Browsing by Subject "Screening"
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Item Open Access Development, validation, and evaluation of a risk assessment tool for personalized screening of gastric cancer in Chinese populations.(BMC medicine, 2023-04) Zhu, Xia; Lv, Jun; Zhu, Meng; Yan, Caiwang; Deng, Bin; Yu, Canqing; Guo, Yu; Ni, Jing; She, Qiang; Wang, Tianpei; Wang, Jiayu; Jiang, Yue; Chen, Jiaping; Hang, Dong; Song, Ci; Gao, Xuefeng; Wu, Jian; Dai, Juncheng; Ma, Hongxia; Yang, Ling; Chen, Yiping; Song, Mingyang; Wei, Qingyi; Chen, Zhengming; Hu, Zhibin; Shen, Hongbing; Ding, Yanbing; Li, Liming; Jin, GuangfuBackground
Effective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population.Methods
In this three-stage multicenter study, we first selected eligible variables by Cox regression models and constructed a GC risk score (GCRS) based on regression coefficients in 416,343 subjects (aged 40-75 years) from the China Kadoorie Biobank (CKB, development cohort). In the same age range, we validated the GCRS effectiveness in 13,982 subjects from another independent Changzhou cohort (validation cohort) as well as in 5348 subjects from an endoscopy screening program in Yangzhou. Finally, we categorized participants into low (bottom 20%), intermediate (20-80%), and high risk (top 20%) groups by the GCRS distribution in the development cohort.Results
The GCRS using 11 questionnaire-based variables demonstrated a Harrell's C-index of 0.754 (95% CI, 0.745-0.762) and 0.736 (95% CI, 0.710-0.761) in the two cohorts, respectively. In the validation cohort, the 10-year risk was 0.34%, 1.05%, and 4.32% for individuals with a low (≤ 13.6), intermediate (13.7~30.6), and high (≥ 30.7) GCRS, respectively. In the endoscopic screening program, the detection rate of GC varied from 0.00% in low-GCRS individuals, 0.27% with intermediate GCRS, to 2.59% with high GCRS. A proportion of 81.6% of all GC cases was identified from the high-GCRS group, which represented 28.9% of all the screened participants.Conclusions
The GCRS can be an effective risk assessment tool for tailored endoscopic screening of GC in China. Risk Evaluation for Stomach Cancer by Yourself (RESCUE), an online tool was developed to aid the use of GCRS.Item Open Access Diagnostic Performance of a Rapid Syphilis Test Among Pregnant Women in Peru(2011) Roehl, Kristen MarieBackground: Maternal and congenital syphilis are pressing concerns in Latin America, with consequences ranging from newborn mental retardation to perinatal death. Widespread, accurate screening and timely penicillin treatment can help. Simple, affordable, point of care rapid syphilis tests (RSTs) promise to improve screening coverage among pregnant women.
Methods: From September 2009 to November 2010, Project CISNE implemented the SD Bioline Syphilis 3.0 RST into two health networks, offering the test to pregnant women aged 16 55 who attended antenatal care, delivery/postpartum, and abortion services. The performance analysis compared Bioline RST results with reference standards TPPA and RPR+TPPA, adjusting estimates according to sampling realities.
Results: 17,147 rapid syphilis tests were performed in the field and 11,169 were screened in the central laboratory. Syphilis prevalence was 1.05% (0.73% adjusted) according to the gold standard vs. 0.90% according to the field RST. The Bioline RST displayed an unadjusted sensitivity of 91.0% (95% CI 86.4 95.0) and specificity of 99.1% (98.1 99.6) compared to TPPA, and an unadjusted sensitivity of 91.5% (84.8 95.8) and specificity of 99.6% (99.4 99.7) compared to RPR+TPPA. When adjusted, overall sensitivity and specificity compared to RPR+TPPA were 86.5% (78.8 92.0) and 99.7% (99.6 99.8), respectively. The Bioline RST yielded more false positive than false negative results due to the observed low prevalence.
Discussion: Despite limitations, this study displays the field RST to be reliable, reproducible, as valid as previous studies, and diagnostically apt for implementation in maternal care services in Peru.
