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Article ; Online: Uses of pathogen detection data to estimate vaccine direct effects in case-control studies.

Lewnard, Joseph A

2020 Volume 17, Issue 169, Page(s) 20200161

Abstract: The fact that many pathogens can be carried or shed without causing symptoms complicates the interpretation of microbiological data when diagnosing certain infectious disease syndromes. Diagnostic criteria that attribute symptoms to a pathogen which is ... ...

Abstract	The fact that many pathogens can be carried or shed without causing symptoms complicates the interpretation of microbiological data when diagnosing certain infectious disease syndromes. Diagnostic criteria that attribute symptoms to a pathogen which is detectable, whether it is or is not the aetiological agent of disease, may lead to outcome misclassification in epidemiological studies. Case-control studies are commonly undertaken to estimate vaccine effectiveness (VE) and present an opportunity to compare pathogen detection among individuals with and without clinically relevant symptoms. Considering this study context, we present a mathematical framework yielding simple estimators for the direct effects of vaccination on various aspects of host susceptibility. These include protection against acquisition of the pathogen of interest and protection against progression of this pathogen to disease following acquisition. We assess the impact of test sensitivity on these estimators and extend our framework to identify a 'vaccine probe' estimator for pathogen-specific aetiological fractions. We also derive biases affecting VE estimates under the test-negative design, a special case enrolling only symptomatic persons. Our results provide strategies for estimating pathogen-specific VE in the absence of a diagnostic gold standard. These approaches can inform the design and analysis of studies addressing numerous pathogens and vaccines.
MeSH term(s)	Bias ; Case-Control Studies ; Humans ; Influenza Vaccines ; Influenza, Human ; Vaccination ; Vaccines
Chemical Substances	Influenza Vaccines ; Vaccines
Language	English
Publishing date	2020-08-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2020.0161
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: On the use of the reproduction number for SARS-CoV-2: Estimation, misinterpretations and relationships with other ecological measures.

Jewell, Nicholas P / Lewnard, Joseph A

Journal of the Royal Statistical Society. Series A, (Statistics in Society)

2022

Abstract: The basic reproduction number, ...

Abstract	The basic reproduction number,
Language	English
Publishing date	2022-06-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1490715-X
ISSN	1467-985X ; 0964-1998 ; 0035-9238
ISSN (online)	1467-985X
ISSN	0964-1998 ; 0035-9238
DOI	10.1111/rssa.12860
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Article: Clinical and Public Health Considerations for HPV Vaccination in Midadulthood: A Narrative Review.

King, Laura M / Lewnard, Joseph A / Niccolai, Linda M

Open forum infectious diseases

2023 Volume 10, Issue 1, Page(s) ofad004

Abstract: Human papillomavirus (HPV) is an important cause of anogenital and oropharyngeal cancers, anogenital warts, and recurrent respiratory papillomatosis. Beginning in 2019, US guidelines recommended shared clinical decision-making (SCDM) for HPV vaccination ... ...

Abstract	Human papillomavirus (HPV) is an important cause of anogenital and oropharyngeal cancers, anogenital warts, and recurrent respiratory papillomatosis. Beginning in 2019, US guidelines recommended shared clinical decision-making (SCDM) for HPV vaccination among midadults (27-45 years). We conducted a narrative review of existing literature on HPV vaccination in midadults. The available evidence demonstrates that HPV vaccination in midadults is safe, efficacious, and likely to benefit both HPV-naïve midadults and those with previous infections. However, gaps in knowledge related to HPV vaccination have been identified among clinicians and midadult patients. Universal midadult HPV vaccination in the United States could avert 20 934-37 856 cancer cases over 100 years, costing $141 000-$1 471 000 per quality-adjusted life-year gained. Wide variation in these estimates reflects uncertainties in sexual behavior, HPV natural history, and naturally acquired immunity. Greater awareness among clinicians and midadult patients and broad implementation of SCDM may accelerate progress toward eliminating HPV-associated cancers and other diseases.
Language	English
Publishing date	2023-01-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad004
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Article ; Online: Ebola virus disease: 11 323 deaths later, how far have we come?

