48 research outputs found
Suitability of databases in the Asia-Pacific for collaborative monitoring of vaccine safety
Introduction:
Information regarding availability of electronic healthcare databases in the Asia-Pacific region is critical for planning vaccine safety assessments particularly, as COVID-19 vaccines are introduced. This study aimed to identify data sources in the region, potentially suitable for vaccine safety surveillance. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE).
Methods:
Nineteen countries targeted for database reporting were identified using published country lists and review articles. Surveillance capacity was assessed using two surveys: a 9-item introductory survey and a 51-item full survey. Survey questions related to database characteristics, covariate and health outcome variables, vaccine exposure characteristics, access and governance, and dataset linkage capability. Other questions collated research/regulatory applications of the data and local publications detailing database use for research.
Results:
Eleven databases containing vaccine-specific information were identified across 8 countries. Databases were largely national in coverage (8/11, 73%), encompassed all ages (9/11, 82%) with population size from 1.4 to 52 million persons. Vaccine exposure information varied particularly for standardized vaccine codes (5/11, 46%), brand (7/11, 64%) and manufacturer (5/11, 46%). Outcome data were integrated with vaccine data in 6 (55%) databases and available via linkage in 5 (46%) databases. Data approval processes varied, impacting on timeliness of data access.
Conclusions:
Variation in vaccine data availability, complexities in data access including, governance and data release approval procedures, together with requirement for data linkage for outcome information, all contribute to the challenges in building a distributed network for vaccine safety assessment in the Asia-Pacific and globally. Common data models (CDMs) may help expedite vaccine safety research across the region
Epidemiology and costs of cervical cancer screening and cervical dysplasia in Italy
<p>Abstract</p> <p>Background</p> <p>We estimated the number of women undergoing cervical cancer screening annually in Italy, the rates of cervical abnormalities detected, and the costs of screening and management of abnormalities.</p> <p>Methods</p> <p>The annual number of screened women was estimated from National Health Interview data. Data from the Italian Group for Cervical Cancer Screening were used to estimate the number of positive, negative and unsatisfactory Pap smears. The incidence of CIN (cervical intra-epithelial neoplasia) was estimated from the Emilia Romagna Cancer Registry. Patterns of follow-up and treatment costs were estimated using a typical disease management approach based on national guidelines and data from the Italian Group for Cervical Cancer Screening. Treatment unit costs were obtained from Italian National Health Service and Hospital Information System of the Lazio Region.</p> <p>Results</p> <p>An estimated 6.4 million women aged 25–69 years undergo screening annually in Italy (1.2 million and 5.2 million through organized and opportunistic screening programs, respectively). Approximately 2.4% of tests have positive findings. There are approximately 21,000 cases of CIN1 and 7,000–17,000 cases of CIN2/3. Estimated costs to the healthcare service amount to €158.5 million for screening and €22.9 million for the management of cervical abnormalities.</p> <p>Conclusion</p> <p>Although some cervical abnormalities might have been underestimated, the total annual cost of cervical cancer prevention in Italy is approximately €181.5 million, of which 87% is attributable to screening.</p
Isotropic 3D Nuclear Morphometry of Normal, Fibrocystic and Malignant Breast Epithelial Cells Reveals New Structural Alterations
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis
MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4
MicroRNA-21 (miR-21) is a key regulator of oncogenic processes. It is significantly elevated in the majority of human tumors and functionally linked to cellular proliferation, survival and migration. In this study, we used two experimental-based strategies to search for novel miR-21 targets. On the one hand, we performed a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE) to identify proteins suppressed upon enhanced miR-21 expression in LNCaP human prostate carcinoma cells. The tumor suppressor acidic nuclear phosphoprotein 32 family, member A (ANP32A) (alias pp32 or LANP) emerged as the most strongly downregulated protein. On the other hand, we applied a mathematical approach to select correlated gene sets that are negatively correlated with primary-miR-21 (pri-miR-21) expression in published transcriptome data from 114 B-cell lymphoma cases. Among these candidates, we found tumor suppressor SMARCA4 (alias BRG1) together with the already validated miR-21 target, PDCD4. ANP32A and SMARCA4, which are both involved in chromatin remodeling processes, were confirmed as direct miR-21 targets by immunoblot analysis and reporter gene assays. Furthermore, knock down of ANP32A mimicked the effect of enforced miR-21 expression by enhancing LNCaP cell viability, whereas overexpression of ANP32A in the presence of high miR-21 levels abrogated the miR-21-mediated effect. In A172 glioblastoma cells, enhanced ANP32A expression compensated for the effects of anti-miR-21 treatment on cell viability and apoptosis. In addition, miR-21 expression clearly increased the invasiveness of LNCaP cells, an effect also seen in part upon downregulation of ANP32A. In conclusion, these results suggest that downregulation of ANP32A contributes to the oncogenic function of miR-21
Risk factors for respiratory syncytial virus bronchiolitis hospital admission in New Zealand.
