Global Mental Health: Where We Are and Where We Are Going.

PURPOSE OF REVIEW: To summarize recent findings in global mental health along several domains including socioeconomic determinants, inequities, funding, and inclusion in global mental health research and practice. RECENT FINDINGS: Mental illness continues to disproportionately impact vulnerable populations and treatment coverage continues to be low globally. Advances in integrating mental health care and adopting task-shifting are accompanied by implementation challenges. The mental health impact of recent global events such as the COVID-19 pandemic, geo-political events, and environmental change is likely to persist and require coordinated care approaches for those in need of psychosocial support. Inequities also exist in funding for global mental health and there has been gradual progress in terms of building local capacity for mental health care programs and research. Lastly, there is an increasing effort to include people with lived experiences of mental health in research and policy shaping efforts. The field of global mental health will likely continue to be informed by evidence and perspectives originating increasingly from low- and middle-income countries along with ongoing global events and centering of relevant stakeholders.

Centering healthcare workers in digital health design: Usability and acceptability of two-way texting to improve retention in antiretroviral therapy in a public HIV clinic in Lilongwe, Malawi.

New initiates on antiretroviral therapy (ART) are at high risk of treatment discontinuation, putting their health at risk. In low- and middle-income countries, like Malawi, appropriate digital health applications (apps) must fit into local clinic, connectivity and resource constraints. We describe the human centered design (HCD) and development process of an open-source, hybrid, two-way texting (2wT) system to improve ART retention. We detail the critical role of diverse healthcare workers (HCWs) in the HCD process to inform app usability, create buy-in, and ensure appropriate optimization for the local context. We optimized 2wT usability and acceptability over three HCD phases: 1) informal feedback sessions with diverse 2wT stakeholders, 2) a small pilot, and 3) key informant interviews. Phase one included four sessions with diverse HCWs, including "expert ART clients", clinical, technical, supervisory, and evaluation teams to inform 2wT design. In phase 2, a small pilot with 50 participating ART clients aimed to inform implementation improvement. Phase three included interviews with ten HCWs to deepen understanding of 2wT acceptability and usability, documenting strengths and weaknesses to inform optimization. Multi-phase feedback sessions with HCWs helped refine 2wT language and message timing for both weekly and tailored client-specific visit reminders. The pilot led to improvements in educational materials to guide client responses and ease interaction with HCWs. In interviews, the HCWs appreciated the HCD co-creation process, suggested ways to increase access for low-literacy clients or those without consistent phone access, and felt integrating 2wT with other eHealth platforms would improve scalability. Inclusion of HCWs across phases of HCD design, adaption, and optimization increased 2wT usability and acceptability among HCWs in this setting. Engaging HCWs into 2wT co-ownership from inception appears successful in co-creation of an app that will meet HCW needs, and therefore, enhance support for 2wT clients to attend visits and remain in care.

Crossing the digital divide: The workload of manual data entry for integration between mobile health applications and eHealth infrastructure.

Background: Many digital health interventions (DHIs), including mobile health (mHealth) apps, aim to improve both client outcomes and efficiency like electronic medical record systems (EMRS). Although interoperability is the gold standard, it is also complex and costly, requiring technical expertise, stakeholder permissions, and sustained funding. Manual data linkage processes are commonly used to "integrate" across systems and allow for assessment of DHI impact, a best practice, before further investment. For mHealth, the manual data linkage workload, including related monitoring and evaluation (M&E) activities, remains poorly understood. Methodology: As a baseline study for an open-source app to mirror EMRS and reduce healthcare worker (HCW) workload while improving care in the Nurse-led Community-based Antiretroviral therapy Program (NCAP) in Lilongwe, Malawi, we conducted a time-motion study observing HCWs completing data management activities, including routine M&E and manual data linkage of individual-level app data to EMRS. Data management tasks should reduce or end with successful app implementation and EMRS integration. Data was analysed in Excel. Results: We observed 69:53:00 of HCWs performing routine NCAP service delivery tasks: 39:52:00 (57%) was spent completing M&E data related tasks of which 15:57:00 (23%) was spent on manual data linkage workload, alone. Conclusion: Understanding the workload to ensure quality M&E data, including to complete manual data linkage of mHealth apps to EMRS, provides stakeholders with inputs to drive DHI innovations and integration decision making. Quantifying potential mHealth benefits on more efficient, high-quality M&E data may trigger new innovations to reduce workloads and strengthen evidence to spur continuous improvement.

