Browsing by Author "Turner, Nicholas A"
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Item Open Access A Cluster of Nontuberculous Mycobacterial Tenosynovitis Following Hurricane Relief Efforts.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-06) Turner, Nicholas A; Sweeney, Mollie I; Xet-Mull, Ana M; Storm, Jeremy; Mithani, Suhail K; Jones, David B; Miles, Jeremy J; Tobin, David M; Stout, Jason EBackground
Nontuberculous mycobacteria (NTM) are a rare cause of infectious tenosynovitis of the upper extremity. Using molecular methods, clinical microbiology laboratories are increasingly reporting identification down to the species level. Improved methods for speciation are revealing new insights into the clinical and epidemiologic features of rare NTM infections.Methods
We encountered 3 cases of epidemiologically linked upper extremity NTM tenosynovitis associated with exposure to hurricane-damaged wood. We conducted whole-genome sequencing to assess isolate relatedness followed by a literature review of NTM infections that involved the upper extremity.Results
Despite shared epidemiologic risk, the cases were caused by 3 distinct organisms. Two cases were rare infections caused by closely related but distinct species within the Mycobacterium terrae complex that could not be differentiated by traditional methods. The third case was caused by Mycobacterium intracellulare. An updated literature review that focused on research that used modern molecular speciation methods found that several species within the M. terrae complex are increasingly reported as a cause of upper extremity tenosynovitis, often in association with environmental exposures.Conclusions
These cases illustrate the importance of molecular methods for speciating phenotypically similar NTM, as well as the limitations of laboratory-based surveillance in detecting point-source outbreaks when the source is environmental and may involve multiple organisms.Item Open Access Addressing the Menace of Enterococcal Endocarditis.(Journal of the American College of Cardiology, 2020-02) Bashore, Thomas M; Turner, Nicholas AItem Open Access Age-related changes in the nasopharyngeal microbiome are associated with SARS-CoV-2 infection and symptoms among children, adolescents, and young adults.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022-03-05) Hurst, Jillian H; McCumber, Alexander W; Aquino, Jhoanna N; Rodriguez, Javier; Heston, Sarah M; Lugo, Debra J; Rotta, Alexandre T; Turner, Nicholas A; Pfeiffer, Trevor S; Gurley, Thaddeus C; Moody, M Anthony; Denny, Thomas N; Rawls, John F; Clark, James S; Woods, Christopher W; Kelly, Matthew SBackground
Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity.Methods
We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (<21 years of age) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms.Results
Nasopharyngeal microbiome composition varied with age (PERMANOVA, p<0.001, R 2=0.06) and between SARS-CoV-2-infected individuals with and without respiratory symptoms (PERMANOVA, p=0.002, R 2=0.009). SARS-CoV-2-infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (odds ratio: 0.38, 95% confidence interval: 0.18-0.81). Using generalized joint attributed modeling, we identified nine bacterial taxa associated with SARS-CoV-2 infection and six taxa that were differentially abundant among SARS-CoV-2-infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age.Conclusions
We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.Item Open Access Age-related changes in the upper respiratory microbiome are associated with SARS-CoV-2 susceptibility and illness severity.