LIVIVO - Search results -

Search results

Result 1 - 10 of total 93

Search options

Article ; Online: Relebactam restores susceptibility of resistant Pseudomonas aeruginosa and Enterobacterales and enhances imipenem activity against chromosomal AmpC-producing species: analysis of global SMART 2018-2020.

Hilbert, David W / DeRyke, C Andrew / Motyl, Mary / Hackel, Meredith / Young, Katherine

2023 Volume 23, Issue 1, Page(s) 165

Abstract: Background: Carbapenem-resistant bacteria are an increasing problem in clinical practice; thus, it is important to identify β-lactamase inhibitors (e.g., relebactam) that can restore carbapenem susceptibility. We report analyses of relebactam ... ...

Abstract	Background: Carbapenem-resistant bacteria are an increasing problem in clinical practice; thus, it is important to identify β-lactamase inhibitors (e.g., relebactam) that can restore carbapenem susceptibility. We report analyses of relebactam enhancement of imipenem activity against both imipenem-nonsusceptible (NS) and imipenem-susceptible (S) Pseudomonas aeruginosa and Enterobacterales. Gram-negative bacterial isolates were collected for the ongoing Study for Monitoring Antimicrobial Resistance Trends global surveillance program. Clinical and Laboratory Standards Institute-defined broth microdilution minimum inhibitory concentrations (MIC) were used to determine the imipenem and imipenem/relebactam antibacterial susceptibilities of P. aeruginosa and Enterobacterales isolates. Results: Between 2018 and 2020, 36.2% of P. aeruginosa (N = 23,073) and 8.2% of Enterobacterales (N = 91,769) isolates were imipenem-NS. Relebactam restored imipenem susceptibility in 64.1% and 49.4% of imipenem-NS P. aeruginosa and Enterobacterales isolates, respectively. Restoration of susceptibility was largely observed among K. pneumoniae carbapenemase-producing Enterobacterales and carbapenemase-negative P. aeruginosa. Relebactam also caused a lowering of imipenem MIC among imipenem-S P. aeruginosa and Enterobacterales isolates from chromosomal Ambler class C β-lactamase (AmpC)-producing species. For both imipenem-NS and imipenem-S P. aeruginosa isolates, relebactam reduced the imipenem MIC mode from 16 μg/mL to 1 μg/mL and from 2 μg/mL to 0.5 μg/mL, respectively, compared with imipenem alone. Conclusions: Relebactam restored imipenem susceptibility among nonsusceptible isolates of P. aeruginosa and Enterobacterales and enhanced imipenem susceptibility among susceptible isolates of P. aeruginosa and isolates from Enterobacterales species that can produce chromosomal AmpC. The reduced imipenem modal MIC values with relebactam may result in a higher probability of target attainment in patients.
MeSH term(s)	Humans ; Imipenem/pharmacology ; Pseudomonas aeruginosa/genetics ; Anti-Bacterial Agents/pharmacology ; Carbapenems ; Gammaproteobacteria
Chemical Substances	Imipenem (71OTZ9ZE0A) ; relebactam (Y1MYA2UHFL) ; Anti-Bacterial Agents ; Carbapenems
Language	English
Publishing date	2023-06-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041505-9
ISSN	1471-2180 ; 1471-2180
ISSN (online)	1471-2180
ISSN	1471-2180
DOI	10.1186/s12866-023-02864-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Controlling CAR T Cell Activity and Specificity with Synthetic SparX Adapters.

Edwards, Justin P / Swers, Jeffrey S / Buonato, Janine M / Zaritskaya, Liubov / Mu, C Jenny / Gupta, Ankit / Shachar, Sigal / LaFleur, David W / Richman, Laura K / Tice, David A / Hilbert, David M

Molecular therapy : the journal of the American Society of Gene Therapy

2024

Abstract: While conventional CAR-T therapies have shown remarkable clinical activity in some settings, they can induce severe toxicities and are rarely curative. To address these challenges, we developed a controllable cell therapy where synthetic D-Domain- ... ...