"We have been so patient because we know where we are coming from" Exploring the acceptability and feasibility of a mobile electronic medical record system designed for community-based antiretroviral therapy in Lilongwe, Malawi.

Background: Mobile health (mHealth) is reshaping healthcare delivery, especially in HIV management. The World Health Organization advocates for mHealth to provide healthcare workers (HCWs) with real-time data, enhancing patient care. However, in Malawi's Lighthouse Trust antiretroviral therapy (ART) clinic, the nurse-led community-based ART (NCAP) program faces hurdles with data management due to lack of access to electronic medical records systems (EMRS) in the community setting. EMRS is not typically available in differentiated service delivery settings where reliable power and internet are often unavailable. We used human-centered design (HCD) processes to create a mobile EMRS prototype, the Community-based ART Retention and Suppression (CARES) app. We explore progress to simplify workflow for HCWs and improve client care. Methods: To evaluate the CARES app's feasibility and acceptability among NCAP HCWs, we conducted in-depth interviews among 15 NCAP HCWs. We used a rapid qualitative analysis approach guided by the extended Technology Acceptance Model. The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ). Results: As a likely result of HCD, HCWs demonstrated high expectations for the CARES app to improve healthcare delivery and data management. However, challenges such as app performance, data integration, and system navigation were significant barriers to acceptance or feasibility. Despite challenges, HCWs remained optimistic about the potential for CARES to enhance NCAP clinical decision-making and data flow. HCWs emphasized the need for continuous training and stakeholder engagement, improved infrastructure, data security protections, and establishing the CARES app and EMRS integration to facilitate CARES' longterm success at scale. Conclusion: The study's findings underscore the importance of HCD for mHealth buy-in. As HCWs were invested in CARES success, they remained optimistic that the app could enhance NCAP services if user experience and app performance improved. Incorporation of HCW feedback would help deliver beyond the promise of CARES.

The effect of proactive, interactive, two-way texting on 12-month retention in antiretroviral therapy: findings from a quasi-experimental study in Lilongwe, Malawi.

Background: Retaining clients on antiretroviral therapy (ART) is challenging especially during the first year on ART. Mobile health (mHealth) interventions show promise to close retention gaps. We aimed to assess reach (who received the intervention?) and effectiveness (did it work?) of a hybrid two-way texting (2wT) intervention to improve ART retention at a large public clinic in Lilongwe, Malawi. Methods: Between August 2021 - June 2023, a quasi-experimental study compared outcomes between two cohorts of new ART clients: 1) those opting into 2wT with combined automated, weekly motivation short messaging service (SMS) messages and response-requested appointment reminders; and 2) a matched historical cohort receiving standard of care (SoC). Reach was defined as "the proportion clients ≤6 months of ART initiation eligible for 2wT". 2wT effectiveness was assessed in time-to-event analysis comparing Kaplan-Meier plots of 6- and 12-month retention between 2wT and SoC using a log-rank test. The effect of 2wT on ART drop out was estimated using multivariable Cox proportional hazard models, adjusting for sex, age and WHO stage at ART initiation. Results: Of the 1,146 clients screened, 645 were ineligible (56%) largely due to lack of phone access (393/645; 61%) and illiteracy (149/645; 23%): a reach of 44%. Among 468 2wT participants, the 12-month probability of ART retention was 91% (95%CI: 88% - 93%) compared to 75% (95%CI: 71% - 79%) among 468 SoC participants (p<0.0001). Compared to SoC participants, 2wT participants had a 62% lower hazard of dropping out of ART care at all time points (hazard ratio 0.38, 95% CI: 0.26-0.54; p<0.001). Conclusions: Not all clients were reached with 2wT. For those who opted-in, 2wT reduced drop out throughout the first year on ART and significantly increased 12-month retention. The proactive 2wT approach should be expanded as a complement to other interventions in routine, low-resource settings to improve ART retention.