(medRxiv, 2021-03-23) Hurst, Jillian H; McCumber, Alexander W; Aquino, Jhoanna N; Rodriguez, Javier; Heston, Sarah M; Lugo, Debra J; Rotta, Alexandre T; Turner, Nicholas A; Pfeiffer, Trevor S; Gurley, Thaddeus C; Moody, M Anthony; Denny, Thomas N; Rawls, John F; Woods, Christopher W; Kelly, Matthew SChildren are less susceptible to SARS-CoV-2 and typically have milder illness courses than adults. We studied the nasopharyngeal microbiomes of 274 children, adolescents, and young adults with SARS-CoV-2 exposure using 16S rRNA gene sequencing. We find that higher abundances of Corynebacterium species are associated with SARS-CoV-2 infection and SARS-CoV-2-associated respiratory symptoms, while higher abundances of Dolosigranulum pigrum are present in SARS-CoV-2-infected individuals without respiratory symptoms. We also demonstrate that the abundances of these bacteria are strongly, and independently, associated with age, suggesting that the nasopharyngeal microbiome may be a potentially modifiable mechanism by which age influences SARS-CoV-2 susceptibility and severity. SUMMARY: Evaluation of nasopharyngeal microbiome profiles in children, adolescents, and young adults with a SARS-CoV-2-infected close contact identified specific bacterial species that vary in abundance with age and are associated with SARS-CoV-2 susceptibility and the presence of SARS-CoV-2-associated respiratory symptoms.Item Open Access Antiplatelet Therapy in Staphylococcus aureus Bacteremia: No Time Like the Past?(Antimicrobial agents and chemotherapy, 2022-06) Mourad, Ahmad; Holland, Thomas L; Turner, Nicholas AIn this invited commentary, we reflect on the accompanying study by A. R. Caffrey, H. J. Appaneal, K. L. LaPlante, V. V. Lopes, et al. (Antimicrob Agents Chemother 66:e02117-21, 2022, https://doi.org/10.1128/aac.02117-21), which analyzed the impact of clopidogrel use on clinical outcomes in Staphylococcus aureus bacteremia.Item Open Access Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.(Nature communications, 2021-05-14) Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; Arabi, Yaseen M; Azhar, Shehnoor; Baden, Lindsey R; Baker, Arthur W; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marvin AH; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z; Cowan, Lisa N; Dalgard, Olav; de Almeida E Val, Fernando F; de Lacerda, Marcus VG; de Melo, Gisely C; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony C; Hernandez-Cardenas, Carmen M; Hills, Thomas; Hoepelman, Andy IM; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S; Kremsner, Peter G; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J; Meza-Meneses, Patricia; Monteiro, Wuelton M; Morpeth, Susan C; Mourad, Ahmad; Mulligan, Mark J; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A; O'Brien, Sean M; Okeke, Nwora Lance; Perez, Léna; Perez-Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E; Rockhold, Frank W; Rodriguez-Llamazares, Sebastian; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson S; Seto, Todd B; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E; Thirion-Romero, Ireri; Troxel, Andrea B; Tseng, Ting-Yu; Turner, Nicholas A; Ulrich, Robert J; Walsh, Stephen R; Webb, Steve A; Weehuizen, Jesper M; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando G; Zhong, Wu; Moher, David; Goodman, Steven N; Ioannidis, John PA; Hemkens, Lars GThe original version of this Article contained an error in the spelling of the author Muhammad Shahzad, which was incorrectly given as Muhammad Shehzad. This has now been corrected in both the PDF and HTML versions of the Article.Item Open Access Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.(Nature communications, 2024-02) Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; Arabi, Yaseen M; Azhar, Shehnoor; Baden, Lindsey R; Baker, Arthur W; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marvin AH; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z; Cowan, Lisa N; Dalgard, Olav; de Almeida E Val, Fernando F; de Lacerda, Marcus VG; de Melo, Gisely C; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony C; Hernandez-Cardenas, Carmen M; Hills, Thomas; Hoepelman, Andy IM; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S; Kremsner, Peter G; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J; Meza-Meneses, Patricia; Monteiro, Wuelton M; Morpeth, Susan C; Mourad, Ahmad; Mulligan, Mark J; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A; O'Brien, Sean M; Okeke, Nwora Lance; Perez, Léna; Perez-Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E; Rockhold, Frank W; Rodriguez-Llamazares, Sebastian; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson S; Seto, Todd B; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E; Thirion-Romero, Ireri; Troxel, Andrea B; Tseng, Ting-Yu; Turner, Nicholas