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  • 1
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    Online Resource
    Evaluation of a National Quality Improvement Collaborative for Improving Cancer Screening
    American Medical Association (AMA) ; 2022
    In:  JAMA Network Open Vol. 5, No. 11 ( 2022-11-16), p. e2242354-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 11 ( 2022-11-16), p. e2242354-
    Abstract: Cancer screening deficits during the first year of the COVID-19 pandemic were found to persist into 2021. Cancer-related deaths over the next decade are projected to increase if these deficits are not addressed. Objective To assess whether participation in a nationwide quality improvement (QI) collaborative, Return-to-Screening, was associated with restoration of cancer screening. Design, Setting, and Participants Accredited cancer programs electively enrolled in this QI study. Project-specific targets were established on the basis of differences in mean monthly screening test volumes (MTVs) between representative prepandemic (September 2019 and January 2020) and pandemic (September 2020 and January 2021) periods to restore prepandemic volumes and achieve a minimum of 10% increase in MTV. Local QI teams implemented evidence-based screening interventions from June to November 2021 (intervention period), iteratively adjusting interventions according to their MTVs and target. Interrupted time series analyses was used to identify the intervention effect. Data analysis was performed from January to April 2022. Exposures Collaborative QI support included provision of a Return-to-Screening plan-do-study-act protocol, evidence-based screening interventions, QI education, programmatic coordination, and calculation of screening deficits and targets. Main Outcomes and Measures The primary outcome was the proportion of QI projects reaching target MTV and counterfactual differences in the aggregate number of screening tests across time periods. Results Of 859 cancer screening QI projects (452 for breast cancer, 134 for colorectal cancer, 244 for lung cancer, and 29 for cervical cancer) conducted by 786 accredited cancer programs, 676 projects (79%) reached their target MTV. There were no hospital characteristics associated with increased likelihood of reaching target MTV except for disease site (lung vs breast, odds ratio, 2.8; 95% CI, 1.7 to 4.7). During the preintervention period (April to May 2021), there was a decrease in the mean MTV (slope, −13.1 tests per month; 95% CI, −23.1 to −3.2 tests per month). Interventions were associated with a significant immediate (slope, 101.0 tests per month; 95% CI, 49.1 to 153.0 tests per month) and sustained (slope, 36.3 tests per month; 95% CI, 5.3 to 67.3 tests per month) increase in MTVs relative to the preintervention trends. Additional screening tests were performed during the intervention period compared with the prepandemic period (170 748 tests), the pandemic period (210 450 tests), and the preintervention period (722 427 tests). Conclusions and Relevance In this QI study, participation in a national Return-to-Screening collaborative with a multifaceted QI intervention was associated with improvements in cancer screening. Future collaborative QI endeavors leveraging accreditation infrastructure may help address other gaps in cancer care.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2022.42354
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 2
    Online Resource
    Online Resource
    Comparison of Western Immunobloting to an Enzyme-Linked Immunosorbent Assay for the Determination of Anti-Bordetella pertussis Antibodies
    American Society for Microbiology ; 2011
    In:  Clinical and Vaccine Immunology Vol. 18, No. 4 ( 2011-04), p. 615-620
    Details
    In: Clinical and Vaccine Immunology, American Society for Microbiology, Vol. 18, No. 4 ( 2011-04), p. 615-620
    Abstract: During Bordetella pertussis infection, it has been established that an increase of anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibodies occurs. Immunoblots from two manufacturers using FHA and PT antigens were compared with an enzyme-linked immunosorbent assay (ELISA) that used both FHA and PT. One manufacturer used two concentrations of PT bands for the IgG immunoblot, calibrated to the World Health Organization standard for PT in international units (IU/ml), 100 IU/ml (PT-100) and 8 IU/ml (PT). The second immunoblot kit measured antibodies to a single calibrated PT band. Both kits measured IgA antibodies, and one additionally measured IgM antibodies. Two of 41 (5%) ELISA IgM positives were confirmed positive by IgM immunoblotting, suggesting poor specificity of the IgM ELISA. The agreements of the IgG and IgA immunoblots with the ELISA ranged from 72.5% to 85.3%, with only 38 to 51% of IgA positives confirmed by immunoblotting and only 61 to 68% of IgG positives confirmed by immunoblotting. The two immunoblots correlated well with each other, with 91.7% and 94.3% agreement for IgG and IgA, respectively. When the FHA band was used with the PT band as the criterion for positivity, significant differences existed in specificity compared to the ELISA (IgG, 84.1% versus 33.3%; IgA, 82.4% versus 71.0%). When the positive IgA immunoblots (evidence of natural recent infection) were compared to the positive PT-100 IgG immunoblots (evidence of recent infection or vaccination), the PT-100 blot showed a 71% sensitivity in detecting natural recent infection. B. pertussis immunoblots, alone or in combination with ELISAs, can aid in the diagnosis of B. pertussis infection.