Cost-effectiveness analysis of two-way texting (2wT) intervention to improve ART retention among newly-initiated antiretroviral therapy clients in Malawi.

Background: Retention in HIV care is crucial for improved health outcomes. Malawi has a high HIV prevalence and struggles with retention despite significant progress in controlling the epidemic. Mobile health (mHealth) interventions, such as two-way texting (2wT), have shown promise in improving anti-retroviral therapy (ART) retention. We explore the cost-effectiveness of a 2wT intervention in Lighthouse Trust's Martin Preuss Center (MPC) in Lilongwe, Malawi, that sends automated SMS visit reminders, weekly motivational messages, and supports direct communication between clients and healthcare workers. Methods: Costs and retention rates were compared between 2wT and standard of care (SOC) for 468 clients enrolled in each. Incremental cost-effectiveness ratios (ICERs) were calculated. Scenario analyses were conducted to estimate costs if 2wT expanded. Results: The 2wT group had higher retention (80%) than SOC (67%) at 12 months post-ART initiation. For 468 clients, the total annual costs for 2wT were $36,670.38 as compared to SOC costs at $33,458.72, resulting in an ICER of $24,705. Among scenarios, the ICER was -$105,315 if 2wT expanded to all new clients (2678 at MPC and -$723,739 as 2wT expanded to other four high-burden facilities (2901 clients), suggesting high cost savings if 2wT was effectively scaled. Conclusion: The 2wT intervention appears cost-effective to improve ART retention among new ART initiates in a high-burden ART clinic. While mHealth interventions have potential limitations, their benefits in improving patient outcomes and cost savings support their integration into HIV care programs.

How much does it cost to retain antiretroviral therapy (ART) clients in care? Routine financial costs of retention interventions at Lighthouse Trust's Martin Preuss Centre (MPC) in Lilongwe, Malawi.

Introduction: Antiretroviral therapy (ART) improves the health of people living with HIV (PLHIV). However, a high loss to follow-up, particularly in the first year after ART initiation, is problematic. The financial expenses related to client retention in low- and middle-income countries (LMICs) in sub-Saharan Africa are not well understood. This study aimed to comprehensively assess and quantify the financial costs associated with routine ART retention care at Lighthouse Trust's (LT) Martin Preuss Centre (MPC), a large, public ART clinic in Lilongwe, Malawi. Methods: We performed activity-based microcosting using routine data to assess the expenses related to routine ART retention services at the MPC for 12 months, January-December 2021. MPC provides an "ART Buddy" from ART initiation to 12 months. The MPC's Back-to-Care (B2C) program traces clients who miss ART visits at any time. Clients may be traced and return to care multiple times per year. We assessed client retention costs for the first 12 months of treatment with ART and conducted a sensitivity analysis. Results: The total annual cost of ART retention interventions at the MPC was $237,564. The proactive Buddy phase incurred $108,504; personnel costs contributed $97,764. In the reactive B2C phase, the total cost was $129,060, with personnel expenses remaining substantial at $73,778. The Buddy unit cost was $34 per client. The reactive B2C intervention was $17 per tracing event. On average, the unit cost for ART retention in the first year of ART averaged $22 per client. Conclusion: This study sheds light on the financial dimensions of ART retention interventions at the MPC of LTs. ART retention is both costly and critical for helping clients adhere to visits and remain in care. Continued investment in the human resources needed for both proactive and reactive retention efforts is critical to engaging and retaining patients on lifetime ART.

Centering healthcare workers in developing digital health interventions: usability and acceptability of a two-way texting retention intervention in a public HIV clinic in Lilongwe, Malawi.