Lewnard, Joseph A

Lancet (London, England)

2018 Volume 392, Issue 10143, Page(s) 189–190

MeSH term(s)	Africa, Western/epidemiology ; Disease Outbreaks/prevention & control ; Early Diagnosis ; Ebola Vaccines ; Hemorrhagic Fever, Ebola/diagnosis ; Hemorrhagic Fever, Ebola/epidemiology ; Hemorrhagic Fever, Ebola/transmission ; Hospitalization ; Humans
Chemical Substances	Ebola Vaccines
Language	English
Publishing date	2018-06-29
Publishing country	England
Document type	Journal Article
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(18)31443-0
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Article ; Online: Attributed causes of excess mortality during the COVID-19 pandemic in a south Indian city.

Lewnard, Joseph A / B, Chandra Mohan / Kang, Gagandeep / Laxminarayan, Ramanan

Nature communications

2023 Volume 14, Issue 1, Page(s) 3563

Abstract: Globally, excess deaths during 2020-21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 ... ...

Abstract	Globally, excess deaths during 2020-21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 deaths from other changes in mortality related to pandemic control measures using medically-certified death registrations from Madurai, India-an urban center with well-functioning vital surveillance. Between March, 2020 and July, 2021, all-cause deaths in Madurai exceeded expected levels by 30% (95% confidence interval: 27-33%). Although driven by deaths attributed to cardiovascular or cerebrovascular conditions, diabetes, senility, and other uncategorized causes, increases in these attributions were restricted to medically-unsupervised deaths, and aligned with surges in confirmed or attributed COVID-19 mortality, likely reflecting mortality among unconfirmed COVID-19 cases. Implementation of lockdown measures was associated with a 7% (0-13%) reduction in all-cause mortality, driven by reductions in deaths attributed to injuries, infectious diseases and maternal conditions, and cirrhosis and other liver conditions, respectively, but offset by a doubling in cancer deaths. Our findings help to account for gaps between documented COVID-19 mortality and excess all-cause mortality during the pandemic in an LMIC setting.
MeSH term(s)	Humans ; COVID-19/epidemiology ; Pandemics ; Cause of Death ; India/epidemiology ; Communicable Disease Control ; Mortality
Language	English
Publishing date	2023-06-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-39322-7
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Article ; Online: Scientific and ethical basis for social-distancing interventions against COVID-19.

Lewnard, Joseph A / Lo, Nathan C

The Lancet. Infectious diseases

2020 Volume 20, Issue 6, Page(s) 631–633

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2 ; Singapore
Keywords	covid19
Language	English
Publishing date	2020-03-23
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(20)30190-0
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Article ; Online: Pneumococcal conjugate vaccines in different settings - Authors' reply.

Hanage, William P / Lewnard, Joseph A

The Lancet. Infectious diseases

2019 Volume 19, Issue 12, Page(s) 1284

MeSH term(s)	Humans ; Pneumococcal Infections ; Pneumococcal Vaccines ; Serogroup ; Vaccines, Conjugate
Chemical Substances	Pneumococcal Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2019-11-29
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(19)30630-9
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Article ; Online: Outpatient visits and antibiotic use due to higher valency pneumococcal vaccine serotypes.

King, Laura M / Andrejko, Kristin L / Kabbani, Sarah / Tartof, Sara Y / Hicks, Lauri A / Cohen, Adam L / Kobayashi, Miwako / Lewnard, Joseph A

The Journal of infectious diseases

2024

Abstract: Background: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children (≤17 years) from 2016-2019 for ... ...

Abstract	Background: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. Methods: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national healthcare surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. Results: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval 1.8-3.9) visits and 2.4 (1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (11.2-20.4) visits and 13.2 (9.9-18.0) antibiotic prescriptions annually per 1,000 children. PCV15/20-additional serotypes account for 0.4% (0.2-0.6%) and 2.1% (1.5-3.0%) of pediatric outpatient antibiotic use. Conclusions: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for >5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.
Language	English
Publishing date	2024-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae142
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Article ; Online: Health-Economic Value of Vaccination Against Group A Streptococcus in the United States.

Andrejko, Kristin / Whittles, Lilith K / Lewnard, Joseph A

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 74, Issue 6, Page(s) 983–992

Abstract: Background: Vaccines are needed to reduce the burden of group A Streptococcus (GAS). We assessed the potential health-economic value of GAS vaccines achievable through prevention of invasive disease and acute upper respiratory infections in the United ... ...

Abstract	Background: Vaccines are needed to reduce the burden of group A Streptococcus (GAS). We assessed the potential health-economic value of GAS vaccines achievable through prevention of invasive disease and acute upper respiratory infections in the United States. Methods: We estimated annual incidence of invasive GAS disease and associated costs incurred from hospitalization and management of long-term sequelae, as well as productivity losses resulting from acute illness, long-term disability, and mortality. We also estimated healthcare and productivity costs associated with GAS pharyngitis, sinusitis, and acute otitis media. We estimated costs averted by prevention of invasive disease and acute upper respiratory infections for vaccines with differing efficacy profiles; our base case considered vaccines meeting the World Health Organization Preferred Product Profile (WHO-PPP) with a 6-year average duration of protection. Results: Costs of invasive GAS disease and acute upper respiratory infections totaled $6.08 (95% confidence interval [CI], $5.33-$6.86) billion annually. Direct effects of vaccines meeting WHO-PPP characteristics and administered at ages 12 and 18 months would avert $609 (95% CI, $558-$663) million in costs annually, primarily by preventing noninvasive disease; with an additional dose at age 5 years, averted costs would total $869 (95% CI, $798-$945) million annually. Adult vaccination at age 65 years would avert $326 (95% CI, $271-$387) million in annual costs associated with invasive GAS disease. Indirect effects of vaccination programs reducing incidence of GAS diseases across all ages by 20% would avert roughly $1 billion in costs each year. Conclusions: The economic burden of GAS is substantial. Our findings should inform prioritization of GAS vaccine development and evaluation.
MeSH term(s)	Adult ; Aged ; Child, Preschool ; Cost-Benefit Analysis ; Humans ; Immunization Programs ; Infant ; Otitis Media/epidemiology ; Otitis Media/prevention & control ; Respiratory Tract Infections/epidemiology ; Respiratory Tract Infections/prevention & control ; Streptococcal Infections/epidemiology ; Streptococcal Infections/prevention & control ; Streptococcus pyogenes ; United States/epidemiology ; Vaccination
Language	English
Publishing date	2021-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab597
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Article ; Online: Association of Pneumococcal Serotype With Susceptibility to Antimicrobial Drugs: A Systematic Review and Meta-analysis.

Andrejko, Kristin / Ratnasiri, Buddhika / Lewnard, Joseph A

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 75, Issue 1, Page(s) 131–140

Abstract: Background: Pneumococcal serotypes differ in antimicrobial susceptibility. However, patterns and causes of this variation are not comprehensively understood.: Methods: We undertook a systematic review of epidemiologic studies of pneumococci isolated ... ...

Abstract	Background: Pneumococcal serotypes differ in antimicrobial susceptibility. However, patterns and causes of this variation are not comprehensively understood. Methods: We undertook a systematic review of epidemiologic studies of pneumococci isolated from carriage or invasive disease among children globally from 2000-2019. We evaluated associations of each serotype with nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. We evaluated differences in the prevalence of nonsusceptibility to major antibiotic classes across serotypes using random-effects meta-regression models and assessed changes in prevalence of nonsusceptibility after implementation of pneumococcal conjugate vaccines (PCVs). We also evaluated associations between biological characteristics of serotypes and their likelihood of nonsusceptibility to each drug. Results: We included data from 129 studies representing 32 187 isolates across 52 countries. Within serotypes, the proportion of nonsusceptible isolates varied geographically and over time, in settings using and those not using PCVs. Factors predicting enhanced fitness of serotypes in colonization as well as enhanced pathogenicity were each associated with higher likelihood of nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. Increases in prevalence of nonsusceptibility following PCV implementation were evident among non-PCV serotypes, including 6A, 6C, 15A, 15B/C, 19A, and 35B; however, this pattern was not universally evident among non-PCV serotypes. Postvaccination increases in nonsusceptibility for serotypes 6A and 19A were attenuated in settings that implemented PCV13. Conclusions: In pneumococci, nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole is associated with more frequent opportunities for antibiotic exposure during both prolonged carriage episodes and when serotypes cause disease. These findings suggest multiple pathways leading to resistance selection in pneumococci.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Child ; Humans ; Infant ; Macrolides/pharmacology ; Nasopharynx ; Penicillins/pharmacology ; Penicillins/therapeutic use ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Pneumococcal Vaccines ; Serogroup ; Streptococcus pneumoniae ; Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; Vaccines, Conjugate
Chemical Substances	Anti-Bacterial Agents ; Macrolides ; Penicillins ; Pneumococcal Vaccines ; Vaccines, Conjugate ; Trimethoprim, Sulfamethoxazole Drug Combination (8064-90-2)
Language	English
Publishing date	2021-10-01
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab852
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