Abstract	While conventional CAR-T therapies have shown remarkable clinical activity in some settings, they can induce severe toxicities and are rarely curative. To address these challenges, we developed a controllable cell therapy where synthetic D-Domain-containing proteins (SparX) bind one or more tumor antigens and mark those cells for elimination by genetically modified T cells (ARC-T). The chimeric antigen receptor was engineered with a D-Domain that specifically binds to the SparX protein via a unique TAG, derived from human alpha-fetoprotein. The interaction is mediated through an epitope on the TAG that is occluded in the native alpha-fetoprotein molecule. In vitro and in vivo data demonstrate that the activation and cytolytic activity of ARC-T cells is dependent on the dose of SparX protein and only occurs when ARC-T cells are engaged SparX proteins bound to antigen-positive cells. ARC-T cell specificity was also redirected in vivo by changing SparX proteins that recognized different tumor antigens to combat inherent or acquired tumor heterogeneity. The ARC-SparX platform is designed to expand patient and physician access to cell therapy by controlling potential toxicities through SparX dosing regimens and enhancing tumor elimination through sequential or simultaneous administration of SparX proteins engineered to bind different tumor antigens.
Language	English
Publishing date	2024-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2024.04.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Preclinical Efficacy of BCMA-Directed CAR T Cells Incorporating a Novel D Domain Antigen Recognition Domain.

Buonato, Janine M / Edwards, Justin P / Zaritskaya, Liubov / Witter, Alexandra R / Gupta, Ankit / LaFleur, David W / Tice, David A / Richman, Laura K / Hilbert, David M

Molecular cancer therapeutics

2022 Volume 21, Issue 7, Page(s) 1171–1183

Abstract: Chimeric antigen receptor (CAR) T-cell therapies directed against B-cell maturation antigen (BCMA) have shown compelling clinical activity and manageable safety in subjects with relapsed and refractory multiple myeloma (RRMM). Prior reported CAR T cells ... ...

Abstract	Chimeric antigen receptor (CAR) T-cell therapies directed against B-cell maturation antigen (BCMA) have shown compelling clinical activity and manageable safety in subjects with relapsed and refractory multiple myeloma (RRMM). Prior reported CAR T cells have mostly used antibody fragments such as humanized or murine single-chain variable fragments or camelid heavy-chain antibody fragments as the antigen recognition motif. Herein, we describe the generation and preclinical evaluation of ddBCMA CAR, which uses a novel BCMA binding domain discovered from our D domain phage display libraries and incorporates a 4-1BB costimulatory motif and CD3-zeta T-cell activation domain. Preclinical in vitro studies of ddBCMA CAR T cells cocultured with BCMA-positive cell lines showed highly potent, dose-dependent measures of cytotoxicity, cytokine production, T-cell degranulation, and T-cell proliferation. In each assay, ddBCMA CAR performed as well as the BCMA-directed scFv-based C11D5.3 CAR. Furthermore, ddBCMA CAR T cells demonstrated in vivo tumor suppression in three disseminated BCMA-expressing tumor models in NSG-immunocompromised mice. On the basis of these promising preclinical data, CART-ddBCMA is being studied in a first-in-human phase I clinical study to assess the safety, pharmacokinetics, immunogenicity, efficacy, and duration of effect for patients with RRMM (NCT04155749).
MeSH term(s)	Animals ; B-Cell Maturation Antigen/metabolism ; Humans ; Immunotherapy, Adoptive ; Mice ; Multiple Myeloma/pathology ; Receptors, Chimeric Antigen/metabolism ; Single-Chain Antibodies/genetics ; T-Lymphocytes
Chemical Substances	B-Cell Maturation Antigen ; Receptors, Chimeric Antigen ; Single-Chain Antibodies
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-21-0552
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5750: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Bacterial Vaginosis-Associated Bacteria and Uterine Fibroids: A Nested Case-Control Study.

Moore, Kristen R / Tomar, Meena / Umbach, David M / Gygax, Scott E / Hilbert, David W / Baird, Donna D

Sexually transmitted diseases

2021 Volume 48, Issue 11, Page(s) 844–850

Abstract: Background: Reproductive tract infections are hypothesized to influence uterine fibroid development, yet few studies have investigated the common condition of bacterial vaginosis (BV). The literature is currently limited to data using self-report of BV.! ...