Background: New initiates on antiretroviral therapy (ART) are at high risk of treatment discontinuation, putting their health at risk. In low-resource settings, like Malawi, appropriate digital health applications must fit into local connectivity and resource constraints. Target users' perspectives are critical for app usability, buy-in and optimization. We describe the formative stages of the design of a two-way text-based (2wT) system of tailored reminders and adherence messages for new ART initiates and share results from key informant interviews with HCWs focused on app usability and acceptability. Methods: Using a co-creation approach with clients, clinical, technical and evaluation teams and over app development, we held four informal user feedback sessions, a small pilot with 50 clients, and ten key informant (KIIs) to deepen our understanding of healthcare workers (HCWs) needs, acceptability and usability. Results: Formative research informed the design of interactive client-to-HCW communication, refining of the language and timing of weekly text blast motivational messages and tailored client-specific visit reminders. Informal feedback from HCW stakeholders also informed educational materials to enhance 2wT client understanding of how to report transfers, request visit date changes and ask questions related to their visits. In KII, HCWs noted their appreciation for the co-creation process, believing that the participatory HCD process and responsive design team enabled the development of a highly acceptable and usable 2wT digital tool. HCWs also suggested future improvements to promote inclusion of clients of varying literacy levels and economic backgrounds as well as integrating with other health platforms to improve uptake of 2wT. Conclusions: Inclusion of HCWs increased perceptions of app usability and acceptability among HCWs. HCWs believe that 2wT will improve on-time ART visit attendance and provide valuable early retention in care support. The co-creation approach appears successful in designing an app that will meet HCW needs and, therefore, support client adherence to visits.

"It reminds me and motivates me": Human-centered design and implementation of an interactive, SMS-based digital intervention to improve early retention on antiretroviral therapy: Usability and acceptability among new initiates in a high-volume, public clinic in Malawi.

BACKGROUND: Early retention of people living with HIV (PLHIV) in antiretroviral therapy (ART) programs is critical to improve individual clinical outcomes and viral load suppression. Although many mobile health (mHealth) interventions aim to improve retention in care, there is still lack of evidence on mHealth success or failure, including from patient's perspectives. We describe the human-centered design (HCD) process and assess patient usability and acceptability of a two-way texting (2wT) intervention to improve early retention among new ART initiates at Lighthouse Trust clinic in Lilongwe, Malawi. METHODS: An iterative HCD approach focused on patient and provider users' needs, incorporating feedback from multidisciplinary teams to adapt 2wT for the local, public clinic context. We present mixed-methods usability and acceptability results from 100 participants, 50 at 3-months and 50 at 6-months, post 2wT enrollment, and observations of these same patients completing core tasks of the 2wT system. RESULTS: Among the 100 usability respondents, 95% were satisfied with visit reminders, and 88% would recommend reminders and motivational messages to friends; however, 17% were worried about confidentiality. In observation of participant task completion, 94% were able to successfully confirm visit attendance and 73% could request appointment date change. More participants in 4-6 months group completed tasks correctly compared to 1-3 months group, although not significantly different (78% vs. 66%, p = 0.181). Qualitative results were overwhelmingly positive, but patients did note confusion with transfer reporting and concern that 2wT would not reach patients without mobile phones or with lower literacy. CONCLUSION: The 2wT app for early ART retention appears highly usable and acceptable, hopefully creating a solid foundation for lifelong engagement in care. The HCD approach put the local team central in this process, ensuring that both patients' and Lighthouse's priorities, policies, and practices were forefront in 2wT optimization, raising the likelihood of 2wT success in other routine program contexts.

Implementing Advanced HIV Disease Care for Inpatients in a Referral Hospital in Malawi - Demand, Results and Cost Implications.

Setting: 100 bed medical ward in referral hospital, Lilongwe, Malawi. Objective: HIV positive patients admitted to hospital often have advanced HIV disease (AHD) and are at risk for mortality. WHO guidelines suggest a package of care for AHD; these are often not implemented, especially in inpatient settings. We describe an implementation model for AHD care, its outcomes in routine care and provide cost estimates. Design: An "AHD care room" was established staffed by HIV counselor, nurse, and clinical officer allowing Provider Initiated Testing and Counseling, diagnostic testing for AHD and ensuring availability of HIV and TB drugs for rapid treatment initiation. Results: In the observation period from January to December 2020, a total of 1549 medical inpatients were tested for HIV (coverage 77.1%); 69 tested positive (yield 4.5%). The total proportion of HIV positive was 32.3% (638 already on ART and 69 newly diagnosed). CD4+ testing was done in 460 medical inpatients (65.1%); 245 (53.2%) were below 200 cells/ml and thus met definition of AHD. A total of 238 received S-CrAg tests; 39 (16.3%) were positive; 62 (28.3%) of 219 U-LAM tests were positive. The cost per identification of HIV positive patient was US$ 110.8; per AHD diagnosis between US$ 17.1 to 78.9; per positive S-CrAg test US$ 18.5 and per positive U-LAM test US$ 17.5. Conclusion: Our model successfully implemented AHD services according to WHO guidelines and provides basic costing data. Similar services could be implemented in other hospitals in LMICs.