Item Open Access Essays on Constrained Information Acquisition(2023) Sassano, TaishiThis dissertation explores the theory of constrained information acquisition and its application. I will provide theoretical models to study how economic agents who are facing limited ability to process information acquire information and how the information acquisition affects the trade mechanism in binary trades.
First, I study a dynamic information acquisition problem of an individual who faces a limited ability to process information. The individual acquires information to predict a payoff-relevant state such as the market condition in two periods. I characterize the optimal information structure and discuss how we can identify the discount factor and the information capacity. Under the optimal information acquisition, he uses three types of learning strategies depending on how certain he is about the state. In addition, I will provide two ways to identify the discount factor and the information capacity from the observed data.
Second, I will explore an application of the costly information acquisition model. I study a trade model where buyers costly acquire information about a good and a seller offers menus of an upfront fee and a strike price to screen the buyers’ ability to process information in order to differentiate the buyers. I first provide the buyer's optimal information acquisition problem and then the seller's optimal selling mechanism. The willingness to pay for the strike price depends on the ability to process information. The seller offers a higher strike price to a buyer with higher ability and a higher participation fee to extract the surplus.
Item Open Access Evaluating the Feasibility of Self-sampling using CareHPV™ and Treatment with Cryotherapy in Haiti(2018) Vaez, AlliaIntroduction: Cervical cancer is one of the leading causes of death for women in Haiti. The purpose of this study was to evaluate the feasibility of HPV self-sampling using CareHPV™ and subsequent treatment with cryotherapy in urban and rural areas of Haiti. CareHPV™ is a vaginal self-sample HPV testing kit used to detect 14 types of high-risk HPV and cryotherapy is a form of treatment that freezes precancerous lesions with CO2 or nitrous oxide. Methods: The study took place in Port-au-Prince and three rural communities within the suburban commune of Leogane. Screening took place at clinics, community centers, and churches. Participants were given consent forms to sign, as well as a demographic questionnaire and an acceptability survey. If their HPV test result was positive, they were called up to three times to go the community clinic for treatment. The number of women that returned for treatment following a positive HPV test result were compared in the urban and rural communities with a chi square test of association and a prevalence rate ratio. Acceptability was measured quantitatively on the Likert Scale. Results: Feasibility was defined as 80% acceptability and 80% treatment uptake. Other factors related to feasibility such as screening numbers and geographical barriers were discussed. Eighty percent acceptability was reached in both rural and urban communities. Eighty percent treatment uptake was only reached in the rural communities, with a treatment uptake of 83.3%. Eighty percent treatment uptake was not reached in the urban communities, with a treatment uptake of 42.1%. The prevalence rate ratio of 1.98 indicates that rural participants were found to be nearly twice as likely to return for treatment than urban participants. The chi square test of association shows that this difference in treatment uptake is significant with an estimated p-value of 0.01 at an alpha of 0.05. Further research is needed to investigate the reasons for higher loss to follow-up for treatment in urban communities to further efforts to establish a national HPV screening program in Haiti.
Item Open Access Functional Interrogation Of Anti-Cancer Drug Resistance(2017) Winter, Peter SavilleTargeted therapeutics are among the most promising approaches for treating diverse forms of malignancies. Indeed, as sequencing prices and technology continue to improve it will be possible to achieve a precise map of each individual cancer’s genomic lesions, providing insights into the best strategies for treatment. However, these approaches will be undermined by cancer’s ability to resist upfront target inhibition (intrinsic resistance) as well as, in cases where tumors are initially sensitive, develop resistance over the course of drug treatment (acquired resistance). The literature to date reveals a problem as complex as the tumor itself; the heterogeneity of cancer as a disease is matched by the myriad ways in which it evades treatment.
Understanding drug resistance as a whole quickly becomes a problem of scale. Not only is there cancer subtype-associated variation to consider, but also intrinsic and acquired resistance profiles can differ based on the type of inhibitor used and at what node the offending pathway is inhibited. Assigning proper treatments to account for these mechanisms adds an additional layer of complexity as the number of FDA-approved and late-stage clinical candidate molecules increases. Here, when applied appropriately, high throughput methods offer the ability to screen thousands of perturbations in parallel, quickly narrowing the search space for a phenotype of interest.
