was significantly shorter than colorectal or prostate cancer TDI [mean difference : 266.3 days (95% CI: 45.9–486.8), P = 0.019; 277.0 days, (32.1–521.9), P = 0.027, respectively]. These differences were explained by the nature and personal interpretation of symptoms, perceived as well as real problems of access to health care, optimism, stoicism, machismo, fear, embarrassment and competing demands. Conclusions. Longer symptom appraisal was observed for colorectal cancer. Participants defined core characteristics of rural Australians as optimism, stoicism and machismo. These features, as well as access to health care, contribute to later presentation of cancer. [ABSTRACT FROM AUTHOR]