This study assessed risk factors for respiratory syncytial virus (RSV) hospitalization and disease severity in Wellington, New Zealand. During the southern hemisphere winter months of 2003--2005, 230 infants aged < 24 months hospitalized with bronchiolitis were recruited. RSV was indentified in 141 (61%) infants. Comparison with data from all live hospital births from the same region (2003--2005) revealed three independent risk factors for RSV hospitalization: birth between February and July [adjusted risk ratio (aRR) 1.62, 95% confidence interval (CI) 1.5-2.29], gestation <37 weeks (aRR 2.29, 95% CI 1.48-3.56) and Māori ethnicity (aRR 3.64, 95% CI 2.27-5.85), or Pacific ethnicity (aRR 3.60, 95% CI 2.14-6.06). The high risk for Māori and Pacific infants was only partially accounted for by other known risk factors. This work highlights the importance of RSV disease in indigenous and minority populations, and identifies the need for further research to develop public health measures that can reduce health disparities
Treatment patterns and associated costs for genital warts in Italy
Objective: Genital warts are caused by human papillomavirus (HPV), principally types 6 and 11, and are highly contagious. This study assessed treatment patterns and costs of management of genital warts in Italy. Research design and methods: This was a retrospective, observational study conducted among gynaecologists, dermatologists, and specialists at sexually transmitted disease clinics in Italy. Resource-use data related to genital warts were collected for patients at risk in the age range 14-64 years examined during 2005. Unit costs were assigned to resource use to provide estimates of the direct, indirect and total costs per case of genital warts. Results: Twenty-eight investigators enrolled 341 patients aged 15-64 years, including 194 (56.9%), 81 (23.7%) and 66 (19.4%) patients with newly diagnosed, recurrent and resistant genital warts, respectively. Most patients (333/341; 97.7%) had at least one outpatient visit, while 43 (12.6%) patients were hospitalised, including 39 patients without an overnight stay (day-hospital cases, 11.4%). Self-applied medication was prescribed for 124 (36.4%) patients. Most outpatient cases (267/333; 80.2%) underwent an office-based procedure. Mean annual direct medical costs per patient, which were funded predominantly by the Italian National Health Service (there was some patient co-payment), were E242 for men and E332 for women. When productivity losses were included, mean total annual costs were E325 for men and E464 for women. Conclusions: This is the first study of treatment patterns and costs for genital warts in Italy. Treatment patterns differ in some respects from those observed in other European countries, but costs generally appear similar. Despite the limitations of physician selection bias and over-representation of North Italy in the patient sample, the findings of this study may be useful in estimating the cost-effectiveness of introducing a quadrivalent HPV vaccination programme in Italy. © 2008 Informa UK Ltd. All rights reserved
Nuclear shape changes are induced by knockdown of the SWI/SNF ATPase BRG1 and are independent of cytoskeletal connections.
Changes in nuclear morphology occur during normal development and have been observed during the progression of several diseases. The shape of a nucleus is governed by the balance of forces exerted by nuclear-cytoskeletal contacts and internal forces created by the structure of the chromatin and nuclear envelope. However, factors that regulate the balance of these forces and determine nuclear shape are poorly understood. The SWI/SNF chromatin remodeling enzyme ATPase, BRG1, has been shown to contribute to the regulation of overall cell size and shape. Here we document that immortalized mammary epithelial cells show BRG1-dependent nuclear shape changes. Specifically, knockdown of BRG1 induced grooves in the nuclear periphery that could be documented by cytological and ultrastructural methods. To test the hypothesis that the observed changes in nuclear morphology resulted from altered tension exerted by the cytoskeleton, we disrupted the major cytoskeletal networks and quantified the frequency of BRG1-dependent changes in nuclear morphology. The results demonstrated that disruption of cytoskeletal networks did not change the frequency of BRG1-induced nuclear shape changes. These findings suggest that BRG1 mediates control of nuclear shape by internal nuclear mechanisms that likely control chromatin dynamics
Farm exposure in utero may protect against asthma, hay fever and eczema.
The aim of the present study was to assess which factors contribute to the lower prevalence of allergic diseases in farmers' children, and the importance of timing of exposure. In a cross-sectional questionnaire survey, asthma symptoms, hay fever and eczema were assessed, as well as current, early and prenatal farm-related exposures in 1,333 farmers' children and 566 reference children aged 5-17 yrs. Farmers' children had a lower incidence of asthma symptoms and eczema. Current and maternal exposure during pregnancy to animals and/or grain and hay reduced the risk of asthma symptoms, hay fever and eczema. The exposure-response association for maternal exposure was nonlinear for most outcomes. After mutual adjustment, the effects of prenatal exposure remained unchanged whereas current exposure remained protective only for asthma medication, asthma ever and hay fever. Exposure during the first 2 yrs was not associated with symptoms, after controlling for prenatal exposure. A combination of prenatal and current exposure was most strongly associated with wheeze (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.80), asthma medication (OR 0.50, 95% CI 0.30-0.82), asthma ever (OR 0.50, 95% CI 0.33-0.76), hay fever (OR 0.47, 95% CI 0.30-0.73) and eczema (OR 0.46, 95% CI 0.30-0.70). Prenatal exposure may contribute to the low prevalence of asthma, hay fever and eczema in farmers' children, but continued exposure may be required to maintain optimal protection