This work applies such methods to the cell-autonomous complexity of drug resistance and seeks to understand (1) mechanisms by which cancer cells evade drug treatment, (2) design concepts for the most effective combinatorial drugging strategies, and (3) how it might be possible to account for resistance-associated heterogeneity by targeting the evolutionary liabilities of resistant cells. Using a combination of open reading frame (ORF), clustered regularly spaced short palindromic repeats (CRISPR), and pharmacologic screening technologies, this work attains the resolution and throughput necessary to address 1-3 above and begins to unravel the complexity of drug resistance.
Item Open Access Health Disparities and Prostate Cancer: Can Educational Status, Race and Geographical Distance to Care Facilities Impact Risk and Severity on Initial Biopsy?(2013) Gaines, Alexis RuthIntroduction: Prostate Cancer (PC) screening has become a controversial topic both in the United States and abroad, stimulating debates surrounding who should and should not be screened. United States (USA) population-based studies have established a link between race and PC risk, but whether race predicts PC after adjusting for clinical characteristics is unclear. In Brazil, where cancer registries are limited, underprivileged men have limited access to both education and health care due to geographic barriers. Thus, we investigated the association between, educational status, geographic distance from screening site to follow-up care facility and non-compliance with having cancer, and, risk of low and high-grade PC in men undergoing initial prostate biopsy in equal access medical centers in the USA and Brazil.
Materials & Methods: In our first analysis, we conducted a retrospective record review of 887 men (49.1% black, 50.9% white) from the Durham Veterans Affairs Medical Center (DVAMC) who underwent initial prostate biopsy between 2001 and 2009. Multivariable logistic regression analysis of race and biopsy outcome was conducted adjusting for age, body mass index (BMI), number of cores taken, prostate specific antigen (PSA), and digital rectal exam (DRE) findings. Multinomial logistic regression was used to test the association between black race and PC grade (Gleason <7 vs. >7). Our second analysis used data from the Barretos Cancer Hospital (BCH) screening study, another retrospective record review of 1,561 men who were recommended to prostate biopsy after obtaining an initial screen on the medical mobile units between 2004 and 2007. Multivariable logistic regression analysis of geographic distance from screening site to BCH (km), maximum level of education achieved, and risk of non-compliance was performed adjusting for age and calendar year of biopsy. Among those who complied with biopsy recommendations and received a biopsy (n=850), multivariable logistic regression analyses were conducted to test the association between geographic distance, educational achievement and having PC. Of those men with PC, a multinomial logistic regression test was used to evaluate the association between geographic distance, educational attainment and risk of low and high-grade PC (Gleason <7 vs. >7).
Results: In the DVAMC study, Black men were younger at biopsy (median: 61 vs. 65 years, p<0.001), and had a higher pre-biopsy total PSA (tPSA, median: 6.6 vs. 5.8ng/ml, p=0.001) than white men. A total of 499 (56.3%) men had PC on biopsy (245 low-grade; 254 high-grade). In multivariable analyses, black race was significantly predictive of PC overall (odds ratio, [OR]: 1.50, 1.12 - 2.00, p=0.006), and high-grade PC (relative risk ratio [RRR]: 1.84, 1.28 - 2.66, p=0.001), but was not significantly associated with low-grade PC (RRR: 1.29, 0.92 - 1.80, p=0.139). In the BCH studies, non-compliant men were older at initial screen (median: 68 vs. 66 years, p<0.001), had a higher tPSA (median: 4.90 vs. 4.2 ng/mL, 0<0.001), were less likely to have an abnormal DRE (19.5% vs. 33.4%, p<0.001), had less education (low education: illiterate or incomplete primary, vs. high education: complete primary, high school or college, 1,402 vs. 159, p=0.14, data not shown) and were more likely to live more than 500km from BCH (66.3% vs. 19.6%, p<0.001) when compared to men who complied with biopsy recommendations. On crude and multivariable analyses, non-compliance was significantly associated with increased distance from screening site to BCH relative to traveling less than 250km for care (250-500km: OR: 2.00, 500-1000km: OR: 5.88, >1000 km: OR: 15.98, p<0.001). On crude and multivariable analysis, increased educational attainment relative to being illiterate had a protective association with non-compliance (incomplete primary: OR: 0.53, complete primary: OR: 0.33, p<0.001, high school + college: OR: 0.87, p=0.64). Of the screened men who were recommended to and had an initial biopsy, 320 men had cancer (207 low-grade, 113 high-grade). Stratified by educational status, illiterate men were older at biopsy (median: 69 vs. 65 vs. 64 vs. 58 years, p<0.001), and had a higher tPSA at screening (median: 6.04 vs. 4.47 vs. 4.73 vs. 4.16, p=0.001). There were no differences, based on education, distance from screen site to Barretos (p=0.43), year of screening (p=0.08), number of abnormal DREs (p=0.42) or family history of cancer, especially PC (p=0.07). Before biopsy, confirmatory median tPSA was 7 (IQR: 4 - 16 ng/mL). With respect to PC on initial biopsy, there was no association between distance from screening site to BCH (relative to < 250km) and increased education achievement. On multinomial analysis, educational achievement showed an association with neither low nor high-grade cancer relative to no cancer. There was no association between increased distance and low-grade PC. There was no association between traveling 500-1000km (p=0.96) or >1000km (p=0.15) and high-grade cancer; however, there was a significant association between traveling 250-500km relative to <250km and high-grade PC risk (RRR: 2.44, 95% p=0.04).