A; Ulrich, Robert J; Walsh, Stephen R; Webb, Steve A; Weehuizen, Jesper M; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando G; Zhong, Wu; Moher, David; Goodman, Steven N; Ioannidis, John PA; Hemkens, Lars GCorrection to: Nature Communicationshttps://doi.org/10.1038/s41467-021-22446-z, published online 15 April 2021 The original version of this article contained an error in Table 1, which misidentified the trial included in the meta-analysis registered as NCT04323527 as CloroCOVID19II instead of CloroCOVID19III. The NCT04323527 registration includes the trials CloroCOVID19I and CloroCOVID19III. CloroCOVID19I was not included in the meta-analysis. In addition, the original version of the Methods section inadvertently omitted details of which formulations of hydroxychloroquine or chloroquine the reported dosages refer to. The following information has been included in the legend for Table 1 and in the corrected methods section: “In all trials that used hydroxychloroquine, dosages refer to hydroxychloroquine sulfate. In trials that used chloroquine, the dosages for ARCHAIC, ChiCTR2000030054 and ChiCTR2000031204 refer to chloroquine phosphate, while those for CloroCOVID19II and CloroCOVID19III refer to chloroquine base. The American Journal of Tropical Medicine and Hygiene has issued a retraction note (1) for one of the trials (2) that had been included in the calculations of our meta-analysis. Exclusion of the data from this trial changes neither the results nor inferences of the meta-analysis. For hydroxychloroquine, the original odds ratio for mortality was 1.11 (95% CI: 1.02–1.20; I2 = 0%; 26 trials; 10,012 patients) and excluding the retracted trial the odds ratio for mortality would remain 1.11 (95% CI: 1.02–1.20, I2 = 0%; 25 trials; 9818 patients). Retraction Notice. The American Journal of Tropical Medicine and Hygiene 107, 728-728, https://doi.org/10.4269/ajtmh.1073ret (2022). Abd-Elsalam, S. et al. RETRACTED: Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study. Am J Trop Med Hyg 103, 1635-1639, https://doi.org/10.4269/ajtmh.20-0873 (2020). The errors in Table 1 and in the Methods section have been corrected in both the PDF and HTML versions of the Article.Item Open Access COVID-19 Trials: Who Participates and Who Benefits?(Southern medical journal, 2022-04) Narayanasamy, Shanti; Mourad, Ahmad; Turner, Nicholas A; Le, Thuy; Rolfe, Robert J; Okeke, Nwora Lance; O'Brien, Sean M; Baker, Arthur W; Wrenn, Rebekah; Rosa, Rossana; Rockhold, Frank W; Naggie, Susanna; Stout, Jason EObjectives
The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities.Methods
We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients.Results
Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution.Conclusions
The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.Item Unknown Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial.(Trials, 2022-05) Turner, Nicholas A; Zaharoff, Smitha; King, Heather; Evans, Scott; Hamasaki, Toshimitsu; Lodise, Thomas; Ghazaryan, Varduhi; Beresnev, Tatiana; Riccobene, Todd; Patel, Rinal; Doernberg, Sarah B; Rappo, Urania; Fowler, Vance G; Holland, Thomas L; Antibacterial Resistance Leadership Group (ARLG)Background
Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15-50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S. aureus bacteremia without the need for durable central venous access.Methods
DOTS is a phase 2b, multicenter, randomized, assessor-blinded, superiority, active-controlled, parallel-group trial. The trial will enroll 200 adults diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy for at least 72 h (maximum 10 days) and with subsequent clearance of bacteremia prior to randomization to study treatment. Subjects will be randomized 1:1 to complete their antibiotic treatment course with either two doses of dalbavancin on days 1 and 8, or with a total of 4-8 weeks of standard intravenous antibiotic therapy. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for patients randomized to dalbavancin versus standard of care. Key secondary endpoints include quality of life outcomes and pharmacokinetic analyses of dalbavancin.Discussion