    Type of Medium: Online Resource
    ISSN: 1556-6811 , 1556-679X
    URL: Article
    DOI: 10.1128/CVI.00450-10
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
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  • 3
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    Ten‐year retrospective review (2003‐2013) of 56 inpatient admissions to stabilize elevated phenylalanine levels
    Wiley ; 2019
    In:  JIMD Reports Vol. 46, No. 1 ( 2019-03), p. 70-74
    Details
    In: JIMD Reports, Wiley, Vol. 46, No. 1 ( 2019-03), p. 70-74
    Abstract: Phenylketonuria (PKU) is an inherited metabolic disorder affecting phenylalanine metabolism. The Irish incidence is 1:4500. Currently, there are 500 patients under the care of the National Centre for Inherited Metabolic Disorders in Temple Street Children's University Hospital. Current practice is to admit PKU patients with phenylalanine (phe) levels that are consistently out of range despite an intensive multidisciplinary team input on an outpatient basis. The aim of this study was to evaluate changes in phe levels pre, during, and post admissions and to examine if there was a sustained impact post discharge. Fifty‐six patients were admitted between January 2003 and December 2013. Patients were all 〈 18 years of age. Greater than 70% (n = 39) of the reasons for admission were due to multiple issues. Average admission time was 5 days. There was a significant decrease in median phe levels from prior to the admission to during the admission. However, there was a significant increase in median phe levels from during the admission (505 μmol/L) to both the 1‐6 months' and 7‐12 months' time points (618 and 651 μmol/L, respectively). The results highlight that while inpatient admissions can stabilize levels within the acute setting, this is not sustained long term. The ward environment does not accurately replicate home circumstances. This study highlighted that the reasons for admission are most often multifactorial, which is less likely to be resolved during a brief admission period.
    Type of Medium: Online Resource
    ISSN: 2192-8312 , 2192-8312
    URL: Issue
    URL: Article
    DOI: 10.1002/jmd2.v46.1
    DOI: 10.1002/jmd2.12019
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 4
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    Online Resource
    Abstract 3096: Mechanisms of synergy of carboplatin and an EphA2-targeted docetaxel antibody-directed nanotherapeutic
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3096-3096
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3096-3096
    Abstract: Platinum-taxane combinations are widely used to treat solid tumors either in first or later lines of therapy. While effective in many settings, platinum-taxane combinatorial regimens are limited by toxicities. We have recently developed an antibody directed nanotherapeutic (MM-310) encapsulating a docetaxel prodrug, targeted to Ephrin receptor A2 (EphA2). Preclinical investigation of MM-310 revealed that the liposomal formulation leads to prolonged docetaxel exposure of the tumor with decreased exposure of normal tissues leading to a shift in toxicity profile and potentially enabling more safe and effective combinations with platinum-based chemotherapeutics. In this study, we evaluated the activity of MM-310 in combination with carboplatin in several xenograft tumor models and compared it to the activity of free docetaxel in combination with carboplatin at equitoxic dosing. Tolerability of MM-310 in combination with carboplatin in mice was evaluated, including assessing hepatotoxicity. Biodistribution, microdistribution, in vivo tumor growth, and mouse survival studies were performed in lung and ovarian cell line-derived (CDX) and patient-derived xenograft (PDX) models. MM-310 in combination with carboplatin was found to be well tolerated, enabling dosing of both drugs at high doses with maximum tolerability when the drugs were dosed three days apart. Carboplatin increased nanotherapeutic delivery to the tumor in a CDX model of triple negative breast cancer and in a PDX model of ovarian cancer. In vivo studies in lung and ovarian cancer xenograft models showed significant synergy between MM-310 and carboplatin when compared to the monotherapies, as well as when compared to free docetaxel with carboplatin, leading to a significant increase in tumor growth delay and survival (docetaxel/ carboplatin vs. MM-310/carboplatin, 0 vs 50% complete tumor regression, 24 vs 80 days median time to regrowth). Additionally, in the same studies, MM-310 and carboplatin was better tolerated than free docetaxel and carboplatin. In conclusion, we found that MM-310 in combination with carboplatin was significantly better