Comparative study of survival among small cell lung cancer patients in the U.S. military health system and those in the surveillance, epidemiology, and end results (SEER) program.

PURPOSE: The U.S. military health system provides universal health care access to beneficiaries. However, whether the universal access has translated into improved patient outcome is unknown. We compared survival of small-cell lung cancer patients in the military health system with that in the U.S. general population. Stage and receipt of cancer treatment were also compared to see if they could contribute to survival difference. METHODS: The data were obtained from The Department of Defense's Automated Central Tumor Registry (ACTUR) and the national Surveillance, Epidemiology, and End Results (SEER) program, respectively. ACTUR (N = 3040) and SEER patients (N = 12,160) were matched on age, sex, race and diagnosis year. Multivariable Cox regression model was used to compare all-cause mortality between ACTUR and SEER. Multivariable logistic regression was performed to compare cancer stage and treatment. RESULTS: ACTUR patients exhibited significantly better survival than SEER counterparts (HR = 0.77, 95% CI= 0.71-0.83). ACTUR and SEER patients had similar stage, but ACTUR patients were more likely to receive radiation treatment (OR = 1.26, 95% CI = 1.12-1.42). The survival advantage of ACTUR patients remained across all tumor stages and radiation groups. CONCLUSIONS: Survival of small-cell lung cancer patients with universal health care access had better survival than similar patients in the U.S. general population. Future studies are warranted to identify factors that may contribute to the improved survival.

Virologic failure and switch to second-line antiretroviral therapy in children with HIV in Lilongwe, Malawi: an observational cohort study.

BACKGROUND: As routine viral load testing among HIV-infected individuals on antiretroviral therapy (ART) expands, virologic failure (VF) among children in developing countries remains poorly understood. We assessed the rate of VF, the proportion failing who were subsequently switched to second-line ART and factors associated with VF among children ≤18 y. METHODS: An observation cohort study among 1312 children at two public clinics in Lilongwe, Malawi who initiated a first-line ART regimen between January 2014 and December 2017 and remained on treatment for ≥6 mo was conducted. Kaplan-Meier methods estimated the probabilities of VF. Univariable and multivariable Poisson regression models were used to explore predictors of VF. RESULT: Overall, 16% (208/1312) of children experienced VF with an incidence rate of 10.1 events per 100 person-years. Of the 208, 184 (88%) were switched to second-line ART: 68 (43%) switched the same day VF was confirmed and 106 (66%) switched within 90 d of confirmed VF. Use of a Nevirapine (NVP)-based regimen and initiating ART in 2016-2017 compared with 2014-2015 were independent predictors of VF. CONCLUSION: VF is common among children receiving ART. The findings suggest that VF can be reduced by phasing out NVP-based regimen and by ensuring optimal adherence to ART.

Race and renal cell carcinoma stage at diagnosis: an analysis of the Surveillance, Epidemiology, and End Results data.