Conclusion: In a USA-based equal access health care facility, black race was associated with greater risk of PC detection on initial biopsy and of high-grade cancer after adjusting for clinical characteristics. In Brazil, where cancer data are limited, education and geographic distance from point of screening to care facility are not associated with having PC on biopsy or biopsy grade. Distance was, however, significantly associated with risk of non-compliance after primary screen. Thus, additional investigation of mechanisms linking black race and PC risk and PC aggressiveness is needed.
Item Open Access Microfluidics-generated Double Emulsion Platform for High-Throughput Screening and Multicellular Spheroid Production with Controllable Microenvironment(2015) Chan, Hon FaiHigh-throughput processing technologies hold critical position in biomedical research. These include screening of cellular response based on phenotypic difference and production of homogeneous chemicals and biologicals for therapeutic applications. The rapid development of microfluidics technology has provided an efficient, controllable, economical and automatable processing platform for various applications. In particular, emulsion droplet gains a lot of attention due to its uniformity and ease of isolation, but the application of water-in-oil (W/O) single emulsion is hampered by the presence of the oil phase which is incompatible with aqueous phase manipulation and the difficulty in modifying the droplet environment.
This thesis presents the development of a double emulsion (DE) droplet platform in microfluidics and two applications: (1) high-throughput screening of synthetic gene and (2) production of multicellular spheroids with adjustable microenvironment for controlling stem cell differentiation and liver tissue engineering. Monodisperse DE droplets with controllable size and selective permeability across the oil shell were generated via two microfluidics devices after optimization of device design and flow rates.
Next, bacterial cells bearing synthetic genes constructed from an inkjet oligonucleotide synthesizer were encapsulated as single cells in DE droplets. Enrichment of fluorescent signals (~100 times) from the cells allowed quantification and selection of functionally-correct genes before and after error correction scheme was employed. Permeation of Isopropyl β-D-1-thiogalactopyranoside (IPTG) molecules from the external phase triggered target gene expression of the pET vector. Fluorescent signals from at least ~100 bacteria per droplet generated clearly distinguishable fluorescent signals that enabled droplets sorting through fluorescence-activated cell sorting (FACS) technique.
In addition, DE droplets promoted rapid aggregation of mammalian cells into single spheroid in 150 min. Size-tunable human mesenchymal stem cells (hMSC) spheroids could be extracted from the droplets and exhibited better differentiation potential than cells cultured in monolayer. The droplet environment could be altered by loading matrix molecules in it to create spheroid-encapsulated microgel. As an example, hMSC spheroid was encapsulated in alginate or alginate-RGD microgel and enhanced osteogenic differentiation was found in the latter case.
Lastly, the capability of forming spheroids in DE droplet was applied in liver tissue engineering, where single or co-culture hepatocyte spheroids were efficiently produced and encapsulated in microgel. The use of alginate-collagen microgel significantly improved the long-term function of the spheroid, in a manner similar to forming co-culture spheroids of hepatocytes and endothelial progenitor cells at a 5 to 1 ratio. The hepatocyte spheroid encapsulated in microgel could be useful for developing bioartificial liver or drug testing platform or applied directly for hepatocyte transplantation.