The DOTS trial will establish whether dalbavancin is superior to standard parenteral antibiotic therapy for the completion of treatment of complicated S. aureus bacteremia.Trial registration
US National Institutes of Health ClinicalTrials.gov NCT04775953 . Registered on 1 March 2021.Item Unknown Determination of plasma protein binding of dalbavancin.(The Journal of antimicrobial chemotherapy, 2022-06) Turner, Nicholas A; Xu, Allan; Zaharoff, Smitha; Holland, Thomas L; Lodise, Thomas PObjectives
Dalbavancin is a lipoglycopeptide with a long half-life, making it a promising treatment for infections requiring prolonged therapy, such as complicated Staphylococcus aureus bacteraemia. Free drug concentration is a critical consideration with prolonged treatment, since free concentration-time profiles may best correlate with therapeutic effect. In support of future clinical trials, we aimed to develop a reliable and reproducible assay for measuring free dalbavancin concentrations.Methods
The ultracentrifugation technique was used to determine free dalbavancin concentrations in plasma at two concentrations (50 and 200 mg/L) in duplicate. Centrifuge tubes and pipette tips were treated for 24 h before use with Tween 80 to assess adsorption. Dalbavancin concentrations were analysed from the plasma samples (total) and middle layer samples (free) by LC/MS/MS with isotopically labelled internal standard. Warfarin served as a positive control with known high protein binding.Results
Measurement of free dalbavancin was sensitive to adsorption onto plastic. Treatment of tubes and pipette tips with ≥2% Tween 80 effectively prevented drug loss during protein binding experiments. By the ultracentrifugation method, dalbavancin's protein binding was estimated to be approximately 99%.Conclusions
Dalbavancin has very high protein binding. Given dalbavancin's high protein binding, accurate measurement of free dalbavancin concentrations should be a key consideration in future exposure-response studies, especially clinical trials. Future investigations should confirm if the active fraction is best predicted by the free or total fraction.Item Unknown Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial.(JAMA internal medicine, 2023-09) Copaescu, Ana Maria; Vogrin, Sara; James, Fiona; Chua, Kyra YL; Rose, Morgan T; De Luca, Joseph; Waldron, Jamie; Awad, Andrew; Godsell, Jack; Mitri, Elise; Lambros, Belinda; Douglas, Abby; Youcef Khoudja, Rabea; Isabwe, Ghislaine AC; Genest, Genevieve; Fein, Michael; Radojicic, Cristine; Collier, Ann; Lugar, Patricia; Stone, Cosby; Ben-Shoshan, Moshe; Turner, Nicholas A; Holmes, Natasha E; Phillips, Elizabeth J; Trubiano, Jason AImportance
Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling.Objective
To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy.Design, setting, and participants
This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies.Interventions
Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm).Main outcome and measure
The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp).Results
A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred.Conclusions and relevance
In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label.Trial registration
ClinicalTrials.gov Identifier: NCT04454229.Item Unknown Epidemiologic Trends in Clostridioides difficile Infections in a Regional Community Hospital Network(JAMA Network Open) Turner, Nicholas A; Grambow, Steven C; Woods, Christopher W; Fowler, Vance G; Moehring, Rebekah W; Anderson, Deverick J; Lewis, Sarah SItem Unknown Hospital Infection Control: Clostridioides difficile.(Clinics in colon and rectal surgery, 2020-03) Turner, Nicholas A; Anderson, Deverick JClostridioides difficile remains a leading cause of healthcare-associated infection. Efforts at C. difficile prevention have been hampered by an increasingly complex understanding of transmission patterns and a high degree of heterogeneity among existing studies. Effective prevention of C. difficile infection requires multimodal interventions, including contact precautions, hand hygiene with soap and water, effective environmental cleaning, use of sporicidal cleaning agents, and antimicrobial stewardship. Roles for probiotics, avoidance of proton pump inhibitors, and isolation of asymptomatic carriers remain poorly defined.Item Unknown Impact of the COVID-19 pandemic on adult mental health-related admissions at a large university health system in North Carolina - one year into the pandemic.(PloS one, 2023-01) Der, Tatyana; Helmke, Nicole; Stout, Jason E; Turner, Nicholas AObjective