To study racial differences in tumor stage at diagnosis among Black and White patients with renal cell carcinoma (RCC) by histologic type and time period. The patients were Black and White patients with RCC from 1999 to 2011 derived from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Multinomial logistic regression was used to assess the associations between cancer stage and race and then stratified by histology and diagnosis year. Compared to Whites, Blacks were less likely to be diagnosed with regional disease [odds ratio (OR)=0.67; 95% confidence interval (CI)=0.60-0.73] or distant disease (OR=0.82; 95% CI=0.74-0.90) after adjusting for age, sex, year of diagnosis, and tumor grade. When stratified by RCC histology, similar results were observed for clear cell (OR=0.71; 95% CI=0.63-0.80), chromophobe (OR=0.51; 95% CI=0.32-0.81), and other histologic type (OR=0.63; 95% CI=0.42-0.96) while the association was not significant for papillary histology. The analyses by time showed a lower likelihood to have regional disease in Black than White in 2003-2006 (OR=0.66; 95% CI=0.55-0.79) and 2007-2011 (OR=0.57; 95% CI=0.49-0.67). Black patients were also less likely to have distant disease in 2007-2011 period (OR=0.76; 95% CI=0.65-0.88). In conclusion, blacks were less likely to be diagnosed at a later stage RCC than Whites regardless of cancer histology. This racial disparity may exist over time during the study period.

Survival among Lung Cancer Patients in the U.S. Military Health System: A Comparison with the SEER Population.

Background: The U.S. military health system (MHS) provides universal health care access to its beneficiaries. However, whether the universal access has translated into improved patient outcome is unknown. This study compared survival of non-small cell lung cancer (NSCLC) patients in the MHS with that in the U.S. general population.Methods: The MHS data were obtained from The Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR), and the U.S. population data were drawn from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. The study subjects were NSCLC patients diagnosed between January 1, 1987, and December 31, 2012, in ACTUR and a sample of SEER patients who were matched to the ACTUR patients on age group, sex, race, and year of diagnosis group with a matching ratio of 1:4. Patients were followed through December 31, 2013.Results: A total of 16,257 NSCLC patients were identified from ACTUR and 65,028 matched patients from SEER. Compared with SEER patients, ACTUR patients had significantly better overall survival (log-rank P < 0.001). The better overall survival among the ACTUR patients remained after adjustment for potential confounders (HR = 0.78, 95% confidence interval, 0.76-0.81). The survival advantage of the ACTUR patients was present regardless of cancer stage, grade, age group, sex, or race.Conclusions: The MHS's universal care and lung cancer care programs may have translated into improved survival among NSCLC patients.Impact: This study supports improved survival outcome among NSCLC patients with universal care access. Cancer Epidemiol Biomarkers Prev; 27(6); 673-9. ©2018 AACR.

Diagnostic performance of urinary IgG antibody detection: A novel approach for population screening of strongyloidiasis.

The diagnosis of strongyloidiasis by coprological methods has a low sensitivity, underestimating the prevalence of Strongyloides stercoralis in endemic areas. Serodiagnostic tests for strongyloidiasis have shown robust diagnostic properties. However, these methods require a blood draw, an invasive and labor-intensive sample collection method, especially in the resource-limited settings where S. stercoralis is endemic. Our study examines a urine-based assay for strongyloidiasis and compares its diagnostic accuracy with coprological and serological methods. Receiver operating characteristic (ROC) curve analyses determined the diagnostic sensitivity (D-Sn) and specificity (D-Sp) of the urine ELISA, as well as estimates its positive predictive value and diagnostic risk. The likelihood ratios of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for each diagnostic positivity threshold. The urine ELISA assay correlated significantly with the serological ELISA assay for strongyloidiasis, with a D-Sn of 92.7% and a D-Sp of 40.7%, when compared to coprological methods. Moreover, the urine ELISA IgG test had a detection rate of 69%, which far exceeds the coprological method (28%). The likelihood of a positive diagnosis of strongyloidiasis by the urine ELISA IgG test increased significantly with increasing units of IgG detected in urine. The urine ELISA IgG assay for strongyloidiasis assay has a diagnostic accuracy comparable to serological assay, both of which are more sensitive than coprological methods. Since the collection of urine is easy and non-invasive, the urine ELISA IgG assay for strongyloidiasis could be used to screen populations at risk for strongyloidiasis in S. stercoralis endemic areas.

Lung, Breast, and Prostate Cancer Patients with Unknown Ethnicity in US Department of Defense Cancer Registry Data: Comparisons to Patients with Known Ethnicity.

INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer death for both men and women in the United States. Several factors can increase one's risk of CRC, including a personal or family history of CRC, a diagnosis or family history of a hereditary colon cancer syndrome, or a diagnosis of chronic inflammatory bowel disease. The purpose of this project was to create a colorectal cancer registry (Co-Care) for individuals with a personal or family history of CRC, and those with disorders of the colon or rectum that are associated with an increased risk for developing CRC. METHODS: To be eligible for the registry, patients either had a personal or family history of CRC, a diagnosis or family history of Lynch syndrome, familial adenomatous polyposis, or a diagnosis of Crohn's colitis or ulcerative colitis with dysplasia. Participants were recruited after seeing their gastroenterologist or genetic counselor, or after undergoing a full or partial colectomy at Mount Sinai Hospital in New York City. Eligible patients who agreed to participate were interviewed by a member of the research staff and asked a wide range of questions pertaining to CRC risk. RESULTS: A total of 224 patients were enrolled in the registry. Participants are mostly white, born in the United States, and married, with a bachelor's or graduate degree, reporting an annual household income of $100,000 or more. The largest portion have a family history of CRC (27.2%), and almost half of participants are of Jewish descent (46.2%) and have undergone full or partial colectomy (48.2%). More than half of participants have neither received genetic counseling (54.5%) nor undergone genetic testing (59.7%). Only 3.6% report that they currently smoke cigarettes, and 41.1% consume alcohol at least once per week. Lastly, 18.3%, 10.3%, and 27.7% of participants report that they currently take aspirin, folic acid/folate pills or tablets, or calcium pills/tablets, respectively. CONCLUSIONS: This registry can improve our understanding of CRC and related diseases, and be used to design future interventions related to disease risk, prognosis, and prevention of CRC.

Advances in the Diagnosis of Human Opisthorchiasis: Development of Opisthorchis viverrini Antigen Detection in Urine.

BACKGROUND: Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV eggs often confused with eggs of minute intestinal flukes (MIFs) in feces. In this study, we developed and evaluated the diagnostic performance of a monoclonal antibody-based enzyme-linked immunosorbent assay for the measurement of OV excretory-secretory (ES) antigens in urine (urine OV-ES assay) for the diagnosis of opisthorchiasis compared to the gold standard detection FECT method. METHODOLOGY: We tested several methods for pre-treating urine samples prior to testing the diagnostic performance of the urine OV-ES assay. Using trichloroacetic acid (TCA) pre-treated urine, we compared detection and quantification of OV infection using the urine OV-ES assay versus FECT in OV-endemic areas in Northeastern Thailand. Receiver operating characteristic (ROC) curves were used to determine the diagnostic sensitivity and specificity of the urine OV-ES assay using TCA pre-treated urine, and to establish diagnostic positivity thresholds. The Positive Predictive Value as well as the likelihood of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for the established diagnostic positivity threshold. Diagnostic risks (Odds Ratios) were estimated using logistic regression. RESULTS: When urine samples were pre-treated with TCA prior to use in the urine OV-ES assay, the analytical sensitivity was significantly improved. Using TCA pre-treatment of urine, the urine OV-ES assay had a limit of detection (LoD) of 39 ng/ml compared to the LoD of 52 ng/mL reported for coprological antigen detection methods. Similarly, the urine OV-ES assay correlated significantly with intensity of OV infection as measured by FECT. The urine OV-ES assay was also able to detect 28 individuals as positive from the 63 (44.4%) individuals previously determined to be negative using FECT. The likelihood of a positive diagnosis of OV infection by urine OV-ES assay increased significantly with the intensity of OV infection as determined by FECT. With reference to FECT, the sensitivity and specificity of the urine OV-ES assay was 81% and 70%, respectively. CONCLUSION: The detection of OV-infection by the urine OV-ES assay showed much greater diagnostic sensitivity and diagnostic specificity than the current "gold standard" FECT method for the detection and quantification of OV infection. Due to its ease-of-use, and noninvasive sample collection (urine), the urine OV-ES assay offers the potential to revolutionize the diagnosis of liver fluke infection and provide an effective tool for control and elimination of these tumorigenic parasites.