Abstract	Background: Reproductive tract infections are hypothesized to influence uterine fibroid development, yet few studies have investigated the common condition of bacterial vaginosis (BV). The literature is currently limited to data using self-report of BV. Methods: We conducted a nested case-control study of 200 women (100 cases and 100 controls) from a large study of 23- to 35-year-old African American women, 1310 of whom were fibroid-free and prospectively followed up for 5 years to identify incident fibroids with standardized ultrasound examinations. We used quantitative polymerase chain reaction, an objective molecular method, to assess 9 BV-associated and 4 Lactobacillus species from vaginal swab specimens. We used hierarchical logistic regression to compute odds ratios and 95% confidence intervals to examine associations between bacterial species (both individually and grouped as (1) "optimal" Lactobacillus and (2) BV-associated species) with fibroid incidence and number. We also examined vaginal imbalance (quantitatively more BV-associated bacteria than optimal Lactobacilli). Results: Contrary to our hypothesis, we found no increase in fibroid incidence or number among women with more BV-associated bacteria. High imbalance (only BV-associated bacteria, no optimal Lactobacillus bacteria) was actually inversely associated with fibroid incidence (odds ratio, 0.38; 95% confidence interval, 0.17-0.81). Conclusions: This is the first study of ultrasound-detected incident fibroids and molecular vaginal bacterial assessment. We found no evidence that BV-associated bacteria increase the risk of fibroid incidence or number.
MeSH term(s)	Adult ; Bacteria ; Case-Control Studies ; Female ; Humans ; Leiomyoma/epidemiology ; Ultrasonography ; Vagina ; Vaginosis, Bacterial/complications ; Vaginosis, Bacterial/epidemiology ; Young Adult
Language	English
Publishing date	2021-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	435191-5
ISSN	1537-4521 ; 0148-5717
ISSN (online)	1537-4521
ISSN	0148-5717
DOI	10.1097/OLQ.0000000000001466
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1217: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Conference proceedings: Meeting report: exploring the biology of the social amoeba Dictyostelium discoideum. international Dictyostelium conference 2004.

Hilbert, David W

Protist

2005 Volume 156, Issue 1, Page(s) 3–8

MeSH term(s)	Animals ; Developmental Biology/trends ; Dictyostelium/classification ; Dictyostelium/genetics ; Dictyostelium/physiology ; Genome, Protozoan ; Molecular Biology/trends
Language	English
Publishing date	2005-06
Publishing country	Germany
Document type	Congresses ; News
ZDB-ID	2036014-9
ISSN	1618-0941 ; 1434-4610
ISSN (online)	1618-0941
ISSN	1434-4610
DOI	10.1016/j.protis.2005.02.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: In Vitro

Karlowsky, James A / Lob, Sibylle H / DeRyke, C Andrew / Hilbert, David W / Wong, Michael T / Young, Katherine / Siddiqui, Fakhar / Motyl, Mary R / Sahm, Daniel F

Antimicrobial agents and chemotherapy

2022 Volume 66, Issue 5, Page(s) e0018922

Abstract: Ceftolozane-tazobactam (C/T), imipenem-relebactam (IMR), and ceftazidime-avibactam (CZA) were tested against 2,531 P. aeruginosa strains isolated from patients in the United States from 2018 to 2020 as part of the SMART (Study for Monitoring ... ...