Pandemic-associated stress may have exacerbated preexisting mental health and substance use disorders (MH/SUD) and caused new MH/SUD diagnoses which would be expected to lead to an increase in visits to emergency departments and hospital admissions for these conditions. This study assessed whether the proportion of hospital and emergency department encounters for MH/SUD diagnoses increased during the first year of the COVID-19 pandemic in the United States.Methods
We conducted a longitudinal (interrupted time series) analysis of 994,724 eligible encounters identified by electronic query between January 1, 2016 and March 31, 2021. Of these, 55,574 encounters involved MH/SUD diagnosis. The pre-pandemic period was defined as January 1, 2016 to March 31, 2020, and the pandemic period was defined as April 1, 2020 to March 31, 2021. All statistical analyses were performed with R.Results
No significant trend in MH/SUD encounters at baseline (rate ratio 1.00, 95% CI 0.99-1.01, p = 0.75) was observed. However, the onset of the pandemic was temporally associated with a significant level increase in the proportion of MH/SUD encounters relative to overall encounters (rate ratio 1.14, 95% CI 1.06-1.21, p<0.001) with no change in the overall trend (rate ratio 0.99, 95% CI 0.90-1.10, p = 0.89).Conclusions
The significant pandemic-associated increase in the proportion of MH/SUD encounters relative to overall encounters was driven largely by sustained numbers of MH/ SUD encounters despite a decrease in total encounters. Increased support for mental health care is needed for these vulnerable patients during pandemics.Item Unknown Influence of Reported Penicillin Allergy on Mortality in MSSA Bacteremia.(Open forum infectious diseases, 2018-03) Turner, Nicholas A; Moehring, Rebekah; Sarubbi, Christina; Wrenn, Rebekah H; Drew, Richard H; Cunningham, Coleen K; Fowler, Vance G; Anderson, Deverick JPenicillin allergy frequently impacts antibiotic choice. As beta-lactams are superior to vancomycin in treating methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, we examined the effect of reported penicillin allergy on clinical outcomes in patients with MSSA bacteremia.In this retrospective cohort study of adults with MSSA bacteremia admitted to a large tertiary care hospital, outcomes were examined according to reported penicillin allergy. Primary outcomes included 30-day and 90-day mortality rates. Multivariable regression models were developed to quantify the effect of reported penicillin allergy on mortality while adjusting for potential confounders.From 2010 to 2015, 318 patients with MSSA bacteremia were identified. Reported penicillin allergy had no significant effect on adjusted 30-day mortality (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.29-1.84; P = .51). Patients with reported penicillin allergy were more likely to receive vancomycin (38% vs 11%, P < .01), but a large number received cefazolin regardless of reported allergy (29 of 66, 44%). Mortality rates were highest among nonallergic patients receiving vancomycin (22.6% vs 7.4% for those receiving beta-lactams regardless of reported allergy, P < .01). In multivariable analysis, beta-lactam receipt was most strongly associated with survival (OR, 0.26; 95% CI, 0.12-0.54).Reported penicillin allergy had no significant effect on 30- or 90-day mortality. Non-penicillin-allergic patients receiving vancomycin for treatment of MSSA bacteremia had the highest mortality rates overall. Receipt of a beta-lactam was the strongest predictor of survival. These results underscore the importance of correct classification of patients with penicillin allergy and appropriate treatment with a beta-lactam when tolerated.Item Unknown Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research(Nature Reviews Microbiology) Turner, Nicholas A; Sharma-Kuinkel, Batu K; Maskarinec, Stacey A; Eichenberger, Emily M; Shah, Pratik P; Carugati, Manuela; Holland, Thomas L; Fowler, Vance GItem Unknown Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.(Nature communications, 2021-04-15) Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; Arabi, Yaseen M; Azhar, Shehnoor; Baden, Lindsey R; Baker, Arthur W; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marvin AH; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z; Cowan, Lisa N; Dalgard, Olav; de Almeida E Val, Fernando F; de Lacerda, Marcus VG; de Melo, Gisely C; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony C; Hernandez-Cardenas, Carmen M; Hills, Thomas; Hoepelman, Andy IM; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S; Kremsner, Peter G; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J; Meza-Meneses, Patricia; Monteiro, Wuelton M; Morpeth, Susan C; Mourad, Ahmad; Mulligan, Mark J; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A; O'Brien, Sean M; Okeke, Nwora Lance; Perez, Léna; Perez-Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E; Rockhold, Frank W; Rodriguez-Llamazares, Sebastian; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson S; Seto, Todd B; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E; Thirion-Romero, Ireri; Troxel, Andrea B; Tseng, Ting-Yu; Turner, Nicholas A; Ulrich, Robert J; Walsh, Stephen R; Webb, Steve A; Weehuizen, Jesper M; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando G; Zhong, Wu; Moher, David; Goodman, Steven N; Ioannidis, John PA; Hemkens, Lars GSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.Item Unknown Novel and emerging sources of Clostridioides difficile infection.(PLoS pathogens, 2019-12-19) Turner, Nicholas A; Smith, Becky A; Lewis, Sarah SItem Unknown Racial, Ethnic, and Geographic Disparities in Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Test Positivity in North Carolina.(Open forum infectious diseases, 2021-01) Turner, Nicholas A; Pan, William; Martinez-Bianchi, Viviana S; Panayotti, Gabriela M Maradiaga; Planey, Arrianna M; Woods, Christopher W; Lantos, Paul MBackground
Emerging evidence suggests that black and Hispanic communities in the United States are disproportionately affected by coronavirus disease 2019 (COVID-19). A complex interplay of socioeconomic and healthcare disparities likely contribute to disproportionate COVID-19 risk.Methods
We conducted a geospatial analysis to determine whether individual- and neighborhood-level attributes predict local odds of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed 29 138 SARS-CoV-2 tests within the 6-county catchment area for Duke University Health System from March to June 2020. We used generalized additive models to analyze the spatial distribution of SARS-CoV-2 positivity. Adjusted models included individual-level age, gender, and race, as well as neighborhood-level Area Deprivation Index, population density, demographic composition, and household size.Results
Our dataset included 27 099 negative and 2039 positive unique SARS-CoV-2 tests. The odds of a positive SARS-CoV-2 test were higher for males (odds ratio [OR], 1.43; 95% credible interval [CI], 1.30-1.58), blacks (OR, 1.47; 95% CI, 1.27-1.70), and Hispanics (OR, 4.25; 955 CI, 3.55-5.12). Among neighborhood-level predictors, percentage of black population (OR, 1.14; 95% CI, 1.05-1.25), and percentage Hispanic population (OR, 1.23; 95% CI, 1.07-1.41) also influenced the odds of a positive SARS-CoV-2 test. Population density, average household size, and Area Deprivation Index were not associated with SARS-CoV-2 test results after adjusting for race.Conclusions
The odds of testing positive for SARS-CoV-2 were higher for both black and Hispanic individuals, as well as within neighborhoods with a higher proportion of black or Hispanic residents-confirming that black and Hispanic communities are disproportionately affected by SARS-CoV-2.Item Unknown Reply to Swindells et al.: Trials of Tuberculosis-Preventive Therapy in People with HIV Infection.(American journal of respiratory and critical care medicine, 2020-07) Stout, Jason E; Turner, Nicholas A; Belknap, Robert W; Horsburgh, C Robert; Sterling, Timothy R; Phillips, Patrick PJ