Item Open Access Prevalence and Risk Factors of Postpartum Depression in Two MOH Areas in Sri Lanka: A Mixed Methods Study(2019) Fan, QipingBackground: Previous studies in Sri Lanka showed a high prevalence- 30% of postpartum depression (PPD). PPD screening using the Edinburgh Postnatal Depression Scales (EPDS) was included in postnatal care in 2012. This study aimed to estimate the prevalence of PPD in 2017 in two medical offices of health (MOH) areas, identify the association between risk factors and presence of postpartum depression, understand current practice, challenges, and suggestions of PPD screening in Sri Lanka.
Methods: The study consists of a population-based quantitative study and a qualitative study. PPD outcomes were assessed by mothers’ responses to the EPDS. Potential factors were extracted from routine paper-based medical records. The association was examined at unadjusted level first, and at adjusted level using multivariate linear regression and multivariate logistic regression models. Individual in-depth interviews were conducted among public health midwives. Framework approach was adopted to analyze the transcripts.
Results: The prevalence of PPD was 15.5% and 7.8% among mothers assessed 10 days postpartum (in Dankotuwa) and 4 weeks postpartum (in Bope Poddala), respectively. PPD was associated with earlier screening time, mothers’ delivery age > 35, >= 4 living children, and mothers’ illness. Mothers who attended prenatal sessions and whose partners were employed were less likely to report potential PPD. Other risk factors of PPD noted from interviews include socio-economic factors, interpersonal relationship, mother’s disease history, delivery method, and baby’s illness. The challenges of screening PPD included social stigma, mother’s difficulty of understanding EPDS and lack of privacy at home.
Conclusions: Mothers exposed to various socio-economic, interpersonal, and other risk factors deserve special attention. Family-based interventions, further cultural validation of EPDS, development of risk-assessing instrument could be introduced for future practice. Future research on other risk factors for PPD with larger sample size should be conducted, and qualitative research could engage other stakeholders in maternal mental health care to assess the accessibility, capacity, and quality of PPD care.
Item Open Access Training Female Community Health Volunteers(FCHVs) for Cardiovascular Risk Screening in Lalitpur, Nepal: A Mixed Methods Feasibility Study(2018) Sun, YuewenBackground: Faced with the surging trends of cardiovascular diseases (CVDs) and the limited numbers of health professionals in Nepal, more innovative measures should be explored to tackle the challenges of CVD prevention and control. This study explored the feasibility of shifting some CVD-related tasks to the community by engaging female community health volunteers (FCHVs) for CVD risk screening. Methods: This study was conducted in a rural and an urban study site in Lalitpur (Kathmandu Valley), Nepal. Mixed methods were employed in this study. Ten FCHVs were recruited and trained to use the Cardiovascular Risk Scoring Chart adapted from the World Health Organization’s Package for Essential Non-Communicable Diseases (PEN). After the training, FCHVs administered cardiovascular risk factor questionnaires and used the risk scoring chart to screen eligible community residents in their catchment area. Using the data collected by FCHVs, a medical doctor calculated the second risk score with the same risk scoring chart. A kappa concordance test was used to compare these two sets of risk screening results for agreement, and a sensitivity and specificity test was conducted to assess the reliability of the FCHVs’ CVD risk screening results. Two focus group discussions were administered to investigate the FCHVs’ training and fieldwork experiences during the study. Results: There were 491 community residents screened for cardiovascular risk at two study sites. The mean level of agreement between the two sets of risk screening results was 94.5% (Kappa = 0.77, P < 0.05). The sensitivity of the FCHV screening test was 90.3% (95% CI [0.801, 0.964]); and the specificity was 97% (95% CI [0.948, 0.984]). In the FGD, FCHVs expressed a strong enthusiasm and readiness for NCD related work. Besides, all FCHVs agreed that they could manage their current workload and were confident that they could perform more tasks for the prevention and control of NCDs with the proper training. More NCD-related programs and training are called for by FCHVs. Conclusions: It is feasible to train FCHVs to use the simple cardiovascular scoring chart to screen and identify community residents at high risk of developing CVDs. Although FCHVs expressed interests in taking on more responsibility regarding the prevention and control of NCDs, further studies are needed to assess the feasibility of engaging FCHVs within the existing healthcare system.