Abstract	Ceftolozane-tazobactam (C/T), imipenem-relebactam (IMR), and ceftazidime-avibactam (CZA) were tested against 2,531 P. aeruginosa strains isolated from patients in the United States from 2018 to 2020 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance program. MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 (2021) breakpoints. Imipenem-, IMR-, or C/T-nonsusceptible isolates were screened for β-lactamase genes: 96.4% of all isolates and ≥70% of multidrug-resistant (MDR), pan-β-lactam-nonsusceptible, and difficult-to-treat resistance (DTR) isolates were C/T-susceptible; 52.2% of C/T-nonsusceptible isolates remained susceptible to IMR compared to 38.9% for CZA; and 1.7% of isolates tested were nonsusceptible to both C/T and IMR versus 2.2% of isolates with a C/T-nonsusceptible and CZA-resistant phenotype (a difference of 12 isolates). C/T and IMR modal MICs for pan-β-lactam-nonsusceptible isolates remained at or below their respective susceptible MIC breakpoints from 2018 to 2020, while the modal MIC for CZA increased 2-fold from 2018 to 2019 and exceeded the CZA-susceptible MIC breakpoint in both 2019 and 2020. Only six of 802 molecularly characterized isolates carried a metallo-β-lactamase, and two isolates carried a GES carbapenemase. Most P. aeruginosa isolates were C/T-susceptible, including many with MDR, pan-β-lactam-nonsusceptible, DTR, CZA-resistant, and IMR-nonsusceptible phenotypes. While C/T was the most active antipseudomonal agent, IMR demonstrated greater activity than CZA against isolates nonsusceptible to C/T.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Azabicyclo Compounds/pharmacology ; Ceftazidime/pharmacology ; Cephalosporins/pharmacology ; Drug Combinations ; Hospitals ; Humans ; Imipenem/pharmacology ; Microbial Sensitivity Tests ; Pseudomonas Infections/drug therapy ; Pseudomonas aeruginosa/genetics ; Tazobactam/pharmacology ; United States ; beta-Lactamases/genetics
Chemical Substances	Anti-Bacterial Agents ; Azabicyclo Compounds ; Cephalosporins ; Drug Combinations ; avibactam, ceftazidime drug combination ; ceftolozane (37A4IES95Q) ; Imipenem (71OTZ9ZE0A) ; Ceftazidime (9M416Z9QNR) ; beta-Lactamases (EC 3.5.2.6) ; Tazobactam (SE10G96M8W) ; relebactam (Y1MYA2UHFL)
Language	English
Publishing date	2022-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/aac.00189-22
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 809: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Einzelsignatur: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mycoplasma genitalium and Bacterial Vaginosis-Associated Bacteria in a Non-Clinic-Based Sample of African American Women.

Moore, Kristen R / Tomar, Meena / Taylor, Brandie D / Gygax, Scott E / Hilbert, David W / Baird, Donna D

Sexually transmitted diseases

2020 Volume 48, Issue 2, Page(s) 118–122

Abstract: Background: Mycoplasma genitalium is associated with adverse reproductive problems. However, prevalence estimates from studies that screen women not seeking care are rare. Studies have reported co-occurrence of M. genitalium with bacterial vaginosis (BV) ...

Abstract	Background: Mycoplasma genitalium is associated with adverse reproductive problems. However, prevalence estimates from studies that screen women not seeking care are rare. Studies have reported co-occurrence of M. genitalium with bacterial vaginosis (BV), but no prior study of specific BV-associated bacteria has been conducted in African Americans whose reproductive tract infection burden is high. Methods: Using quantitative polymerase chain reaction, we screened vaginal swabs for M. genitalium, 9 BV-associated bacteria, and 4 Lactobacillus species from 200 participants drawn from a cohort of African Americans 23 to 35 years old. Sexual history, herpes serostatus, and Nugent score had been assessed. Prevalence of M. genitalium was computed. The associations of other vaginal bacteria with M. genitalium were examined with binomial regression. Results: M. genitalium prevalence was 18%. Detection and quantity of 2 BV-associated bacteria were significantly associated with a higher prevalence of M. genitalium (Leptotrichia/Sneathia: detection prevalence ratio (PR) of 2.9 [95% confidence interval {CI}, 1.1-7.7] and quantity PR of 1.2 [95% CI, 1.0-1.3]; Megasphaera phylotype 1: detection PR of 2.2 [95% CI, 1.2-4.2] and quantity PR of 1.1 [95% CI, 1.0-1.2]). Increased quantity of L. iners was also positively associated with M. genitalium (PR, 1.3 [95% CI, 1.0-1.8]). Nugent ≥7, herpes serostatus, and lifetime number of sex partners were not associated with M. genitalium. Conclusions: Specific BV-associated microbes and L. iners were associated with M. genitalium, but Nugent ≥7 was not. Studies are needed to confirm a high prevalence of M. genitalium in African Americans and to understand its interactions with other vaginal bacteria.
MeSH term(s)	Adult ; Black or African American ; Bacteria ; Female ; Humans ; Mycoplasma genitalium/genetics ; Vagina ; Vaginosis, Bacterial/epidemiology ; Young Adult
Language	English
Publishing date	2020-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	435191-5
ISSN	1537-4521 ; 0148-5717
ISSN (online)	1537-4521
ISSN	0148-5717
DOI	10.1097/OLQ.0000000000001275
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1217: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Chimeric Antigen Receptors Incorporating D Domains Targeting CD123 Direct Potent Mono- and Bi-specific Antitumor Activity of T Cells.