tolerated and more effective than free docetaxel in combination with carboplatin. Mechanistically, the synergistic anti-tumor activity of MM-310 with carboplatin may be partially due to a carboplatin mediated enhancement of nanotherapeutic delivery. The increased preclinical activity of the MM-310/carboplatin combination, together with the high tolerability following scheduling optimization tested in mice, makes this combination a promising regimen that warrants evaluation in clinical trials. Citation Format: Walid S. Kamoun, Andrew J. Sawyer, Christine Pien, Alexander Koshkaryev, Lia Luus, Samantha Merrigan, Gang Sun, Sergey Kozin, Zhaohua Richard Huang, Suresh K. Tipparaju, Dmitri B. Kirpotin, Hannah Xu, Vasileios Askoxylakis, Patrick C. Reynolds, Daryl C. Drummond. Mechanisms of synergy of carboplatin and an EphA2-targeted docetaxel antibody-directed nanotherapeutic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3096. doi:10.1158/1538-7445.AM2017-3096
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-3096
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    Preparatory teachers’ perceptions of school readiness: a survey of Victorian teachers
    Springer Science and Business Media LLC ; 2014
    In:  The Australian Educational Researcher Vol. 41, No. 1 ( 2014-3), p. 109-124
    Details
    In: The Australian Educational Researcher, Springer Science and Business Media LLC, Vol. 41, No. 1 ( 2014-3), p. 109-124
    Type of Medium: Online Resource
    ISSN: 0311-6999 , 2210-5328
    URL: Article
    DOI: 10.1007/s13384-013-0126-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
    detail.hit.zdb_id: 2130100-1
    SSG: 5,3
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  • 6
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    Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease
    Springer Science and Business Media LLC ; 2021
    In:  Orphanet Journal of Rare Diseases Vol. 16, No. 1 ( 2021-12)
    Details
    In: Orphanet Journal of Rare Diseases, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2021-12)
    Abstract: Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, significantly impacts cellular function. Untreated patients die within the first 12 months of life. Clinically, patients present severely malnourished, with diarrhoea and hepatosplenomegaly, many have an inflammatory phenotype, including with hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplant (HCT) had been historically the only treatment available but has a high procedure-related mortality because of disease progression and disease-associated morbidities. More recently, enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) has significantly improved patient survival. However, ERT is life long, expensive and its utility is limited by anti-drug antibodies (ADA) and the need for central venous access. Results We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT—multimodal therapy. In 3/5 an initial response to ERT was attenuated by ADA with associated clinical and laboratory features of deterioration. 1/5 developed anaphylaxis to ERT and the other patient died post HCT with ongoing HLH. All patients received allogeneic HCT. 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. The gastrointestinal symptoms are particularly improved after HCT, with reduced diarrhoea and vomiting. This allows gradual structured normalisation of diet with improved tolerance of dietary fat. Histologically there are reduced cholesterol clefts, fewer foamy macrophages and an improved villous structure. Disease biomarkers also show improvement with ERT, immunotherapy and HCT. Three patients have mixed chimerism after HCT, indicating a likely engraftment-defect in this condition. Conclusion We describe combined ERT, DSR and HCT, multimodal treatment for Wolman disease. ERT and DSR stabilises the sick infant and reduces the formerly described prohibitively high, transplant-associated mortality in this condition. HCT abrogates the problems of ERT, namely attenuating ADA, the need for continuing venous access, and continuing high cost drug treatment. HCT also brings improved efficacy, particularly evident in improved gastrointestinal function and histology. Multimodal therapy should be considered a new paradigm of treatment for Wolman disease patients where there is an attenuated response to ERT, and for all patients where there is a well-matched transplant donor, in order to improve long term gut function, tolerance of a normal diet and quality of life.
    Type of Medium: Online Resource
    ISSN: 1750-1172
    URL: Article
    DOI: 10.1186/s13023-021-01849-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2225857-7
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