Qin, Haiying / Edwards, Justin P / Zaritskaya, Liubov / Gupta, Ankit / Mu, C Jenny / Fry, Terry J / Hilbert, David M / LaFleur, David W

Molecular therapy : the journal of the American Society of Gene Therapy

2019 Volume 27, Issue 7, Page(s) 1262–1274

Abstract: Chimeric antigen receptor (CAR) T cell therapies have demonstrated impressive initial response rates in hematologic malignancies. However, relapse rates are significant, and robust efficacies in other indications, such as solid tumors, will likely ... ...

Abstract	Chimeric antigen receptor (CAR) T cell therapies have demonstrated impressive initial response rates in hematologic malignancies. However, relapse rates are significant, and robust efficacies in other indications, such as solid tumors, will likely require novel therapeutic strategies and CAR designs. To that end, we sought to develop simple, highly selective targeting domains (D domains) that could be incorporated into complex, multifunctional therapeutics. Herein, we describe the identification and characterization of D domains specific for CD123, a therapeutic target for hematologic malignancies, including acute myelogenous leukemia (AML). CARs comprised of these D domains mediate potent T cell activation and cytolysis of CD123-expressing target cells and induce complete durable remission in two AML xenograft models. We describe a strategy of engineering less immunogenic D domains through the identification and removal of putative T cell epitopes and investigate the binding kinetics and affinity requirements of the resultant D domain CARs. Finally, we extended the utility of D domains by generating functional, bi-specific CARs comprised of a CD123-specific D domain and a CD19-specific scFv. The properties of D domains suggest that this class of targeting domain may facilitate the development of multi-functional CARs where conventional, scFv-based designs may be suboptimal.
MeSH term(s)	Animals ; Antigens, CD19/immunology ; Antineoplastic Agents/immunology ; Antineoplastic Agents/therapeutic use ; Epitopes, T-Lymphocyte/immunology ; HEK293 Cells ; Humans ; Immunotherapy, Adoptive/methods ; Interleukin-3 Receptor alpha Subunit/immunology ; K562 Cells ; Leukemia, Myeloid, Acute/therapy ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Protein Binding/immunology ; Protein Domains/immunology ; Proteins/immunology ; Proteins/therapeutic use ; Receptors, Chimeric Antigen/immunology ; Receptors, Chimeric Antigen/therapeutic use ; Single-Chain Antibodies/immunology ; T-Lymphocytes/immunology ; Transfection ; Xenograft Model Antitumor Assays
Chemical Substances	Antigens, CD19 ; Antineoplastic Agents ; CD19 molecule, human ; Epitopes, T-Lymphocyte ; IL3RA protein, human ; Interleukin-3 Receptor alpha Subunit ; Proteins ; Receptors, Chimeric Antigen ; Single-Chain Antibodies ; alpha3D protein, synthetic
Language	English
Publishing date	2019-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2019.04.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Indoor air pollutants and respiratory symptoms among residents of an informal urban settlement in Uganda: A cross-sectional study.

Wafula, Solomon T / Nalugya, Aisha / Mendoza, Hilbert / Kansiime, Winnifred K / Ssekamatte, Tonny / Walekhwa, Abel W / Mugambe, Richard K / Walter, Florian / Ssempebwa, John C / Musoke, David

PloS one

2023 Volume 18, Issue 8, Page(s) e0290170

Abstract: Background: Indoor air pollutants (IAP) and household conditions such as dampness, crowding and chemical exposures have been associated with acute and chronic respiratory infections. In Uganda, literature on the effects of IAP on respiratory outcomes in ...

Abstract	Background: Indoor air pollutants (IAP) and household conditions such as dampness, crowding and chemical exposures have been associated with acute and chronic respiratory infections. In Uganda, literature on the effects of IAP on respiratory outcomes in informal settlements is limited. Methods: We describe the baseline household characteristics of 284 adults and their children in an informal settlement in Uganda from April to May 2022. We monitored same-day indoor concentrations of particulate matter PM2.5, PM10, Carbon monoxide (CO), relative humidity %, and temperature from 9 am to 2 pm and interviewed caregivers/mothers about their respiratory symptoms and those of their children in the previous 30 days. We employed robust Poisson regressions to evaluate the associations between indoor air indicators and respiratory health symptoms. Results: Approximately 94.7% of households primarily used biomass fuels and 32.7% cooked from inside their dwelling rooms. The median PM2.5, PM10 and CO levels were 49.5 (Interquartile range (IQR) = 31.1,86.2) μg/m3, 73.6 (IQR = 47.3,130.5) μg/m3 and 7.70 (IQR = 4.1,12.5) ppm respectively. Among adults, a 10 unit increase in PM2.5 was associated with cough (Prevalence Ratio (PR) = 3.75, 95%CI 1.15-1.55). Dwelling unit dampness was associated with phlegm (PR = 2.53, 95%CI = 1.39-4.61) and shortness of breath (PR = 1.78, 95% CI 1.23-2.54) while cooking from outside the house was protective against shortness of breath (PR = 0.62, 95% CI = 0.44-0.87). In children, dampness was associated with phlegm (PR = 13.87, 95% CI 3.16-60.91) and cough (PR = 1.62, 95% CI 1.12-2.34) while indoor residual spraying was associated with phlegm (PR = 3.36, 95%CI 1.71-6.61). Conclusion: Poor indoor air conditions were associated with respiratory symptoms in adults and children. Efforts to address indoor air pollution should be made to protect adults and children from adverse health effects.
MeSH term(s)	Adult ; Child ; Humans ; Air Pollutants/adverse effects ; Cross-Sectional Studies ; Uganda/epidemiology ; Cough/epidemiology ; Cough/etiology ; Particulate Matter/adverse effects ; Alarmins ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea
Chemical Substances	Air Pollutants ; Particulate Matter ; Alarmins
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0290170
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Population pharmacokinetic/pharmacodynamic assessment of imipenem/cilastatin/relebactam in patients with hospital-acquired/ventilator-associated bacterial pneumonia.

Patel, Munjal / Bellanti, Francesco / Daryani, Naveen M / Noormohamed, Nadia / Hilbert, David W / Young, Katherine / Kulkarni, Pooja / Copalu, William / Gheyas, Ferdous / Rizk, Matthew L

Clinical and translational science

2021 Volume 15, Issue 2, Page(s) 396–408

Abstract: In the phase III RESTORE-IMI 2 study (ClinicalTrials.gov: NCT02493764), the combination antibacterial agent imipenem/cilastatin/relebactam (IMI/REL) demonstrated noninferiority to piperacillin/tazobactam for the end points of all-cause mortality at day ... ...

Abstract	In the phase III RESTORE-IMI 2 study (ClinicalTrials.gov: NCT02493764), the combination antibacterial agent imipenem/cilastatin/relebactam (IMI/REL) demonstrated noninferiority to piperacillin/tazobactam for the end points of all-cause mortality at day 28 and favorable clinical response at the early follow-up visit in adult participants with gram-negative hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP). Existing population pharmacokinetic models for imipenem (IPM) and REL were updated using data from patients with HABP/VABP from RESTORE-IMI 2. Creatinine clearance (CrCl), body weight, infection type, and ventilation status were significant covariates in the updated model. The following simulations were performed to calculate the pharmacokinetic/pharmacodynamic joint probability of target attainment among patients with HABP/VABP and varying degrees of renal function: augmented renal clearance (CrCl ≥150 ml/min), normal renal function (CrCl ≥90 to <150 ml/min), renal impairment (mild, CrCl ≥60 to <90 ml/min; moderate, CrCl ≥30 to <60 ml/min; or severe, CrCl ≥15 to <30 ml/min), and end-stage renal disease (CrCl <15 ml/min). At the recommended IMI/REL dosing regimens across renal categories, greater than 90% of patients in all renal function groups were predicted to achieve joint pharmacokinetic/pharmacodynamic targets at a minimum inhibitory concentration breakpoint of ≤2 μg/ml, regardless of ventilation status. This modeling and simulation analysis supports use of the recommended IMI/REL dosing regimens, adjusted based on renal function, in patients with HABP/VABP.
MeSH term(s)	Adult ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Azabicyclo Compounds ; Cilastatin/therapeutic use ; Hospitals ; Humans ; Imipenem/pharmacology ; Imipenem/therapeutic use ; Pneumonia, Bacterial/drug therapy ; Ventilators, Mechanical
Chemical Substances	Anti-Bacterial Agents ; Azabicyclo Compounds ; Cilastatin (141A6AMN38) ; Imipenem (71OTZ9ZE0A) ; relebactam (Y1MYA2UHFL)
Language	English
Publishing date	2021-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.13158
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito